title: Body temperature affects cerebral hemodynamics in acutely brain injured patients: an observational transcranial color-coded duplex sonography study.

text: INTRODUCTION Temperature changes are common in patients in a neurosurgical intensive care unit (NICU): fever is frequent among severe cases and hypothermia is used after cardiac arrest and is currently being tested in clinical trials to lower intracranial pressure (ICP). This study investigated cerebral hemodynamics when body temperature varies in acute brain injured patients. METHODS We enrolled 26 patients, 14 with acute brain injury who developed fever and were given antipyretic therapy (defervescence group) and 12 who underwent an intracranial neurosurgical procedure and developed hypothermia in the operating room; once admitted to the NICU, still under anesthesia, they were re-warmed before waking (re-warming group). We measured cerebral blood flow velocity (CBF-V) and pulsatility index (PI) at the middle cerebral artery using transcranial color-coded duplex sonography (TCCDS). RESULTS In the defervescence group mean CBF-V decreased from 75 ± 26 (95% CI 65 to 85) to 70 ± 22 cm/s (95% CI 61 to 79) (P = 0.04); the PI also fell, from 1.36 ± 0.33 (95% CI 1.23 to 1.50) to 1.16 ± 0.26 (95% CI 1.05 to 1.26) (P = 0.0005). In the subset of patients with ICP monitoring, ICP dropped from 16 ± 8 to 12 ± 6 mmHg (P = 0.003). In the re-warming group mean CBF-V increased from 36 ± 10 (95% CI 31 to 41) to 39 ± 13 (95% CI 33 to 45) cm/s (P = 0.04); the PI rose from 0.98 ± 0.14 (95% CI 0.91 to 1.04) to 1.09 ± 0.22 (95% CI 0.98 to 1.19) (P = 0.02). CONCLUSIONS Body temperature affects cerebral hemodynamics as evaluated by TCCDS; when temperature rises, CBF-V increases in parallel, and viceversa when temperature decreases. When cerebral compliance is reduced and compensation mechanisms are exhausted, even modest temperature changes can greatly affect ICP.


The Invisible Hand - Medical Care during the Pandemic.


title: Retained Needle in the AirSeal Trocar During Robot-Assisted Laparoscopic Radical Prostatectomy: Lessons Learned.

text: Background: Unique case of retained needle in the AirSeal trocar during robot-assisted laparoscopic radical prostatectomy. Case Presentation: A 68-year-old male with prostate cancer underwent robot-assisted laparoscopic radical prostatectomy. Upon laparoscopic removal of final intra-abdominal suture by bedside assistant, needle became dislodged from suture and was unable to be located after a standard systematic search. Ultimately, needle was found caught in the assistant's AirSeal trocar device. Conclusion: Intraoperative loss of a foreign body should include inspection, and possible radiographic evaluation, of the trocar mechanism as part of a complete systematic approach.


Total or partial removal of infected mesh? Invited comment.


title: Carers' Experiences, Needs, and Preferences During Inpatient Stroke Rehabilitation: A Systematic Review of Qualitative Studies.

text: OBJECTIVE To report and synthesize the experiences, needs, and preferences of carers of stroke survivors undergoing inpatient rehabilitation. DATA SOURCES MEDLINE, CINAHL, Embase, PsycINFO, and Web of Science were searched to March 2016. Reference lists of relevant publications were searched. No language restrictions were applied. STUDY SELECTION Eligible qualitative studies reported the experiences of carers of stroke survivors who underwent inpatient rehabilitation. The search yielded 3532 records; 93 full-text publications were assessed for eligibility, and 34 documents (33 studies) were included. Comprehensiveness of reporting was assessed using the Consolidated Criteria for Reporting Qualitative Health Research framework. DATA EXTRACTION Data on the characteristics of included studies were independently extracted by 2 authors. Differences in data extraction between authors were resolved through discussion or by a third author. All text in studies' results and discussion sections were extracted for analysis. DATA SYNTHESIS Extracted texts were analyzed inductively using thematic synthesis. Seven analytical themes were developed that related to the carers' experiences, needs, and preferences: (1) overwhelmed with emotions; (2) recognition as a stakeholder in recovery; (3) desire to be heard and informed; (4) persisting for action and outcomes; (5) being legitimate clients; (6) navigating an alien culture and environment; and (7) managing the transition home. CONCLUSIONS This systematic review provides new insights into the experiences, needs, and preferences of carers of stroke survivors undergoing inpatient rehabilitation. Carers experienced distress as they navigated a foreign culture and environment without adequate communication and processes in place for their inclusion. We recommend deliberate efforts to provide a more inclusive environment that better supports and prepares carers for their new role.


title: Totally laparoscopic feeding jejunostomy - a technique modification.

text: In oncological patients with upper gastrointestinal tract tumours, dysphagia and cachexy necessitate gastrostomy or jejunostomy as the only options of enteral access for long-term feeding. In this article the authors describe a modified technique of laparoscopic feeding jejunostomy applied during the staging laparoscopy. A 48-year-old male patient with gastroesophageal junction tumour and a 68-year-old male patient with oesophageal tumour were operated on using the described technique. Exploratory laparoscopy was performed. Then the feeding jejunostomy was made using a Cystofix(®) TUR catheter. The jejunum was fixed to the abdominal wall with four 2.0 Novafil™ transabdominal stitches. Two additional sutures were placed caudally about 4 cm and 8 cm from the jejunostomy, aiming at prevention of jejunal torsion. Total operating time was 45 min. There was no blood loss. There were no intraoperative complications. The only adverse event was one jejunostomy wound infection that responded well to oral antibiotics. There were no mortalities. The described technique has most of the benefits of laparoscopic feeding jejunostomy with some steps added from the open operation making the procedure easier to perform as part of a staging operation with a relatively short additional operating time. The proposed transabdominal stitches make the technique easier to apply. Two additional 'anti-torsion sutures' prevent postoperative volvulus. Use of the Cystofix catheter allows easy introduction of the catheter into the peritoneal cavity and the jejunal lumen, providing a good seal at the same time. Further studies on larger groups of patients are required to assess long-term outcomes of the proposed modified technique.


title: A novel, helminth-derived immunostimulant enhances human recall responses to hepatitis C virus and tetanus toxoid and is dependent on CD56+ cells for its action.

text: We have described previously an immunostimulant derived from Onchocerca volvulus, the helminth parasite that causes onchocerciasis. Recombinant O. volvulus activation-associated secreted protein-1 (rOv-ASP-1) was a potent adjuvant for antibody and cellular responses to protein, polypeptide and small peptide antigens. Our aims were to determine whether rOv-ASP-1 is immunostimulatory for human peripheral blood mononuclear cells (PBMC) and, if so, whether it could augment cellular responses against human pathogen antigens in vitro. Cytokines from rOv-ASP-1-stimulated human PBMC were measured by a fluorescence activated cell sorter-based multiplex assay. Recall responses of normal healthy donor (NHD) and chronic hepatitis C virus (c-HCV)-infected patient PBMC to tetanus toxoid (TT) or HCV core (HCVco) antigen, respectively, were measured by interferon-gamma enzyme-linked immunospot assays. Interferon-gamma was the predominant cytokine induced by rOv-ASP-1. 77.3% of NHD anti-TT and 88.9% of c-HCV anti-HCVco responses were enhanced by rOv-ASP-1. The immunostimulant effect was dependent upon contact between CD56+ and CD56- fractions of PBMC. We have described a helminth-derived protein that can act as an immunostimulant for human recall responses in vitro to TT and, perhaps more importantly, HCV antigens in patients with chronic HCV infection. Our longer-term goal would be to boost anti-viral responses in chronic infections such as HCV.


title: Broadly neutralizing immune responses against hepatitis C virus induced by vectored measles viruses and a recombinant envelope protein booster.

text: Hepatitis C virus (HCV) infection remains a serious public health problem worldwide. Treatments are limited, and no preventive vaccine is available. Toward developing an HCV vaccine, we engineered two recombinant measles viruses (MVs) expressing structural proteins from the prototypic HCV subtype 1a strain H77. One virus directs the synthesis of the HCV capsid (C) protein and envelope glycoproteins (E1 and E2), which fold properly and form a heterodimer. The other virus expresses the E1 and E2 glycoproteins separately, with each one fused to the cytoplasmic tail of the MV fusion protein. Although these hybrid glycoproteins were transported to the plasma membrane, they were not incorporated into MV particles. Immunization of MV-susceptible, genetically modified mice with either vector induced neutralizing antibodies to MV and HCV. A boost with soluble E2 protein enhanced titers of neutralizing antibody against the homologous HCV envelope. In animals primed with MV expressing properly folded HCV C-E1-E2, boosting also induced cross-neutralizating antibodies against two heterologous HCV strains. These results show that recombinant MVs retain the ability to induce MV-specific humoral immunity while also eliciting HCV neutralizing antibodies, and that anti-HCV immunity can be boosted with a single dose of purified E2 protein. The use of MV vectors could have advantages for pediatric HCV vaccination.


title: Laparoscopic resectional gastric bypass: initial experience in morbidly obese Korean patients.

text: PURPOSE Roux-en-Y gastric bypass (RYGB) is thought to be the gold standard treatment for morbid obesity. However, concerns have been raised by investigators in areas where gastric cancer is prevalent regarding the inaccessibility of the excluded stomach to regular surveillance. This study aimed to evaluate the technical feasibility and short-term surgical outcomes of resectional RYGB. METHODS Sixteen consecutive patients who underwent laparoscopic gastric bypass with distal gastric resection for the primary purpose of weight loss between January 2011 and December 2013 were retrospectively reviewed. The perioperative outcomes and weight loss results of these patients were analyzed. RESULTS All procedures were successfully performed laparoscopically. The mean length of the operation and the mean hospital stay were 170 min (range 110-225) and 4 days (range 2-7), respectively. The prevalence of early postoperative complications reached 18.7% after resectional RYGB, but a severe complication requiring reoperation occurred in only one patient (6.3%). The percent of excess weight loss was 78.9% over a mean follow-up period of 14 months. Obesity-related comorbidities including diabetes, hypertension and dyslipidemia resolved or improved after surgery in most patients. CONCLUSION Resectional RYGB is technically feasible and can be a viable option in countries with a high risk of gastric cancer, where surgeons are already well trained in laparoscopic gastrectomy.


title: A Rapid Review of Sexual Wellbeing Definitions and Measures: Should We Now Include Sexual Wellbeing Freedom?

text: An increasing number of studies refer to sexual wellbeing and/or seek to measure it, and the term appears across various policy documents, including sexual health frameworks in the UK. We conducted a rapid review to determine how sexual wellbeing has been defined, qualitatively explored and quantitatively measured. Eligible studies selected for inclusion from OVID Medline, PsychInfo, PubMed, Embase, CINAHL were: in English language, published after 2007, were peer-reviewed full articles, focused on sexual wellbeing (or proxies for, e.g. satisfaction, function), and quantitatively or qualitatively assessed sexual wellbeing. We included studies with participants aged 16-65. Given study heterogeneity, our synthesis and findings are reported using a narrative approach. We identified 162 papers, of which 10 offered a definition of sexual wellbeing. Drawing upon a socio-ecological model, we categorised the 59 dimensions we identified from studies under three main domains: cognitive-affect (31 dimensions); inter-personal (22 dimensions); and socio-cultural (6 dimensions). Only 11 papers were categorised under the socio-cultural domain, commonly focusing on gender inequalities or stigma. We discuss the importance of conceptualising sexual wellbeing as individually experienced but socially and structurally influenced, including assessing sexual wellbeing freedom: a person's freedom to achieve sexual wellbeing, or their real opportunities and liberties.


title: A Commentary on Safety Precautions for Otologic Surgery during the COVID-19 Pandemic.

text: There are insufficient data regarding the safety of otologic procedures in the setting of the coronavirus disease 2019 (COVID-19) pandemic. Given the proclivity for respiratory pathogens to involve the middle ear and the significant aerosolization associated with many otologic procedures, safety precautions should follow current recommendations for procedures involving the upper airway. Until preoperative diagnostic testing becomes standardized and readily available, elective cases should be deferred and emergent/urgent cases should be treated as high risk for COVID-19 exposure. Necessary otologic procedures on positive, suspected, or unknown COVID-19 status patients should be performed using enhanced personal protective equipment, including an N95 respirator and eye protection or powered air-purifying respirator (PAPR, preferred), disposable cap, disposable gown, and gloves. Powered instrumentation should be avoided unless absolutely necessary, and if performed, PAPR or sealed eye protection is recommended.


title: Parents' and healthcare professionals' experiences of care after stillbirth in low- and middle-income countries: a systematic review and meta-summary.

text: BACKGROUND Stillbirth has a profound impact on women, families, and healthcare workers. The burden is highest in low- and middle-income countries (LMICs). There is need for respectful and supportive care for women, partners, and families after bereavement. OBJECTIVE To perform a qualitative meta-summary of parents' and healthcare professionals' experiences of care after stillbirth in LMICs. SEARCH STRATEGY Search terms were formulated by identifying all synonyms, thesaurus terms, and variations for stillbirth. Databases searched were AMED, EMBASE, MEDLINE, PsychINFO, BNI, CINAHL. SELECTION CRITERIA Qualitative, quantitative, and mixed method studies that addressed parents' or healthcare professionals' experience of care after stillbirth in LMICs. DATA COLLECTION AND ANALYSIS Studies were screened, and data extracted in duplicate. Data were analysed using the Sandelowski meta-summary technique that calculates frequency and intensity effect sizes (FES/IES). MAIN RESULTS In all, 118 full texts were screened, and 34 studies from 17 countries were included. FES range was 15-68%. Most studies had IES 1.5-4.5. Women experience a broad range of manifestations of grief following stillbirth, which may not be recognised by healthcare workers or in their communities. Lack of recognition exacerbates negative experiences of stigmatisation, blame, devaluation, and loss of social status. Adequately developed health systems, with trained and supported staff, are best equipped to provide the support and information that women want after stillbirth. CONCLUSIONS Basic interventions could have an immediate impact on the experiences of women and their families after stillbirth. Examples include public education to reduce stigma, promoting the respectful maternity care agenda, and investigating stillbirth appropriately. TWEETABLE ABSTRACT Reducing stigma, promoting respectful care and investigating stillbirth have a positive impact after stillbirth for women and families in LMICs.


title: Amicus or adversary: platelets in lung biology, acute injury, and inflammation.

text: Platelets are the chief effector cells in hemostasis and have additional major functions in inflammation, vascular integrity, and tissue repair. Platelets and the lungs have interrelated activities. Previous studies provide evidence that platelets contribute to pulmonary vascular barrier function and are required for defense against pulmonary hemorrhage, and that the lungs can influence platelet number and distribution. There is also evidence that platelets contribute to pathologic syndromes of pulmonary inflammation and thrombosis. Thus, platelets have an "amicus or adversary" relationship with the lung. Recent observations and discoveries have established new paradigms relevant to influences of platelets on lung cell and molecular biology. These new findings are in a variety of areas including thrombopoieis, nontraditional activities of platelets, new synthetic capabilities and mechanisms of post-translational gene expression, interactions of platelets with endothelial cells and contributions to alveolar capillary barrier permeability, interactions of platelets with myeloid leukocytes, and platelet involvement in stem cell signaling and vascular repair. These issues are considered in a translational approach, with an emphasis on acute lung injury and the acute respiratory distress syndrome.


title: The scientific basis for postoperative respiratory care.

text: Postoperative pulmonary complications (PPCs) are common and expensive. Costs, morbidity, and mortality are higher with PPCs than with cardiac or thromboembolic complications. Preventing and treating PPCs is a major focus of respiratory therapists, using a wide variety of techniques and devices, including incentive spirometry, CPAP, positive expiratory pressure, intrapulmonary percussive ventilation, and chest physical therapy. The scientific evidence for these techniques is lacking. CPAP has some evidence of benefit in high risk patients with hypoxemia. Incentive spirometry is used frequently, but the evidence suggests that incentive spirometry alone has no impact on PPC. Chest physical therapy, which includes mechanical clapping and postural drainage, appears to worsen atelectasis secondary to pain and splinting. As with many past respiratory therapy techniques, the profession needs to take a hard look at these techniques and work to provide only practices based on good evidence. The idea of a PPC bundle has merit and should be studied in larger, multicenter trials. Additionally, intraoperative ventilation may play a key role in the development of PPCs and should receive greater attention.


title: Investigation of Nosocomial SARS-CoV-2 Transmission from Two Patients to Health Care Workers Identifies Close Contact but not Airborne Transmission Events.

text: OBJECTIVE To describe the pattern of transmission of SARS-CoV-2 during 2 nosocomial outbreaks of COVID-19 with regard to the possibility of airborne transmission. DESIGN Contact investigations with active case finding were used to assess the pattern of spread from 2 COVID-19 index patients. SETTING A community hospital and university medical center in the United States, in February and March, 2020, early in the COVID-19 pandemic. PATIENTS Two index patients and 421 exposed health care workers. METHODS Exposed staff were identified by analyzing the EMR and conducting active case finding in combination with structured interviews. Staff were tested for COVID-19 by obtaining oropharyngeal/nasopharyngeal specimens, with RT-PCR testing to detect SARS-CoV-2. RESULTS Two separate index patients were admitted in February and March 2020, without initial suspicion for COVID-19 and without contact or droplet precautions in place; both patients underwent several aerosol generating procedures in this context. A total of 421 health care workers were exposed in total, and the results of the case contact investigations identified 8 secondary infections in health care workers. In all 8 cases, the staff had close contact with the index patients without sufficient personal protective equipment. Importantly, despite multiple aerosol generating procedures, there was no evidence of airborne transmission. CONCLUSION These observations suggest that, at least in a healthcare setting, a majority of SARS-CoV-2 transmission is likely to take place during close contact with infected patients through respiratory droplets, rather than by long-distance airborne transmission.


title: Similarities and differences in estimates of sleep duration by polysomnography, actigraphy, diary, and self-reported habitual sleep in a community sample.

text: OBJECTIVES To compare estimates of sleep duration defined by polysomnography (PSG), actigraphy, daily diary, and retrospective questionnaire and to identify characteristics associated with differences between measures. DESIGN Cross-sectional. SETTING Community sample. PARTICIPANTS The sample consisted of 223 Black, White, and Asian middle- to older-aged men and women residing in the Pittsburgh, PA area. INTERVENTIONS Not applicable. MEASUREMENTS Two nights of in-home PSG; 9 nights of wrist actigraphy and sleep diaries; retrospective sleep questionnaires; and measures of sociodemographic, psychosocial, and adiposity characteristics. RESULTS All measures of sleep duration differed significantly, with modest associations between PSG-assessed and retrospective questionnaire-assessed sleep duration. Individuals estimated their habitual sleep duration about 20-30 minutes longer by questionnaire and their prospective sleep diaries compared with both PSG- and actigraphy-assessed sleep duration. Persons reporting higher hostility had smaller associations between PSG-assessed sleep duration and other methods compared with those with lower hostility; those reporting more depressive symptoms and poorer overall health had smaller associations between actigraphy-assessed sleep duration and questionnaire and diary measures. Apnea-hypopnea index was not related to differences among estimates of sleep duration. CONCLUSIONS PSG, actigraphy, diary, and retrospective questionnaire assessments yield different estimates of sleep duration. Hostility, depressive symptoms, and perceptions of poor health were associated with the magnitude of differences among some estimates. These findings may be useful in understanding the health consequences of short or long self-reported sleep duration and for guiding investigator decisions about choices of measures in specific populations.


title: Vaccines, new opportunities for a new society.

text: Vaccination is the most effective medical intervention ever introduced and, together with clean water and sanitation, it has eliminated a large part of the infectious diseases that once killed millions of people. A recent study concluded that since 1924 in the United States alone, vaccines have prevented 40 million cases of diphtheria, 35 million cases of measles, and a total of 103 million cases of childhood diseases. A report from the World Health Organization states that today vaccines prevent 2.5 million deaths per year: Every minute five lives are saved by vaccines worldwide. Overall, vaccines have done and continue to do an excellent job in eliminating or reducing the impact of childhood diseases. Furthermore, thanks to new technologies, vaccines now have the potential to make an enormous contribution to the health of modern society by preventing and treating not only communicable diseases in all ages, but also noncommunicable diseases such as cancer and neurodegenerative disorders. The achievement of these results requires the development of novel technologies and health economic models able to capture not only the mere cost-benefit of vaccination, but also the value of health per se.


Non-contact tonometer use during the COVID-19 pandemic.


title: Epidemiology of Barrett's Esophagus and Esophageal Adenocarcinoma.

text: Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC), a disease with increasing burden in the Western world, especially in white men. Risk factors for BE include obesity, tobacco smoking, and gastroesophageal reflux disease (GERD). EAC is the most common form of esophageal cancer in the United States. Risk factors include GERD, tobacco smoking, and obesity, whereas nonsteroidal antiinflammatory drugs and statins may be protective. Factors predicting progression from nondysplastic BE to EAC include dysplastic changes on esophageal histology and length of the involved BE segment. Biomarkers have shown promise, but none are approved for clinical use.


title: Small bowel volvulus following peritoneal closure using absorbable knotless device during laparoscopic sacral colpopexy.

text: As laparoscopic sacral colpopexy is associated with long operation times, barbed suture can be used to reduce the time needed to accomplish peritoneal closure. However, little is known about the adverse events of this new technique. We report on the case of a small bowel volvulus following peritoneal closure using a barbed suture. The patient presented with acute abdominal pain and a bowel obstruction syndrome 1 month after laparoscopic sacral colpopexy.


Case records of the Massachusetts General Hospital. Case 27-2011. A 17-year-old boy with abdominal pain and weight loss.


title: Transanal natural orifice transluminal endoscopic surgery (NOTES) rectal resection: "down-to-up" total mesorectal excision (TME)--short-term outcomes in the first 20 cases.

text: BACKGROUND The transanal minilaparoscopy-assisted natural orifice transluminal endoscopic surgery (NOTES) approach holds significant promise as a safe and less morbid alternative to conventional low anterior rectal resection. Previous reports have shown satisfactory short-term oncologic results. We evaluated the safety and short-term outcomes in rectal cancer subjects who underwent transanal minilaparoscopy-assisted natural orifice surgery total mesorectal excision (TME) rectal resection. METHODS Twenty selected patients with rectal cancer were enrolled onto a prospective study of minilaparoscopy-assisted natural orifice surgery TME rectal resection. The study endpoints were safety of access (intra- or postoperative morbidity) and adequacy of oncological resection criteria; intact TME; distal and circumferential margins; and number of lymph nodes retrieved. RESULTS All procedures were successfully completed with the transanal NOTES and minilaparoscopy technique. The mean age was 65 ± 10 years; 55% of patients were male; the mean body mass index was 25.3 ± 3.8 kg/m(2). Thirty-five percent of tumors were in the distal rectum, 50% in midrectum, and 15% in proximal rectum. Coloanal anastomoses were hand sewn in 65% and stapled in 35%. Mean operative time was 235 ± 56 min. There were no procedure-related complications. Pathologic analysis demonstrated negative distal and circumferential margins in all patients. An average of 15.9 ± 4.3 lymph nodes were retrieved. The mesorectal fascia was intact in all the specimens. CONCLUSIONS This study demonstrates that transanal NOTES with minilaparoscopic assistance in the hands of a specialized team is safe; meets the oncologic requirements for high-quality rectal cancer surgery; and may offer advantages over pure laparoscopic approaches for visualizing and dissecting out the distal mesorectum. Minilaparoscopic assistance allows one to compensate for the limitations of current NOTES instrumentation to ensure the safety and adequacy of oncologic resection in these difficult cases. Careful patient selection, a specialized team, and long-term outcome evaluation are critical before this procedure can be considered for routine clinical use.


title: Synthetic anti-lipopolysaccharide peptides and hepatitis C virus infection.

text: INTRODUCTION Hepatitis C virus (HCV) infection is a leading cause of cirrhosis and hepatocellular carcinoma. Although antiviral therapy has been markedly improved by the licensing of direct-acting antivirals, safety, resistance, high costs and difficult-to-treat patients remain important challenges. AREAS COVERED This article focuses and comments on the recent development of synthetic anti-lipopolysaccharide peptides (SALPs) which bind to highly sulfated glycosaminoglycan/heparan sulfate (HS) on cell surface. HS serves as a primary docking site for several viruses to their respective host cells before the viruses interact with their cell surface receptor(s). In vitro studies have shown that SALPs inhibit entry of HCV without cell toxicity. EXPERT OPINION SALPs prevent viral infection in cell culture model systems. Treatment studies of established HCV infection in cell culture models as well as proof-of-concept and safety studies in animal models are needed to evaluate their potential for drug development. The mechanism of action of SALPs as entry inhibitors suggests a potential application for HCV-infected patients to prevent reinfection of the liver graft in liver transplantation. Potential limitations may include high doses to obtain an antiviral effect and a target which is widely expressed and has a key function in cell physiology.


title: Preparing for and responding to pandemic influenza: implications for people with disabilities.

text: State, local, tribal, and territorial emergency managers and public health officials must address the specific needs of people with disabilities in their pandemic influenza plans. Evidence from Hurricane Katrina indicated that this population was disproportionately affected by the storm and aftermath. People with disabilities, particularly those who require personal assistance and those who reside in congregate care facilities, may be at increased risk during an influenza pandemic because of disrupted care or the introduction of the virus by their caregivers. Emergency and public health planners must ensure that personal assistance agencies and congregate care operators make provisions for backup staffing and that those who provide critical care are given adequate antiviral drugs and vaccines as they become available.


title: Effect of informed consent on patient characteristics in a stroke thrombolysis trial.

text: OBJECTIVE To determine whether the manner of consent, i.e., informed consent by patients themselves or informed consent by proxy, affects clinical characteristics of samples of acute stroke patients enrolled in clinical trials. METHODS We analyzed the manner of obtaining informed consent in the first 1,005 patients from WAKE-UP, an investigator-initiated, randomized, placebo-controlled trial of MRI-based thrombolysis in stroke patients with unknown time of symptom onset running in 6 European countries. Patients providing informed consent by themselves were compared with patients enrolled by proxy consent. Baseline clinical measures were compared between groups. RESULTS In 359 (35.7%) patients, informed consent was by proxy. Patients with proxy consent were older (median 71 vs 66 years, p < 0.0001) and had a higher frequency of arterial hypertension (58.2% vs 43.4%, p < 0.0001). They showed higher scores on the NIH Stroke Scale (median 11 vs 5, p < 0.0001) and more frequently aphasia (73.7% vs 20.0%, p < 0.0001). The rate of proxy consent varied among countries (p < 0.0001), ranging from 77.1% in Spain to 1.2% in Denmark. CONCLUSIONS Patients recruited by proxy consent were older, had more severe strokes, and had higher prevalence of aphasia than those with capacity to give personal consent. Variations in the manner of consent across countries may influence trial results. CLINICALTRIALSGOV AND CLINICALTRIALSREGISTEREU IDENTIFIERS NCT01525290 (clinicaltrials.gov); 2011-005906-32 (clinicaltrialsregister.eu).


Coagulation Factor XIII in Cerebral Venous Thrombosis.


title: Tor Vergata University-Hospital in the Beginning of COVID-19-Era: Experience and Recommendation for Breast Cancer Patients.

text: COVID-19 has been officially declared as a pandemic by the WHO. Italy was the first European country to be strongly affected by this outbreak. All elective and health promotion activities were reduced. Accordingly, Italian Breast Units and breast cancer (BC) screening programs scaled down significantly their activities. The aim of this study was to evaluate measures that could potentially reduce the clinical impact of COVID-19 on BC patients. Temporary recommendations are needed that could assist specialists in preventing COVID-19 infection and optimizing resources for diagnosis and treatment of BC patients.


title: Preoperative endoscopy localization error rate in patients with colorectal cancer.

text: BACKGROUND Preoperative repeat endoscopy in colorectal cancer (CRC) patients is considered by many to be an integral component of surgical planning. Little is known, however, about the utility of re-endoscopy. METHODS A retrospective review of 342 consecutive patients undergoing elective surgical resection for CRC from January 2008 to December 2011 was performed. Patients were included if the initial endoscopist was different than the operating surgeon. A localization error was recorded if the final tumor location identified during surgery was in a different anatomical segment than that identified by endoscopy. The Chi-squared test was used to compare categorical variables. An error rate with a 95% confidence interval was obtained using the exact binomial distribution. RESULTS 298 patients were identified, 118 (39.6%) of whom also underwent a preoperative re-endoscopy by the operating surgeon or partner. Nineteen patients had incorrect tumor localization at initial endoscopy, equivalent to a 6.4% error rate (95% CI 3.88-9.78). In comparison, there were two localization errors on re-endoscopy, 1.69% (95% CI 0.21-6.00). Re-endoscopy was found to be protective against localization errors (P < 0.05), correcting 10 of the 12 errors made at the initial endoscopy. The sensitivity of re-endoscopy as a diagnostic tool to detect errors was 83% with a corresponding specificity of 100%. The overall accuracy of re-endoscopy in preventing endoscopic localization errors was 92% (95% CI 81-100). CONCLUSIONS There is a small but important localization error rate in preoperative endoscopic evaluation of colorectal tumors. Re-endoscopy appears to be safe and may potentially identify and correct these errors and help with preoperative planning at the expense of delaying surgery. Further research is necessary to find ways to improve localization and identify which patients would benefit from re-endoscopy.


title: Whatever Happened to Evidence-Based Practice During COVID-19?

text: Contemporary medical practice is grounded in rigorous scientific evidence in concert with best clinical practices and informed shared decision making with patients. During these times of uncertainty, disruption, and even anxiety, it becomes critical that we engage with our patients and communities in thoughtful dialogue and realistic expectations regarding treatments surrounding COVID-19. The hope for a "miracle" cure and urgency to return back to normal times can stimulate irrational thought and behavior and even desperate measures by individuals or groups. It becomes especially important that we continue to use reasonable, informed clinical judgment in discussing the various options with patients.


title: Design of the liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results (LEADER) trial.

text: BACKGROUND Diabetes is a multisystem disorder associated with a nearly twofold excess risk for a broad range of adverse cardiovascular outcomes including coronary heart disease, stroke, and cardiovascular death. Liraglutide is a human glucagon-like peptide receptor analog approved for use in patients with type 2 diabetes mellitus (T2DM). STUDY DESIGN To formally assess the cardiovascular safety of liraglutide, the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial was commenced in 2010. LEADER is a phase 3B, multicenter, international, randomized, double-blind, placebo-controlled clinical trial with long-term follow-up. Patients with T2DM at high risk for cardiovascular disease (CVD) who were either drug naive or treated with oral antihyperglycemic agents or selected insulin regimens (human NPH, long-acting analog, or premixed) alone or in combination with oral antihyperglycemics were eligible for inclusion. Randomized patients are being followed for up to 5 years. The primary end point is the time from randomization to a composite outcome consisting of the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. CONCLUSIONS LEADER commenced in September 2010, and enrollment concluded in April 2012. There were 9,340 patients enrolled at 410 sites in 32 countries. The mean age of patients was 64.3 ± 7.2 years, 64.3% were men, and mean body mass index was 32.5 ± 6.3 kg/m2. There were 7,592 (81.3%) patients with prior CVD and 1,748 (18.7%) who were high risk but without prior CVD. It is expected that LEADER will provide conclusive data regarding the cardiovascular safety of liraglutide relative to the current standard of usual care for a global population of patients with T2DM.


title: A methodological approach to identify the most reliable human milk collection method for compositional analysis: a systematic review protocol.

text: BACKGROUND Breast milk composition has been reported to vary significantly between individual women and between different populations. However, the composition is also known to vary within the same woman between different days, within the same day, and even across the same feed. Therefore, it is unclear to what extent variations in composition are due to variations in sampling methodology between studies. The purpose of this systematic review is to compare the results obtained for breast milk macronutrient composition between studies utilizing different sampling methodologies and to use this as a basis to determine the most robust and consistent sampling approach as an alternative to full expression (gold standard). METHODS The EMBASE, MEDLINE/PubMed, Cochrane Library, Scopus, Web of Science, and ProQuest Dissertations and Theses Global databases will be searched for relevant articles. Observational studies, including cross-sectional, comparative cohort, and longitudinal cohort studies which involve lactating women who are breastfeeding (exclusively or not) or expressing (manually or using a breast pump) at any lactation stage will be included. This review will compare different methods of breast milk collection used in research studies which report macronutrient levels (protein, fat, lactose). Two review authors will independently screen titles and abstracts of studies identified by the literature search to determine articles for the full text screening. Quality assessment of included articles will be conducted independently by two review authors using the Newcastle-Ottawa scale. DISCUSSION It is important to identify the most reliable and practical method of human milk collection which best represents the average composition of the milk that is being consumed by the infant. This systematic review will be critical for ensuring that we determine a robust and consistent sampling approach to use in future studies of evaluating breast milk composition in a larger population. Identifying a recommended standard collection protocol will also provide more opportunities for sharing and combining data from different research groups, thus enhancing replicability and knowledge in the field. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42017072563.


title: [Countermeasures and treatment for aortic acute syndrome with 2019 coronavirus disease].

text: The 2019 coronavirus disease(COVID-19) has cost a great loss to the health and economic property of Chines people. Under such a special circumstance, how to deal with such patients with acute aortic syndrome has become a serious challenge. Rapid diagnosis of concomitant COVID-19, safe and effective transportation, implementation of the interventional procedure, protection of vascular surgical team and postoperative management and follow-up of such patients have become urgent problems for us. Combined with the latest novel government documents, the literature and the experiences from Wuhan, we answered the above questions briefly and plainly. We also hope to inspire the national vascular surgeons to manage critical emergencies in vascular surgery and even routine vascular diseases with COVID-19, as a final point to limit the severe epidemic situation, and minimize the damage of COVID-19.


title: Structural and Biochemical Characterization of Endoribonuclease Nsp15 Encoded by Middle East Respiratory Syndrome Coronavirus.

text: Nonstructural protein 15 (Nsp15) encoded by coronavirus (CoV) is a nidoviral uridylate-specific endoribonuclease (NendoU) that plays an essential role in the life cycle of the virus. Structural information on this crucial protein from the Middle East respiratory syndrome CoV (MERS-CoV), which is lethally pathogenic and has caused severe respiratory diseases worldwide, is lacking. Here, we determined the crystal structure of MERS-CoV Nsp15 at a 2.7-Å resolution and performed the relevant biochemical assays to study how NendoU activity is regulated. Although the overall structure is conserved, MERS-CoV Nsp15 shows unique and novel features compared to its homologs. Serine substitution of residue F285, which harbors an aromatic side chain that disturbs RNA binding compared with that of other homologs, increases catalytic activity. Mutations of residues residing on the oligomerization interfaces that distort hexamerization, namely, N38A, Y58A, and N157A, decrease thermostability, decrease affinity of binding with RNA, and reduce the NendoU activity of Nsp15. In contrast, mutant D39A exhibits increased activity and a higher substrate binding capacity. Importantly, Nsp8 was found to interact with both monomeric and hexameric Nsp15. The Nsp7/Nsp8 complex displays a higher binding affinity for Nsp15. Furthermore, Nsp8 and the Nsp7/Nsp8 complex also enhance the NendoU activity of hexameric Nsp15 in vitro Taking the findings together, this work first provides evidence on how the activity of Nsp15 may be functionally mediated by catalytic residues, oligomeric assembly, RNA binding efficiency, or the possible association with other nonstructural proteins.IMPORTANCE The lethally pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV) and the severe acute respiratory syndrome coronavirus (SARS-CoV) pose serious threats to humans. Endoribonuclease Nsp15 encoded by coronavirus plays an important role in viral infection and pathogenesis. This study determines the structure of MERS-CoV Nsp15 and demonstrates how the catalytic activity of this protein is potentially mediated, thereby providing structural and functional evidence for developing antiviral drugs. We also hypothesize that the primase-like protein Nsp8 and the Nsp7/Nsp8 complex may interact with Nsp15 and affect enzymatic activity. This contributes to the understanding of the association of Nsp15 with the viral replication and transcription machinery.


title: Cerebral Oximetry as an Auxiliary Diagnostic Tool in the Diagnosis of Brain Death.

text: AIM To investigate the efficacy of cerebral oximetry (CO) as an auxiliary diagnostic tool in brain death (BD). MATERIALS AND METHODS This observational case-control study was performed on patients with suspected BD. Patients with diagnosis of BD confirmed by the brain death committee were enrolled as the BD group and other patients as the non-BD group. CO monitoring was performed at least 6 h, and cerebral tissue oxygen saturation (ScO2) parameters were compared. RESULTS Mean ScO2 level in the BD group was lower than non-brain-dead patients: mean difference for right lobe = 6.48 (95% confidence interval [CI] 0.08-12.88) and for left lobe = 6.09 (95% CI -0.22-12.41). Maximum ScO2 values in the BD group were significantly lower than the non-BD group: mean difference for right lobe = 8.20 (95% CI 1.64-14.77) and for left lobe = 9.54 (95% CI 3.06-16.03). The area under the curve for right lobe maximum ScO2 was 0.69 (95% CI 0.55-0.81) and for left lobe was 0.72 (95% CI 0.58-0.84). CONCLUSION Maximum ScO2 in brain-dead patients at CO monitoring is significantly low. However, this cannot be used to differentiate brain-dead and non-brain-dead patients. CO monitoring is therefore not an appropriate auxiliary diagnostic tool for confirming BD.


title: The Unique Impact of COVID-19 on Older Adults in Rural Areas.

text: Older adults in rural areas of the U.S. face unique risks related to COVID-19. Rural areas are older, on average, than urban areas, and have more underlying health conditions and fewer economic resources. Rural health care is more limited, as is access to technology and online connectivity. Altogether, this puts rural older adults at risk of not only the virus, but of not being able to meet their health care, social, and basic needs. Rural/urban inequities, combined with within-rural inequities in health, health care, and financial resources cause particular challenges to health and well-being from COVID-19 for some older adults.


Reply to the letter concerning Kawasaki Disease and Covid-19.


title: Replication of Human Norovirus RNA in Mammalian Cells Reveals Lack of Interferon Response.

text: UNLABELLED Human noroviruses (HuNoVs), named after the prototype strain Norwalk virus (NV), are a leading cause of acute gastroenteritis outbreaks worldwide. Studies on the related murine norovirus (MNV) have demonstrated the importance of an interferon (IFN) response in host control of virus replication, but this remains unclear for HuNoVs. Despite the lack of an efficient cell culture infection system, transfection of stool-isolated NV RNA into mammalian cells leads to viral RNA replication and virus production. Using this system, we show here that NV RNA replication is sensitive to type I (α/β) and III (interleukin-29 [IL-29]) IFN treatment. However, in cells capable of a strong IFN response to Sendai virus (SeV) and poly(I·C), NV RNA replicates efficiently and generates double-stranded RNA without inducing a detectable IFN response. Replication of HuNoV genogroup GII.3 strain U201 RNA, generated from a reverse genetics system, also does not induce an IFN response. Consistent with a lack of IFN induction, NV RNA replication is enhanced neither by neutralization of type I/III IFNs through neutralizing antibodies or the soluble IFN decoy receptor B18R nor by short hairpin RNA (shRNA) knockdown of mitochondrial antiviral signaling protein (MAVS) or interferon regulatory factor 3 (IRF3) in the IFN induction pathways. In contrast to other positive-strand RNA viruses that block IFN induction by targeting MAVS for degradation, MAVS is not degraded in NV RNA-replicating cells, and an SeV-induced IFN response is not blocked. Together, these results indicate that HuNoV RNA replication in mammalian cells does not induce an IFN response, suggesting that the epithelial IFN response may play a limited role in host restriction of HuNoV replication. IMPORTANCE Human noroviruses (HuNoVs) are a leading cause of epidemic gastroenteritis worldwide. Due to lack of an efficient cell culture system and robust small-animal model, little is known about the innate host defense to these viruses. Studies on murine norovirus (MNV) have shown the importance of an interferon (IFN) response in host control of MNV replication, but this remains unclear for HuNoVs. Here, we investigated the IFN response to HuNoV RNA replication in mammalian cells using Norwalk virus stool RNA transfection, a reverse genetics system, IFN neutralization reagents, and shRNA knockdown methods. Our results show that HuNoV RNA replication in mammalian epithelial cells does not induce an IFN response, nor can it be enhanced by blocking the IFN response. These results suggest a limited role of the epithelial IFN response in host control of HuNoV RNA replication, providing important insights into our understanding of the host defense to HuNoVs that differs from that to MNV.


title: Early postoperative recovery in operating room after desflurane anesthesia combined with Bispectral index (BIS) monitoring and warming in lengthy abdominal surgery: a randomized controlled study.

text: BACKGROUND This study aimed to determine whether the use of desflurane (DES) anesthesia combined with bispectral index (BIS) monitoring and warming is effective in reducing anesthesia-controlled operating room time (ACT) in patients undergoing lengthy abdominal surgery. METHODS Seventy patients, 40 years of age or older, undergoing abdominal surgery expected to last three to five hours were randomly assigned to the DES group (n = 35) or the control group (n = 35). Patients in the DES group were maintained with desflurane anesthesia and received BIS monitoring and warming. Patients in the control group were given non-desflurane anesthesia for maintenance, and the usage of BIS monitoring and warming were not mandatory and determined by anesthesia care providers. Early postoperative recovery times were recorded. RESULTS The times to extubation (8.8 ± 8.5 vs 14.7 ± 13.7 min, P = 0.035), eye opening (8.4 ± 8.6 vs 14.4 ± 13.4 min, P = 0.028), responds on command (8.2 ± 8.5 vs 14.4 ± 13.0 min, P = 0.022), and the ACT (23.8 ± 11.4 vs 32.7 ± 15.4 min, P = 0.009) were significantly less in the DES group than that in the control group. The postanesthesia care unit (PACU) length of stay, incidence of prolonged extubation, and surgeon and anesthesiologist satisfaction were similar in two groups. Also, the result of multivariable linear regressions showed that patients who were younger, female, lower BMI and non-DES anesthesia regimen resulted in prolonged extubation. CONCLUSIONS Desflurane anesthesia combined with BIS monitoring and warming is associated with early postoperative recovery in lengthy abdominal surgery. TRIAL REGISTRATION ChiCTR-INR-17013333 . Date of registration: November 11, 2017.


title: Thoracoscopic segmentectomy for congenital and acquired pulmonary disease: a case for lung-sparing surgery.

text: PURPOSE Over the last 15 years thoracoscopic lobectomy for congenital and acquired lesions has become an accepted modality in pediatric thoracic surgery. There is still debate about the need to perform a complete lobectomy for some of these lesions, and some advocate observation rather than resection, despite possible long-term complications of untreated lesions. High-resolution computed tomography (CT) scans and physical findings at the time of surgery, along with new advanced techniques, now allow for discrete partial anatomic resections, which may preserve normal lung. This study evaluates the feasibility and early results using these techniques in selected cases. PATIENTS AND METHODS With institutional review board approval, the records of all patients undergoing thoracoscopic lung resection were reviewed. From January 2006 to December 2012, 23 patients, ranging from 1 month to 16 years of age and weighing 3.8-42 kg, underwent thoracoscopy for planned resection. Pathology was congenital cystic lung disease in 19 patients, bronchiectasis in 3 patients, and arteriovenous malformation in 1 patient. In each case findings on CT scan and at the time of surgery warranted consideration of lung-preserving surgery. Procedures were performed through three ports using single lung ventilation and CO2 insufflation to achieve lung collapse. The LigaSure™ device (Covidien, Norwalk, CT) was the primary instrument used to seal and divide the lung parenchyma and seal vessels. RESULTS All procedures were completed successfully thoracoscopically. An anatomic segmental resection was achieved in 22 of 23 cases. Operative time ranged from 30 to 300 minutes (mean, 120 minutes). Segmental resections included the left upper lobe apical/posterior (n=4), lingula (n=3), left lower lobe superior (n=5), medial or posterior basal (n=3), right middle lobe medial (n=1), right upper lobe apical (n=1), right lower lobe superior (n=4), and posterior basal (n=2). Two patients had more than one segment excised. Chest tubes were left in for 24 hours in 16 cases, 48 hours in 4 cases, and 5 days in 1 case. Hospital stay ranged from 1 to 6 days (mean, 2 days). Follow-up CT scans obtained at 1-6 years (mean, 28 months) show no residual disease in 20 of 21 patients. One patient underwent a nonanatomic resection and had evidence of recurrent congenital pulmonary airway malformation at the 4-year follow-up. This patient underwent a secondary thoracoscopic resection. CONCLUSIONS Thoracoscopic lung-conserving therapy is technically feasible and safe in infants and children. The magnification provided by a thoracoscopic approach makes identification of segmental anatomic planes easier, aiding in safe dissection and resection. Anatomic resection appears to be associated with a low morbidity. It may be appropriate in the case of bilateral or extensive disease or in cases where the diseased tissue is clearly limited to an anatomic segment. Continued long-term follow-up is needed.


title: Analysis of thulium fiber laser induced bubble dynamics for ablation of kidney stones.

text: The Thulium fiber laser (TFL) is being explored as an alternative to the Holmium : YAG laser for lithotripsy. TFL parameters differ in several fundamental ways from Holmium laser, including smaller fiber delivery, more strongly absorbed wavelength, low pulse energy/high pulse rate operation, and more uniform temporal pulse structure. High speed imaging of laser induced bubbles was performed at 105,000 frames per second and 10 μm spatial resolution to determine influence of these laser parameters on bubble formation and needle hydrophone data was also used to measure pressure transients. The TFL was operated at 1908 nm with pulse energies of 5-65 mJ, and pulse durations of 200-1000 μs, delivered through 105-μm-core and 270-μm-core silica optical fibers. Bubble dynamics using Holmium laser at a wavelength of 2100 nm with pulse energies of 200-1000 mJ and pulse duration of 350 μs was studied, for comparison. A single, 500 μs TFL pulse produced a bubble stream extending 1200 ± 90 μm and 1070 ± 50 μm from fiber tip, with maximum bubble widths averaging 650 ± 20 μm and 870 ± 40 μm (n = 4), for 105 μm and 270 μm fibers, respectively. These observations are consistent with previous studies which reported TFL ablation stallout at working distances beyond 1.0 mm. TFL bubble dimensions were four times smaller than for Holmium laser due to lower peak power and smaller fiber diameter used. The maximum pressure transients measured 0.6 bars at 35 mJ pulse energy for TFL and 7.5 bars at 600 mJ pulse energy for Holmium laser. These fundamental studies of bubble dynamics as a function of specific laser and fiber parameters may assist with optimization of the TFL parameters for safe and efficient lithotripsy in the clinic. Image of bubble formation during fiber optic delivery of Thulium fiber laser energy in saline (35 mJ, 500 μs).


title: Pen Torch Transillumination: Difficult Venepuncture Made Easy.

text: INTRODUCTION Our novel technique of pen torch transillumination (PTI) uses a cheap and easily available instrument (Penlite-LP212®, Energizer®, Missouri, USA) to visualize superficial veins invisible to the naked eye. We evaluate the efficacy of PTI in improving venepuncture success rate (SR) for patients with poor venous access. METHODS This prospective randomized controlled trial looked at adult patients (n = 69) aged 21-90 with difficult venous access (history of ≥3 consecutive attempts required for successful cannulation during the current admission) requiring non-emergent venepuncture. Patients underwent venepuncture over the upper-limb using one of the following: conventional venepuncture (control); Veinlite® EMS (TransLite®, Texas, USA), a commercial transillumination device; PTI. Outcome measures were: successful cannulation within 2 attempts and total duration of venepuncture. Fisher's exact and Kruskal-Wallis tests were performed. RESULTS A significantly larger number of patients had successful venepuncture within 2 attempts using PTI (22/23, 95.7%) and Veinlite (23/23, 100%), compared to the controls (7/23, 30.4%) (p < 0.05). The total duration required for successful venepuncture was significantly shorter for Veinlite (mean 3.7 min, 1.0-5.3 min) and PTI (mean 8.5 min, range 1.08-27 min) compared to the controls (mean 23.2 min, range 1.88-46.5 min) (p < 0.05). CONCLUSIONS PTI allows users to visualize veins invisible to the naked eye. Thrombosed/tortuous veins, branch points and valves, are easily identified and avoided. It has comparable efficacy to Veinlite® and is cheaper (Veinlite®-USD 227 vs. Penlite-LP212®-USD 7.00) and more easily available. PTI improves patient care, especially in developing regions where costs are a concern.


Is there a beneficial effect of adding azathioprine to adalimumab in Crohn's disease patients?


title: Microbial peptidyl-prolyl cis/trans isomerases (PPIases): virulence factors and potential alternative drug targets.

text: Initially discovered in the context of immunomodulation, peptidyl-prolyl cis/trans isomerases (PPIases) were soon identified as enzymes catalyzing the rate-limiting protein folding step at peptidyl bonds preceding proline residues. Intense searches revealed that PPIases are a superfamily of proteins consisting of three structurally distinguishable families with representatives in every described species of prokaryote and eukaryote and, recently, even in some giant viruses. Despite the clear-cut enzymatic activity and ubiquitous distribution of PPIases, reports on solely PPIase-dependent biological roles remain scarce. Nevertheless, they have been found to be involved in a plethora of biological processes, such as gene expression, signal transduction, protein secretion, development, and tissue regeneration, underscoring their general importance. Hence, it is not surprising that PPIases have also been identified as virulence-associated proteins. The extent of contribution to virulence is highly variable and dependent on the pleiotropic roles of a single PPIase in the respective pathogen. The main objective of this review is to discuss this variety in virulence-related bacterial and protozoan PPIases as well as the involvement of host PPIases in infectious processes. Moreover, a special focus is given to Legionella pneumophila macrophage infectivity potentiator (Mip) and Mip-like PPIases of other pathogens, as the best-characterized virulence-related representatives of this family. Finally, the potential of PPIases as alternative drug targets and first tangible results are highlighted.


title: Adherence to guideline-recommended therapies among patients with diverse manifestations of vascular disease.

text: BACKGROUND Current guidelines recommend aspirin, statins, angiotensin-converting enzyme inhibitors (ACEIs), and smoking abstinence for all patients with vascular disease. There is little data on the variation in adherence to guideline-recommended therapies among patients with different clinical manifestations of vascular disease. PURPOSE To analyze the variation in adherence to guideline-recommended therapies among patients with diverse manifestations of vascular disease. METHODS We analyzed a comprehensive database of all patients with critical limb ischemia, claudication, acute limb ischemia, carotid artery stenosis, subclavian artery stenosis, renal artery stenosis, or mesenteric ischemia who underwent angiography between 2006 and 2013 at a multidisciplinary vascular center. RESULTS Among 1,114 patients with vascular disease, adherence to guideline-recommended therapy at time of angiography included use of aspirin in 936 (84%), statins in 753 (68%), ACEIs in 673 (60%), and smoking abstinence in 788 (71%). A total of 335 (30%) patients utilized all four guideline-recommended therapies. Adherence to four guideline-recommended therapies was lowest among patients with acute limb ischemia (14%) and highest among patients with renal artery stenosis (37%). Among all patients with vascular disease, the range of adherence to individual guidelines was 64%-91% for aspirin, 43%-83% for statins, 49%-66% for ACEIs, and 47%-78% for smoking abstention. CONCLUSION The majority of patients with diverse manifestations of vascular disease take aspirin and abstain from smoking while fewer patients are prescribed ACEIs and statins. Among the current recommendations, statins have the widest variation in adherence. Less than one-third of patients with diverse manifestations of vascular disease are prescribed all four guideline-recommended therapies.


title: Incidence of hypochloremic metabolic alkalosis in dogs and cats with and without nasogastric tubes over a period of up to 36 hours in the intensive care unit.

text: OBJECTIVE To evaluate the incidence of hypochloremic metabolic alkalosis (HCMA) in dogs and cats in the ICU that had intermittent nasogastric tube (NGT) aspiration for up to 36 hours. DESIGN Prospective cohort study (December 2013 to October 2014). SETTING Privately owned emergency and referral teaching hospital. ANIMALS Forty-nine client-owned dogs and 16 client-owned cats. INTERVENTIONS Patients wherein NGT placement was recommended and client consent was obtained were included in the interventional group. Those with an NGT placed (NGT group) had the NGT aspirated every 4 hours. Patients for whom placement of a NGT was declined by the owner served as a reference group (NoNGT). Venous blood gas and electrolyte values were obtained every 12 hours. MEASUREMENTS AND MAIN RESULTS Thirty-five dogs and cats had an NGT placed. Thirty dogs and cats did not have an NGT placed. The serum venous blood gas and electrolyte changes were compared over time within the NGT group and between the NGT and NoNGT groups. No cases developed HCMA. In the NGT group, blood pH increased over time. There was no significant difference between the NGT and the NoNGT group in the average value of pH, HCO3- , base excess, chloride, or corrected chloride. Serum venous blood gas, chloride, and corrected chloride changes were not associated with the volumes of gastric fluid aspirated over time. CONCLUSIONS In this small population of dogs and cats, intermittent NGT aspiration was not associated with the development of HCMA over a period of up to 36 hours after NGT placement.


title: Mini open versus open repair techniques in Achilles tendon rupture: clinical and isokinetic evaluation.

text: Background The aim of the study was to compare the mini-open to the classic open repair techniques for Achilles tendon ruptures. Methods We retrospectively evaluated at a minimum of 2 years follow-up 32 subcutaneous Achilles tendon ruptures; 17 underwent mini-open surgery (Group A) and 15 the open technique (Group B). Results No difference in Achilles Tendon Total Rupture Score and in modified Leppillahti score was observed. With respect to the contralateral side the width of the operated Achilles tendon was 4.07 mm thicker in Group A and 7.67 mm in Group B (p<.05); the calf circumference reduction was respectively 10 mm and 23.75 mm (p<.05). Iso-kinetic peak force measurement of the calf muscle strength showed a loss of 8.21% in Group A versus 17.25% in Group B (p <.05). The mean Patient Satisfaction Score was 96.76 in Group A and 88.67 in Group B (p<.01); respectively 82.3% vs 66.7% of patients were able to return to previous levels of sporting activity. There were two post-operative complications in Group B and one in Group A. Conclusion Mini-open technique minimizes the risk of complications, leads to an improved tendon healing process and functional recovery with higher patient satisfaction. Level of evidence IV.


title: Psychosocial Reactions to Plagues in the Cultural History of Medicine: A Medical Humanities Approach.

text: The aim of this work is to elucidate psychosocial reactions to plagues by analyzing three landmark descriptions from different eras: Thucydides' description of the plague of Athens (430 BC) in The History of the Peloponnesian War, Giovanni Boccaccio's description of the plague in Florence (1348) in The Decameron, and Albert Camus' description in The Plague (1947). Using a narrative inquiry, we found psychosocial reactions to be complex and ambivalent and could discern several coping strategies. We propose that this knowledge can help psychiatrists and other healthcare professionals during the ongoing COVID-19 pandemic.


title: A review of equine laparoscopy.

text: Minimally invasive surgery in the human was first identified in mid 900's. The procedure as is more commonly practiced now was first reported in 1912. There have been many advances and new techniques developed in the past 100 years. Equine laparoscopy, was first reported in the 1970's, and similarly has undergone much transformation in the last 40 years. It is now considered the standard of care in many surgical techniques such as cryptorchidectomy, ovariectomy, nephrosplenic space ablation, standing abdominal exploratory, and many other reproductive surgeries. This manuscript describes the history of minimally invasive surgery, and highlights many of the techniques that are currently performed in equine surgery. Special attention is given to instrumentation, ligating techniques, and the surgical principles of equine minimally invasive surgery.


title: Single port laparoscopic cholecystectomy: which technique, which surgeon, for which patient? A study of the implementation in a teaching hospital.

text: BACKGROUND Single port cholecystectomy is increasingly performed. This procedure can be challenging, and we lack factors predicting the operative difficulty. AIMS To assess the role of surgeon experience and identify possible predictive factors of intraoperative difficulties. PATIENTS AND METHODS Sixty-one selected patients were prospectively enrolled between January 2008 and August 2010. Six surgeons were involved (3 seniors, 3 juniors). Anthropometrics of the patients, types of ports, exposure methods and intraoperative data were recorded. Pain was assessed with the visual analogic scale at postoperative day 1 (POD 1 VAS). RESULTS Fifty-eight patients with symptomatic gallstones and three with acute cholecystitis underwent single port cholecystectomy. The mean BMI, weight and height were 25.7 kg/m(2) (SD 4.45), 71.8 kg (SD 14.83) and 166 cm SD 0.07, respectively. Mean operative time was 68.4 min (SD 26.98). Anthropometrics had no influence on operative time. Senior surgeons performed more rapidly, but the difference was not significant. The overall mean POD 1 VAS was 2.26, (SD 1.81). The mean hospital stay was 2.22 days, (SD 0.9). No complications occurred. An additional exposure method was necessary in 19 procedures. This cluster presented a significantly higher operating time (81.5 min, SD 31.69 vs. 62.7, SD 22.74; p = 0.01) and POD 1 VAS (1.92 vs. 3; p = 0.031). CONCLUSION Single trocar cholecystectomy can be implemented safely in teaching hospitals. Anthropometrics are not predictive of operative difficulties. The need for additional exposure systems affects the operative time and pain negatively, reflecting greater technical difficulties. Research to optimize instruments may help to solve these problems.


title: Cap-assisted ERCP with a forward-viewing gastroscope as a rescue endoscopic intervention in patients with Billroth II anatomy.

text: BACKGROUND ERCP, especially therapeutic, is difficult in patients with Billroth II surgical reconstruction and is associated with a higher rate of complications. This has led to controversy on the choice between a forward-viewing and side-viewing endoscope for performing the procedure. A previous case series from Asia reported a high rate of success with a cap-fitted ERCP technique. To our knowledge, the utility of cap-assisted ERCP with a forward-viewing gastroscope when other techniques fail has not been reported. We describe and demonstrate a novel rescue approach using a cap-fitted, forward-viewing gastroscope in patients with Billroth II anatomy, when attempts with duodenoscopes, pediatric colonoscopes, and gastroscopes previously failed. METHODS Retrospective case series. Inclusion criteria were: (a) documented Billroth II anatomy; and (b) use of cap-assisted ERCP as a rescue intervention on the first endoscopic encounter after failed attempts to perform ERCP with a duodenoscope. Patients were excluded if they successfully underwent ERCP with a duodenoscope. One advanced endoscopist and one advanced endoscopy fellow performed all but one of the procedures. RESULTS Five cap-assisted ERCP procedures were performed in three patients with Billroth II anatomy. A wide variety of diagnostic and therapeutic endoscopic maneuvers were technically feasible and successful, including the endoscopic treatment of an afferent limb perforation caused by a duodenoscope. CONCLUSIONS Cap-assisted ERCP is a novel and underutilized technique that adds to the armamentarium of experienced therapeutic endoscopists. This approach may help ensure a successful endoscopic outcome and spare patients with Billroth II anatomy a percutaneous or surgical approach when ERCP with a duodenoscope, pediatric colonoscope or non-cap-fitted gastroscope fails.


title: Intravascular frequency-domain optical coherence tomography assessment of carotid artery disease in symptomatic and asymptomatic patients.

text: OBJECTIVES The goal of this study was to investigate carotid plaque characteristics in symptomatic versus asymptomatic patients with the use of nonocclusive optical coherence tomography (OCT). BACKGROUND The identification of asymptomatic patients with carotid disease who are at risk of stroke remains a challenge. There is an increasing awareness that plaque characteristics may best risk-stratify this population. We hypothesized that OCT, a new high-resolution (∼ 10 μm) imaging modality, might be useful for the identification of low-risk versus high-risk carotid plaque features and help us to understand the relationship between carotid diameter stenosis and plaque morphology to ischemic stroke. METHODS Fifty-three patients undergoing diagnostic carotid angiography were studied with OCT. Data analysis was carried out by imaging experts who were unaware of the clinical characteristics of the study population. RESULTS Plaque with American Heart Association type VI complicated features was more common in symptomatic than asymptomatic patients (74.1% vs. 36.4%, p = 0.02). This was largely driven by differences in the incidence of thin-cap fibroatheroma with rupture (40.7% vs. 13.6%, p = 0.056) and thrombus (67.7% vs. 36.4%, p = 0.034). Conversely, non-type VI plaques were more common in asymptomatic than symptomatic patients (63.6% vs. 25.9%, p = 0.02). No association between the degree of stenosis and plaque morphology was identified. CONCLUSIONS This retrospective analysis of carotid OCT data supports the hypothesis that the evaluation of carotid plaque characteristics with this high-resolution imaging technique has the potential to alter the understanding and treatment of carotid artery disease.


title: TMPRSS2 and COVID-19: Serendipity or opportunity for intervention?

text: TMPRSS2 is both the most frequently altered gene in primary prostate cancer and a critical factor enabling cellular infection by coronaviruses, including SARS-CoV-2. The modulation of its expression by sex steroids could contribute to the male predominance of severe infections and given that TMPRSS2 has no known indispensable functions, and inhibitors are available, it is an appealing target for prevention or treatment of respiratory viral infections.


title: Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from colorectal cancer: a case-control study from a Chinese center.

text: BACKGROUND Advanced colorectal cancer (CRC) is prone to developing peritoneal carcinomatosis (PC). This case-control study was to compare the efficacy and safety of cytoreductive surgery (CRS) versus CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC) in Chinese patients with CRC PC. METHODS The 62 consecutive PC patients were treated with CRS (Control group, n = 29) or CRS + HIPEC (Study group, n = 33). The primary end point was overall survival (OS), the secondary end points were perioperative safety profiles. RESULTS For the comparison of Control versus Study groups, the peritoneal cancer index (PCI) ≤20 was 13 (44.8%) versus 16 (48.5%) patients (P = 0.78), complete cytoreduction (CC0-1) was achieved in 9 (31.0%) versus 14 (42.4%) cases (P = 0.36). At the median OS was 8.5 (95% confidence interval [CI] 4.7-12.4) versus 13.7 (95% CI 10.0-16.5) months (P = 0.02), the 1-, 2-, and 3-year survival rates were 27.5% versus 63.6%, 12.0% versus 20.0%, and 0.0% versus 16.0%, respectively. Serious adverse events in postoperative 30 days were 9.4% versus 28.6% (P = 0.11). Multivariate analysis revealed that CRS + HIPEC, CC0-1, adjuvant chemotherapy ≥6 cycles were independent factors for OS benefit. CONCLUSION CRS + HIPEC could improve OS for CRC PC patients, with acceptable perioperative safety.


title: A prospective comparison of a noninvasive cardiac output monitor versus esophageal Doppler monitor for goal-directed fluid therapy in colorectal surgery patients.

text: BACKGROUND Goal-directed fluid therapy (GDFT) is associated with improved outcomes after surgery. The esophageal Doppler monitor (EDM) is widely used, but has several limitations. The NICOM, a completely noninvasive cardiac output monitor (Cheetah Medical), may be appropriate for guiding GDFT. No prospective studies have compared the NICOM and the EDM. We hypothesized that the NICOM is not significantly different from the EDM for monitoring during GDFT. METHODS One hundred adult patients undergoing elective colorectal surgery participated in this study. Patients in phase I (n = 50) had intraoperative GDFT guided by the EDM while the NICOM was connected, and patients in phase II (n = 50) had intraoperative GDFT guided by the NICOM while the EDM was connected. Each patient's stroke volume was optimized using 250-mL colloid boluses. Agreement between the monitors was assessed, and patient outcomes (postoperative pain, nausea, and return of bowel function), complications (renal, pulmonary, infectious, and wound complications), and length of hospital stay (LOS) were compared. RESULTS Using a 10% increase in stroke volume after fluid challenge, agreement between monitors was 60% at 5 minutes, 61% at 10 minutes, and 66% at 15 minutes, with no significant systematic disagreement (McNemar P > 0.05) at any time point. The EDM had significantly more missing data than the NICOM. No clinically significant differences were found in total LOS or other outcomes. The mean LOS was 6.56 ± 4.32 days in phase I and 6.07 ± 2.85 days in phase II, and 95% confidence limits for the difference were -0.96 to +1.95 days (P = 0.5016). CONCLUSIONS The NICOM performs similarly to the EDM in guiding GDFT, with no clinically significant differences in outcomes, and offers increased ease of use as well as fewer missing data points. The NICOM may be a viable alternative monitor to guide GDFT.


title: Flexor tendons repair: effect of core sutures caliber with increased number of suture strands and peripheral sutures. A sheep model.

text: BACKGROUND Surgeons have aimed to achieve strong repair so as to begin early active rehabilitation programs for flexor tendon injury. Multi-strand suture techniques were developed to gain improved gap resistance and ultimate force compared with the respective two-strand techniques. In vivo studies indicate that multiple strands may cause ischemia during the intrinsic healing process by decreasing the total cross-sectional area of the injured site, unless the total cross-sectional area of the sutures is not decreased. HYPOTHESIS The hypothesis was to design an in vitro study to understand the biomechanical relationship between suture calibers of core sutures with increased number of suture strands and peripheral suture on final repair strength. MATERIALS AND METHODS Sixty fresh sheep forelimb flexor digitorum profundus tendons were randomly placed into three groups (A, B, and C), each containing 20 specimens, for tendon repair. Two-, four-, and eight-strand suture techniques were respectively used in Groups A, B, and C. A simple running peripheral suture technique was used in Subgroups A2, B2, and C2. For each repaired tendon, the 2-mm gap-formation force, 2-mm gap-formation strength, maximum breaking force and maximum breaking strength were determined. RESULTS Differences in 2-mm gap-formation force and 2-mm gap-formation strength were found between Subgroups A1 and A2, B1 and B2, and C1 and C2. Between Groups A and B, A and C, and B and C, there was no difference as well. CONCLUSION Both the number of strands and the ratio between the total suture volume and tendon volume at the repair site are important for ideal repair. If the total cross-sectional area of the sutures is equal in 2-strand, 4-strand, and 8-strand procedure, there is no difference in the strength of the repair. A decrease in caliber size suture requires more passes to achieve the same strength. Instead, it is much better to use peripheral suture techniques to improve the strength of the repair with larger diameter 2-strand core sutures.


title: COVID-19 Pandemic in India: Present Scenario and a Steep Climb Ahead.

text: Amid the ongoing COVID-19 pandemic, India has witnessed a massive surge of cases in the past 3 weeks. As of April 30, 33 610 confirmed cases and 1075 deaths have been reported from 32 states/union territories in India. Apart from the nationwide lockdown, India has increased its testing rate and has markedly strengthened the health care sector to combat COVID-19. With India's population of more than 1.3 billion people at a significant population density compared with the rest of the world, the lack of universal access to clean water and overall poor socioeconomic status, all have posed a major challenge to India's fight against COVID-19. Failure to contain the pandemic in India could have disastrous consequences with widespread cases and thousands of deaths that could easily overwhelm the health care infrastructure. Unabated spread of the pandemic could make India the next COVID-19 hotspot; hence the World Health Organization has recently stated that the "future of the pandemic will depend on how India handles it." Here, we have summarized the present scenario of the pandemic in India and the myriad challenges being faced by the country in its fight against COVID-19.


title: Recommendations for Deep Brain Stimulation Device Management During a Pandemic.

text: Most medical centers are postponing elective procedures and deferring non-urgent clinic visits to conserve hospital resources and prevent spread of COVID-19. The pandemic crisis presents some unique challenges for patients currently being treated with deep brain stimulation (DBS). Movement disorder (Parkinson's disease, essential tremor, dystonia), neuropsychiatric disorder (obsessive compulsive disorder, Tourette syndrome, depression), and epilepsy patients can develop varying degrees of symptom worsening from interruption of therapy due to neurostimulator battery reaching end of life, device malfunction or infection. Urgent intervention to maintain or restore stimulation may be required for patients with Parkinson's disease who can develop a rare but potentially life-threatening complication known as DBS-withdrawal syndrome. Similarly, patients with generalized dystonia can develop status dystonicus, patients with obsessive compulsive disorder can become suicidal, and epilepsy patients can experience potentially life-threatening worsening of seizures as a result of therapy cessation. DBS system infection can require urgent, and rarely emergent surgery. Elective interventions including new implantations and initial programming should be postponed. For patients with existing DBS systems, the battery status and electrical integrity interrogation can now be performed using patient programmers, and employed through telemedicine visits or by phone consultations. The decision for replacement of the implantable pulse generator to prevent interruption of DBS therapy should be made on a case-by-case basis taking into consideration battery status and a patient's tolerance to potential therapy disruption. Scheduling of the procedures, however, depends heavily on the hospital system regulations and on triage procedures with respect to safety and resource utilization during the health crisis.


title: Microbial integrity of preservative-free alfaxalone in a multiple-use system for two storage conditions and three handling techniques.

text: OBJECTIVE To evaluate the microbial integrity of preservative-free cyclodextrin-based alfaxalone in a multiple-use system. SAMPLE 22 vials of preservative-free alfaxalone. PROCEDURES 2 storage conditions (room temperature, 22°C; refrigerated temperature, 4°C) and 3 handling techniques (closed system transfer device, nonclosed dispensing pin, and manufacturer-supplied vial stopper) comprised 6 treatment groups (3 replicates/group). An aliquot (0.5 mL) was withdrawn from each vial daily for 14 days. Samples were immediately inoculated into tryptic soy broth and incubated at 36°C for 24 hours; samples were subcultured onto 5% Columbia sheep blood agar and incubated for 48 hours. Isolated colonies were evaluated for identification. RESULTS There was no evidence of microbial contamination of vials stored for 7 days in refrigeration and handled with a protected port (closed system transfer device or nonclosed dispensing pin). CONCLUSIONS AND CLINICAL RELEVANCE The US FDA prohibits the use of alfaxalone beyond 6 hours after the vial stopper is broached (punctured), as mandated for a preservative-free injectable medication. Findings for the study reported here supported the use of alfaxalone for 7 days when refrigerated and handled with a single puncture of the stopper by use of a protected port (closed system transfer device or nonclosed dispensing pin). This would appear to be a practical alternative for an injectable anesthetic. It would minimize drug waste and the subsequent environmental impact for disposal of unused drug and allow standardization of storage and handling protocols for alfaxalone use in veterinary practices across the United States.


title: The impact of stent design on the structural mechanics of the crossing Y-stent: an in vitro study.

text: INTRODUCTION Crossing Y-stent technique is a valid option for coiling wide-necked bifurcation aneurysms. Two main designs of stents, the closed- (CCS) and open-cell (OCS), are used in combination for a crossing Y-construct. This in vitro study was conducted to assess the mechanical characteristics of each stent-combination and to suggest an optimal combination for clinical practice. METHODS The Enterprise and the Neuroform3 stents were used as closed-cell and open-cell stents, respectively. Four different Y-stent combinations; double CCSs (CCS-CCS; Enterprise-Enterprise), OCS followed by CCS (OCS-CCS; Neuroform-Enterprise), CCS followed by OCS (CCS-OCS; Enterprise-Neuroform), and double OCSs (OCS-OCS; Neuroform-Neuroform) were tested in a bifurcation aneurysm model. Images of the model were obtained by digital subtraction angiography (DSA), and morphological changes of Y-constructs caused by interaction between stents were compared. RESULTS Double OCSs showed the best stent apposition to model branches and no collapse of the second stent at the intersection, whereas Y-stent combinations using a CCS as the second stent showed tubular collapse of the second stent at the crossing point. These combinations revealed unsatisfactory apposition to the model branch in which the second stent was deployed. Most narrowing of the second stent was noted in the double CCSs construct, which resulted in poorest stent apposition. CONCLUSION Based on a simple in vitro experiment, we suggest that double OCSs Y-construct is optimal for achieving best stent-wall apposition. Furthermore, our findings suggest that Y-stent combinations utilizing a CCS as the second stent may increase the risk of thromboembolic complications due to poor stent-wall apposition.


title: Chicken galectin-1B inhibits Newcastle disease virus adsorption and replication through binding to hemagglutinin-neuraminidase (HN) glycoprotein.

text: Galectin-1 is an important immunoregulatory factor and can mediate the host-pathogen interaction via binding glycans on the surface of various viruses. We previously reported that avian respiratory viruses, including lentogenic Newcastle disease virus (NDV), can induce up-regulation of chicken galectin (CG)-1B in the primary target organ. In this study, we investigated whether CG-1B participated in the infectious process of NDV in chickens. We demonstrated that velogenic NDV induced up-regulation of CG-1B in target organs. We also found that CG-1B directly bound to NDV virions and inhibited their hemagglutination activity in vitro We confirmed that CG-1B interacted with NDV hemagglutinin-neuraminidase (HN) glycoprotein, in which the specific G4 N-glycans significantly contributed to the interaction between CG-1B and HN glycoprotein. The presence of extracellular CG-1B, rather than the internalization process, inhibited adsorption of NDV. The interaction between intracellular CG-1B and NDV HN glycoproteins inhibited cell-surface expression of HN glycoprotein and reduced the titer of progeny virus in NDV-infected DF-1 cells. Significantly, the replication of parental and HN glycosylation mutant viruses in CG-1B knockdown and overexpression cells demonstrated that the replication of NDV was correlated with the expression of CG-1B in a specific glycan-dependent manner. Collectively, our results indicate that CG-1B has anti-NDV activity by binding to N-glycans on HN glycoprotein.


title: Verification of the Heska Element Point-of-Care blood gas instrument for use with venous blood from alpacas and llamas, with determination of reference intervals.

text: BACKGROUND The Heska Element POC ("EPOC") is a blood gas instrument intended for use with canine, feline, and equine whole blood; no verification for use with camelid specimens has been reported. OBJECTIVES Using camelid specimens and commercial quality control materials (QCM), we investigatee EPOC analytical performance and establish EPOC camelid reference intervals (RIs). METHODS Camelid blood (n = 124) was analyzed using the EPOC (pH, pCO2 , pO2 , HCO3 , base excess, SO2 , sodium, potassium, chloride, ionized calcium, TCO2 , anion gap, HCT, HGB, glucose, lactate, and creatinine); plasma was analyzed using a Roche Cobas c501 (sodium, potassium, chloride, TCO2 , anion gap, glucose, and creatinine). Method comparison data were assessed using Pearson's correlation, Passing-Bablok regression, and Bland-Altman plots. EPOC precision was evaluated using QCM and camelid blood. RESULTS For all measurands except anion gap, the EPOC vs Cobas instrument correlation was r > .85. Except for pO2 and pCO2 , EPOC precision (QCM and blood) ranged from a repeatability CV <1%-6.3%. Mild constant bias for chloride, glucose, TCO2 , anion gap, and creatinine, and mild proportional bias for chloride, glucose, and anion gap were present. The total error (QCM data) for the EPOC instrument was below the ASVCP-recommended allowable total error. Alpacas had higher potassium and lactate, while llamas had higher creatinine, sodium, chloride, ionized calcium, pO2 , and SO2 . Statistical RIs based on alpaca (n = 74-96) and llama data (n = 12-17) are reported descriptively. CONCLUSIONS The EPOC analyzer shows good performance with camelid blood. A lack of complete agreement with automated chemistry analyzers highlights the importance of interpreting patient data using instrument-specific RIs.


title: Policy Recommendations to Address High Risk of COVID-19 Among Immigrants.

text: The health and economic consequences of COVID-19 will be devastatingly widespread, but the populations that will suffer most are those who have experienced longstanding health disparities. For example, emerging evidence strongly suggests that incidence and case fatality rates are higher among Blacks than Whites.1 Immigrants are among the groups most likely to experience disproportionate effects from COVID-19. Unlike race/ethnicity, however, nativity and citizenship status are not included on the Centers for Disease Control and Prevention's (CDC's) coronavirus case report form,2 so data regarding testing and spread across immigrant groups are likely to remain scarce. Information from other health and social surveys-including data that I present in Table 1-suggest that noncitizens experience barriers to physical distancing that will place them at high risk of contracting COVID-19 and have high levels of disadvantage that leave them vulnerable to its economic effects. I recommend three policy changes to address the high health and economic risk among noncitizens, goals that are in the best interest of public health and the broader economy. (Am J Public Health. Published online ahead of print June 25, 2020: e1-e3. doi:10.2105/AJPH.2020.305792).


title: Characterization of pneumonia due to Streptococcus equi subsp. zooepidemicus in dogs.

text: Streptococcus equi subsp. zooepidemicus has been linked to cases of acute fatal pneumonia in dogs in several countries. Outbreaks can occur in kenneled dog populations and result in significant levels of morbidity and mortality. This highly contagious disease is characterized by the sudden onset of clinical signs, including pyrexia, dyspnea, and hemorrhagic nasal discharge. The pathogenesis of S. equi subsp. zooepidemicus infection in dogs is poorly understood. This study systematically characterized the histopathological changes in the lungs of 39 dogs from a large rehoming shelter in London, United Kingdom; the dogs were infected with S. equi subsp. zooepidemicus. An objective scoring system demonstrated that S. equi subsp. zooepidemicus caused pneumonia in 26/39 (66.7%) dogs, and most of these dogs (17/26 [65.4%]) were classified as severe fibrino-suppurative, necrotizing, and hemorrhagic. Three recently described superantigen genes (szeF, szeN, and szeP) were detected by PCR in 17/47 (36.2%) of the S. equi subsp. zooepidemicus isolates; however, there was no association between the presence of these genes and the histopathological score. The lungs of S. equi subsp. zooepidemicus-infected dogs with severe respiratory signs and lung pathology did however have significantly higher mRNA levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 8 (IL-8) than in uninfected controls, suggesting a role for an exuberant host immune response in the pathogenesis of this disease.


title: Heritability of language laterality assessed by functional transcranial Doppler ultrasound: a twin study.

text: Background: Prior studies have estimated heritability of around 0.25 for the trait of handedness, with studies of structural brain asymmetry giving estimates in a similar or lower range. Little is known about heritability of functional language lateralization. This report describes heritability estimates using functional language laterality and handedness phenotypes in a twin sample previously reported by Wilson and Bishop (2018). Methods: The total sample consisted of 194 twin pairs (49% monozygotic) aged from 6 to 11 years. A language laterality index was obtained for 141 twin pairs, who completed a protocol where relative blood flow through left and right middle cerebral arteries was measured using functional transcranial Doppler ultrasound (fTCD) while the child described animation sequences. Handedness data was available from the Edinburgh Handedness Inventory (EHI) and Quantification of Hand Preference (QHP) for all 194 pairs. Heritability was assessed using conventional structural equation modeling, assuming no effect of shared environment (AE model). Results: For the two handedness measures, heritability estimates were consistent with prior research: 0.23 and 0.22 respectively for the EHI and QHP. For the language laterality index, however, the twin-cotwin correlations were close to zero for both MZ and DZ twins, and the heritability estimate was zero. Conclusions: A single study cannot rule out a genetic effect on language lateralisation. It is possible that the low twin-cotwin correlations were affected by noisy data: although the split-half reliability of the fTCD-based laterality index was high (0.85), we did not have information on test-retest reliability in children, which is likely to be lower. We cannot reject the hypothesis that there is low but nonzero heritability for this trait, but our data suggest that individual variation in language lateralisation is predominantly due to stochastic variation in neurodevelopment.


title: Synonymous and Biased Codon Usage by MERS CoV Papain-Like and 3CL-Proteases.

text: Middle East respiratory syndrome coronavirus (MERS CoV) is a recently evolved fatal respiratory disease that poses a concern for a global epidemic. MERS CoV encodes 2 proteases, 3C-like protease (3CLpro) and papain-like protease (PLpro). These proteases share in processing MERS CoV polyproteins at different sites to yield 16 nonstructural proteins. In this work, we provide evidence that MERS CoV 3CLpro and PLpro are subject to different genetic and evolutionary influences that shape the protein sequence, codon usage pattern, and codon usage bias. Compositional bias is present in both proteins due to a preference for AT nucleotides. Thymidine (T) was highly preferred at the third position of codons, preferred and overrepresented codons in PLpro, but was replaced by guanosine (G) in 3CLpro. Compositional constraints were important in PLpro but not in 3CLpro. Directed mutation pressure seems to have a strong influence on 3CLpro codon usage, which is more than 30-fold higher than that in PLpro. Translational selection was evident with PLpro but not with 3CLpro. Both proteins are less immunogenic by showing low CpG frequencies. Correspondence analysis reveals the presence of 3 genetic clusters based on codon usage in PLpro and 3CLpro. Every protein had one common cluster and 2 different clusters. As revealed by correspondence analysis, the number of influences on codon usage are restricted in MERS CoV 3CLpro. In contrast, PLpro is controlled by a broader range of compositional, mutational, and other influences. This may be due to the multifunctional protease, deubiquitination, and innate immunity suppressing profiles of PLpro.


title: Regional Cerebral Oxygen Saturation Decreases During Primary Hip Arthroplasty: An Analysis of Perioperative Regional Cerebral Oxygenation (rSO2), S100 Calcium-Binding Protein B (S100B) and Glial Fibrillary Acidic Protein (GFAP) Values. A Pilot Study.

text: BACKGROUND The incidence of postoperative cognitive dysfunction (POCD) after major joint arthroplasty is high. In the etiology of POCD, many factors have been cited, including thromboembolic complications. The incidence of cerebral embolization after lower extremity arthroplasty may be as high as 40-60%. The potential events of cerebral embolization could lead to a decrease in the regional cerebral oxygenation (rSO2) and increased serum levels of biochemical markers of brain damage. The objective of the study was to test whether there are any changes in the rSO2 values and serum markers of brain damage in patients who underwent total hip arthroplasty. MATERIAL AND METHODS Fifteen patients who underwent primary hip arthroplasty under spinal anesthesia were analyzed. The rSO2 was monitored using infrared spectroscopy. Biochemical analyses of S100 calcium-binding protein B (S100B) protein and fibrillary acidic protein (GFAP) serum concentrations were performed using immunoassay methods. RESULTS The values of rSO2 decreased during the surgery, but this was not related to mean arterial pressure variations or hemoglobin saturation. The concentration of S100B was increased compared to its preoperative values, and there were no changes in GFAP values. The changes in rSO2 readings correlated with the biomarkers' levels just after the surgery. CONCLUSIONS Our results suggest that S100B may be a more specific marker of astroglial damage in patients after primary total hip arthroplasty. The decrease in rSO2 readings may be due to micro-thromboembolic events that occurred during the surgery. However, the results of this study are preliminary, and further studies are needed to establish its clinical efficacy.


title: In situ removal of the pipeline embolization device: the 'corking' and 'pseudo-corking' techniques.

text: The pipeline embolization device (PED) is a revolutionary tool for the endovascular treatment of intracranial aneurysms by flow diversion. Treatment using the PED often requires considerable manipulation and customization by the neurointerventionalist at the time of deployment. Proper use of the PED involves a novel set of techniques and associated jargon, which must be learned by all neurointerventionalists, fellows and residents for safe treatment of patients with this device. In this report, the PED removal techniques referred to as 'corking' and 'pseudo-corking' are described. Corking is used for the removal of a partially deployed in situ PED when the pusher wire is intact whereas 'pseudo-corking' is used if the pusher wire is fractured or disconnected. Knowledge of both techniques is necessary for withdrawing the PED in situations of malposition or failed expansion.


title: Interventional therapy for hypertension: Back on track again?

text: Treatment-resistant hypertension, or resistant hypertension, is defined as blood pressure that remains above target despite concurrent use of at least three antihypertensive agents from different classes at optimal doses, one of which should be a diuretic. Important considerations in the diagnosis of treatment-resistant hypertension include the exclusion of pseudoresistance and the evaluation of potential secondary causes of hypertension and of concomitant conditions that maintain high blood pressure. The ability to diagnose true treatment-resistant hypertension is important for selection of patients who may be appropriately treated with an invasive therapy. Currently, there are three interventional approaches to treat resistant hypertension, namely: (1) reduction of the activity of the sympathetic nervous system by renal nerve ablation, (2) stimulation of baroreceptors and (3) creation of a peripheral arterial venous anastomosis. This review focuses on the rationale behind these invasive approaches and the clinical results.