title: Soy Isoflavones and Gastrointestinal Health.

text: PURPOSE OF REVIEW Soy isoflavones are known to have beneficial effects on several aspects of gastrointestinal physiological functions (contractility or motility, secretion, morphology, and barrier function). In this review, we discuss the effects of soy isoflavones on the overall gut function and inflammation and assess how these effects might be implicated in the treatment of several gut-related diseases. RECENT FINDINGS Soy isoflavones influence several key aspects of gastrointestinal health: improve basal intestinal secretion, alleviate inflammation, limit intestinal morphological damage, and improve epithelial barrier function in several clinically relevant murine models of gastrointestinal diseases. Dietary supplementation with isoflavones proves to be a key means to improve the overall gut function and health. Future mechanistic studies with isoflavone interventions will help treat clinically related diseases such as cystic fibrosis and inflammatory-related gut problems such as colitis and diabetes.


title: Predicting the need for nonstandard tracheostomy tubes in critically ill patients.

text: PURPOSE Few guidelines exist regarding the selection of a particular type or size of tracheostomy tube. Although nonstandard tubes can be placed over the percutaneous kit dilator, clinicians often place standard tracheostomy tubes and change to nonstandard tubes only after problems arise. This practice risks early tracheostomy tube change, possible bleeding, or loss of the airway. We sought to identify predictors of nonstandard tracheostomy tubes. MATERIALS AND METHODS In this matched case-control study at an urban, academic, tertiary care medical center, we reviewed 1220 records of patients who received a tracheostomy. Seventy-seven patients received nonstandard tracheostomy tubes (cases), and 154 received standard tracheostomy tubes (controls). RESULTS Sex, endotracheal tube size, severity of illness, and computed tomography scan measurement of the distance from the trachea to the skin at the level of the superior aspect of the anterior clavicle were significant predictors of nonstandard tracheostomy tubes. Specifically, trachea-to-skin distance >4.4 cm and endotracheal tube sizes ≥8.0 were associated with nonstandard tracheostomy. CONCLUSIONS The findings suggest that clinicians should consider using nonstandard tracheostomy tubes as the first choice if the patient is male with an endotracheal tube size ≥8.0 and has a trachea-to-skin distance >4.4 cm on the computed tomography scan.


Coronavirus: NHS staff get power to keep patients in isolation as UK declares "serious threat".


Letter to the Editor (COVID-19 and Stroke).


title: Lymphangiography to treat postoperative lymphatic leakage: a technical review.

text: In addition to imaging the lymphatics and detecting various types of lymphatic leakage, lymphangiography is a therapeutic option for patients with chylothorax, chylous ascites, and lymphatic fistula. Percutaneous thoracic duct embolization, transabdominal catheterization of the cisterna chyli or thoracic duct, and subsequent embolization of the thoracic duct is an alternative to surgical ligation of the thoracic duct. In this pictorial review, we present the detailed technique, clinical applications, and complications of lymphangiography and thoracic duct embolization.


[Recommendations for the Treatment of Elderly Patients with COVID-19 from the Taskforce for Gerontopneumology].


Lessons learned from SARS outbreak prompt rapid response to new coronavirus.


title: Does aptitude influence the rate at which proficiency is achieved for laparoscopic appendectomy?

text: BACKGROUND The attainment of technical competence for surgical procedures is fundamental to a proficiency-based surgical training program. We hypothesized that aptitude may directly affect one's ability to successfully complete the learning curve for minimally invasive procedures. The aim was to assess whether aptitude has an impact on ability to achieve proficiency in completing a simulated minimally invasive surgical procedure. The index procedure chosen was a laparoscopic appendectomy. STUDY DESIGN Two groups of medical students with disparate aptitude were selected. Aptitude (visual-spatial, depth perception, and psychomotor ability) was measured by previously validated tests. Indicators of technical proficiency for laparoscopic appendectomy were established by trained surgeons with an individual case volume of more than 150. All subjects were tested consecutively on the ProMIS III (Haptica) until they reached predefined proficiency in this procedure. Simulator metrics, critical error scores, and Objective Structured Assessment of Technical Skills (OSATS) scores were recorded. RESULTS The mean numbers of attempts to achieve proficiency in performing a laparoscopic appendectomy for group A (high aptitude) and B (low aptitude) were 6 (range 4 to 7) and 14 (range 10 to 18), respectively (p < 0.0001). Significant differences were found between the 2 groups for path length (p = 0.014), error score (p = 0.021), and OSATS score (p < 0.0001) at the initial attempt. CONCLUSIONS High aptitude is directly related to a rapid attainment of proficiency. These findings suggest that resource allocation for proficiency-based technical training in surgery may need to be tailored according to a trainee's natural ability.


title: COVID - A Caring Reflection.

text: Those of us who can come to work every day and provide emotional and spiritual support to the patients, families, staff, and to each other despite all challenges. COVID-19 has not robbed us of our ability to care. COVID-19 has not robbed us of our voices in using kind words, thoughts, sentiments, and prayers to comfort others and each other. Most importantly, COVID-19 has not broken us.


title: Robotic resection of Stage III lung cancer: an international retrospective study.

text: OBJECTIVES Minimally invasive surgery is accepted for early-stage lung cancer, but its role in locally advanced disease is controversial, especially using a robotic platform. The aim of this retrospective study was to assess the safety and effectiveness of robot-assisted resection in patients with Stage IIIA non-small-cell lung cancer (NSCLC) or carcinoid tumours in the series as a whole and in different subgroups according to adjuvant treatment. METHODS This was a retrospective multicentre study of consecutive patients with clinically evident or occult N2 disease (210 NSCLC and 13 carcinoid) who, in 2007-2016, underwent robot-assisted resection at 7 high-volume centres. Perioperative outcomes, recurrences and overall survival were assessed. RESULTS N2 disease was diagnosed preoperatively in 72 (32%) patients and intraoperatively in 151 (68%) patients. Surgical margins were negative in 98.4% of cases with available data. Thirty-four (15.2%) patients received neoadjuvant treatment, 140 (63%) patients received postoperative treatment, and 49 (22%) patients underwent surgery only. There were 22 (9.9%) conversions to thoracotomy, 23 (10.3%) had serious (Grades III-IV) postoperative morbidity and the mean hospital stay was 5.3 days. Complications and outcomes did not differ significantly between treatment groups. Of the 34 patients who were given neoadjuvant chemotherapy, all had R0 resection, 5 (15%) patients required conversion but none required conversion because of bleeding and 4 (12%) patients had Grade III or IV postoperative complications. After a median of 18 (interquartile range 8-33) months, 3-year overall survival in NSCLC patients was 61.2% and 60.3% (P = 0.6) of patients in the subgroup were given induction treatment. However, overall survival was significantly better (P = 0.012) in NSCLC patients with ≤2 positive nodes (vs >2). Nineteen (8.5%) patients developed local recurrence. CONCLUSIONS Robot-assisted lobectomy is safe and effective in patients with Stage III NSCLC or carcinoid tumours with low conversions and complications. Among patients with NSCLC, including those who were given induction chemotherapy, survival was similar to that reported for open surgery.


title: Vascular imaging of the foot: the first step toward endovascular recanalization.

text: In the past 5 years, with the introduction of new techniques and dedicated materials, endovascular recanalization of distal tibial and pedal vessels has become a valid alternative to inframalleolar bypass for limb salvage in patients with severe arterial occlusive disease, particularly diabetics. Revascularization of the foot is now often performed by using percutaneous transluminal angioplasty; over a 4-year period, the authors performed more than 2500 antegrade interventional procedures in patients with critical limb ischemia, diabetes, and infrainguinal arterial disease. Intraprocedural angiography of the foot is crucial for successful planning and guidance of percutaneous transluminal angioplasty in tibial and pedal arteries, and its effective use requires both anatomic knowledge and technical skill. To select the best revascularization strategy and obtain optimal clinical results, interventional radiologists, cardiologists, and vascular surgeons performing below-the-knee endovascular procedures also must be familiar with the functional aspects of circulation in the foot. Supplemental material available at http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.316115511/-/DC1.


The Roadmap to Pituitary in COVID-19 Crisis.


title: Delayed Posttreatment Residual Flow into Aneurysm After Flow Diverter Placement.

text: BACKGROUND Inflow into an aneurysm sac immediately following flow diverter (FD) treatment is an assumed cause of delayed aneurysmal rupture. The significance of delayed posttreatment residual flow occurring months after FD treatment is unknown. CASE DESCRIPTION A 76-year-old woman with a large intracranial aneurysm measuring 23.0 × 18.1 mm in the cavernous segment of the right internal carotid artery was treated with placement of a single FD (Pipeline Embolization Device, Covidien, Irvine, California, USA). Postprocedure digital subtraction angiography (DSA) demonstrated flow stagnation inside the aneurysm dome. The patient was discharged 9 days post procedure without new neurologic deficits. A 6-month follow-up DSA demonstrated delayed posttreatment residual flow into the aneurysm sac. Although she was scheduled for additional FD placement because of concern for aneurysmal rupture, the operation was not conducted due to an interim motor vehicle accident. Oral treatment with aspirin (100 mg/day) and clopidogrel (75 mg/day) was continued during her recovery. DSA performed 12 months post procedure showed that the aneurysm had completely thrombosed. CONCLUSIONS Our findings suggest that delayed post-treatment residual flow into an aneurysm may form part of the normal clinical course post FD placement and may not preclude eventual thrombosis of the aneurysm. Larger studies are needed to determine whether more frequent follow-up DSAs after FD placement are necessary and whether all patients exhibiting delayed post-treatment residual flow into an aneurysm require additional FD placement or if watchful waiting is a more suitable course.


title: Cellular localisation of the proteins of region 3 of feline enteric coronavirus.

text: Feline enteric coronaviruses have three open reading frames (ORFs) in region 3 (3a, 3b, and 3c). All three ORFs were expressed with C-terminal eGFP and 3xFLAG tags in different cell lines and their localisation was determined. ORF 3a is predicted to contain DNA-binding and transcription activator domains, and it is localised in the nucleus and in the cytoplasm. ORF 3b is also predicted to contain DNA-binding and activator domains, and was found to localise in the mitochondrion. Besides that, in some of the non-infected and FIPV-infected cells nucleolar, perinuclear or nuclear membrane accumulation of the eGFP-tagged 3b was observed. The exact compartmental localisation of ORF 3c is yet to be determined. However, based on our co-localisation studies 3c does not seem to be localised in the ER-Golgi network, ERGIC or peroxisomes. The expression of 3c-eGFP is clearly cell type dependent, it is more stable in MARC 145 cells than in Fcwf-4 or CrFK cells, which might reflect in vivo stability differences of 3c in natural target cells (enterocytes vs. monocytes/macrophages).


title: Giant squamous cell carcinoma as a complication of a chronic enterocutaneous fistula: complex parietal reconstruction.

text: Treatment of an enterocutaneous fistula is complex and may require multidisciplinary management, especially when associated with a neoplastic process. Here, we describe the case of a 59-year-old patient with a squamous cell carcinoma that had invaded the abdominal wall through a chronic enterocutaneous fistula identified 30 years ago. We combined parietectomy with small intestine and colon resection and inguinal lymphadenectomy in order to obtain clear surgical margins. At the same time, plastic surgery involved the implementation of a large bioprosthesis and coverage with a vastus lateralis muscle free flap.


title: How did lomustine become standard of care in recurrent glioblastoma?

text: Glioblastomas are the most common malignant primary intrinsic brain tumors. Their incidence increases with age, and males are more often affected. First-line management includes maximum safe surgical resection followed by involved-field radiotherapy plus concomitant and six cycles of maintenance temozolomide chemotherapy. Standards of care at recurrence are much less well defined. Minorities of patients are offered second surgery or re-irradiation, but data on a positive impact on survival from randomized trials are lacking. The majority of patients who are eligible for salvage therapy receive systemic treatment, mostly with nitrosourea-based regimens or, depending on availability, bevacizumab alone or in various combinations. In clinical trials, lomustine alone has been increasingly used as a control arm, assigning this drug a standard-of-care position in the setting of recurrent glioblastoma. Here we review the activity of lomustine in the treatment of diffuse gliomas of adulthood in various settings. The most compelling data for lomustine stem from three randomized trials when lomustine was combined with procarbazine and vincristine as the PCV regimen in the newly diagnosed setting together with radiotherapy; improved survival with PCV was restricted to patients with isocitrate dehydrogenase-mutant tumors. No other agent with the possible exception of regorafenib has shown superior activity to lomustine in recurrent glioblastoma, but activity is largely restricted to patients with tumors with O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Hematological toxicity, notably thrombocytopenia often limits adequate exposure.


title: Predicting ICU admission in community-acquired pneumonia: clinical scores and biomarkers.

text: Community-acquired pneumonia (CAP) remains a common and serious worldwide health problem. Despite all the advances in therapy, significant interest has focused on the identification of patients with CAP who require intensive care unit admission to improve their outcomes. The severity assessment of CAP provides an important guide to clinicians in deciding the site of care and the use of empiric antibiotics and adjuvant therapy. For years, several clinical assessment scores have been suggested and validated to achieve this goal. The recent introduction of biomarkers as prognostic indicators of severe CAP, whether used alone or in conjunction with other clinical severity of illness scores, has been investigated. An objective scoring system with a high level of sensitivity and specificity to predict the severity of CAP and the need for high levels of care do not exist. Today, the addition of clinical scores and biomarkers to clinical judgment is the best approach to optimize the care of severe CAP. Future research will allow validation of these and newer tools to improve the prognosis of patients with CAP.


title: Genome-wide study of Pseudomonas aeruginosa outer membrane protein immunogenicity using self-assembling protein microarrays.

text: Pseudomonas aeruginosa is responsible for potentially life-threatening infections in individuals with compromised defense mechanisms and those with cystic fibrosis. P. aeruginosa infection is notable for the appearance of a humoral response to some known antigens, such as flagellin C, elastase, alkaline protease, and others. Although a number of immunogenic proteins are known, no effective vaccine has been approved yet. Here, we report a comprehensive study of all 262 outer membrane and exported P. aeruginosa PAO1 proteins by a modified protein microarray methodology called the nucleic acid-programmable protein array. From this study, it was possible to identify 12 proteins that trigger an adaptive immune response in cystic fibrosis and acutely infected patients, providing valuable information about which bacterial proteins are actually recognized by the immune system in vivo during the natural course of infection. The differential detections of these proteins in patients and controls proved to be statistically significant (P<0.01). The study provides a list of potential candidates for the improvement of serological diagnostics and the development of vaccines.


title: AAGL practice report: Practice Guidelines on the Prevention of Apical Prolapse at the Time of Benign Hysterectomy.

text: Pelvic organ prolapse may adversely impact physical, sexual and emotional health. Women with symptomatic prolapse often experience altered bladder and bowel function, increased pelvic pressure, diminution of sexual satisfaction, and altered body image. With increasing vaginal descent, various bladder, bowel, and prolapse symptoms are increased. Approximately 200,000 women undergo inpatient procedures for prolapse in the United States each year, with regional and racial differences in rates of surgery reported. The demand for health care services related to pelvic floor disorders will increase at twice the rate of the population itself.


title: Surgical wait list management in Canada during a pandemic: many challenges ahead.

text: Summary The coronavirus disease 2019 (COVID-19) pandemic has had a massive impact on waits for elective operations, with tens of thousands of scheduled surgeries being cancelled or postponed across Canada. Provincial governments will likely not only reopen elective surgical capacity when it is deemed safe, but also target new funding to address the backlog of cases. There is a dearth of research on whether the provinces' approaches to managing wait lists are equitable from a patients' needs perspective or if they are associated with patients' perception of outcomes. The surgical cost models used in the past won't be useful to governments and hospital managers. New models based on hospitals' marginal costs, associated with running on weekends or off-hours and social distancing parameters, will be needed. Surgeon input, collaboration and leadership during the strategy development, implementation and management of surgical wait lists postpandemic will be imperative, as these decisions will significantly affect the health and lives of many Canadians.


title: [Initial results of robotic esophagectomy for esophageal cancer].

text: INTRODUCTION There is scant experience with robot-assisted esophagectomy in cases of esophageal and gastro-esophageal junction cancer. Our aim is to report our current experience. PATIENTS AND METHODS Observational cohort study of the first 32 patients who underwent minimally invasive esophagectomy for esophageal cancer from September 2011 to June 2014. The gastric tube was created laparoscopically. In the thoracic field, a robot-assisted thoracoscopic approach was performed in the prone position with intrathoracic robotic hand-sewn anastomosis. Patient and tumour characteristics, surgical technique, short-term outcomes (morbidity and mortality) and oncological results (radicality and number of removed nodes) were evaluated. RESULTS Thirty-two patients, with a mean age of 58 years (34-74) were treated by a totally minimally invasive esophagectomy: robotic laparoscopy and thoracoscopy (11 McKeown and 21 Ivor-Lewis). Twenty-nine received neoadjuvant chemoradiotherapy. There were no conversions to open surgery. Console time was 218minutes (190-285). Blood loss was 170ml (40-255). One patient died from cardiac disease. Nine patients had a major complication (Dindo-Clavien grade II or higher). There was no case of respiratory complication or recurrent laryngeal nerve palsy. Five patients had intrathoracic fistula, 4 radiological and one clinical. Three had chylothorax, 2 cervical fistula and one gastric tube necrosis. The median hospital stay was 12 days (8-50). All the resections were R0 and the median of removed lymph nodes was 16 (2-23). CONCLUSIONS Our results suggest that minimally invasive esophagectomy with robot-assisted thoracoscopy is safe and achieves oncological standards.


title: Patient blood management during the COVID-19 pandemic - a narrative review.

text: As COVID-19 disease escalates globally, optimising patient outcome during this catastrophic health care crisis is the number one priority. The principles of patient blood management are fundamental strategies to improve patient outcomes and should be given high priority in this crisis situation. The aim of this expert review is to provide clinicians and health care authorities with information regarding how to apply established principles of patient blood management during the COVID-19 pandemic. In particular, this review considers the impact of the COVID-19 pandemic on the blood supply and specifies important aspects of donor management. We further discuss how preventative and control measures implemented during the COVID-19 crisis could affect the prevalence of anaemia, and highlight issues regarding the diagnosis and treatment of anaemia in patients requiring elective or emergency surgery. In addition, we review aspects related to patient blood management of critically ill patients with known or suspected COVID-19, and discuss important alterations of the coagulation system in patients hospitalised due to COVID-19. Finally, we address special considerations pertaining to supply-demand and cost-benefit issues of patient blood management during the COVID-19 pandemic.


title: What Was the Change in Telehealth Usage and Proportion of No-show Visits for an Orthopaedic Trauma Clinic During the COVID-19 Pandemic?

text: BACKGROUND In response to the coronavirus disease 2019 (COVID-19) pandemic, the Centers for Medicare and Medicaid Services pledged payment for telehealth visits for the duration of this public health emergency in an effort to decrease COVID-19 transmission and allow for deployment of residents and attending physicians to support critical-care services. Although the COVID-19 pandemic has vastly expanded telehealth use, no studies to our knowledge have analyzed the implementation and success of telehealth for orthopaedic trauma. This population is unique in that patients who have experienced orthopaedic trauma range in age from early childhood to late adulthood, they vary across the socioeconomic spectrum, may need to undergo emergent or urgent surgery, often have impaired mobility, and, historically, do not always follow-up consistently with healthcare providers. QUESTIONS/PURPOSES (1) To what extent did telehealth usage increase for an outpatient orthopaedic trauma clinic at a Level 1 trauma center from the month before the COVID-19 stay-at-home order compared with the month immediately following the order? (2) What is the proportion of no-show visits before and after the implementation of telehealth? METHODS After nonurgent clinic visits were postponed, telehealth visits were offered to all patients due to the COVID-19 stay-at-home order. Patients with internet access who had the ability to download the MyChart application on their mobile device and agreed to a telehealth visit were seen virtually between March 16, 2020 and April 10, 2020 (COVID-19) by three attending orthopaedic trauma surgeons at a large, urban, Level 1 trauma center. Clinic schedules and patient charts were reviewed to determine clinical volumes and no-show proportions. The COVID-19 period was compared with the 4 weeks before March 16, 2020 (pre-COVID-19), when all visits were conducted in-person. The overall clinic volume decreased from 340 to 233 (31%) between the two periods. The median (range) age of telehealth patients was 46 years (20 to 89). Eighty-four percent (72 of 86) of telehealth visits were postoperative and established nonoperative patient visits, and 16% (14 of 86) were new-patient visits. To avoid in-person suture or staple removal, patients seen for their 2-week postoperative visit had either absorbable closures, staples, or nonabsorbable sutures removed by a home health registered nurse or skilled nursing facility registered nurse. If radiographs were indicated, they were obtained at outside facilities or our institution before patients returned home for their telehealth visit. RESULTS There was an increase in the percentage of office visits conducted via telehealth between the pre-COVID-19 and COVID-19 periods (0% [0 of 340] versus 37% [86 of 233]; p < 0.001), and by the third week of implementation, telehealth comprised approximately half of all clinic visits (57%; [30 of 53]). There was no difference in the no-show proportion between the two periods (13% [53 of 393] for the pre-COVID-19 period and 14% [37 of 270] for the COVID-19 period; p = 0.91). CONCLUSIONS Clinicians should consider implementing telehealth strategies to provide high-quality care for patients and protect the workforce during a pandemic. In a previously telehealth-naïve clinic, we show successful implementation of telehealth for a diverse orthopaedic trauma population that historically has issues with mobility and follow-up. Our strategies include postponing long-term follow-up visits, having sutures or staples removed by a home health or skilled nursing facility registered nurse, having patients obtain pertinent imaging before the visit, and ensuring that patients have access to mobile devices and internet connectivity. Future studies should evaluate the incidence of missed infections or stiffness as a result of telehealth, analyze the subset of patients who may be more vulnerable to no-shows or technological failures, and conduct patient surveys to determine the factors that contribute to patient preferences for or against the use of telehealth. LEVEL OF EVIDENCE Level III, therapeutic study.


title: Pipeline embolization device: a new source for embolic retinal vascular occlusion.

text: A 57-year-old woman underwent treatment of a left internal carotid artery aneurysm with a Pipeline embolization device. She subsequently experienced multiple branch retinal artery occlusions in her left eye. Although rare, ophthalmic complications may follow this new technique in the treatment of intracranial aneurysms.


title: Quantifying cerebral hypoxia by near-infrared spectroscopy tissue oximetry: the role of arterial-to-venous blood volume ratio.

text: Tissue oxygenation estimated by near-infrared spectroscopy (NIRS) is a volume-weighted mean of the arterial and venous hemoglobin oxygenation. In vivo validation assumes a fixed arterial-to-venous volume-ratio (AV-ratio). Regulatory cerebro-vascular mechanisms may change the AV-ratio. We used hypotension to investigate the influence of blood volume distribution on cerebral NIRS in a newborn piglet model. Hypotension was induced gradually by inflating a balloon-catheter in the inferior vena cava and the regional tissue oxygenation from NIRS ( rStO 2 , NIRS ) was then compared to a reference ( rStO 2 , COX ) calculated from superior sagittal sinus and aortic blood sample co-oximetry with a fixed AV-ratio. Apparent changes in the AV-ratio and cerebral blood volume (CBV) were also calculated. The mean arterial blood pressure (MABP) range was 14 to 82 mmHg. PaCO 2 and SaO 2 were stable during measurements. rStO 2 , NIRS mirrored only 25% (95% Cl: 21% to 28%, p < 0.001 ) of changes in rStO 2 , COX . Calculated AV-ratio increased with decreasing MABP (slope: ? 0.007 · mmHg ? 1


EAHP launches COVID-19 resource centre for hospital pharmacists.


title: The response of Synechococcus sp. PCC 7002 to micro-/nano polyethylene particles - Investigation of a key anthropogenic stressor.

text: Microplastics or plastic particles less than 5 mm in size are a ubiquitous and damaging pollutant in the marine environment. However, the interactions between these plastic particles and marine microorganisms are just starting to be understood. The objective of this study was to measure the responses of a characteristic marine organism (Synechococcus sp. PCC 7002) to an anthropogenic stressor (polyethelene nanoparticles and microparticles) using molecular techniques. This investigation showed that polyethylene microparticles and nanoparticles have genetic, enzymatic and morphological effects on Synechococcus sp. PCC 7002. An RT-PCR analysis showed increases in the expression of esterase and hydrolase genes at 5 days of exposure to polyethylene nanoparticles and at 10 days of exposure to polyethylene microparticles. A qualitative enzymatic assay also showed esterase activity in nanoparticle exposed samples. Cryo-scanning electron microscopy was used to assess morphological changes in exopolymer formation resulting from exposure to polyethylene microparticles and nanoparticles. The data from this paper suggests that microplastic and nanoplastics could be key microbial stressors and should be investigated in further detail.


title: Creating an Artificial Tail Anchor as a Novel Strategy To Enhance the Potency of Peptide-Based HIV Fusion Inhibitors.

text: 20 (enfuvirtide) and other peptides derived from the human immunodeficiency virus type 1 (HIV-1) gp41 C-terminal heptad repeat (CHR) region inhibit HIV fusion by binding to the hydrophobic grooves on the N-terminal heptad repeat (NHR) trimer and blocking six-helix-bundle (6-HB) formation. Several strategies focusing on the binding grooves of the NHR trimer have been adopted to increase the antiviral activity of the CHR peptides. Here, we developed a novel and simple strategy to greatly enhance the potency of the existing peptide-based HIV fusion inhibitors. First, we identified a shallow pocket adjacent to the groove in the N-terminal region of NHR trimer as a new drug target, and then we designed several short artificial peptides to fit this target. After the addition of IDL (Ile-Asp-Leu) to the C terminus of CHR peptide WQ or MT-WQ, the conjugated peptides, WQ-IDL and MT-WQ-IDL, showed much more potent activities than WQ and T20, respectively, in inhibiting HIV-1 IIIB infection. WQ-IDL and MT-WQ-IDL were also more effective than WQ in blocking HIV-1 Env-mediated membrane fusion and had higher levels of binding affinity with NHR peptide N46. We solved the crystal structure of the 6-HB formed by MT-WQ-IDL and N46 and found that, besides the N-terminal MT hook tail, the IDL tail anchor of MT-WQ-IDL also binds with the shallow hydrophobic pocket outside the groove of the NHR trimer, resulting in enhanced inhibition of HIV-1 fusion with the target cell. It is expected that this novel approach can be widely used to improve the potency of peptidic fusion inhibitors against other enveloped viruses with class I fusion proteins. IMPORTANCE The hydrophobic groove of the human immunodeficiency virus type 1 (HIV-1) gp41 NHR trimer has been known as the classic drug target to develop fusion inhibitors derived from the gp41 CHR. Here, we developed a novel and simple strategy to improve the existing peptide-based HIV fusion inhibitors. We identified a shallow pocket adjacent to the groove in the NHR trimer and added a short artificial peptide consisting of three amino acids (IDL) to the C terminus of a fusion inhibitor to fit this new target. The inhibition activity of this new conjugated peptide was significantly enhanced, by 77-fold, making it much more potent than T20 (enfuvirtide) and suggesting that the IDL tail can be adopted for optimizing existing HIV-1 CHR peptide fusion inhibitors. This new approach of identifying a potential binding pocket outside the traditional target and creating an artificial tail anchor can be widely applied to design novel fusion inhibitors against other class I enveloped viruses, such as Middle East respiratory syndrome coronavirus (MERS-CoV).


title: Minority patient preferences, barriers, and facilitators for shared decision-making with health care providers in the USA: A systematic review.

text: OBJECTIVES This systematic review of contemporary literature sought to better understand racial and ethnic minority patients' shared decision-making (SDM) preferences, challenges and facilitators. METHODS Data sources were PubMed, CINAHL, Embase, Google Scholar, PsycINFO, Sociological Abstracts, and Web of Science databases for publications between 2011 and 2016. Publications were included if they studied SDM during the clinical encounter for minority adults in clinical care in the United States. We conducted a narrative, descriptive synthesis of each study. RESULTS From over 5000 publications identified through the search strategy, 18 met eligibility criteria following an abstract and full text (n = 685) review in Covidence. Studies focused on SDM in developing treatment plans (n = 10), and were conducted in primary care (n = 6) or hospital/health system settings (n = 6). Patients' decision preferences ranged from physician-driven altogether or initially, to patient-driven style. A comprehensive list of SDM facilitators and barriers was developed. CONCLUSION Despite strong policy and research SDM support to increase patient communication and a growing published literature, results suggest lack of representation of minority populations in contemporary literature. PRACTICE IMPLICATIONS Provider training may be needed to facilitate patient-provider transition from a passive toward a more active SDM engagement over time while confidence, trust and rapport is established.


title: Hormonal contraception and HIV acquisition among women: an updated systematic review.

text: OBJECTIVE To update a 2016 systematic review on hormonal contraception use and HIV acquisition. METHODS We searched Pubmed and Embase between 15 January 2016 and 26 June 2019 for longitudinal studies comparing incident HIV infection among women using a hormonal contraceptive method and either non-users or users of another specific hormonal contraceptive method. We extracted information from newly identified studies, assessed study quality, and updated forest plots and meta-analyses. RESULTS In addition to 31 previously included studies, five more were identified; three provided higher quality evidence. A randomised clinical trial (RCT) found no statistically significant differences in HIV risk among users of intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG implant) or the copper intrauterine device (Cu-IUD). An observational study found no statistically significant differences in HIV risk among women using DMPA, norethisterone enanthate (NET-EN), implants (type not specified) or Cu-IUD. Updated results from a previously included observational study continued to find a statistically significant increased HIV risk with oral contraceptives and DMPA compared with no contraceptive use, and found no association between LNG implant and HIV risk. CONCLUSIONS High-quality RCT data comparing use of DMPA, LNG implant and Cu-IUD does not support previous concerns from observational studies that DMPA-IM use increases the risk of HIV acquisition. Use of other hormonal contraceptive methods (oral contraceptives, NET-EN and implants) is not associated with an increased risk of HIV acquisition.


title: Transvaginal and transrectal natural orifice translumenal endoscopic surgery nephrectomy in a porcine survival model: comparison with conventional laparoscopic nephrectomy.

text: PURPOSE We analyzed the technical feasibility, physiological influence, and safety of transvaginal (TV) and transrectal (TR) natural orifice translumenal endoscopic surgery (NOTES) nephrectomy compared with conventional laparoscopic surgery in a porcine survival model. METHODS Fifteen female pigs (32.8-37.2 kg) were randomly assigned to undergo TV NOTES (n=5), TR NOTES (n=5), or conventional laparoscopic nephrectomy (n=5). Postoperatively, all animals were observed for global health status during the recovery from anesthesia. Variable laboratory parameters and inflammatory cytokines were compared among the groups during the entire experimental period. Postmortem examination was performed 1 week after operation for assessment of abdominal complications and cultures for microorganisms. RESULTS All experiments were completed successfully without insertion of an extra port or conversion to laparoscopic or open surgery. Although mean operative times were longer in TV and TR NOTES groups than in the conventional laparoscopy group (61 vs 84 vs 24 min, P<0.001), there were no signs of visceral injury or peritonitis on postmortem examination. None of the laboratory parameters, including white blood cell count, tumor necrosis factor-α, interleukin (IL)-1, and IL-6 differed among the groups during the entire experimental period. CONCLUSIONS TV and TR NOTES nephrectomy could be completed successfully with similar physiologic influence to those of conventional laparoscopic nephrectomy in a porcine survival model.


Novel Coronavirus and Orthopaedic Surgery: Early Experiences from Singapore.


title: Does Gastrostomy Placement With Concurrent Fundoplication Increase the Risk of Gastrostomy-related Complications?

text: OBJECTIVE To compare the incidence of complications with a primary gastrostomy versus gastrostomy with concurrent fundoplication and evaluating the impact of the method of gastrostomy tube placement. Neurologically impaired children were compared with neurologically normal children. Two low profile devices were compared for longevity. METHODS Ninety-eight patients (58 boys, mean age 4.66 years) with 107 gastrostomies inserted between April 2004 and May 2008 were included in this retrospective, single institution audit. Minimum follow-up period was 1 year. Specific complications reviewed were tube and site related. Logistic regression analysis examined the relationship between complications, type of procedure, method of placement, and neurological status. Survival analysis with log-rank test was used to compare the duration of the low-profile devices. RESULTS There were 63 primary gastrostomies and 44 with concurrent fundoplication, 71 children were neurologically impaired. Mean (±SD) follow-up time was 35.6 ± 1.4 months. There was a significant association between concurrent gastrostomy insertion with fundoplication and incidence of infection (odds ratio = 2.4, 95% confidence interval (CI) 1.02-5.56, P = 0.02) and excoriation (odds ratio = 2.5, 95% CI 1.09-5.71, P = 0.015). There were no associations between the complications with gastrostomy placement and neurological status. Failure rate of the balloon device was significantly greater than the fixed bolster device with a Hazard Ratio for survival of 3.2 (95% CI 2.2-4.6). CONCLUSIONS Gastrostomy site-related problems were more common than generally reported. There was a higher incidence of site infection and skin excoriation for gastrostomy placement with concurrent fundoplication. There was no significant difference in complications between the method of gastrostomy placement or neurological status. Balloon devices were changed 3 times more often than bolster retention devices.


title: A user report on the trial use of gesture commands for image manipulation and X-ray acquisition.

text: Touchless environment for image manipulation and X-ray acquisition may enhance the current infection control measure during X-ray examination simply by avoiding any touch on the control panel. The present study is intended at designing and performing a trial experiment on using motion-sensing technology to perform image manipulation and X-ray acquisition function (the activities a radiographer frequently performs during an X-ray examination) under an experimental setup. Based on the author's clinical experience, several gesture commands were designed carefully to complete a single X-ray examination. Four radiographers were randomly recruited for the study. They were asked to perform gesture commands in front of a computer integrated with a gesture-based touchless controller. The translational movements of the tip of their thumb and index finger while performing different gesture commands were recorded for analysis. Although individual operators were free to decide the extent of movement and the speed at which their fingers and thumbs moved while performing these gesture commands, the result of our study demonstrated that all operators could perform our proposed gesture commands with good consistency, suggesting that motion-sensing technology could, in practice, be integrated into radiographic examinations. To summarize, although the implementation of motion-sensing technology as an input command in radiographic examination might inevitably slow down the examination throughput considering that extra procedural steps are required to trigger specific gesture commands in sequence, it is advantageous in minimizing the potential of the pathogen contamination during image operation and image processing that leads to cross infection.


title: Independent Validation of the Hematoma Expansion Prediction Score: A Non-contrast Score Equivalent in Accuracy to the Spot Sign.

text: BACKGROUND AND PURPOSE The computed tomography angiography (CTA) spot sign is widely used to assess the risk of hematoma expansion following acute intracerebral hemorrhage (ICH). However, not all patients can receive intravenous contrast nor are all hospital systems equipped with this technology. We aimed to independently validate the Hematoma Expansion Prediction (HEP) Score, an 18-point non-contrast prediction scale, in an external cohort and compare its diagnostic capability to the CTA spot sign. METHODS We performed a retrospective analysis of the predicting hematoma growth and outcome in intracerebral hemorrhage using contrast bolus CT (PREDICT) Cohort Study. Primary outcome was significant hematoma expansion (≥ 6 mL or ≥ 33%). We generated a receiver operating characteristic (ROC) curve comparing the HEP score to significant expansion. We calculated sensitivity, specificity, positive and negative predictive values (PPV/NPV) for each score point. We determined independent predictors of significant hematoma expansion via logistic regression. RESULTS A total of 292 patients were included in primary analysis. Hematoma growth of ≥ 6 mL or ≥ 33% occurred in 94 patients (32%). The HEP score was associated with significant expansion (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 1.01-1.30). ROC curves comparing HEP score to significant expansion had an area under the curve of 0.64 (95% CI 0.57-0.71). Youden's method showed an optimum score of 4. HEP Scores ≥ 4 (n = 100, sensitivity 49%, specificity 73%, PPV 46%, NPV 75%, aOR 1.99, 95% CI 1.09-3.64) accurately predicted significant expansion. PPV increased with higher HEP scores, but at the cost of lower sensitivity. The diagnostic characteristics of the spot sign (n = 82, Sensitivity 49%, Specificity 81%, PPV 55%, NPV 76%, aOR 2.95, 95% CI 1.61-5.42) were similar to HEP scores ≥ 4. CONCLUSION The HEP score is predictive of significant expansion (≥ 6 mL or ≥ 33%) and is comparable to the spot sign in diagnostic accuracy. Non-contrast prediction tools may have a potential role in the recruitment of patients in future intracerebral hemorrhage trials.


title: Transpulmonary pressure and gas exchange during decremental PEEP titration in pulmonary ARDS patients.

text: BACKGROUND Selection of the PEEP associated with the best compliance of the respiratory system during decremental PEEP titration can be used for the treatment of patients suffering from ARDS. We describe changes in transpulmonary pressure (Ptp) and gas exchange during a decremental PEEP titration maneuver in subjects with pulmonary ARDS. METHODS Eleven subjects with early ARDS were included. After a recruitment maneuver they were ventilated in volume-controlled ventilation and PEEP was decreased from 30 to 0 cm H2O by steps of 3 cm H2O. Static airway pressure (Paw), esophageal pressure (Pes), Ptp (Paw - Pes), the ratio of dead space to tidal volume (VD/VT), and PaO2 were recorded at each step. RESULTS A linear correlation was found between Paw and Ptp. Expiratory Ptp became negative in all subjects when PEEP decreased below 8.9 ± 5.2 cm H2O. VD/VT was 0.67 ± 0.06 with 30 cm H2O of PEEP, and decreased 15.4 ± 8.5% during the maneuver, when PEEP and expiratory Ptp were 10.6 ± 4.1 cm H2O and 1.2 ± 2.8 cm H2O, respectively. VD/VT was significantly higher during ventilation at high (> 18 cm H2O), compared to low, inspiratory Ptp values (P < .001). PaO2 decreased when expiratory Ptp became negative (P < .001). CONCLUSIONS During decremental PEEP titration we sequentially observed high inspiratory Ptp that stressed lung tissue and increased VD/VT, and negative Ptp, indicating high risk of alveolar collapse, explaining worse oxygenation. PEEP selection based on Ptp and VD/VT in ARDS may help to avoid these situations.


title: Clinical course of COVID-19 pneumonia in a patient undergoing pneumonectomy and pathology findings during the incubation period.

text: BACKGROUND The cause of coronavirus disease 2019 (COVID-19) is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical information about patients undergoing lung resection while infected with this virus and pathological information about early COVID-19 pneumonia are still scarce. CASE PRESENTATION A 69-year-old male patient underwent a right pneumonectomy for squamous cell lung carcinoma. Until the fourth postoperative day, the patient, who had minor radiological changes on chest x-ray, was asymptomatic. From this day, the COVID-19 test, which was performed after the appearance of symptoms such as fever and shortness of breath, lymphopenia and diffuse ground glass opacity in the left lung on computed tomography, was reported to be positive. The patient was given NIMV (non-invasive mechanical ventilation), and hydroxychloroquine, favipiravir and azithromycin in isolation intensive care, with the diagnosis of severe pneumonia. He was discharged on the 17th postoperative day with healing of the lung lesions. The pathology specimen of the patient, who was found to have been infected with SARS-CoV-2 before the day of surgery, was examined retrospectively. Irregular and severe pneumocyte hyperplasia, interstitial thickening, oedema, pronounced protein exudates, diffuse enlargement of the alveolar walls, macrophage infiltration and fibroblastic proliferation, which is an indicator of early organisation, were detected. CONCLUSION We believe that the clinical course and pathology findings obtained after right pneumonectomy in a patient with pre-symptomatic COVID-19 pneumonia will guide the diagnosis and treatment of patients infected with SARS-CoV-2.


title: Infectious Bronchitis Coronavirus Limits Interferon Production by Inducing a Host Shutoff That Requires Accessory Protein 5b.

text: UNLABELLED During infection of their host cells, viruses often inhibit the production of host proteins, a process that is referred to as host shutoff. By doing this, viruses limit the production of antiviral proteins and increase production capacity for viral proteins. Coronaviruses from the genera Alphacoronavirus and Betacoronavirus, such as severe acute respiratory syndrome coronavirus (SARS-CoV), establish host shutoff via their nonstructural protein 1 (nsp1). The Gammacoronavirus and Deltacoronavirus genomes, however, do not encode nsp1, and it has been suggested that these viruses do not induce host shutoff. Here, we show that the Gammacoronavirus infectious bronchitis virus (IBV) does induce host shutoff, and we find that its accessory protein 5b is indispensable for this function. Importantly, we found that 5b-null viruses, unlike wild-type viruses, induce production of high concentrations of type I interferon protein in vitro, indicating that host shutoff by IBV plays an important role in antagonizing the host's innate immune response. Altogether, we demonstrate that 5b is a functional equivalent of nsp1, thereby answering the longstanding question of whether lack of nsp1 in gammacoronaviruses is compensated for by another viral protein. As such, our study is a significant step forward in the understanding of coronavirus biology and closes a gap in the understanding of some IBV virulence strategies. IMPORTANCE Many viruses inhibit protein synthesis by their host cell to enhance virus replication and to antagonize antiviral defense mechanisms. This process is referred to as host shutoff. We studied gene expression and protein synthesis in chicken cells infected with the important poultry pathogen infectious bronchitis virus (IBV). We show that IBV inhibits synthesis of host proteins, including that of type I interferon, a key component of the antiviral response. The IBV-induced host shutoff, however, does not require degradation of host RNA. Furthermore, we demonstrate that accessory protein 5b of IBV plays a crucial role in the onset of host shutoff. Our findings suggest that inhibition of host protein synthesis is a common feature of coronaviruses and primarily serves to inhibit the antiviral response of the host.


Important role of emergency department doctors after the outbreak of covid-19 in China.


title: Endotracheal tubes and the cricoid: Is there a good fit?

text: BACKGROUND Choosing an appropriately sized endotracheal tube (ETT) is important in pediatric patients as an inappropriately sized ETT may result in multiple endotracheal intubation attempts or excessive pressure on the tracheal mucosa with the potential for airway damage. Although age-based formulas are generally used with choice of an ETT based on the internal diameter (ID), measurements of the outer diameter (OD) of the ETT would seem to be a more scientific approach to determine the proper size of an ETT. However, the variable OD of the ETT despite the same ID makes the selection of a proper sized ETT more difficult. The current study compares airway dimensions measured using computed tomography (CT) with the OD of ETTs from various manufacturers. METHODS The outer diameter of commonly used ETTs (12 cuffed and 5 uncuffed) were measured and compared with CT-based cricoid measurements obtained from a previous study involving 130 pediatric patients, ranging in age from 1 month to 10 years. These data were used to determine the likelihood of a clinically acceptable match. RESULTS The differences of the cricoid dimensions between the 5th and the 95th percentile in each group ranged from a minimum of 2.23mm to a maximum of 6.51mm. Depending on the manufacturer, there was significant variation in the OD of the ETTs with the same ID. These discrepancies, which varied according to manufacturer and were greater with uncuffed as compared to cuffed ETTs, impacted the chances of an acceptable fit with the cricoid diameters. CONCLUSION When choosing an ETT, age-based formulas which use the ID may not be uniformly accurate in ensuring the appropriately-sized ETT given the variation in the OD despite the same ID. These issues further support the use of cuffed ETTs as the variation in fit can be adjusted by inflation of the cuff to provide an adequate tracheal seal.


title: Cyclin D1 overexpression supports stable EBV infection in nasopharyngeal epithelial cells.

text: Undifferentiated nasopharyngeal carcinomas (NPCs) are commonly present with latent EBV infection. However, events regulating EBV infection at early stages of the disease and the role of EBV in disease pathogenesis are largely undefined. Genetic alterations leading to activation of cyclin D1 signaling in premalignant nasopharyngeal epithelial (NPE) cells have been postulated to predispose cells to EBV infection. We previously reported that loss of p16, a negative regulator of cyclin D1 signaling, is a frequent feature of NPC tumors. Here, we report that early premalignant lesions of nasopharyngeal epithelium overexpress cyclin D1. Furthermore, overexpression of cyclin D1 is closely associated with EBV infection. Therefore we investigated the potential role of cyclin D1 overexpression in dysplastic NPE cells in vitro. In human telomerase reverse transcriptase-immortalized NPE cells, overexpression of cyclin D1 or a p16-resistant form of CDK4 (CDK4(R24C)) suppressed differentiation. This suppression may have implications for the close association of EBV infection with undifferentiated NPC. In these in vitro models, we found that cellular growth arrest and senescence occurred in EBV-infected cell populations immediately after infection. Nevertheless, overexpression of cyclin D1 or a p16-resistant form of CDK4 or knockdown of p16 in the human telomerase reverse transcriptase-immortalized NPE cell lines could counteract the EBV-induced growth arrest and senescence. We conclude that dysregulated expression of cyclin D1 in NPE cells may contribute to NPC pathogenesis by enabling persistent infection of EBV.


title: Single-Port Laparoscopic Repair of Perforated Duodenal Ulcers.

text: BACKGROUND Laparoscopic single-port surgery has widely been introduced for the treatment of various abdominal conditions. But controversies still exist regarding its potential advantages and risks, especially for emergency surgery. The aim of this study was to evaluate the results of a single-port laparoscopic repair using straight laparoscopic instruments for the treatment of perforated duodenal ulcers. METHODS A prospective consecutive case series was conducted including all patients with a perforated duodenal ulcer who underwent a laparoscopic single-port repair at a single institution from January 2012 to June 2018. The operation was performed through a single port using conventional straight laparoscopic instruments and intra-corporeal knot tying techniques. RESULTS Out of 75 patients, simple closure of the perforation without omental patch was accomplished in 96% of cases. Conversion to an open operation was required in one patient (1.3%) due to a posterior duodenal perforation, and additional trocar placement was needed in another patient (1.3%). The mean incision length was 2.0 ± 0.2 cm. The mean operation time was 63.0 ± 26.6 min. Meantime a nasogastric tube remained in place was 2.9 ± 0.8 days. Mean duration of analgesic use was 2.8 ± 0.8 days. The rate of postoperative complications was 2.7%, including two patients with wound infections. There were no instances of intestinal leak or abscess. The postoperative hospital stay was 5.7 ± 1.2 days. CONCLUSION Laparoscopic single-port repair using conventional straight laparoscopic instruments with intra-corporeal knot tying technique was safe and feasible for patients with perforated duodenal ulcers with low risk factors. This method offers results comparable to those expected with the standard multiport laparoscopic approach with the addition of improved cosmetic outcomes.


Visual Dermatology: Acral Erythemato-purpuric Lesions During COVID-19 Pandemic.


title: Baseline Blood Pressure Effect on the Benefit and Safety of Intra-Arterial Treatment in MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands).

text: BACKGROUND AND PURPOSE High blood pressure (BP) is associated with poor outcome and the occurrence of symptomatic intracranial hemorrhage in acute ischemic stroke. Whether BP influences the benefit or safety of intra-arterial treatment (IAT) is not known. We aimed to assess the relation of BP with functional outcome, occurrence of symptomatic intracranial hemorrhage and effect of IAT. METHODS This is a post hoc analysis of the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands). BP was measured at baseline, before IAT or stroke unit admission. We estimated the association of baseline BP with the score on the modified Rankin Scale at 90 days and safety parameters with ordinal and logistic regression analysis. Effect of BP on the effect of IAT was tested with multiplicative interaction terms. RESULTS Systolic BP (SBP) had the best correlation with functional outcome. This correlation was U-shaped; both low and high baseline SBP were associated with poor functional outcome. Higher SBP was associated with symptomatic intracranial hemorrhage (adjusted odds ratio, 1.25 for every 10 mm Hg higher SBP [95% confidence interval, 1.09-1.44]). Between SBP and IAT, there was no interaction for functional outcome, symptomatic intracranial hemorrhage, or other safety parameters; the absolute benefit of IAT was evident for the whole SBP range. The same was found for diastolic BP. CONCLUSIONS BP does not affect the benefit or safety of IAT in patients with acute ischemic stroke caused by proximal intracranial vessel occlusion. Our data provide no arguments to withhold or delay IAT based on BP. CLINICAL TRIAL REGISTRATION URL: http://www.isrctn.com. Unique identifier: ISRCTN10888758.


Respiratory infections.


title: Notice to Readers: Final 2015 Reports of Nationally Notifiable Infectious Diseases and Conditions.

text: The table listed in this report on pages 1307-1321 presents finalized data, as of June 30, 2016, from the National Notifiable Diseases Surveillance System (NNDSS) for 2015. These data will be published in more detail in the Summary of Notifiable Infectious Diseases and Conditions - United States, 2015 (1). Because no cases were reported in the United States during 2015, the following diseases do not appear in this early release table: anthrax; dengue hemorrhagic fever; diphtheria; eastern equine encephalitis virus disease, nonneuroinvasive; poliomyelitis, paralytic; poliovirus infection, nonparalytic; severe acute respiratory syndrome-associated coronavirus disease (SARS-CoV); smallpox; western equine encephalitis virus disease, neuroinvasive and nonneuroinvasive; yellow fever; and viral hemorrhagic fevers.


title: COVID-19 Pandemic: Exacerbating Racial/Ethnic Disparities in Long-Term Services and Supports.

text: What services are available and where racial and ethnic minorities receive long-term services and supports (LTSS) have resulted in a lower quality of care and life for racial/ethnic minority users. These disparities are only likely to worsen during the COVID-19 pandemic, as the pandemic has disproportionately affected racial and ethnic minority communities both in the rate of infection and virus-related mortality. By examining these disparities in the context of the pandemic, we bring to light the challenges and issues faced in LTSS by minority communities with regard to this virus as well as the disparities in LTSS that have always existed.


title: Cerebrovascular autoregulation and neurologic injury in neonatal hypoxic-ischemic encephalopathy.

text: BACKGROUND Neonates with hypoxic-ischemic encephalopathy (HIE) are at risk of cerebral blood flow dysregulation. Our objective was to describe the relationship between autoregulation and neurologic injury in HIE. METHODS Neonates with HIE had autoregulation monitoring with the hemoglobin volume index (HVx) during therapeutic hypothermia, rewarming, and the first 6 h of normothermia. The 5-mm Hg range of mean arterial blood pressure (MAP) with best vasoreactivity (MAPOPT) was identified. The percentage of time spent with MAP below MAPOPT and deviation in MAP from MAPOPT were measured. Neonates received brain magnetic resonance imaging (MRI) 3-7 d after treatment. MRIs were coded as no, mild, or moderate/severe injury in five regions. RESULTS HVx identified MAPOPT in 79% (19/24), 77% (17/22), and 86% (18/21) of the neonates during hypothermia, rewarming, and normothermia, respectively. Neonates with moderate/severe injury in paracentral gyri, white matter, basal ganglia, and thalamus spent a greater proportion of time with MAP below MAPOPT during rewarming than neonates with no or mild injury. Neonates with moderate/severe injury in paracentral gyri, basal ganglia, and thalamus had greater MAP deviation below MAPOPT during rewarming than neonates without injury. CONCLUSION Maintaining MAP within or above MAPOPT may reduce the risk of neurologic injuries in neonatal HIE.


title: Tibiopedal access for lower extremity arterial intervention: when to use and how to perform.

text: Tibiopedal artery access is being used with increasing frequency as an alternative access to facilitate procedural success in lower extremity arterial intervention. This technique is usually employed in the setting of critical limb ischemia and tibial artery intervention, but it may offer potential practical advantages for popliteal artery and even superficial femoral artery intervention in unique situations. As in all cases of lower extremity arterial intervention, consideration of access is important not only for initial approach to any obstructing lesion but also for exit strategy. The dorsalis pedis artery and posterior tibial artery can be readily accessed if necessary owing to their relatively superficial position in the foot or the ankle, yet their normal diameter and the presence of significant calcification (a common finding in patients with tibial occlusive disease and critical limb ischemia) can pose difficulties as well. In addition, the peroneal artery in the lower leg can be accessed percutaneously; however, its size and depth may present additional challenges. Meticulous attention to detail is paramount in avoiding complications in what may be the only distal vessel supplying the foot. This article describes common techniques in using tibiopedal artery access as a means of alternative access for successful infrainguinal intervention.


title: [Study on medication regularity of traditional Chinese medicine in treatment of COVID-19 based on data mining].

text: The coronavirus disease 2019(COVID-19) is developing rapidly and posing great threat to public health. There is no specific medicine available for treating the disease. Luckily, traditional Chinese medicine has played a positive role in the fighting against COVID-19. In this paper, We collected and sorted the prescriptions of modern Chinese medicine for COVID-19 released by national government, different provinces, autonomous regions and municipalities, as well as online databases, such as CNKI, WanFang medical network, and VIP database. These prescriptions were combined with the inheritance of traditional Chinese medicine auxiliary V2.5, and the complex system entropy clustering method was used to determine the association rules and frequency of single drug and drug combination in the prescription. In the end, 96 effective prescriptions were included. Among them, the four properties were mainly concentrated in temperature, cold and level, the five tastes were mainly concentrated in bitter, hot and sweet, and the meridians were mainly concentrated in lung, stomach and spleen. The high-frequency drugs were Glycyrrhizae Radix et Rhizoma, Armeniacae Semen Amarum, Gypsum Fibrosum, etc., and the high-frequency combinations are Gypsum Fibrosum-Armeniacae Semen Amarum, Gypsum Fibrosum-Glycyrrhizae Radix et Rhizoma, Armeniacae Semen Amarum-Glycyrrhizae Radix et Rhizoma, the core combinations are Lepidii Semen-Armeniacae Semen Amarum-Gypsum Fibrosum, Pogostemonis Herba-Zingiberis Rhizoma Recens-Magnoliae Officinalis Cortex, Ophiopogonis Radix-Armeniacae Semen Amarum-Scutellariae Radix and so on. Form new prescriptions Lepidii Semen, Armeniacae Semen Amarum, Gypsum Fibrosum, Pogostemonis Herba, Zingiberis Rhizoma Recens, Magnoliae Officinalis Cortex. Ophiopogonis Radix, Armeniacae Semen Amarum, Scutellariae Radix, Schisandrae Sphenantherae Fructus, Panacis Quinquefolii Radix. From the medicinal properties to high-frequency drugs and new prescriptions, it could be seen that the overall treatment of COVID-19 by traditional Chinese medicine was to strengthen body resistance, eliminate pathogenic factors, and give attention to Qi and Yin.


title: A prognostic nomogram for colorectal cancer liver metastases after percutaneous thermal ablation.

text: PURPOSE To assess the efficacy of percutaneous thermal ablation in treating colorectal cancer liver metastases (CRCLM), and to propose a prognostic nomogram for overall survival (OS). MATERIALS AND METHODS Seventy-one patients with CRCLM undergoing thermal ablation at our institute from 2009 to 2013 were identified and analysed to formulate a prognostic nomogram. The concordance index (C-index) and calibration curve were calculated to evaluate the predictive accuracy of the nomogram. The nomogram was compared with two current prognostic nomograms for patients with CRCLM who had undergone hepatectomy (Kattan) and selective internal radiation therapy (Fendler). Predictive validity was assessed in the validation cohort of 25 patients who had undergone thermal ablation from 2014 to 2016. RESULTS The median OS in the primary cohort was 26.4 months, whereas the 1-, 3- and 5-year OS rates were 72.2%, 37.2% and 17%, respectively. The median progression-free survival was 4.2 months. After univariate and multivariate analysis, a prognostic nomogram was formulated based on four predictors, including the number of tumours, maximum diameter of the tumour, CA19-9 level and ablation margin. The C-index of the nomogram was 0.815. Based on the patients of this study, the C-index was significantly higher than that of the Fendler nomogram (C-index, 0.698) and Kattan nomogram (C-index, 0.514, p < 0.001). Predictive accuracy of the proposed nomogram was also satisfactory in the validation cohort, with a C-index of 0.884. CONCLUSIONS Thermal ablation was an effective therapy for CRCLM. Moreover, the nomogram was effective and simple for CRCLM patients undergoing thermal ablation.


Covid-19: Ethnic minority doctors feel more pressured and less protected than white colleagues, survey finds.


title: The risk of umbilical hernia and other complications with laparoendoscopic single-site surgery.

text: STUDY OBJECTIVE To estimate the risk of umbilical hernia and other latent complications in women who underwent laparoendoscopic single-site surgery (LESS) for a gynecologic indication. DESIGN Retrospective, nonrandomized clinical study (Canadian Task Force classification II-2). SETTING Four tertiary care academic medical centers. PATIENTS Women undergoing LESS for a benign or malignant gynecologic indication from 2009 to 2011. INTERVENTIONS A total of 211 women underwent LESS via a single 1.5- to 2.0-cm umbilical incision. All surgeries were performed by advanced gynecologic laparoscopists. Incisions were repaired with a running, delayed absorbable suture. Subject demographics and clinical variables were collected and surgical outcomes analyzed. MEASUREMENTS AND MAIN RESULTS Median age and body mass index were 45 years and 30 kg/m(2), respectively. Approximately half of study subjects underwent a hysterectomy with or without salpingo-oophorectomy, and 15% had a diagnosis of cancer. Overall, 0.9% of women were diagnosed with a preoperative umbilical hernia, and 2.4% of women experienced a major perioperative complication. After a median postoperative follow-up time of 16 months, 2.4% had development of an umbilical hernia. However, 4/5 of these women had significant risk factors for fascial weakening independent of LESS, including requirement for a second abdominal surgery in 1 subject and a cancer diagnosis with postoperative chemotherapy administration in 2 subjects. When these subjects deemed "high risk" for incisional disruption were excluded from the analysis, the umbilical hernia rate was 0.5% (1/207). On univariable analysis, obesity was the only factor associated with complications (p = .04). CONCLUSION When performed by advanced laparoscopic surgeons, laparoendoscopic single-site gynecologic surgery is associated with a low risk of major adverse events. Additionally, the overall umbilical hernia rate was 2.4% and was lower (0.5%) in subjects without significant comorbidities.


title: Bipolar disorder and antithyroid antibodies: review and case series.

text: Mood disorders and circulating thyroid antibodies are very prevalent in the population and their concomitant occurrence may be due to chance. However, thyroid antibodies have been repeatedly hypothesized to play a role in specific forms of mood disorders. Potentially related forms include treatment-refractory cases, severe or atypical depression, and depression at specific phases of a woman's life (early gestation, postpartum depression, perimenopausal). With regard to bipolar disorder, studies of specific subgroups (rapid cycling, mixed, or depressive bipolar) have reported associations with thyroid antibodies. Offspring of bipolar subjects were found more vulnerable to develop thyroid antibodies independently from the vulnerability to develop psychiatric disorders. A twin study suggested thyroid antibodies among possible endophenotypes for bipolar disorder. Severe encephalopathies have been reported in association with Hashimoto's thyroiditis. Cases with pure psychiatric presentation are being reported, the antithyroid antibodies being probably markers of some other autoimmune disorders affecting the brain. Vasculitis resulting in abnormalities in cortical perfusion is one of the possible mechanisms.


title: Ex vivo pneumostasis evaluation of a variable-height staple design.

text: OBJECTIVE This study examined the effect of using a variable-height staple construct containing three rows of staples with heights of 3.0, 3.5, and 4.0 mm (staple leg length, medial to lateral) versus standard three-row single-height staplers (with staple heights of either 3.5 or 4.8 mm) for pneumostasis in healthy porcine and canine lung parenchyma to determine whether a single stapler that uses variable staple heights could perform as well as, or better than, existing single-height stapling devices. The work presented here used healthy animal tissues, in lieu of diseased tissue, which is extremely difficult to obtain and quantify. METHODS Briefly, fresh explanted porcine and canine trachea-lung blocs were used for all testing. Tissue thicknesses were measured with a custom-design spring-loaded caliper before stapling with control and test articles to ensure that the tissue was of "appropriate" thickness for the stapler size (staple height) selected (per manufacturer's instructions for use). All tissue measurements were comparable across each area of lung tested, and both test and control devices were fired into the same tissue thicknesses. After stapling, the lungs were submerged in water, insufflated, checked for air leaks at four discrete (increasing) pressures, and scored using a predetermined scale. Statistical analysis was performed for n = 26 (3.5-mm staples), n = 29 (4.8-mm staples), and n = 26 or 29 (paired to the standard group) for the variable-height stapler (3.0-, 3.5-, and 4.0-mm staples). RESULTS The results demonstrated that the test article comprising three rows of variable-height staples provided comparable pneumostasis with the standard three-row single-height staplers (with staple heights of either 3.5 or 4.8 mm) under the test conditions described. CONCLUSIONS A novel test article containing three rows of staples with heights of 3.0, 3.5, and 4.0 mm (variable-height stapler) showed promising results when compared with standard commercially available single-height staplers, performing as well as or better than the standard single-height staplers. This work demonstrates important first steps to proving equivalent device performance, which might facilitate the use of a variable-height stapler in place of multiple single-height staplers.


title: Speed spinal anesthesia revisited: new drugs and their clinical effects.

text: PURPOSE OF REVIEW Spinal anesthesia (SPA) has not been popular for day-case surgery because of prolonged neurologic blockade with long-acting local anesthetics such as bupivacaine, thereby delaying discharge. Although the intermediate duration of action of lidocaine and mepivacaine appears to be more suitable for day-case surgery, their use is not deemed appropriate by many because of a high incidence of transient neurologic symptoms (TNSs). The present review summarizes recent clinical data on the intrathecal use of alternative local anesthetics and adjuvants that may offer valuable alternatives to general anesthesia in day-case surgery. RECENT FINDINGS Prilocaine has a similar intrathecal pharmacokinetic profile as lidocaine but with a significantly lower risk of TNSs. Onset of spinal after 2-chloroprocaine is comparable with lidocaine or prilocaine, but with a considerably shorter duration of action. Also, TNS is clearly less frequent compared with lidocaine. Although its intrathecal use has recently been approved in Europe, this is still considered to be off-label in the USA. Articaine provides an extraordinary fast onset and a short duration of spinal block, the latter being approximately intermediate between chloroprocaine and prilocaine. However, articaine is associated with a high risk for intraoperative hypotension and a small risk for TNS, albeit but less frequent than after lidocaine. Concerns regarding possible neurotoxicity of articaine remain to be resolved. SUMMARY SPA for day cases might become a most valuable method for ambulatory surgery when using short acting local anesthetics. This, however, not only depends on drugs being used but also on infrastructure (post anaesthesia care unit) and organizational issues.


title: "Subintimal external crush" technique for a "balloon uncrossable" chronic total occlusion.

text: Chronic total occlusion (CTO) revascularization is traditionally limited by the challenges related to lesion crossing. In a smaller number of cases, however, inability to advance the balloon catheter to the crossing site can account for recanalization failure ("balloon uncrossable" CTO). We describe a case of a "balloon uncrossable" CTO in which balloon crossing was achieved after subintimal dilation and "external crushing" of the CTO lesion resulting in significant modification of the CTO atheromatous plaque.


Whither pediatric physician-scientist training in the COVID-19 era.


title: Retraction of the Research Article: "Police Violence and the Health of Black Infants".

text: [This retracts the article DOI: 10.1126/sciadv.aax7894.].


title: Uterosacral ligament vaginal vault suspension using delayed absorbable monofilament suture.

text: INTRODUCTION AND HYPOTHESIS We investigated the incidence of suture complications and recurrent prolapse following uterosacral ligament suspension (USLS) using delayed absorbable polyglyconate monofilament suture (Maxon). METHODS We reviewed the medical records of subjects who underwent vaginal USLS using polyglyconate suture. Primary outcomes were suture complications and anatomic failures defined as recurrent apical prolapse stage 1 or greater. Secondary outcomes were subjective failures and reoperation rate for apical prolapse. RESULTS Fifty-seven out of 68 subjects who underwent USLS with polyglyconate suture over the study period were included in analysis. At median follow-up of 12 months, 3.5% had suture complications. The anatomic and symptomatic failure rate was 7%. One subject underwent repeat surgery for prolapse. CONCLUSIONS Suture complications are uncommon using polyglyconate suture for USLS, and failure rates are low. This is in comparison to a 44.6% suture erosion rate with permanent suture reported by our institution using the same surgical technique.


title: Temperature measurement methods during direct heat arterial tissue fusion.

text: Fusion of biological tissues through direct and indirect heating is a growing area of medical research, yet there are still major gaps in understanding this procedure. Several companies have developed devices which fuse blood vessels, but little is known about the tissue's response to the stimuli. The need for accurate measurements of tissue behavior during tissue fusion is essential for the continued development and improvement of energy delivery devices. An experimental study was performed to measure the temperatures experienced during tissue fusion and the resulting burst pressure of the fused arteries. An array of thermocouples was placed in the lumen of a porcine splenic artery segment and sealed using a ConMed Altrus thermal fusion device. The temperatures within the tissue, in the device, and at the tissue-device interface were recorded. These measurements were then analyzed to calculate the temperature profile in the lumen of the artery. The temperature in the artery at the site of tissue fusion was measured to range from 142 to 163 °C using the ConMed Altrus. The corresponding burst pressure for arteries fused at this temperature was measured as 416 ± 79 mmHg. This study represents the first known experimental measurement of temperature at the site of vessel sealing found in the literature.


title: Discontinued drugs in 2008: anti-infectives.

text: Of the many drugs dropped from development in 2008, 27 were under development for therapy or prophylaxis of infectious diseases. The majority of these were for diseases of viral etiology (15 agents), while nine were antibacterials and the remaining three were directed against fungal and protozoan pathogens. The antiviral agents were primarily against HIV and hepatitis C virus, together with agents against hepatitis B virus and West Nile virus. The antibacterial agents were mostly from known classes (carbapenems, fluoroquinolones, oxazolidinones), but also included several novel compounds and approaches. With regard to drug type, 19 were small-molecule therapeutics, seven were biologics comprising five vaccines and two antibodies, and one was a high-molecular-weight polymer. Each of these agents is briefly reviewed and the reasons for failure are discussed.


title: Comparison of pulmonary availability and anti-inflammatory effect of dehydroandrographolide succinate via intratracheal and intravenous administration.

text: Dehydroandrographolide succinate (DAS) injection, which was approved in China for the treatment of viral pneumonia and upper respiratory tract infections, is often off-label used for nebulization therapy to avoid the adverse drug reactions associated with the injection. However, the aerodynamic properties and pulmonary fate of nebulized DAS was largely uninvestigated. In this study, the main objectives were to evaluate the in vitro aerodynamic deposition profiles of nebulizer generated aerosols and comparatively investigate the local drug availability and anti-inflammatory efficacy of DAS between intratracheal and intravenous dosing. The in vitro evaluation of aerodynamic characteristics and droplet size distribution showed more than 50% aerosol particles with size being < 5 μm, allowing the aerosols to reach the lower respiratory tract. Following intratracheal administration, the drug underwent pulmonary absorption into the bloodstream, rendering an absolute bioavailability of 47.3%. Compared to the intravenous delivery, the intratracheal administration dramatically increased the drug availability in the lung tissue in rats by more than 80-fold, leading to an improved and prolonged local anti-inflammatory efficacy in a lipopolysaccharide induced lung injury model in mice. The present results demonstrated that inhalation delivery of DAS is a convenient and effective alternative to intravenous injections.


title: Prognostic significance of delayed intraventricular haemorrhage in the INTERACT studies.

text: BACKGROUND AND PURPOSE Intraventricular extension of intracerebral haemorrhage (ICH) predicts poor outcome, but the significance of delayed intraventricular haemorrhage (dIVH) is less well defined. We determined the prognostic significance of dIVH in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trials (INTERACT 1 and 2). METHODS Pooled analyses of the INTERACT CT substudies-international, multicentre, prospective, open, blinded end point, randomised controlled trials of patients with acute spontaneous ICH and elevated systolic blood pressure (SBP)-randomly assigned to intensive (<140 mm Hg) or guideline-based (<180 mm Hg) SBP management. Participants had blinded central analyses of baseline and 24 h CTs, with dIVH defined as new intraventricular haemorrhage (IVH) on the latter scan. Outcomes of death and major disability were defined by modified Rankin Scale scores at 90 days. RESULTS There were 349 (27%) of 1310 patients with baseline IVH, and 107 (11%) of 961 initially IVH-free patients who developed dIVH. Significant associations of dIVH were prior warfarin anticoagulation, high (≥15) baseline National Institutes of Health Stroke Scale score, larger (≥15 mL) ICH volume, greater ICH growth and higher achieved SBP over 24 h. Compared with those who were IVH-free, dIVH had greater odds of 90-day death or major disability versus initial IVH (adjusted ORs 2.84 (95% CI 1.52 to 5.28) and 1.87 (1.36 to 2.56), respectively (p trend <0.0001)). CONCLUSIONS Although linked to factors determining greater ICH growth including poor SBP control, dIVH is independently associated with poor outcome in acute small to moderate-size ICH. TRIAL REGISTRATION NUMBERS NCT00226096 and NCT00716079.


Orthopaedic surgeons and orthopaedic surgery in the era of COVID-19.


title: Using Machine Learning to Estimate Unobserved COVID-19 Infections in North America.

text: BACKGROUND The detection of coronavirus disease 2019 (COVID-19) cases remains a huge challenge. As of April 22, 2020, the COVID-19 pandemic continues to take its toll, with >2.6 million confirmed infections and >183,000 deaths. Dire projections are surfacing almost every day, and policymakers worldwide are using projections for critical decisions. Given this background, we modeled unobserved infections to examine the extent to which we might be grossly underestimating COVID-19 infections in North America. METHODS We developed a machine-learning model to uncover hidden patterns based on reported cases and to predict potential infections. First, our model relied on dimensionality reduction to identify parameters that were key to uncovering hidden patterns. Next, our predictive analysis used an unbiased hierarchical Bayesian estimator approach to infer past infections from current fatalities. RESULTS Our analysis indicates that, when we assumed a 13-day lag time from infection to death, the United States, as of April 22, 2020, likely had at least 1.3 million undetected infections. With a longer lag time-for example, 23 days-there could have been at least 1.7 million undetected infections. Given these assumptions, the number of undetected infections in Canada could have ranged from 60,000 to 80,000. Duarte's elegant unbiased estimator approach suggested that, as of April 22, 2020, the United States had up to >1.6 million undetected infections and Canada had at least 60,000 to 86,000 undetected infections. However, the Johns Hopkins University Center for Systems Science and Engineering data feed on April 22, 2020, reported only 840,476 and 41,650 confirmed cases for the United States and Canada, respectively. CONCLUSIONS We have identified 2 key findings: (1) as of April 22, 2020, the United States may have had 1.5 to 2.029 times the number of reported infections and Canada may have had 1.44 to 2.06 times the number of reported infections and (2) even if we assume that the fatality and growth rates in the unobservable population (undetected infections) are similar to those in the observable population (confirmed infections), the number of undetected infections may be within ranges similar to those described above. In summary, 2 different approaches indicated similar ranges of undetected infections in North America. LEVEL OF EVIDENCE Prognostic Level V. See Instructions for Authors for a complete description of levels of evidence.


I don't feel confident providing remote consultations. What do I need to know?


title: Enteropathogens identified in dogs entering a Florida animal shelter with normal feces or diarrhea.

text: OBJECTIVE To determine the frequency of enteropathogens in dogs entering an animal shelter with normal feces or diarrhea. DESIGN Cross-sectional study. ANIMALS 100 dogs evaluated at an open-admission municipal animal shelter in Florida. PROCEDURES Fecal samples were collected within 24 hours after admission from 50 dogs with normal feces and 50 dogs with diarrhea. Feces were tested by fecal flotation, antigen testing, PCR assay, and electron microscopy for selected enteropathogens. RESULTS 13 enteropathogens were identified. Dogs with diarrhea were significantly more likely to be infected with ≥ 1 enteropathogens (96%) than were dogs with normal feces (78%). Only Clostridium perfringens enterotoxin A gene was significantly more common in dogs with diarrhea (64%) than in dogs with normal feces (40%). Other enteropathogens identified in dogs with and without diarrhea included hookworms (58% and 48%, respectively), Giardia spp (22% and 16%, respectively), canine enteric coronavirus (2% and 18%, respectively), whipworms (12% and 8%, respectively), Cryptosporidium spp (12% and 2%, respectively), ascarids (8% and 8%, respectively), Salmonella spp (2% and 6%, respectively), Cystoisospora spp (2% and 4%, respectively), canine distemper virus (8% and 0%, respectively), Dipylidium caninum (2% and 2%, respectively), canine parvovirus (2% and 2%, respectively), and rotavirus (2% and 0%, respectively). CONCLUSIONS AND CLINICAL RELEVANCE Dogs entered the shelter with a variety of enteropathogens, many of which are pathogenic or zoonotic. Most infections were not associated with diarrhea or any specific dog characteristics, making it difficult to predict the risk of infection for individual animals. Guidelines for preventive measures and empirical treatments that are logistically and financially feasible for use in shelters should be developed for control of the most common and important enteropathogens.


title: 2013 AAFP Feline Vaccination Advisory Panel Report.

text: RATIONALE This Report was developed by the Feline Vaccination Advisory Panel of the American Association of Feline Practitioners (AAFP) to provide practical recommendations to help clinicians select appropriate vaccination schedules for their feline patients based on risk assessment. The recommendations rely on published data as much as possible, as well as consensus of a multidisciplinary panel of experts in immunology, infectious disease, internal medicine and clinical practice.


title: P2 porous titanium implants improve tendon healing in an acute rat supraspinatus repair model.

text: BACKGROUND Current techniques in rotator cuff repair often lack structural integrity. P2 porous titanium-coated constructs (DJO Surgical, Austin, TX, USA) promote osseointegration and soft tissue ingrowth. This study examined the ability of this material to improve the structural integrity of supraspinatus tendon repair in a rat model. We hypothesized that P2 implants placed at the tendon-to-bone interface would improve mechanical and histologic measures of supraspinatus healing. METHODS Forty rats underwent supraspinatus repairs with P2 implants in 1 shoulder and standard repair in the other. Rats were humanely killed at time 0 (n = 3), 2 weeks (n = 8), 4 weeks (n = 15), and 12 weeks (n = 14). Tendon-to-bone composite specimens were harvested and evaluated mechanically and histologically. RESULTS Tendon cross-sectional area was decreased in the P2 implant group at 4 weeks, percentage of relaxation was increased at 2 weeks, elastic modulus was increased at 4 weeks, and maximum load and maximum stress were both increased at 2 and 4 weeks. Histologic analysis revealed no foreign body reactions within or around the P2 implant, and healthy viable bone was visible within the P2 implant. CONCLUSION The results support our hypothesis, specifically in early healing, in this randomized controlled animal study. These data support the use of P2 porous titanium implants to improve tendon-to-bone healing.


title: The PERK Arm of the Unfolded Protein Response Negatively Regulates Transmissible Gastroenteritis Virus Replication by Suppressing Protein Translation and Promoting Type I Interferon Production.

text: Coronavirus replication is closely associated with the endoplasmic reticulum (ER), the primary cellular organelle for protein synthesis, folding, and modification. ER stress is a common consequence in coronavirus-infected cells. However, how the virus-induced ER stress influences coronavirus replication and pathogenesis remains controversial. Here, we demonstrated that infection with the alphacoronavirus transmissible gastroenteritis virus (TGEV) induced ER stress and triggered the unfolded protein response (UPR) in vitro and in vivo, and ER stress negatively regulated TGEV replication in vitro Although TGEV infection activated all three UPR pathways (activating transcription factor 6 [ATF6], inositol-requiring enzyme 1 [IRE1], and protein kinase R-like ER kinase [PERK]), the virus-triggered UPR suppressed TGEV replication in both swine testicular (ST) and IPEC-J2 cells primarily through activation of the PERK-eukaryotic initiation factor 2α (eIF2α) axis, as shown by functional studies with overexpression, small interfering RNA (siRNA), or specific chemical inhibitors. Moreover, we demonstrated that PERK-eIF2α axis-mediated inhibition of TGEV replication occurs through phosphorylated eIF2α-induced overall attenuation of protein translation. In addition to direct inhibition of viral production, the PERK-eIF2α pathway activated NF-κB and then facilitated type I IFN production, resulting in TGEV suppression. Taken together, our results suggest that the TGEV-triggered PERK-eIF2α pathway negatively regulates TGEV replication and represents a vital aspect of host innate responses to invading pathogens.IMPORTANCE The induction of ER stress is a common outcome in cells infected with coronaviruses. The UPR initiated by ER stress is actively involved in viral replication and modulates the host innate responses to the invading viruses, but these underlying mechanisms remain incompletely understood. We show here that infection with the alphacoronavirus TGEV elicited ER stress in vitro and in vivo, and the UPR PERK-eIF2α branch was predominantly responsible for the suppression of TGEV replication by ER stress. Furthermore, the PERK-eIF2α axis inhibited TGEV replication through direct inhibition of viral proteins due to global translation inhibition and type I IFN induction. These findings highlight a critical role of the UPR PERK-eIF2α pathway in modulating host innate immunity and coronavirus replication.


title: Density functional theory study on adsorption of L-cysteine by Y, Zr, Nb, Mo-doped graphenes.

text: The adsorption properties of l-cysteine (L-cys) on [Kr] 4d1-4 (Y-Mo) doped graphenes with single and double vacancies are studied by using density functional theory calculations with dispersion correction. The results showed that Y, Zr, Nb and Mo doped single-vacancy and double-vacancy graphenes show chemical adsorption characteristics towards L-cys. For the respective S, O and N-end adsorption, the binding strengths of L-cys on XSVs decrease from Y to Nb, and then increase. The binding strengths of L-cys on XDVs have no regular trend. Nb-doped graphene exhibits the most stable adsorption characteristics in the [Kr] 4d1-4 element series, which is independent of the vacancy type. Zr-doped single and double vacancy graphene sensors have higher sensitivity than Y, Nb, Mo.


title: The Effects of 11-Ketotestosterone Implants on Transcript Levels of Gonadotropin Receptors, foxl2 and dmrt1 Genes in the Previtellogenic Ovary of Cultured Beluga (Huso huso).

text: The in vivo effect of 11-ketotestosterone (11KT) on transcript levels of the gonadotropin receptors (fshr and lhr) and sex differentiation-related genes (dmrt1 and foxl2) was examined in ovaries of immature female beluga. For this purpose, six fish were treated with implants containing 2.5 mg 11KT and a placebo group of six females of the same age and gametogenic stage were given a blank implant. The implants were intraperitoneally inserted into 4-year-old females at the previtellogenic stage (mean body weight 5580 ± 165 g) and maintained under culture conditions for 8 weeks. Ovary samples for gene expression analysis of lhr, fshr, dmrt1 and foxl2 were collected by biopsy at 3 and 8 weeks post-implantation. Diameters of oocytes increased in response to 11KT treatment, both at 3 and at 8 weeks post-implantation, but no obvious changes were evident in cytology. Three weeks of 11KT treatment did not affect target gene expression, but a tendency for a time-dependent decrease of lhr and dmrt1 mRNA levels was observed in both treatment and placebo groups. By 8 weeks of treatment, however, 11KT implants provoked the upregulation of fshr and foxl2 transcript levels. Furthermore, lhr and dmrt1 transcript abundances recovered by 8 weeks of exposure in both blank- and 11KT-implanted beluga. These results suggest that 11KT, either directly or indirectly, may affect gametogenesis and regulate some key components of the reproductive axis in female beluga. This article is protected by copyright. All rights reserved.


title: Pharmacokinetics of Fentanyl Sublingual Spray in Opioid-Naïve Participants: Results of a Phase 1, Multiple Ascending Dose Study.

text: BACKGROUND AND OBJECTIVES Fentanyl sublingual spray may be a viable alternative to intravenous (IV) opioids for the treatment of acute pain. As patients with acute pain may include those who have limited prior exposure to opioids, this phase 1, open-label, randomized, multiple ascending-dose study was conducted to assess the pharmacokinetics, pharmacodynamics, safety, and tolerability of multiple doses of fentanyl sublingual spray in opioid-naïve participants. This article primarily reports the pharmacokinetics results. METHODS Study drugs were administered in four dosing cohorts: every 0.5, 1, 2, or 4 h for a maximum of three doses per cohort. Eight fasted individuals per cohort were randomized to either fentanyl sublingual spray (100, 200, or 400 µg) or fentanyl citrate IV 50 µg (6:2 ratio). Blood samples were collected pre-dose through 24 h post first dose. RESULTS A total of 98 healthy adults were enrolled and 96 completed the study. Mean plasma fentanyl concentrations increased with increasing doses of fentanyl sublingual spray administered every 0.5-4 h. With multiple doses, systemic exposure increased relative to the first dose; shorter dosing intervals resulted in higher concentrations. Analysis of dose proportionality suggested that systemic exposure increased in a linear but slightly greater than dose-proportional manner. Accumulation between the first and last doses of fentanyl sublingual spray was more pronounced with shorter dosing intervals. CONCLUSION Dose-dependent fentanyl pharmacokinetics following multiple doses of fentanyl sublingual spray were well characterized in an opioid-naïve population. CLINICALTRIALS. GOV IDENTIFIER NCT02641340.


Cassandra's curse and covid-19: why do governments listen to businesses over doctors?


title: MRI criteria of subtypes of adenomas and epithelial cysts of the pituitary gland.

text: This study aimed to assess the clinical applicability of MRI criteria for differentiation of pituitary adenomas and cystic pituitary lesions. One hundred ninety-eight consecutive patients with surgical resection of a pituitary adenoma/cystic pituitary lesion were retrospectively analyzed, blinded to clinical data and histopathological diagnosis. Different morphologic criteria were assessed: signal intensity in T2/T1w images, pattern of contrast enhancement, size, super-/infrasellar extension, and invasion of the cavernous sinus. For validation of the criteria, a second independent patient cohort (n = 102) was analyzed for diagnostic accuracy of the criteria. We identified differences between subtypes of pituitary adenomas regarding morphological MRI criteria. Especially, ACTH-producing adenomas and GH-producing adenomas showed partially specific imaging features. Application of our criteria on the second patient cohort (n = 102) did however not significantly improve diagnostic accuracy. Only differentiation between cystic pituitary lesions and adenomas was facilitated using these criteria, but did not reach statistical significance in this cohort (P = 0.352). MRI criteria might facilitate differentiation between pituitary adenomas and cystic pituitary lesions, but not between subtypes of pituitary adenomas. These subtypes show partially specific MR imaging features, however, due to a high variability knowledge of clinical symptoms and laboratory findings remain essential for the correct diagnosis.


title: Molecular epidemiology of coronavirus in faeces of Brazilian calves and Peruvian camelid herds.

text: INTRODUCTION The enteric disorders represent a serious hazard for bovine and camelid breeding. The aim of this study was to examine the frequency of detection and molecular characteristics of enteric coronavirus (CoV) infections in cattle, alpaca, and llama herds bred in family-based farms in Brazil and Peru. METHODOLOGY Stool samples were collected from calves from Brazil and camelids from Peru for detection and characterization of CoV by reverse transcription polymerase chain reaction (RT-PCR) and sequence analysis. RESULTS 46.5% (47/101) samples from calves and 26.8% (70/261) from alpaca tested positive for CoV. All strains belong to lineage A1 of the Betacoronavirus genus. Phylogenetic analysis showed high identity between CoV strains detected in calves and alpacas. CONCLUSIONS This study characterised CoV strains from dairy cattle herds in the state of Rio de Janeiro, Brazil, and indicated that this virus is spread among the state herds. The results also indicate widespread circulation of CoV among the alpacas of Cuzco, Peru.


Flattening the Curve for Incarcerated Populations - Covid-19 in Jails and Prisons.