title: Identifying and mapping biopsychosocial factors associated with pain in adults with advanced liver disease: protocol for a scoping review.

text: INTRODUCTION Pain is highly prevalent in the adult population diagnosed with liver disease. Those progressing to advanced liver disease often experience persistent pain and poor pain relief. There is presently limited guidance for the management of pain and associated symptoms in this population. The current literature lacks attention on how physical, psychological and social domains of liver disease modulate the pain experience. In this paper, we outline our scoping review protocol to systematically review the literature from academic bibliographic databases and grey sources to identify and map the biopsychosocial factors associated with pain in adults with advanced liver disease. METHODS AND ANALYSIS Arksey and O'Malley's methodology, and Tricco et al's Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews, will guide the process for this scoping review. The literature search will include electronic and hand-searching methods using scholarly and grey sources. Scholarly databases include Medline, Embase, Allied and Complementary Medicine and Cumulative Index to Nursing and Allied Health Literature. Grey databases will focus on research studies not captured in the scholarly databases including those by government agencies and professional organisations. Two members of the research team will independently screen the resulting publications following specific inclusion and exclusion criteria. Quality appraisal of the included research studies will employ the use of the Mixed Methods Appraisal Tool version 2018. Data collection and extraction of study characteristics will use a data extraction tool developed iteratively by the research team. Analysis of the factors associated with pain outcomes will be mapped and described according to the domains of the biopsychosocial model of pain. ETHICS AND DISSEMINATION The scoping review involves analysis of the published literature on pain and advanced liver disease and does not require ethics approval. The results will be shared with expert stakeholders to help establish clinical significance. We will disseminate the findings through publication in a scholarly journal: local, provincial, national and international scientific and professional conferences. PROSPERO REGISTRATION NUMBER CRD42019135677.


title: Relationship Between Physician and Hospital Procedure Volume and Mortality After Carotid Artery Stenting Among Medicare Beneficiaries.

text: BACKGROUND Clinical trials demonstrated the efficacy of carotid artery stenting (CAS) relative to carotid endarterectomy when performed by physicians with demonstrated proficiency. It is unclear how CAS performance may be influenced by the diversity in CAS and non-CAS provider volumes in routine clinical practice. METHODS AND RESULTS We linked Medicare claims to the Centers for Medicare and Medicaid Services' CAS Database (2005-2009). We assessed the association between 30-day mortality and past-year physician (0, 1-4, 5-9, 10-19, ≥20) and hospital (<10, 10-19, 20-39, ≥40) CAS volumes and past-year hospital coronary and peripheral stenting volumes (<200, 200-399, 400-849, ≥850) among beneficiaries at least 66 years of age. Unadjusted 30-day mortality risk was 1.8% (95% confidence interval [CI], 1.6-2.0) for 19 724 patients undergoing CAS by 2045 physicians in 729 hospitals. Median past-year CAS volume was 9 (interquartile range, 4-19) for physicians and 23 (interquartile range, 12-41) for hospitals. Compared to physicians performing ≥20 CAS in the past year, lower CAS volumes were associated with higher adjusted risks of 30-day morality (P value for trend < 0.05): 1.4 (95% CI, 0.9-2.3) for 0 past-year CAS, 1.3 (95% CI, 0.9-1.8) for 1 to 4, 1.1 (95% CI, 0.8-1.6) for 5 to 9, and 0.9 (95% CI, 0.7-1.4) for 10 to 19. An inverse relationship between 30-day mortality and past-year CAS hospital volume as well as past-year hospital non-CAS volume, past-year hospital non-CAS volume, and 30-day mortality was also noted. CONCLUSIONS Among Medicare patients, an inverse relationship exists between physician and hospital CAS volumes and hospital non-CAS stenting volume and 30-day mortality, even after adjusting for all pertinent patient- and hospital-level factors.


title: Superiority of needle-free transdermal plasmid delivery for the induction of antigen-specific IFNgamma T cell responses in the dog.

text: Although successful needle-free DNA vaccination has been described on several occasions, the true benefit of this delivery technology over needle-based injections for DNA vaccination of dogs has not yet been documented. We conducted a side-by-side comparison of needle-free transdermal plasmid delivery vs. intramuscular vs. intradermal needle-based delivery of the same plasmid in dogs. Our data confirmed the importance of the route of plasmid delivery and further established the unique potential of needle-free transdermal plasmid delivery to elicit strong antigen-specific, hTyr-specific IFNgamma T in the dog. Further, this study demonstrated that properly enabled DNA vaccination has the potential to trigger very significant cell-based immune responses in dogs, establishing needle-free transdermal plasmid delivery as a critical technology for successful immunotherapy of cancer and/or chronic infectious diseases in companion animal medicine.


title: Perioperative Management of Adult Patients With External Ventricular and Lumbar Drains: Guidelines From the Society for Neuroscience in Anesthesiology and Critical Care.

text: External ventricular drains and lumbar drains are commonly used to divert cerebrospinal fluid and to measure cerebrospinal fluid pressure. Although commonly encountered in the perioperative setting and critical for the care of neurosurgical patients, there are no guidelines regarding their management in the perioperative period. To address this gap in the literature, The Society for Neuroscience in Anesthesiology & Critical Care tasked an expert group to generate evidence-based guidelines. The document generated targets clinicians involved in perioperative care of patients with indwelling external ventricular and lumbar drains.


COVID-19: Pentoxifylline as a potential adjuvant treatment.


title: Spatial and temporal epidemiology of porcine epidemic diarrhea (PED) in the Midwest and Southeast regions of the United States.

text: Emergence of porcine epidemic diarrhea virus (PEDV) in the US in 2013 caused a major impact in the swine industry due to its high mortality and rapid spread through the country. Even though the role of potential sources of infection in the epidemiology of the disease at the farm level (feed, fomites) has been extensively investigated, there is a lack of knowledge about the dynamics of disease spread at the regional level. Here, we investigated the dissemination of PEDV infection in two areas located in the regions with the highest swine density in the country (Southeast and Midwest) including more than 2400 farms. Location and date of outbreaks were used to assess the spatial and temporal clustering of cases using global (Cuzick-Edwards, Knox and directional tests) and local (Bernouilli model of the spatial scan statistic) techniques in the first 10 months of the epidemic. A strong spatio-temporal pattern was detected in both areas of study, with an increased risk of disease at <2km distances of recently (<7 days) infected farms, although extent of clustering was higher in the Southeast. Results, computed for two different locations in the first months of the epidemic, suggest that local transmission from infected farms into neighboring PEDV-free sites is a likely explanation for a substantial proportion of the reported PEDV-positive farms and consistent with the rapid spread of a highly infectious disease in the absence of immunity.


title: Modifying Risk Factors: Strategies That Work Diabetes Mellitus.

text: An estimated 29.1 million Americans are currently diagnosed with diabetes, and this number is expected to increase to 48.3 million Americans by 2050. Correspondingly, the present burden of diabetes among patients undergoing total joint arthroplasty is significant and rising. Diabetes as a chronic condition is a well-established risk factor for complication after total joint arthroplasty. A growing body of evidence also indicates that hyperglycemia in the perioperative period, and not the diagnosis of diabetes alone, is similarly associated with increased complication risk. As a result, a coordinated approach to preoperative screening and optimization, combined with judicious perioperative glycemic control, may present an opportunity to improve outcomes, reduce complications, and avoid complication-related costs for patients undergoing total joint arthroplasty.


title: Transrectal Rigid-Hybrid Natural Orifice Translumenal Endoscopic Sigmoidectomy for Diverticular Disease: A Prospective Cohort Study.

text: BACKGROUND Our goal was to evaluate the feasibility of transrectal rigid hybrid natural orifice translumenal endoscopic surgery (NOTES) sigmoidectomy (trNS) in a series of consecutive prospective patients with diverticular disease. The NOTES for left colectomy offers patients reduced pain and easier recovery. Limited data are available for trNS, which is considered safe for various indications. However, the technique is not standardized, and patients in the reported series are highly selected. STUDY DESIGN Patients scheduled for trNS were entered into a prospective registry on an intention-to-treat basis. The primary endpoint was trNS feasibility, and secondary endpoints were morbidity, pain, length of stay, and inflammatory response. A medial-to-lateral dissection with full mobilization of the splenic flexure and total intracorporeal anastomosis was performed. The rectum was covered with a wound protector for transrectal extraction. RESULTS Of 95 elective sigmoidectomies, 81% (n = 77) were enrolled for either transvaginal NOTES resection (n = 37) or trNS (n = 40). There was no difference in body mass index or indication between patients undergoing laparoscopic-assisted sigmoidectomy (LAS), transvaginal resection, or trNS, although trNS patients were younger. Mainly because of a mismatch of bulky specimen and narrow pelvis, 17.5% of trNS were converted to LAS. Major morbidity was 10%, including 2 septic complications. During the study, the anastomosis technique was changed from double stapled end-to-end to side-to-end anastomosis. CONCLUSIONS Transrectal rigid hybrid natural orifice translumenal endoscopic sigmoidectomy is feasible and safe in a high proportion of unselected consecutive patients with diverticular disease undergoing elective treatment. Intracorporeal side-to-end anastomosis is the preferred technique, and trNS should be offered for elective sigmoidectomy presupposing advanced laparoscopic experience.


title: Quantitative Analysis of Endothelial Cell Loss in Preloaded Descemet Membrane Endothelial Keratoplasty Grafts.

text: PURPOSE Availability of preloaded Descemet membrane endothelial keratoplasty (pDMEK) tissue may increase acceptance of DMEK in surgical management of endothelial disease. The goal of this study was to determine the safety of pDMEK grafts for 24 hours before surgery by analyzing endothelial cell loss (ECL) using 2 image analysis software programs. METHODS A total of 18 cadaveric corneas were prepared for DMEK using a standardized technique and loaded in a modified Jones tube injector. Nine of the corneas were injected into Calcein AM vital dye after 1 minute (controls), and the remaining 9 corneas were left preloaded for 24 hours before injection into vital dye for staining. The stained corneas were imaged using an inverted confocal microscope. ECL was then analyzed and quantified by 2 different graders using 2 image analysis software programs. RESULTS The control DMEK tissue resulted in 22.0% ± 4.0% ECL compared with pDMEK tissue, which resulted in 19.2% ± 7.2% ECL (P = 0.31). Interobserver agreement was 0.93 for MetaMorph and 0.92 for Fiji. The average time required to process images with MetaMorph was 2 ± 1 minutes and with Fiji was 20 ± 10 minutes. Intraobserver agreement was 0.97 for MetaMorph and 0.93 for Fiji. CONCLUSIONS Preloading DMEK tissue is safe and may provide an alternative technique for tissue distribution and surgery for DMEK. The use of MetaMorph software for quantifying ECL is a novel and accurate imaging method with increased efficiency and reproducibility compared with the previously validated Fiji.


Bringing fungal infections in from the cold.


title: Use of self-retaining barbed sutures decreases cold ischemia time in open nephron-sparing surgery.

text: PURPOSE In the present study, we aimed to determine whether the use of self-retaining barbed sutures (SRBS) instead of conventional sutures during open partial nephrectomy leads to improved surgical outcomes. PATIENTS, MATERIALS AND METHODS A retrospective analysis of 50 consecutive patients who underwent open partial nephrectomy for a unicentric renal tumor was performed. In 15 patients, SRBS were used for parenchymal repair during open partial nephrectomy, and in 35 patients, conventional sutures were used. The parameters related to surgical outcomes were recorded and analysis of the total patient population and subgroup analysis according to the preoperative aspects and dimensions used for an anatomical (PADUA) score classification was performed. RESULTS The preoperative baseline values did not statistically differ between the groups. Analysis of the total patient population showed a significant difference regarding ischemia time (mean ± standard deviation) between the SRBS group (15.2 ± 6.9 min), and the conventional suture group (25.7 ± 11.8 min). There was no significant difference between the barbed and conventional sutures with regard to postoperative hemoglobin levels, decline in hemoglobin percentage, or renal function parameters. In subgroup-analysis, a significant difference in ischemia time was only found for PADUA scores 6 and 7, without any effect on the outcome parameters. CONCLUSIONS The use of SRBS in parenchymal repair during open partial nephrectomy appears to be a safe and feasible option with decreased cold ischemia time when compared with conventional sutures. In PADUA subgroup-analysis this difference was only observed for PADUA scores 6 and 7.


title: COVID-19 and diabetes: What have we learned so far?

text: COVID-19 and diabetes are both pandemics with major impacts on global public health. While the response to COVID-19 has been rapid and progressive to reduce risk of harm, the response to the diabetes pandemic has been somewhat more muted. People with diabetes have been disproportionately affected by COVID-19, with growing evidence of higher mortality and morbidity. In this article, we discuss the impact of COVID-19 on our diabetes service in an urban area in the UK. We discuss the impact on our patients and ourselves, and the possible lessons we can carry into the future.


Impact of COVID-19 on family planning services in India.


Immune status could determine efficacy of COVID-19 therapies.


title: Biosensors for Monitoring Airborne Pathogens.

text: Airborne pathogens affect both humans and animals and are often highly and rapidly transmittable. Many problematic airborne pathogens, both viral (influenza A/H1N1, Rubella, and avian influenza/H5N1) and bacterial (Mycobacterium tuberculosis, Streptococcus pneumoniae, and Bacillus anthracis), have huge impacts on health care and agricultural applications, and can potentially be used as bioterrorism agents. Many different laboratory-based methods have been introduced and are currently being used. However, such detection is generally limited by sample collection, including nasal swabs and blood analysis. Direct identification from air (specifically, aerosol samples) would be ideal, but such detection has not been very successful due to the difficulty in sample collection and the extremely low pathogen concentration found in aerosol samples. In this review, we will discuss the portable biosensors and/or micro total analysis systems (µTAS) that can be used for monitoring such airborne pathogens, similar to smoke detectors. Current laboratory-based methods will be reviewed, and possible solutions to convert these lab-based methods into µTAS biosensors will be discussed.


title: The highly cited SARS research literature.

text: A chronically weak area in research papers, reports, and reviews is the complete identification of important background reference documents that formed the building blocks for the research. A method for systematically determining these important references is presented. Citation-Assisted Background (CAB) is based on the assumption that important documents tend to be highly cited. Application of CAB to the field of Severe Acute Respiratory Syndrome (SARS) research is presented. While CAB is a highly systematic approach for identifying highly cited references, it is not a substitute for the judgment of the researchers, and serves as a supplement.


title: Separate and combined effects of local and systemic hypoxia in resistance exercise.

text: PURPOSES This study quantified performance, physiological, and perceptual responses during resistance exercise to task failure with blood flow restriction (BFR), in systemic hypoxia, and with these stimuli combined. METHODS Fourteen young men were tested for 1-repetition maximum (1RM) in the barbell biceps curl and lying triceps extension exercises. On separate visits, subjects performed exercise trials (4 sets to failure at 70% 1RM with 90 s between sets) in six separate randomized conditions, i.e., in normoxia or hypoxia (fraction of inspired oxygen = 20.9% and 12.9%, respectively) combined with three different levels of BFR (0%, 45%, or 60% of resting arterial occlusion pressure). Muscle activation and oxygenation were monitored via surface electromyography and near-infrared spectroscopy, respectively. Arterial oxygen saturation, heart rate, and perceptual responses were assessed following each set. RESULTS Compared to set 1, the number of repetitions before failure decreased in sets 2, 3, and 4 for both exercises (all P < 0.001), independently of the condition (P > 0.065). Arterial oxygen saturation was lower with systemic hypoxia (P < 0.001), but not BFR, while heart rate did not differ between conditions (P > 0.341). Muscle oxygenation and activation during exercise trials remained unaffected by the different conditions (all P ≥ 0.206). A significant main effect of time, but not condition, was observed for overall perceived discomfort, difficulty breathing, and limb discomfort (all P < 0.001). CONCLUSION Local and systemic hypoxic stimuli, or a combination of both, did not modify the fatigue-induced change in performance, trends of muscle activation or oxygenation, nor exercise-related sensations during a multi-set resistance exercise to task failure.


title: Pediatric tracheotomy wound complications: incidence and significance.

text: OBJECTIVES To determine the incidence and to describe wound complications and associated risk factors of pediatric tracheotomy. DESIGN Retrospective case series. SETTING Freestanding tertiary care academic pediatric hospital. PATIENTS Sixty-five consecutive children undergoing tracheotomy over 15 months. MAIN OUTCOME MEASURES Postoperative wound complications objectively and independently documented by an advanced practice nurse specializing in tracheotomy care. Secondary outcome measures included comorbidities, mortality rates, and wound status after subsequent examinations and management. RESULTS The mean (SEM) patient age at tracheotomy was 45 (8.7) months (median age, 9.1 months). The most common indication for tracheotomy was pulmonary disease (36.9%), followed by neurologic impairment and laryngeal abnormalities. There were 19 patients (29%) with and 46 patients (71%) without wound complications. There were no significant differences between the 2 groups in age (P = .68) or weight (P = .55); however, infants younger than 12 months had an increased complication rate (39% vs. 17%, P = .04). The type of tracheotomy tube was predictive of postoperative wound complications (P = .02). All patients with wounds received aggressive local wound care. Five of 13 patients had complete resolution of stomal wounds, whereas 8 patients had persistent wound issues. There were 5 non-wound-related mortalities. CONCLUSIONS With attempts to classify tracheotomy wound breakdowns as reportable events, including never events, increasing emphasis is being placed on posttracheotomy care. This study demonstrates that wound breakdown in pediatric tracheotomy patients is common. These complications can be mitigated, although not prevented completely, with aggressive wound surveillance and specialized wound care.


title: Enteroplication in cats with intussusception: a retrospective study (2001-2016).

text: OBJECTIVES The aim of this study was to report complications, as well as short- and long-term clinical outcomes of cats suffering from surgically reduced intussusception with and without enteroplication. METHODS Medical records of cats presented at our institution with intussusception between 2001 and 2016 were reviewed. The following data were retrieved: signalment; history; physical examination; diagnostic imaging, surgical and histological findings; and outcomes. Animals were grouped as with or without enteroplication. Duration of surgery, survival, complication and recurrence rates, duration of hospitalisation, and short- and long-term outcomes were compared. RESULTS Cats with intussusception presented with unspecific type and duration of clinical signs. Male or male castrated cats and Maine Coons were over-represented in both groups. Enteroplication was performed in 48% (10/21) of the cats. Cats in the enteroplication group were significantly younger than those in the non-enteroplication group ( P = 0.023). Duration of surgery, time of hospitalisation, complication rate and outcomes did not differ between the two groups. Two complications in the short term and one complication in the long term were possibly associated with enteroplication. A recurrence of intussusception was seen in 2/17 cats approximately 12 months after initial surgery, both previously treated with enteroplication. CONCLUSIONS AND RELEVANCE Although the number of cases was limited, our results suggest that enteroplication should be cautiously performed in cats with intussusception as it may be associated with major complications in the short and long term, and its efficacy remains unclear. Based on this study, the need for enteroplication in cats following a correction of intussusception could be questioned.


Re: Antonella Giannantoni, Vittorio Bini, Roger Dmochowski, et al. Contemporary management of the painful bladder: a systematic review. Eur Urol 2012;61:29-53.


title: Urinary Incontinence Before and After Bariatric Surgery.

text: IMPORTANCE Among women and men with severe obesity, evidence for improvement in urinary incontinence beyond the first year after bariatric surgery-induced weight loss is lacking. OBJECTIVES To examine change in urinary incontinence before and after bariatric surgery and to identify factors associated with improvement and remission among women and men in the first 3 years after bariatric surgery. DESIGN, SETTING, AND PARTICIPANTS The Longitudinal Assessment of Bariatric Surgery 2 is an observational cohort study at 10 US hospitals in 6 geographically diverse clinical centers. Participants were recruited between February 21, 2005, and February 17, 2009. Adults undergoing first-time bariatric surgical procedures as part of clinical care by participating surgeons between March 14, 2006, and April 24, 2009, were followed up for 3 years (through October 24, 2012). INTERVENTION Participants undergoing bariatric surgery completed research assessments before the procedure and annually thereafter. MAIN OUTCOMES AND MEASURES The frequency and type of urinary incontinence episodes in the past 3 months were assessed using a validated questionnaire. Prevalent urinary incontinence was defined as at least weekly urinary incontinence episodes, and remission was defined as change from prevalent urinary incontinence at baseline to less than weekly urinary incontinence episodes at follow-up. RESULTS Of 2458 participants, 1987 (80.8%) completed baseline and follow-up assessments. At baseline, the median age was 47 years (age range, 18-78 years), the median body mass index was 46 kg/m2 (range, 34-94 kg/m2), and 1565 of 1987 (78.8%) were women. Urinary incontinence was more prevalent among women (49.3%; 95% CI, 46.9%-51.9%) than men (21.8%; 95% CI, 18.2%-26.1%) (P < .001). After a mean 1-year weight loss of 29.5% (95% CI, 29.0%-30.1%) in women and 27.0% (95% CI, 25.9%-28.6%) in men, year 1 urinary incontinence prevalence was significantly lower among women (18.3%; 95% CI, 16.4%-20.4%) and men (9.8%; 95% CI, 7.2%-13.4%) (P < .001 for all). The 3-year prevalence was higher than the 1-year prevalence for both sexes (24.8%; 95% CI, 21.8%-26.5% among women and 12.2%; 95% CI, 9.0%-16.4% among men) but was substantially lower than baseline (P < .001 for all). Weight loss was independently related to urinary incontinence remission (relative risk, 1.08; 95% CI, 1.06-1.10 in women and 1.07; 95% CI, 1.02-1.13 in men) per 5% weight loss, as were younger age and the absence of a severe walking limitation. CONCLUSIONS AND RELEVANCE Among women and men with severe obesity, bariatric surgery was associated with substantially reduced urinary incontinence over 3 years. Improvement in urinary incontinence may be an important benefit of bariatric surgery.


title: Atorvastatin preconditioning improves the forward blood flow in the no-reflow rats.

text: Atorvastatin is not only an antilipemic but also used as an anti-inflammatory medicine in heart disease. Our working hypothesis was that atorvastatin preconditioning could improve the forward blood flow in the no-reflow rats associated with inflammation. We investigated that two doses of atorvastatin preconditioning (20 and 5 mg/kg/day) could alleviate deterioration of early cardiac diastolic function in rats with inflammation detected by echocardiography and haemodynamics. This benefit was obtained from the effect of atorvastatin preconditioning on improving forward blood flow and preserving the infarct cardiomyocytes, which was estimated by Thioflavin S and TTC staining in rats with myocardial ischemia/reperfusion. Subsequently, the improving of forward blood flow was ascribed to reduction of microthrombus in microvascular and myocardial fibrosis observed by MSB and Masson's trichrome staining with atorvastatin preconditioning. Ultimately, we found that atorvastatin preconditioning could reduce inflammation factor, such as tumor necrosis factor-α and fibrinogen-like protein 2, both in myocardial and in mononuclear cells, which probably attribute to microcirculation dysfunction in no-reflow rats detected by immunohistochemistry staining, western blot, and ELISA detection, respectively. In conclusion, atorvastatin preconditioning could alleviate deterioration of early cardiac diastolic function and improve the forward blood flow in the no-reflow rats attributing to reduction of TNF-α and fgl-2 expression.


title: The biotechnology era: has the promise been fulfilled?

text: Biotechnological advances have changed the traditional landscape of the drug discovery process. Mutually beneficial relationships between small, innovative and nimble biotechnology companies and experienced, well-funded pharmaceutical companies have resulted in a more rapid application of new technologies to drug development and diversification. Protein-based drugs, such as therapeutic monoclonal antibodies, exemplify the fulfillment of the promise of the biotechnology revolution.


title: Inverse intubation in entrapped trauma casualties: a simulator based, randomised cross-over comparison of direct, indirect and video laryngoscopy.

text: BACKGROUND Airway management in entrapped casualties with restricted access to the head is challenging. If tracheal intubation is required and conventional laryngoscopy is not possible, intubation must be attempted in a face-to-face approach. Traditionally, this is performed with a standard laryngoscope held in the right hand with the blade facing upward. Recently, alternative methods have been developed to facilitate difficult intubations, and we hypothesised that such techniques are also useful for face-to-face intubations. METHODS 24 (trainee) anaesthesiologists attempted tracheal intubation in a patient simulator (SimMan, Laerdal, Norway) using three techniques in random order: (1) direct laryngoscopy (Macintosh blade #3), (2) indirect optical laryngoscopy (Airtraq, Prodol, Spain) and (3) video laryngoscopy (McGrath, Aircraft Medical, UK). The manikin was sitting with the neck immobilised and only accessible from the left anterolateral side. Success rate (percentage (95% CI)) and tube insertion time (median (IQR)) were recorded. RESULTS Success rate did not differ significantly (Airtraq and McGrath 100% (84% to 100%), direct laryngoscopy 88% (68% to 96%)). Intubation was faster with Airtraq (25 s (22-34), p<0.001) and direct laryngoscopy (34 s (22-48), p<0.05) compared with the McGrath technique (55 s (37-96)). CONCLUSIONS All three techniques have a high success rate, but the usefulness of the video laryngoscope is limited due to longer intubation duration. Inverse direct laryngoscopy showed reasonable intubation times and, given the widespread availability of Macintosh laryngoscopes, seems a useful technique. Intubation was always successful and tended to be fastest with the Airtraq device, suggesting that this technique may be a promising alternative.


title: A HER2-binding Affibody molecule labelled with 68Ga for PET imaging: direct in vivo comparison with the 111In-labelled analogue.

text: PURPOSE Overexpression of HER2 receptors is a prognostic and predictive biomarker in breast cancer and a number of other malignancies. Radionuclide molecular imaging of HER2 overexpression may influence patient management making treatment more personalized. Earlier, (111)In-DOTA-Z(HER2:342-pep2) (ABY-002) Affibody molecule demonstrated excellent imaging of HER2-expressing xenografts in mice shortly after injection. The use of the positron-emitting nuclide (68)Ga instead of (111)In might increase both the sensitivity of HER2 imaging and accuracy of expression quantification. The goal of this study was to prepare and characterize (68)Ga-labelled ABY-002. METHODS (68)Ga labelling of ABY-002 was optimized. In vitro cell binding and procession of (68)Ga-ABY-002 was evaluated. Biodistribution and tumour targeting of (68)Ga-ABY-002 and (111)In-ABY-002 was compared in vivo by paired-label experiments. RESULTS ABY-002 was incubated with (68)Ga at 90 degrees C for 10 min resulting in a radiochemical labelling yield of over 95%. Capacity for specific binding to HER2-expressing cells was retained. In vivo, both (68)Ga-ABY-002 and (111)In-ABY-002 demonstrated specific targeting of SKOV-3 xenografts and high-contrast imaging. Background radioactivity in blood, lungs, gastrointestinal tract and muscle fell more rapidly for (68)Ga-ABY-002 compared with (111)In-ABY-002 favouring imaging shortly after injection. For (68)Ga-ABY-002, a tumour uptake of 12.4 +/- 3.8%ID/g and a tumour to blood ratio of 31 +/- 13 were achieved at 2 h post-injection. CONCLUSION (68)Ga-ABY-002 is easy to label and provides high-contrast imaging within 2 h after injection. This makes it a promising candidate for clinical molecular imaging of HER2 expression in malignant tumours.


title: COVID-19 and US Health Financing: Perils and Possibilities.

text: While the COVID-19 pandemic presents every nation with challenges, the United States' underfunded public health infrastructure, fragmented medical care system, and inadequate social protections impose particular impediments to mitigating and managing the outbreak. Years of inadequate funding of the nation's federal, state, and local public health agencies, together with mismanagement by the Trump administration, hampered the early response to the epidemic. Meanwhile, barriers to care faced by uninsured and underinsured individuals in the United States could deter COVID-19 care and hamper containment efforts, and lead to adverse medical and financial outcomes for infected individuals and their families, particularly those from disadvantaged groups. While the United States has a relatively generous supply of Intensive Care Unit beds and most other health care infrastructure, such medical resources are often unevenly distributed or deployed, leaving some areas ill-prepared for a severe respiratory epidemic. These deficiencies and shortfalls have stimulated a debate about policy solutions. Recent legislation, for instance, expanded coverage for testing for COVID-19 for the uninsured and underinsured, and additional reforms have been proposed. However comprehensive health care reform - for example, via national health insurance - is needed to provide full protection to American families during the COVID-19 outbreak and in its aftermath.


title: "Knowing Well, Being Well: Well-Being Born of Understanding." Introducing a New Open-Access Section for the American Journal of Health Promotion.

text: A time-honored principle in education is that changes in knowledge, attitudes, and beliefs are precursors to changes in actions or behaviors. Nevertheless, health promotion professionals occasionally hear the bromide that "people know what they're supposed to do, they just don't do it!" What does it mean to know something really well? And when is knowledge influential enough that it affects our very way of being? This editorial introduces a new section for the American Journal of Health Promotion called "Knowing Well, Being Well: Well-being born of understanding" (KWBW). Premiering in this issue of the journal, KWBW will be led by coeditors Drs Sara Johnson and David Katz, two of the most recognized and respected leaders in health promotion. Although today's health promotion practitioners seem intent on moving "from wellness to well-being," our discipline is in the nascent stages of reconciling theories of behavior change and pathways to well-being. "Knowing Well, Being Well" will chart a course to explore how knowledge, supportive environments, and purposeful living contribute to health, happiness, and life satisfaction.


title: Pharmacological and non-surgical renal protective strategies for cardiac surgery patients undergoing cardiopulmonary bypass: a systematic review.

text: BACKGROUND Post-operative acute kidney injury after cardiopulmonary bypass (AKI-CPB) for cardiac surgery is a frequent complication. It may require renal replacement therapy (RRT), which is associated with an increased morbidity and mortality. This review explores the efficacy of proposed pharmacological and non-surgical renal protective strategies. METHODS A comprehensive literature search was done using Ovid MEDLINE, Embase and Scopus databases. Keywords included were cardiopulmonary bypass, cardiac surgery, coronary artery bypass, renal protection and renal preservation. Eligible articles consisted of all studies on patients who had undergone cardiac surgery via CPB with an outcome of AKI and/or RRT reported. All studies underwent a quality check via the risk of bias tool. The three most researched interventions (based on number of randomized controlled trials and total patients analysed) and their renal outcomes were then analysed with Review Manager Software. RESULTS Eighty-eight articles were extracted. A total of 26 management strategies for renal protection following CPB were identified. N-acetylcysteine (NAC), remote ischaemic preconditioning (RIPC) and the use of volatile anaesthetic agents (VAAs) were further analysed. NAC, RIPC and VAA had no statistically significant benefit in reducing either AKI-CPB or the need for RRT following CPB. CONCLUSION NAC, RIPC and VAA were found to have no statistical significant benefit in reducing either AKI-CPB or the need for RRT following CPB. There remains clinical uncertainty with all currently proposed pharmacological and non-surgical renal protective strategies for CPB. Future research in this area should analyse the effects of combined interventions or specifically focus on 'at-risk' patients.


title: Mesh extrusion through the internal cervical os: an unusual complication following laparoscopic sacrocervicopexy.

text: Mesh extrusion or exposure is a known complication of procedures using synthetic mesh for vaginal vault and pelvic organ suspension. Preservation of the uterine cervix is thought to be protective against such complications, as the well-vascularized in situ cervix provides an added barrier between the mesh and the colpotomy incision, limiting potential exposure to the vaginal flora. We describe a case of a 55-year-old multipara, who presented with vaginal discharge following a supracervical hysterectomy with sacrocervicopexy and was found to have a delayed mesh extrusion though the endocervical os.


title: Single-incision laparoscopic splenectomy for idiopathic thrombocytopenic purpura: report of a case.

text: We herein report a case of single-incision laparoscopic access (SILA) splenectomy for idiopathic thrombocytopenic purpura (ITP). A 24-year-old female patient with a diagnosis of ITP received corticosteroid therapy. However, as the side effects became serious, a splenectomy option was chosen. The SILA splenectomy using a transumbilical approach is cosmetically more attractive than a conventional laparoscopic approach, but it has an increased risk of major bleeding due to technical considerations. Therefore, we prioritized the patient's safety during the SILA splenectomy by choosing a left lower abdominal approach. The operating time was 123 min and blood loss was 1 ml. This was comparable to a conventional laparoscopic splenectomy. The present case appears to be the first SILA splenectomy reported in Japan. In our experience, a SILA splenectomy is feasible and safe, with favorable perioperative and shortterm patient outcomes. Further studies are necessary before the universal adoption of this new technique.


title: Viral strategies for triggering and manipulating mitophagy.

text: Viral infection causes many physiological alterations in the host cell, and many of these alterations can affect the host mitochondrial network, including mitophagy induction. A substantial amount of literature has been generated that advances our understanding of the relationship between mitophagy and several viruses. Some viruses trigger mitophagy directly, and indirectly and control the mitophagic process via different strategies. This enables viruses to promote persistent infection and attenuate the innate immune responses. In this review, we discuss the events of virus-regulated mitophagy and the functional relevance of mitophagy in the pathogenesis of viral infection and disease. Abbreviation: ATG: autophagy related; BCL2L13: BCL2 like 13; BNIP3L/NIX: BCL2 interacting protein 3 like; CL: cardiolipin; CSFV: classical swine fever virus; CVB: coxsackievirus B; DENV: dengue virus; DNM1L: dynamin 1 like; FIS1: fission, mitochondrial 1; FUNDC1: FUN14 domain containing 1; HPIV3: human parainfluenza virus 3; HSV-1: herpes simplex virus type 1; IMM: inner mitochondrial membrane; IAV: influenza A virus; IFN: interferon; IKBKE/IKKε: inhibitor of nuclear factor kappa B kinase subunit epsilon; LUBAC: linear ubiquitin assembly complex; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MeV: measles virus; MAVS: mitochondrial antiviral signaling protein; MFF: mitochondria fission factor; NLRP3: NLR family pyrin domain containing 3; NDV: Newcastle disease virus; NR4A1: nuclear receptor subfamily 4 group A member 1; OMM: outer mitochondrial membrane; OPA1: OPA1, mitochondrial dynamin like GTPase; PRKN: parkin RBR E3 ubiquitin protein ligase; PINK1: PTEN induced putative kinase 1; PHB2: prohibitin 2; PRRSV: porcine reproductive and respiratory syndrome virus; PRRs: pattern-recognition receptors; RLRs: RIG-I-like receptors; ROS: reactive oxygen species; RIPK2: receptor interacting serine/threonine kinase 2; SESN2: sestrin 2; SNAP29: synaptosome associated protein 29; STX17: syntaxin 17; TGEV: transmissible gastroenteritis virus; TUFM: Tu translation elongation factor, mitochondrial; TRAF2: TNF receptor associated factor 2; TRIM6: tripartite motif containing 6; Ub: ubiquitin; ULK1: unc-51 like autophagy activating kinase 1; VZV: varicella-zoster virus.


Considerations for cancer immunotherapy biomarker research during COVID-19.


Third time's the charm: COVID-19 testing issues.


Segmental Pulmonary Vascular Changes in COVID-19 Pneumonia.


title: Perioperative outcomes of bipolar energy instruments in total laparoscopic hysterectomy.

text: OBJECTIVES To compare conventional and advanced bipolar energy instruments in terms of perioperative outcomes inpatients who underwent total laparoscopic hysterectomy (TLH). MATERIAL AND METHODS The data of 101 patients who underwent TLH between June 2017 and December 2018 for benigngynecological disorders were analyzed retrospectively. Conventional bipolar forceps (Robi forceps) were used in 37 patientsand advanced bipolar instruments (LigaSure) were used in 64 patients. Data about the characteristics of the patients, operationtime, estimated blood loss, length of hospital stay and other perioperative outcomes were compared. RESULTS The mean ages of the patients in the conventional bipolar and LigaSure groups were 47.6 ± 6.5 and 48.1 ± 7 years,respectively (p > 0.05). There was no statistically significant difference between the two groups with regard to all otherpatient characteristics; body mass index, parity, previous pelvic operation and indications of hysterectomy (p > 0.05). Themean operation time (41 ± 13.2 vs 37 ± 11.5 min), estimated intraoperative blood loss (70 ± 22 vs 65 ± 21 mL) and absolutechange in hemoglobin (-1.23 ± 1.12 vs -1.11 ± 1.14 g/dL) were slightly higher in the conventional bipolar group. However,there was no statistical significance with respect to these differences between the groups (p > 0.05). CONCLUSIONS Our findings indicate that a conventional bipolar system is as safe and effective as LigaSure, and it may beused as an alternative option for patients undergoing TLH in low-income hospitals.


title: Percutaneous Thermal Ablation of Breast Cancer Metastases in Oligometastatic Patients.

text: OBJECTIVE To evaluate prognostic factors associated with local control and disease-free-survival (DFS) of oligometastatic breast cancer patients treated by percutaneous thermal ablation (PTA). MATERIALS AND METHODS Seventy-nine consecutive patients (54.5 ± 11.2 years old) with 114 breast cancer metastases (28.9 ± 16.1 mm in diameter), involving the lungs, the liver, and/or the bone, were treated using PTA with a curative intent. The goal was to achieve a complete remission in association with systemic chemotherapy and hormonal therapy. We retrospectively evaluated the prognostic factors associated with 1- and 2-year local control and the 1- and 2-year DFS rates. RESULTS The 1- and 2-year local control rates were 83.0 and 76.1 %, respectively. Tumor burden was associated with a poorer outcome for local control after PTA (HR 1.027 by additional millimeter, p = 0.026; >4 cm HR 3.90). The 1- and 2-year DFS rates were 54.2 and 30.4 %, respectively. In multivariate analysis, triple-negative histological subtype and increased size of treated metastases were associated with a poorer DFS (HR 2.22; 95 % CI [1.13-4.36]; p = 0.02 and HR 2.43; 95 % CI [1.22-4.82]; p = 0.011, respectively). CONCLUSION PTA is effective for local control of breast cancer oligometastases. Tumor burden >4 cm and triple-negative histological subtype are associated with a poorer outcome.


title: Transmissible gastroenteritis coronavirus genome packaging signal is located at the 5' end of the genome and promotes viral RNA incorporation into virions in a replication-independent process.

text: Preferential RNA packaging in coronaviruses involves the recognition of viral genomic RNA, a crucial process for viral particle morphogenesis mediated by RNA-specific sequences, known as packaging signals. An essential packaging signal component of transmissible gastroenteritis coronavirus (TGEV) has been further delimited to the first 598 nucleotides (nt) from the 5' end of its RNA genome, by using recombinant viruses transcribing subgenomic mRNA that included potential packaging signals. The integrity of the entire sequence domain was necessary because deletion of any of the five structural motifs defined within this region abrogated specific packaging of this viral RNA. One of these RNA motifs was the stem-loop SL5, a highly conserved motif in coronaviruses located at nucleotide positions 106 to 136. Partial deletion or point mutations within this motif also abrogated packaging. Using TGEV-derived defective minigenomes replicated in trans by a helper virus, we have shown that TGEV RNA packaging is a replication-independent process. Furthermore, the last 494 nt of the genomic 3' end were not essential for packaging, although this region increased packaging efficiency. TGEV RNA sequences identified as necessary for viral genome packaging were not sufficient to direct packaging of a heterologous sequence derived from the green fluorescent protein gene. These results indicated that TGEV genome packaging is a complex process involving many factors in addition to the identified RNA packaging signal. The identification of well-defined RNA motifs within the TGEV RNA genome that are essential for packaging will be useful for designing packaging-deficient biosafe coronavirus-derived vectors and providing new targets for antiviral therapies.


title: Evaluation of a second-generation self-expanding variable-porosity flow diverter in a rabbit elastase aneurysm model.

text: BACKGROUND AND PURPOSE The self-expanding V-POD is a second-generation flow-diverting device with a low-porosity PTFE patch on a self-expanding microstent. The authors evaluated this device for the treatment of elastase-induced aneurysms in rabbits. MATERIALS AND METHODS Three V-POD types (A, circumferential patch closed-cell stent [n = 9]; B, asymmetric patch closed-cell stent [n = 7]; and C, asymmetric patch open-cell stent [n = 4]) were evaluated by using angiography, conebeam micro-CT, histology, and SEM. Aneurysm flow modifications were expressed in terms of immediate poststent/prestent ratios of maximum CA volume entering the aneurysm dome tracked on procedural angiograms. Flow modifications were correlated with 4 weeks' follow-up angiographic, micro-CT, histologic, and SEM results. RESULTS Mechanical stent-deployment difficulties in 4 aneurysms (1 type A; 3 type B) led to suboptimal results and exclusion from analysis. Of the remaining 16 aneurysms, 4-week post-treatment angiograms showed no aneurysm filling in 10 (63%), 3 (∼19%) had no filling with a small remnant neck, and 3 (∼19%) had <0.25 filling. Successfully treated aneurysms (n = 16) demonstrated an immediate poststent/prestent CA maximum volume ratio of 0.13 ± 0.18% (0.0%-0.5%). Favorable contrast-flow modification on immediate angiography after deployment correlated significantly with aneurysm occlusion on follow-up angiography, micro-CT, and histology. The occlusion percentage derived from micro-CT was 96 ± 6.8%. Histology indicated advanced healing (grade ≥3) in the aneurysm dome in 13 of 16 cases. SEM revealed 15 of 16 stents in an advanced state of endothelialization. CONCLUSIONS This study showed the feasibility and effectiveness of V-POD for aneurysm healing in a rabbit elastase model.


title: Boston children's hospital community asthma initiative: Five-year cost analyses of a home visiting program.

text: OBJECTIVE To evaluate the costs and benefits of the Boston Children's Hospital Community Asthma Initiative (CAI) through reduction of Emergency Department (ED) visits and hospitalizations for the full pilot-phase program participants. METHODS A cost-benefit analyses was conducted using hospital administrative data to determine an adjusted Return on Investment (ROI): on all 268 patients enrolled in the CAI program during the 33-month pilot program phase of CAI intervention between October 1, 2005 and June 30, 2008 using a comparison group of 818 patients from a similar cohort in neighboring ZIP codes without CAI intervention. Cost data through June 30, 2013 were used to examine cost changes and calculate an adjusted ROI over a 5-year post-intervention period. RESULTS CAI patients had a cost reduction greater than the comparison group of $1,216 in Year 1 (P = 0.001), $1,320 in Year 2 (P < 0.001), $1,132 (P = 0.002) in Year 3, $1,123 (P = 0.004) in Year 4, and $997 (P = 0.022) in Year 5. Adjusting for the cost savings for the comparison group, the cost savings from the intervention resulted in an adjusted ROI of 1.91 over 5 years. CONCLUSIONS Community-based, multidisciplinary, coordinated disease management programs can decrease the incidence of costly hospitalizations and ED visits from asthma. An ROI of greater than one, as found in this cost analysis, supports the business case for the provision of community-based asthma services as part of patient-centered medical homes and Accountable Care Organizations.


title: Current Therapeutic Options for Esophageal Motor Disorders as Defined by the Chicago Classification.

text: With the development of high-resolution manometry and specific metrics to characterize esophageal motility, the Chicago Classification has become the gold standard for the diagnosis of esophageal motor disorders. Major and significant disorders, that is, never observed in healthy subjects, are achalasia, esophagogastric junction outflow obstruction, distal esophageal spasm, absent peristalsis, and hypercontractile (Jackhammer) esophagus. Achalasia subtyping is relevant to predict the response to endoscopic and surgical therapies as several studies suggest that, pneumatic dilation is less effective than Heller myotomy, in type III achalasia. Peroral endoscopic myotomy, initially developed in expert centers, is a promising technique for the treatment of achalasia. The medical therapeutic options for distal esophageal spasm and hypercontractile esophagus are smooth muscle relaxants and pain modulators. Intraesophageal injection of botulinum toxin might be an interesting option for treatment of these disorders but further studies are required to determine the optimal injection protocol and the best candidates based on manometric patterns. The treatment of hypotensive motility disorders is disappointing and relies mainly on dietary and lifestyle changes as no effective esophageal prokinetic is currently available.


title: Endovascular intervention for tibial artery occlusive disease in patients with critical limb ischemia.

text: Surgical bypass has traditionally been the gold standard for treating critical limb ischemia caused by isolated infrapopliteal arterial disease (IP CLI). However, as endovascular techniques continue to progress, they are increasingly applied to this patient population, especially to the high-risk surgical cohort or patients with limited surgical options. This enthusiasm to employ endovascular interventions in IP CLI is accompanied by persistent controversies, as demonstrated in the recent literature. Percutaneous transluminal balloon angioplasty has been the predominant endovascular intervention applied to treat IP CLI and recent literature supports its role. The durability of percutaneous transluminal balloon angioplasty is limited, and thus this intervention is recommended for high-risk patients with limited life expectancy. Bare-metal stents for IP CLI currently do not have supportive data to warrant their use as a primary treatment. Newer drug-eluting stents improve patency and prevent restenosis, but they do not significantly improve patient clinical status compared with bare-metal stents alone. Drug-coated balloons are still relatively new tools in this arena and evidence of their safety and clear efficacy are still lacking. The data on atherectomy, in all of its forms, for IP CLI are overall variable, without any clear benefit to justify its increased complication risks and costs over other modalities. Use of retrograde tibial/pedal access for treating IP CLI as a viable alternative to antegrade access and treatment from a totally retrograde approach has recently been described. Level I evidence to aid in clarifying the true efficacy for each of these endovascular modalities is greatly needed. As we await these data, we must remember that, as with any arterial intervention, proper patient selection is extremely important and the intervention, whether endovascular or open surgical repair, should be tailored to the individual patient's anatomy and disease characteristics.


title: The Impact of Mass Spectrometry-Based Proteomics on Fundamental Discoveries in Virology.

text: In recent years, mass spectrometry has emerged as a core component of fundamental discoveries in virology. As a consequence of their coevolution, viruses and host cells have established complex, dynamic interactions that function either in promoting virus replication and dissemination or in host defense against invading pathogens. Thus, viral infection triggers an impressive range of proteome changes. Alterations in protein abundances, interactions, posttranslational modifications, subcellular localizations, and secretion are temporally regulated during the progression of an infection. Consequently, understanding viral infection at the molecular level requires versatile approaches that afford both breadth and depth of analysis. Mass spectrometry is uniquely positioned to bridge this experimental dichotomy. Its application to both unbiased systems analyses and targeted, hypothesis-driven studies has accelerated discoveries in viral pathogenesis and host defense. Here, we review the contributions of mass spectrometry-based proteomic approaches to understanding viral morphogenesis, replication, and assembly and to characterizing host responses to infection.


Covid-19: "Huge rise" in deaths at home is not fully explained by virus, say experts.


title: Endoscopic cerebrospinal fluid leak closure in an infected field.

text: BACKGROUND Sinonasal cerebrospinal fluid (CSF) leaks during an active infection present the unique challenge of preventing spread of infection without compromising the integrity of the closure. We describe the technique and clinical course of patients undergoing endoscopic CSF leak repair in an actively infected field. OBJECTIVE To evaluate the safety and efficacy of endoscopic CSF leak repair in an actively infected field. METHODS Retrospective chart review of patients with sinonasal CSF leaks that were endoscopically repaired during an acute infection. RESULTS Nine patients were identified. Etiologies of CSF leak were iatrogenic after endoscopic sinus surgery (n = 5, 55.6%) or revision craniopharyngioma resection (n = 1, 11.1%), spontaneous (n = 1, 11.1%), anterior skull base meningocele with CSF leak (n = 1, 11.1%), and posttraumatic (n = 1, 11.1%). The locations of the leaks were ethmoid in five patients, frontoethmoid in three patients, and sphenoid in three patients. Seven patients had acute sinusitis (77.8%) and two patients had meningitis (22.2%) at the time of closure. Two patients (22.2%) had failure of previous CSF leak closure. All leaks were repaired in a multilayered fashion with multiple graft types, including septal or conchal cartilage, temporalis fascia, fascia lata, fat, Medpor, and tissue sealant. Three patients additionally had mucosal flaps or grafts. The patients were treated with an average of 11.1 days (range, 6-14 days) of antibiotics. The average hospital stay was 4.1 days (range, 2-7 days), and the mean follow-up time was 8.7 months (range, 2.9-19.3 months). No patients experienced recurrence of CSF leak or postoperative complication or infection. CONCLUSION Endoscopic closure of skull base defects was successfully performed in nine patients during acute infections without complications, recurrent infection, or need for revision CSF leak closure. Endoscopic CSF leak repair appears to be safe and effective in patients with active infection with sinusitis or meningitis.


Comment on "Tracheotomy in Ventilated Patients with COVID-19".


title: Accuracy of continuous noninvasive hemoglobin monitoring: a systematic review and meta-analysis.

text: BACKGROUND Noninvasive hemoglobin (Hb) monitoring devices are available in the clinical setting, but their accuracy and precision against central laboratory Hb measurements have not been evaluated in a systematic review and meta-analysis. METHODS We conducted a comprehensive search of the literature (2005 to August 2013) with PubMed, Web of Science and the Cochrane Library, reviewed references of retrieved articles, and contacted manufactures to identify studies assessing the accuracy of noninvasive Hb monitoring against central laboratory Hb measurements. Two independent reviewers assessed the quality of studies using recommendations for reporting guidelines and quality criteria for method comparison studies. Pooled mean difference and standard deviation (SD) (95% limits of agreement) across studies were calculated using the random-effects model. Heterogeneity was assessed using the I statistic. RESULTS A total of 32 studies (4425 subjects, median sample size of 44, ranged from 10 to 569 patients per study) were included in this meta-analysis. The overall pooled random-effects mean difference (noninvasive-central laboratory) and SD were 0.10 ± 1.37 g/dL (-2.59 to 2.80 g/dL, I = 95.9% for mean difference and 95.0% for SD). In subgroup analysis, pooled mean difference and SD were 0.39 ± 1.32 g/dL (-2.21 to 2.98 g/dL, I = 93.0%, 71.4%) in 13 studies conducted in the perioperative setting and were -0.51 ± 1.59 g/dL (-3.63 to 2.62 g/dL, I = 83.7%, 96.4%) in 5 studies performed in the intensive care unit setting. CONCLUSIONS Although the mean difference between noninvasive Hb and central laboratory measurements was small, the wide limits of agreement mean clinicians should be cautious when making clinical decisions based on these devices.


title: Phosphorus recovery from sewage with a sustainable and low-cost treatment system.

text: This study proposes a technology conceived based on an integrative approach that aims to promote phosphorus recovery and to recycle ferric water treatment sludge (FWTS), using it as a phosphorus adsorbent which may be applied as a soil ameliorant after reaching saturation. The assessed pilot plant operated with a daily influent flow of 360 litres and presented a removal efficiency of 94.4% ± 3.2% for chemical oxygen demand (COD) and of 91.2% ± 7.8% for suspended solids. It also presented promising results for phosphorus removal. The maximum efficiency of dissolved reactive phosphorus removal was 95% on the first day and it decreased until reaching adsorbent saturation. The estimated breakthrough time was one year in the condition in which the filling medium of a second constructed wetland was only FWTS. In this situation, the effluent phosphorus concentration was 0.2 mg·L-1. The authors concluded that the application of FWTS in a constructed wetland bed is an interesting alternative. Batch adsorption experiments were run using phosphorus stock solution. Langmuir and Freundlich adsorption isotherm models were obtained for different initial pH values. The maximum adsorption capacity decreased as the initial pH was increased; values ranged from 4.76 mg P·g-1 (pH = 3.9) to 1.44 mg P·g-1 (pH = 9.0).


title: Hypomethylating Agent Azacitidine Is Effective in Treating Brain Metastasis Triple-Negative Breast Cancer Through Regulation of DNA Methylation of Keratin 18 Gene.

text: Breast cancer patients presenting with symptomatic brain metastases have poor prognosis, and current chemotherapeutic agents are largely ineffective. In this study, we evaluated the hypomethylating agent azacitidine (AZA) for its potential as a novel therapeutic in preclinical models of brain metastasis of breast cancer. We used the parental triple-negative breast cancer MDA-MB-231 (231) cells and their brain colonizing counterpart (231Br) to ascertain phenotypic differences in response to AZA. We observed that 231Br cells have higher metastatic potential compared to 231 cells. With regard to therapeutic value, the AZA IC50 value in 231Br cells is significantly lower than that in parental cells (P < .01). AZA treatment increased apoptosis and inhibited the Wnt signaling transduction pathway, angiogenesis, and cell metastatic capacity to a significantly higher extent in the 231Br line. AZA treatment in mice with experimental brain metastases significantly reduced tumor burden (P = .0112) and increased survival (P = .0026) compared to vehicle. Lastly, we observed a decreased expression of keratin 18 (an epithelial maker) in 231Br cells due to hypermethylation, elucidating a potential mechanism of action of AZA in treating brain metastases from breast cancer.


title: Preoperative Anemia Treatment With Intravenous Iron in Patients Undergoing Major Orthopedic Surgery: A Systematic Review.

text: Introduction Based upon the Third National Health and Nutrition Examination Survey data, iron deficiency anemia is the cause of at least 20% of cases of anemia in adults over the age of 65. This is especially relevant in patients undergoing major orthopedic surgery as substantial perioperative blood loss is possible, leading to a high rate of allogeneic blood transfusion in total hip replacements, total knee replacements, and hip fracture repairs. Significance The results of this systematic review may be of interest to clinicians and hospital administrators evaluating the clinical efficacy and cost effectiveness of intravenous (IV) iron administration prior to major orthopedic surgery. Materials and Methods The original studies considered for this review included patients who were over 18 years of age, undergoing major orthopedic surgery, and who received an IV iron treatment in the preoperative setting. A total of 1083 articles were identified and reviewed. After removing duplicates, 1031 publications were screened, and 105 full-text studies were assessed for eligibility. A total of 98 were excluded and 7 articles remained which met the criteria for this review. The primary outcome examined in the included studies was the allogeneic blood transfusion rate. The secondary areas of interest were changes in serum hemoglobin, morbidity and mortality, length of stay, and cost effectiveness. Results This systematic review found little evidence that IV iron therapy is effective at reducing transfusion in patients undergoing major orthopedic surgery. Conclusions We do not recommend preoperative IV iron therapy for all patients scheduled for major orthopedic surgery.


title: Chemical Degradation of End-of-Life Poly(lactic acid) into Methyl Lactate by a Zn(II) Complex.

text: The catalyzed methanolysis of end-of-life poly(lactic acid) (PLA) products by an ethylenediamine Zn(II) complex to form biodegradable methyl lactate was studied experimentally at 70, 90, and 110 °C. The PLA samples consisted of typical consumer waste materials, including a cup, a toy, and a three-dimensional (3D) printing material. High selectivities and yields (>94%) were possible depending on temperature and reaction time. Additionally, and to develop a predictive kinetic model, kinetic parameters (pre-exponential factor and activation energies) of the PLA transesterification reaction were first obtained from virgin PLA. These parameters were subsequently used to estimate the conversion of PLA, selectivity, and yield of methyl lactate after 1 and 4 h of the reaction, and the results were compared with the experimental values of the end-of-life PLA. Despite the presence of unknown additives in the PLA waste material and uncontrolled particle size, the model was able to predict the overall conversion, selectivity, and yield to an average deviation of 5, 7, and 12%, respectively. A greater agreement between the model and experimental values is observed for the higher temperatures and the longer reaction time. Larger deviations were observed for the PLA toy, which we attribute to the presence of additives, since despite its lower molecular weight, it possessed a higher structural strength.


title: Production of Pseudotyped Particles to Study Highly Pathogenic Coronaviruses in a Biosafety Level 2 Setting.

text: The protocol aims to generate coronavirus (CoV) spike (S) fusion protein pseudotyped particles with a murine leukemia virus (MLV) core and luciferase reporter, using a simple transfection procedure of the widely available HEK-293T cell line. Once formed and released from producer cells, these pseudovirions incorporate a luciferase reporter gene. Since they only contain the heterologous coronavirus spike protein on their surface, the particles behave like their native coronavirus counterparts for entry steps. As such, they are the excellent surrogates of native virions for studying viral entry into host cells. Upon successful entry and infection into target cells, the luciferase reporter gets integrated into the host cell genome and is expressed. Using a simple luciferase assay, transduced cells can be easily quantified. An important advantage of the procedure is that it can be performed in biosafety level 2 (BSL-2) facilities instead of BSL-3 facilities required for work with highly pathogenic coronaviruses such as Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Another benefit comes from its versatility as it can be applied to envelope proteins belonging to all three classes of viral fusion proteins, such as the class I influenza hemagglutinin (HA) and Ebola virus glycoprotein (GP), the class II Semliki forest virus E1 protein, or the class III vesicular stomatitis virus G glycoprotein. A limitation of the methodology is that it can only recapitulate virus entry steps mediated by the envelope protein being investigated. For studying other viral life cycle steps, other methods are required. Examples of the many applications these pseudotype particles can be used in include investigation of host cell susceptibility and tropism and testing the effects of virus entry inhibitors to dissect viral entry pathways used.


title: Accuracy of a new intraocular lens power calculation method based on artificial intelligence.

text: PURPOSE The purpose of this study is to develop and assess the accuracy of a new intraocular lens (IOL) power calculation method based on machine learning techniques. METHODS The following data were retrieved for 260 eyes of 260 patients undergoing cataract surgery: preoperative simulated keratometry, mean keratometry of posterior surface, axial length, anterior chamber depth, lens thickness, and white-to-white diameter; model and power of implanted IOL; and subjective refraction at 3 months post surgery. These data were used to train different machine learning models (k-Nearest Neighbor, Artificial Neural Networks, Support Vector Machine, Random Forest, etc). Implanted lens characteristics and biometric data were used as input to predict IOL power and refractive outcomes. For external validation, a dataset of 52 eyes was used. The accuracy of the trained models was compared with that of the power formulas Holladay 2, Haigis, Barrett Universal II, and Hill-RBF v2.0. RESULTS The SD of the prediction error in order of lowest to highest was the new method (designated Karmona) (0.30), Haigis (0.36), Holladay 2 (0.38), Barrett Universal II (0.38), and Hill-RBF v2.0 (0.40). Using the Karmona method, 90.38% and 100% of eyes were within ±0.50 and ±1.00 D respectively. CONCLUSIONS The method proposed emerged as the most accurate to predict IOL power.


title: Towards Contactless Patient Positioning.

text: The ongoing COVID-19 pandemic, caused by the highly contagious SARS-CoV-2 virus, has overwhelmed healthcare systems worldwide, putting medical professionals at a high risk of getting infected themselves due to a global shortage of personal protective equipment. This has in-turn led to understaffed hospitals unable to handle new patient influx. To help alleviate these problems, we design and develop a contactless patient positioning system that can enable scanning patients in a completely remote and contactless fashion. Our key design objective is to reduce the physical contact time with a patient as much as possible, which we achieve with our contactless workflow. Our system comprises automated calibration, positioning, and multi-view synthesis components that enable patient scan without physical proximity. Our calibration routine ensures system calibration at all times and can be executed without any manual intervention. Our patient positioning routine comprises a novel robust dynamic fusion (RDF) algorithm for accurate 3D patient body modeling. With its multi-modal inference capability, RDF can be trained once and used across different applications (without re-training) having various sensor choices, a key feature to enable system deployment at scale. Our multi-view synthesizer ensures multi-view positioning visualization for the technician to verify positioning accuracy prior to initiating the patient scan. We conduct extensive experiments with publicly available and proprietary datasets to demonstrate efficacy. Our system has already been used, and had a positive impact on, hospitals and technicians on the front lines of the COVID-19 pandemic, and we expect to see its use increase substantially globally.


title: Chemotherapeutic control of Gram-positive infection in white sea bream (Diplodus sargus, Linnaeus 1758) broodstock.

text: Aim This study aimed to identify the pathogenic bacteria responsible for the septicemic disease affecting white sea bream brooders and determining the sensitivity of the recovered isolates to different antibiotics followed by estimation of long-acting oxytetracycline (OTC) efficacy in controlling this disease, and finally, determining the proper dose regimen. Materials and Methods Biolog microbial identification system was used for determination of the pathogens which are responsible for this disease. Agar disk diffusion test and minimum inhibitory concentration (MIC) were used to determine the antibiotic susceptibility of recovered isolates. Oxytetracycline (OTC) was used at a dose level of 100 mg/kg body weight for the treatment of diseased fish, and the OTC concentration in the serum samples was determined by high-performance liquid chromatography. Results Fifteen Staphylococcus epidermidis and 11 Bacillus cereus isolates were recovered from the lesion of muscle, tail, eye, and heart blood. S. epidermidis isolates were sensitive to OTC, ciprofloxacin, enrofloxacin, spiramycin, erythromycin (E), and florfenicol. B. cereus isolates were sensitive to all mentioned antibiotics except E. Based on the MIC test, all B. cereus isolates were sensitive to OTC with MIC ranging between <0.125 and 4 µg/ml and 11 S. epidermidis isolates were sensitive with MIC ranging between <0.125 and 8 µg/ml, while four isolates were resistant. Different degrees of degenerative changes were present in the hepatopancreas, posterior kidney, eye, and skin tissues of diseased fish. Conclusion Single intraperitoneal injection of long-acting OTC at a dose of 100 mg/kg body weight was effective in termination of S. epidermidis and B. cereus infection in white sea bream (D. sargus) broodstock.


title: Evaluation of local recurrence after treatment for hepatocellular carcinoma by contrast-enhanced ultrasonography using Sonazoid: comparison with dynamic computed tomography.

text: PURPOSE To evaluate the effectiveness of contrast-enhanced ultrasonography (CEUS) using Sonazoid for the diagnosis of the local recurrence after treatment for hepatocellular carcinoma (HCC) by comparing it with dynamic CT. METHODS Seventy-one patients with 87 HCC lesions (mean +/- SD; 19.5 +/- 9.6 mm) underwent CEUS using Sonazoid and dynamic CT after radiofrequency ablation (n = 55), transcatheter arterial chemoembolization (n = 22), or radiofrequency ablation combined with transcatheter arterial chemoembolization (n = 10). Two hepatologists (observer 1; 10 years of experience, and 2; 20 years of experience) reviewed the CEUS and dynamic CT images independently and evaluated presence or absence of the local recurrence. Diagnostic performance for the local recurrence was assessed using receiver operating characteristic curve analysis. RESULTS The Az value for dynamic CT was significantly lower in observer 1 than 2 (p < 0.05). The sensitivity of CEUS was 79% in observer 1 and 83.9% in observer 2, and that of dynamic CT was 83.9% and 90.3%, respectively. The specificity of CEUS was 96%, and that of dynamic CT was 92%, in both observers. CONCLUSION This study suggests that CEUS using Sonazoid is less affected by the observer's experience and is more accurate in the diagnosis of local recurrence after treatment for HCC than dynamic CT.


Novel Wuhan (2019-nCoV) Coronavirus.


title: Ribosome Profiling Reveals Translational Upregulation of Cellular Oxidative Phosphorylation mRNAs during Vaccinia Virus-Induced Host Shutoff.

text: Vaccinia virus infection causes a host shutoff that is marked by global inhibition of host protein synthesis. Though the host shutoff may facilitate reallocation of cellular resources for viral replication and evasion of host antiviral immune responses, it poses a challenge for continuous synthesis of cellular proteins that are important for viral replication. It is, however, unclear whether and how certain cellular proteins may be selectively synthesized during the vaccinia virus-induced host shutoff. Using simultaneous RNA sequencing and ribosome profiling, two techniques quantifying genome-wide levels of mRNA and active protein translation, respectively, we analyzed the responses of host cells to vaccinia virus infection at both the transcriptional and translational levels. The analyses showed that cellular mRNA depletion played a dominant role in the shutoff of host protein synthesis. Though the cellular mRNAs were significantly reduced, the relative translation efficiency of a subset of cellular mRNAs increased, particularly those involved in oxidative phosphorylation that are responsible for cellular energy production. Further experiments demonstrated that the protein levels and activities of oxidative phosphorylation increased during vaccinia virus infection, while inhibition of the cellular oxidative phosphorylation function significantly suppressed vaccinia virus replication. Moreover, the short 5' untranslated region of the oxidative phosphorylation mRNAs contributed to the translational upregulation. These results provide evidence of a mechanism that couples translational control and energy metabolism, two processes that all viruses depend on host cells to provide, to support vaccinia virus replication during a host shutoff.IMPORTANCE Many viral infections cause global host protein synthesis shutoff. While host protein synthesis shutoff benefits the virus by relocating cellular resources to viral replication, it also poses a challenge to the maintenance of cellular functions necessary for viral replication if continuous protein synthesis is required. Here we measured the host mRNA translation rate during a vaccinia virus-induced host shutoff by analyzing total and actively translating mRNAs in a genome-wide manner. This study revealed that oxidative phosphorylation mRNAs were translationally upregulated during vaccinia virus-induced host protein synthesis shutoff. Oxidative phosphorylation is the major cellular energy-producing pathway, and we further showed that maintenance of its function is important for vaccinia virus replication. This study highlights the fact that vaccinia virus infection can enhance cellular energy production through translational upregulation in the context of an overall host protein synthesis shutoff to meet energy expenditure.


title: Semiconductor quantum dots for multiplexed bio-detection on solid-state microarrays.

text: Understanding cellular systems requires identification and analysis of their multiple components and determination of how they act together and are regulated. Microarray technology is one of the few tools that is able to solve such problems. It is based on high-throughput recognition of a target to the probe and has the potential to simultaneously measure the presence of numerous molecules in multiplexed tests, all contained in a small drop of test fluid. Microarrays allow the parallel analysis of genomic or proteomic content in healthy versus disease-affected or altered tissues or cells. The signal read-out from the microarrays is done with organic dyes which often suffer of photobleaching, low brightness and background fluorescence. Recent data show that the use of fluorescent nanocrystals named "quantum dots" (QDs) allows to push these limits away. QDs are sufficiently bright to be detected as individual particles, extremely resistant against photobleaching and provide unique possibilities for multiplexing, thus supplying the microarray technology with a novel read-out option enabling the sensitivity of detection to reach the single-molecule level. This paper reviews QDs applications to microarray-based detection and demonstrates how the combination of microarray and QDs technologies may increase sensitivity and highly parallel capacities of multiplexed microarrays. Such a combination should provide the breakthrough results in drug discovery, cancer diagnosis and establish new therapeutic approaches through the identification of binding target molecules and better understanding of cell signalling pathways.


Water Analysis: Emerging Contaminants and Current Issues.


title: Combination of MIDGE-Th1 DNA vaccines with the cationic lipid SAINT-18: studies on formulation, biodistribution and vector clearance.

text: We have previously shown that the combination of MIDGE-Th1 DNA vectors with the cationic lipid SAINT-18 increases the immune response to the encoded antigen in mice. Here, we report on experiments to further optimize and characterize this approach. We evaluated different formulations of MIDGE-Th1 vectors with SAINT-18 by assessing their influence on the transfection efficiency in cell culture and on the immune response in mice. We found that high amounts of SAINT-18 in formulations with a w/w ratio MIDGE Th1/SAINT-18 of 1:4.8 are beneficial for cell transfection in vitro. In contrast, the formulation of HBsAg-encoding MIDGE-Th1 DNA vectors with the lowest amount of SAINT-18 (w/w ratio MIDGE Th1/SAINT-18 of 1:0.5) resulted in the highest serum IgG1 and IgG2a levels after intradermal immunization of mice. Consequently, latter formulation was selected for a comparative biodistribution study in rats. Following intradermal administration of both naked and formulated MIDGE-Th1 DNA, the vectors localized primarily at the site of injection. Vector DNA levels decreased substantially over the two months duration of the study. When administered in combination with SAINT-18, the vectors were found in significantly higher amounts in draining lymph nodes in comparison to administration of naked MIDGE-Th1 DNA. We propose that the high immune responses induced by MIDGE-Th1/SAINT-18 lipoplexes are mediated by enhanced transfection of cells in vivo, resulting in stronger antigen expression and presentation. Importantly, the combination of MIDGE-Th1 vectors with SAINT-18 was well tolerated in mice and rats and is expected to be safe in human clinical applications.


title: Bench evaluation of commercially available and newly developed interfaces for mouthpiece ventilation.

text: INTRODUCTION Mouthpiece ventilation represents a valuable treatment for patients needing daytime non-invasive ventilation. This modality is however underused, in part because of limitations in the available equipment. OBJECTIVE To develop a new flexible and moldable mouthpiece, aiming to address some of the issues of the currently available interfaces. METHODS We compared two commercially available and the newly developed mouthpieces in a bench test using four life-support home ventilators and three settings per ventilator. RESULTS The three interfaces showed marked differences in their resistive characteristics. In the volume-controlled setting (VC-CMV) with 500 mL tidal volume (VT ), the delivered VT , ranged between 459 ± 7 mL (-8%) and 501 ± 4 mL (+0.2%), according to the used ventilator. In the VC-CMV setting with VT 1000 mL, one of the ventilators did not assure the set VT with the new mouthpiece, because of the high-pressure limitation. In the pressure-controlled setting (PC-CMV at 20 cmH2 O), the effective pressure differed between the tested interfaces according to their resistance, resulting in a decrease in the delivered VT . CONCLUSIONS They found measurable differences in the ventilation's performances comparing the interfaces for mouthpiece ventilation, which seem to have a minor clinical relevance in the most settings, but should be systematically checked. They validated in-vitro the newly developed mouthpiece with respect to the ventilation performances; a clinical study is needed to investigate the potential advantages we expect from the new mouthpiece.


title: COVID-19: A Personalized Cardiometabolic Approach for Reducing Complications and Costs. The Role of Aging Beyond Topics

text: COVID 19 is much more than an infectious disease by SARS-CoV-2 followed by a disproportionate immune response. An older age, diabetes and history of cardiovascular disease, especially hypertension, but also chronic heart failure and coronary artery disease among others, are between the most important risk factors. In addition, during the hospitalization both hyperglycaemia and heart failure are frequent. Less frequent are acute coronary syndrome, arrhythmias and stroke. Accordingly, not all prolonged stays or even deaths are due directly to SARS-CoV-2. To our knowledge, this is the first review, focusing both on cardiovascular and metabolic aspects of this dreadful disease, in an integrated and personalized way, following the guidelines of the Cardiometabolic Health/Medicine. Therefore, current personalized aspects such as ACEIs and ARBs, the place of statins and the most appropriate management of heart failure in diabetics are analysed. Aging, better than old age, as a dynamic process, is also considered in this review for the first time in the literature, and not only as a risk factor attributed to cardiovascular and non-cardiovascular comorbidities. Immunosenescence is also approached to build healthier elders, so they can resist present and future infectious diseases, and not only in epidemics or pandemics. In addition, to do this we must start knowing the molecular mechanisms that underlying Aging process in general, and immunosenescence in particular. Surprisingly, the endoplasmic reticulum stress and autophagy are implicated in both process. Finally, with a training in all the aspects covered in this review, not only the hospital stay, complications and costs of this frightening disease in high-risk population should be reduced. Likely, this paper will open a gate to the future for open-minded physicians.


title: Critical Care Nutrition: Where's the Evidence?

text: The surgical critically ill patient is subject to a variable and complex metabolic response, which has detrimental effects on immunity, wound healing, and preservation of lean body muscle. The concept of nutrition support has evolved into nutrition therapy, whereby the primary objectives are to prevent oxidative cell injury, modulate the immune response, and attenuate the metabolic response. This review outlines the metabolic response to critical illness, describes nutritional risk; reviews the evidence for the role, dose, and timing of enteral and parenteral nutrition, and reviews the evidence for immunonutrition in the surgical intensive care unit.


title: Onset to reperfusion time as a determinant of outcomes across a wide range of ASPECTS in endovascular thrombectomy: pooled analysis of the SWIFT, SWIFT PRIME, and STAR studies.

text: BACKGROUND The time-benefit relationship of endovascular thrombectomy (EVT) according to the size of the core infarct has been incompletely explored in prior studies. We investigated whether established infarct core size on baseline imaging modifies the relationship between onset-to-reperfusion time (OTR) and functional outcomes in patients with acute ischemic stroke treated with EVT. METHODS We analyzed a database containing individual patient data pooled from three prospective Solitaire stent retriever studies. The inclusion criteria were treatment with a Solitaire device and achievement of substantial reperfusion (modified Thrombolysis in Cerebral Infarction 2b-3). Main analyses were performed in patients with baseline Alberta Stroke Program Early CT Scores (ASPECTSs) of 7-10. RESULTS Among the 305 patients (mean age 67±13 years, 58% women), the proportions of patients in different categories of pretreatment infarct extent were: small (ASPECTS 9-10) 52.0%, moderate (ASPECTS 7-8) 37.1%, and large (ASPECTS 0-6) 7.6%. The mean OTR was 297±95 min. At 3 months, 60.1% of the patients achieved a good outcome. For OTRs of 2-8 hours, the rates of good outcomes at all time points were higher with higher baseline ASPECTS but declined with similar steepness. Both baseline ASPECTS (OR 1.23 (95% CI 1.04 to 1.45)) and OTR (every 30 min delay, OR 0.80 (95% CI 0.73 to 0.88)) were independently associated with a good 3-month outcome. No interaction between OTR and baseline ASPECTS was observed. CONCLUSIONS Although patients with higher baseline ASPECTS are more likely to have good clinical outcomes at all OTR intervals after 2 hours, this benefit consistently declines with time, even in patients with a small infarct core, reinforcing the need to treat all patients as quickly as possible.


title: An update on Middle East respiratory syndrome: 2 years later.

text: Middle East respiratory syndrome coronavirus (MERS-CoV) was first recognized in 2012 and since then has resulted in cases in 23 countries in four continents. The majority of these cases were reported from the Kingdom of Saudi Arabia. The disease caused a spectrum of illness, from asymptomatic to severe and possibly fatal disease. Recent studies showed that the transmission of MERS-CoV among family contacts remains relatively low. Currently, there are no approved vaccines or therapeutics for MERS-CoV.


title: Role and Management of a Head and Neck Department during the COVID-19 Outbreak in Lombardy.

text: The recent Italian outbreak of coronavirus disease 2019 led to an unprecedented burden on our health care system. Despite head and neck-otolaryngology not being a front-line specialty in dealing with this disease, our department had to face several specific issues. Despite a massive reallocation of resources in the hospital, we managed to keep the service active, improving safety measures for our personnel, specifically during common otolaryngologic maneuvers known to produce aerosols. Furthermore, we strived to maintain our teaching role, giving residents an inclusive role in managing the response to the emergency state, and we progressively integrated our inactive specialists into other service rotations to relieve front-line colleagues' burden. Specific issues and management decisions are discussed in detail in the article.


title: Evaluation of respiratory viral pathogens in acute asthma exacerbations during childhood.

text: OBJECTIVE Common upper respiratory tract viruses are the most frequent and important causes of asthma exacerbations in both children and adults. Prospective epidemiologic studies report that up to 80% of childhood exacerbations are associated with viral upper respiratory tract infections. MATERIALS AND METHODS The study group consisted of 104 children with asthma aged 3-17 years who received treatment for asthma exacerbations in our clinic between September 2009 and 2010. Nasopharyngeal and nasal swabs were obtained from all patients during an acute attack, and from the control group (31 subjects). These specimens were investigated for the presence of viral respiratory pathogens using a real-time multiplex PCR method. The patients were compared for the presence of respiratory pathogens and factors related to the severity of the asthma exacerbation. RESULTS A pathogenic respiratory virus was detected in 53.8% of patients in the acute exacerbation group. The most commonly encountered viral agent was Rhinovirus (35.6%). Patients who had an acute exacerbation with or without a detectable viral pathogen were compared according to the severity of the exacerbation, the need for systemic steroids, and hospitalization rates. No statistically significant difference was found. CONCLUSION Although viral upper respiratory tract infections are the most common cause of asthma exacerbations, the severity level of the exacerbation seems to be independent of whether a respiratory virus has been detected.


title: Bovine type III interferon significantly delays and reduces the severity of foot-and-mouth disease in cattle.

text: Interferons (IFNs) are the first line of defense against viral infections. Although type I and II IFNs have proven effective to inhibit foot-and-mouth disease virus (FMDV) replication in swine, a similar approach had only limited efficacy in cattle. Recently, a new family of IFNs, type III IFN or IFN-λ, has been identified in human, mouse, chicken, and swine. We have identified bovine IFN-λ3 (boIFN-λ3), also known as interleukin 28B (IL-28B), and demonstrated that expression of this molecule using a recombinant replication-defective human adenovirus type 5 (Ad5) vector, Ad5-boIFN-λ3, exhibited antiviral activity against FMDV in bovine cell culture. Furthermore, inoculation of cattle with Ad5-boIFN-λ3 induced systemic antiviral activity and upregulation of IFN-stimulated gene expression in the upper respiratory airways and skin. In the present study, we demonstrated that disease could be delayed for at least 6 days when cattle were inoculated with Ad5-boIFN-λ3 and challenged 24 h later by intradermolingual inoculation with FMDV. Furthermore, the delay in the appearance of disease was significantly prolonged when treated cattle were challenged by aerosolization of FMDV, using a method that resembles the natural route of infection. No clinical signs of FMD, viremia, or viral shedding in nasal swabs was found in the Ad5-boIFN-λ3-treated animals for at least 9 days postchallenge. Our results indicate that boIFN-λ3 plays a critical role in the innate immune response of cattle against FMDV. To this end, this work represents the most successful biotherapeutic strategy so far tested to control FMDV in cattle.


title: Small molecule inhibitors of ebola virus infection.

text: Ebola viruses are extremely virulent and highly transmissible. They are responsible for sporadic outbreaks of severe hemorrhagic fevers with human mortality rates of up to 90%. No prophylactic or therapeutic treatments in the form of vaccine, biologicals or small molecule, currently exist. Yet, a wealth of antiviral research on ebola virus is being generated and potential inhibitors have been identified in biological screening and medicinal chemistry programs. Here, we detail the state-of-the-art in small molecule inhibitors of ebola virus infection, with >60 examples, including approved drugs, compounds currently in clinical trials, and more exploratory leads, and summarize the associated in vitro and in vivo evidence for their effectiveness.


title: The Science Underlying COVID-19: Implications for the Cardiovascular System.

text: Corona Virus Disease 2019 (COVID-19) pandemic has impacted health and economy worldwide on an unprecedented scale. Patients have diverse clinical outcomes, but those with pre-existing cardiovascular (CV) disease, hypertension, and related conditions incur disproportionately worse outcome. The high infectivity of the SARS-CoV-2 virus is in part related to new mutations in the receptor binding domain, and acquisition of a furin cleavage site in the S spike protein. The continued viral shedding in the asymptomatic and pre-symptomatic individuals enhances its community transmission. The virus uses the ACE2 receptor for internalization, aided by TMPRSS2 protease. The tissue localization of the receptors correlates with COVDI-19 presenting symptoms and organ dysfunction. Virus-induced ACE2 down regulation may attenuate its function, diminish its anti-inflammatory role, and heightened angiotensin II effects in the predisposed patients. Lymphopenia occurs early and is prognostic, potentially associated with reduction of the CD4+ and some CD8+ T cells. This leads to imbalance of the innate/acquired immune response, delayed viral clearance, and hyper stimulated macrophages and neutrophils. Appropriate type I interferon pathway activation is critical for virus attenuation, and balanced immune response. Persistent immune activation in predisposed patients, such as the elderly and those with CV risk, can lead to hemophagocytosis like syndrome, with uncontrolled amplification of cytokine production, leading to multi-organ failure and death. In addition to the airways and lungs, the cardiovascular system is often involved in COVID-19 early, reflected in the release of highly sensitive troponin and natriuretic peptides, which are all extremely prognostic, particularly in those showing continued rise, along with cytokines such as IL-6. Inflammation in the vascular system can result in diffuse microangiopathy with thrombosis. Inflammation in the myocardium can result in myocarditis, heart failure, cardiac arrhythmias, acute coronary syndrome, rapid deterioration and sudden death. Aggressive support based on early prognostic indicators with expectant management can potentially improve recovery. Appropriate treatment for heart failure, arrhythmias, acute coronary syndrome and thrombosis remain important. Specific evidence based treatment strategies for COVID-19 will emerge with ongoing global collaboration on multiple approaches being evaluated. To protect the wider population, antibody testing and effective vaccine will be needed to make COVID-19 history.


title: Relationship of suicide rates to economic variables in Europe: 2000-2011.

text: BACKGROUND It is unclear whether there is a direct link between economic crises and changes in suicide rates. AIMS The Lopez-Ibor Foundation launched an initiative to study the possible impact of the economic crisis on European suicide rates. METHOD Data was gathered and analysed from 29 European countries and included the number of deaths by suicide in men and women, the unemployment rate, the gross domestic product (GDP) per capita, the annual economic growth rate and inflation. RESULTS There was a strong correlation between suicide rates and all economic indices except GPD per capita in men but only a correlation with unemployment in women. However, the increase in suicide rates occurred several months before the economic crisis emerged. CONCLUSIONS Overall, this study confirms a general relationship between the economic environment and suicide rates; however, it does not support there being a clear causal relationship between the current economic crisis and an increase in the suicide rate.


title: Determinants of public phobia about infectious diseases in South Korea: effect of health communication and gender difference.

text: This study investigated the individual and social determinants of the public's phobia of infectious diseases in South Korea, where collective action was recently fueled by the public phobia over mad cow disease (bovine spongiform encephalopathy [BSE]). Gender-specific multivariate regression was used to compare the public perception of BSE and highly pathogenic avian influenza (HPAI). The analysis results differentiated between the determinants of the phobia for the 2 diseases, BSE and HPAI (N = 1002). As with HIV/AIDS and leprosy, the public fear of HPAI was expressed as a disease phobia that seeks to ensure the social exclusion of infection sources, whereas the fear of BSE was influenced by social and communication factors. Therefore, BSE, unlike previous HPAI, can be rapidly amplified amid the growing distrust in health communication, in which case the social determinants of disease phobia are associated with communicator trust, social values, and political attitude toward diseases rather than disease perception.


title: Percutaneous radiofrequency ablation for pulmonary metastases from hepatocellular carcinoma: results of a multicenter study in Japan.

text: PURPOSE To retrospectively evaluate technical success, effectiveness, complications, patient survival, and prognostic factors with percutaneous radiofrequency (RF) ablation for pulmonary metastases resulting from hepatocellular carcinoma (HCC). MATERIALS AND METHODS Thirty-two patients from six institutions were included, with a total of 83 pulmonary metastases treated in 65 sessions. RF ablation was always performed percutaneously with computed tomography (CT) guidance. Primary endpoints were technical success and technique effectiveness. Technique effectiveness was evaluated based on sequential follow-up CT images. Secondary study endpoints were complications, patient survival, and determination of prognostic factors. Complications were classified as major or minor. Prognostic factors were determined by analyzing multiple variables with the log-rank test. RESULTS Technical success rate was 100%. Primary technique effectiveness rates were 92% each at 1, 2, and 3 years. Major and minor complications occurred after 16 (25%) and 23 (35%) of the 65 sessions, respectively. The median follow-up period was 20.5 months. Overall survival rates were 87% at 1 year and 57% each at 2 and 3 years (median and mean survival times, 37.7 mo and 43.2 mo, respectively). Significantly better survival rates were obtained in cases of (i) no viable intrahepatic recurrence (P < .001), (ii) Child-Pugh class A disease (P < .001), (iii) absence of liver cirrhosis (P < .001), (iv) absence of hepatitis C virus infection (P = .006), and (v) α-fetoprotein level of 10 ng/mL or lower (P = .007) at the time of RF ablation. CONCLUSIONS RF ablation appears effective, with an acceptable safety profile, in selected patients with pulmonary metastases resulting from HCC.


The five "W" of cognitive telerehabilitation in the Covid-19 era.


Protecting older people from COVID-19: should the United Kingdom start at age 60?