title: Opioid formulations with sequestered naltrexone: a perspective review.

text: In response to good-intentioned efforts to correct the traditional undertreatment of pain, opioid prescribing experienced a dramatic increase over the past decade. But there is now concern that the pendulum has swung too far in the opposite direction, with a rise in morbidity and mortality associated with prescription opioid misuse and abuse. Yet despite potential problems, opioids are a mainstay for the treatment of pain and are an important component of a comprehensive pain management strategy. Therefore, the overall goal of pain management is to decrease pain and to improve patient functioning and quality of life, while monitoring for adverse effects or aberrant behaviors. That is, to balance effective chronic pain management with appropriate use of opioids. Toward this end, several abuse deterrent strategies (formulations) have been, and continue to be, developed. Several major ones are reviewed here. These products should be a first step in trying to address diversion and abuse in a manner that does not discriminate against any particular patient and aligns with universal prescribing precautions. They should also comprise only one aspect of an overall opioid risk management plan.


title: Mental health crisis of Japanese health care workers under COVID-19.

text: During the COVID-19 outbreak, the mental health of health care workers has become a major public health concern. Particularly in Japan, women health care workers are experiencing a mental health crisis because of gender imbalance. In addition to honoring health care workers as heroes, we must promote efforts to compensate health care workers, strengthen infection prevention, and promote mental health. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: The development of a cryptoglandular Anal Fistula Core Outcome Set (AFCOS): an international Delphi study protocol.

text: PURPOSE Cryptoglandular anal fistula is a disorder with an incidence of around 1 per 5,000 people per year in European countries. Many studies have been conducted to evaluate the effectiveness of interventions for anal fistula. However, there is considerable heterogeneity in the outcomes assessed and reported in these studies. This limits research quality and complicates evidence synthesis. A solution for heterogeneity in outcome reporting is the development of a Core Outcome Set (COS). This paper describes the protocol for the development of a European COS for Anal Fistula (AFCOS). METHODS The first step will be a systematic review of the literature to identify potential outcomes that may be included in the COS. Patient interviews will be conducted in The United Kingdom and The Netherlands to ensure that both clinician-important and patient-important outcomes are captured. The outcomes will be categorized using the COMET taxonomy and taken forward to a Delphi consensus exercise. In up to three web-based Delphi surveys the outcomes will be prioritized by patients, clinicians (surgeons, gastroenterologists, and radiologists), and (clinical) researchers. The responses will be summarized and reported anonymously in subsequent round(s) facilitating convergence to a consensus opinion. The final COS will be decided during a face-to-face consensus meeting with patients, clinicians, and (clinical) researchers. DISCUSSION This study protocol describes the development of a European COS for anal fistula to improve research quality, evidence synthesis, and patient care.


Letter: Neurosurgeons and Curves: The Need for Critical Appraisal of Modeling in the Post-COVID Era.


title: Impact of prostate weight on perioperative outcomes of robot-assisted laparoscopic prostatectomy with a posterior approach to the seminal vesicle.

text: BACKGROUND To determine the effect of prostate weight on the preoperative and postoperative outcomes of robotic-assisted laparoscopic radical prostatectomy with a posterior approach to the seminal vesicle. METHODS This retrospective study examined prospectively collected data on 219 robotic-assisted laparoscopic radical prostatectomies performed from May 2011 to February 2013. Patients were divided into four groups based on pathologic prostate weight: <30 g, 30-49 g, 50-79 g, and ≥80 g. Continence and sexual function were assessed using validated questionnaires. RESULTS Of the 219 patients, 19, 143, 51, and 6 had prostates weighing <30 g, 30-49 g, 50-79 g, and ≥80 g, respectively. Significant differences were found between the preoperative Gleason scores, total operative times, and robotic times of the groups. Both estimated blood loss and anastomosis time tended to be greater in the higher prostate weight groups, but the differences were not significant. No significant differences were observed in transfusion rate, length of catheterization, complication incidence, or positive surgical margins. The return of urinary function, as determined by questionnaire scores, was not affected by prostate weight. CONCLUSIONS Robotic-assisted laparoscopic radical prostatectomy can be performed safely and with similar perioperative outcomes, regardless of prostate weight. Indeed, oncological outcome, urinary continence, and complications were similar across the prostate weight groups, suggesting that robotic-assisted laparoscopic radical prostatectomy with a posterior approach to the seminal vesicle may be performed effectively on men with large prostates, despite greater surgical times.


title: Laparoscopic surgery for a Bochdalek hernia triggered by pregnancy in an adult woman: A case report.

text: INTRODUCTION A Bochdalek hernia (BH) is a type of congenital diaphragmatic hernia. We herein describe an adult woman with a BH triggered by pregnancy and treated by laparoscopic surgery. PRESENTATION OF CASE A 26-year-old woman was referred to our hospital because of abdominal pain and dyspnea resulting from a left diaphragmatic hernia. She was diagnosed with a BH and underwent laparoscopic surgery. Her postoperative progress was satisfactory, and no recurrence was found at follow-up approximately 1 year later. DISCUSSION A recently published study reviewing detailed cases of laparoscopic and/or thoracoscopic repair of adult BH from 1999 to 2016 identified 30 cases. A laparoscopic approach for treatment of BH has recently attracted increasing interest. CONCLUSION Laparoscopic surgery can be safely performed on adults with BH without complications.


title: Restorative restproctectomy as single-port surgery through the ostomy site in a three-stage procedure.

text: PURPOSE Single-port laparoscopic surgery as an alternative to traditional laparoscopic technique is anticipated to be beneficial in the early postoperative course. We describe restorative restproctectomy as single-port surgery through the ostomy site in a three-stage procedure for refractory ulcerative colitis 12 weeks after laparoscopic subtotal colectomy. SURGICAL TECHNIQUE After release of the terminal ileostomy, creating the ileal J pouch extra-abdominally, a single-port device was placed. Through this, the rectal stump was mobilized and extracorporeally closed. The ileal pouch anal anastomosis was created using circular double-stapling technique. The single-port device was removed, and the loop ileostomy was placed at the same site. RESULTS We employed this technique in a 54 year-old patient who had suffered from ulcerative colitis. No postoperative complications were observed. CONCLUSIONS Restorative restproctectomy as single-port surgery through the ostomy site is safe and feasible. No additional incision is necessary. The trauma of conventional laparoscopic access can be further reduced.


title: Recovery of duck hepatitis A virus 3 from a stable full-length infectious cDNA clone.

text: Recently, duck hepatitis A virus 3 (DHAV-3) with genetically distinct characteristics from DHAV-1 and DHAV-2 was recognized in South Korea and China. In this short communication, we successfully constructed a stable full-length infectious cDNA clone derived from DHAV-3 by solving instability of cloned full-length cDNA in Escherichia coli (E. coli). The cDNA fragments amplified from the genome of DHAV-3 were assembled and inserted into a low-copy-number plasmid. Finally, a full-length cDNA clone containing an engineered SacII site that served as a genetic marker was obtained. The cDNA clone showed stable by serial passages in E. coli when propagated at 25°C under low level of antibiotic selection. BHK-21 cells were transfected with transcribed RNA from the full-length cDNA clone; infectious viral particles were rescued, showing its fatality to 10-day-old duck embryos. The results indicated that the constructed full-length cDNA clone of DHAV-3 is infectious. By various virological assays, our results indicated that the rescued virus exhibited similar biological properties with the parental virus. Animal experiments revealed that the rescued virus retained the high pathogenicity to 1-day-old ducklings and could induce a fatal hepatitis indistinguishable from its parental virus. Our present studies provide a useful tool for future research on genomic functions and molecular pathogenesis of DHAV-3.


title: COVID-19, Australia: Epidemiology Report 14 (Reporting week to 23:59 AEST 3 May 2020).

text: Confirmed cases in Australia notified up to 03 May 2020: notifications = 6,784; deaths = 89. The reduction in international travel and domestic movement, social distancing measures and public health action have likely slowed the spread of COVID-19 in Australia. Currently new notifications in Australia are mostly considered to be locally-acquired with some cases still reported among people with recent overseas travel. Most locally-acquired cases can be linked back to a confirmed case or known cluster, with a small portion unable to be epidemiologically linked to another case. The ratio of overseas-acquired cases to locally-acquired cases varies by jurisdiction. The crude case fatality rate (CFR) in Australia remains low (1.3%) compared to the World Health Organization's globally-reported rate (7.1%) and to other comparable high-income countries such as the United States of America (5.7%) and the United Kingdom (15.4%). The lower CFR in Australia is likely reflective of high case ascertainment including detection of mild cases. Internationally, cases continue to increase. The rates of increase have started to slow in several regions, although it is too soon to tell whether this trend will be sustained.


title: Vaccines for healthcare-associated infections: present, future, and expectations.

text: INTRODUCTION In spite of the widespread implementation of preventive strategies, the prevalence of healthcare-associated infections (HAIs) remains high. HAIs are associated with multidrug resistant organisms, and in the post-antibiotic era, alternative strategies such as vaccines are needed for their management. AREAS COVERED Vaccines to prevent HAIs could be proposed to at-risk patients, or to healthcare workers (HCWs) to prevent cross-transmission. After searches in Pubmed and clinicaltrials.gov, existing vaccines and vaccines under clinical development are presented in this narrative review. Issues associated with the use of vaccines to prevent HAIs are discussed. EXPERT COMMENTARY Future vaccines against HAIs will contribute to fight antibiotic resistance and thus reduce the burden of HAIs. At this stage, the goal of obtaining effective vaccines against S.aureus, C. difficile and gram-negative bacteria has not yet been achieved. Obtaining an efficient response to vaccines in at-risk patients for HAIs is also challenging, and future strategies of vaccination need to address this difficulty. The efficacy of vaccines for HCWs in reducing the spread of nosocomial outbreaks is counterbalanced by the lack of adherence to vaccine policies among HCWs. The acceptance of future vaccines to prevent carriage and infection with organisms involved in HAIs in HCWs will probably be a challenge.


title: Evolving Practice Patterns in Singapore's Public Sector Ophthalmology Centers During the COVID-19 Pandemic.

text: Coronavirus disease 19 (COVID-19) was first reported in Wuhan, China, in December 2019, and has since become a global pandemic. Singapore was one of the first countries outside of China to be affected and reported its first case in January 2020. Strategies that were deployed successfully during the 2003 outbreak of severe acute respiratory syndrome have had to evolve to contain this novel coronavirus. Like the rest of the health care services in Singapore, the practice of ophthalmology has also had to adapt to this rapidly changing crisis. This article discusses the measures put in place by the 3 largest ophthalmology centers in Singapore's public sector in response to COVID-19, and the challenges of providing eye care in the face of stringent infection control directives, staff redeployments and "social distancing." The recently imposed "circuit breaker," effectively a partial lockdown of the country, has further limited our work to only the most essential of services. Our staff are also increasingly part of frontline efforts in the screening and care of patients with COVID-19. However, this crisis has also been an opportunity to push ahead with innovative practices and given momentum to the use of teleophthalmology and other digital technologies. Amidst this uncertainty, our centers are already planning for how ophthalmology in Singapore will be practiced in this next stage of the COVID-19 pandemic, and beyond.


title: Laparoscopic sleeve gastrectomy for super obese patients: forty-eight percent excess weight loss after 6 to 8 years with 93% follow-up.

text: OBJECTIVES In this study, we report long-term outcomes of high-risk, high-BMI (body mass index) patients who underwent laparoscopic sleeve gastrectomy (LSG). BACKGROUND Short- and medium-term data appear to support the effectiveness of LSG, but long-term data to support its durability are sparse. METHODS A prospective database was reviewed on all high-risk patients who underwent LSG as part of a staged approach for surgical treatment of severe obesity between January 2002 and February 2004. We included only patients who did not proceed to second-stage surgery (gastric bypass). Analyzed data included demographics, BMI, comorbidities, and surgical outcomes. All partial gastrectomies were performed using a 50F bougie. RESULTS Seventy-four patients underwent LSG, and follow-up data were available on 69 of 74 patients (93%). The mean age was 50 years (25-78) and the mean number of co-morbidities was 9.6. Perioperative mortality (<30 days) was zero, and the incidence of short- and long-term postoperative complications was 15%. The mean overall follow-up time period was 73 months (38-95). Mean excess weight loss (EWL) at 72, 84, and 96 months after LSG was 52%, 43%, and 46%, respectively, with an overall EWL of 48%. The mean BMI decreased from 66 kg/m(2) (43-90) to 46 kg/m(2) (22-73). Seventy-seven percent of the diabetic patients showed improvement or remission of the disease. CONCLUSIONS This study reports the longest follow-up of LSG patients thus far and supports the effectiveness, safety, and durability of laparoscopic sleeve gastrectomy as a definitive therapeutic option for severe obesity, even in high-risk, high-BMI patients.


title: Visualisation of dual radiolabelled poly(lactide-co-glycolide) nanoparticle degradation in vivo using energy-discriminant SPECT.

text: The determination of nanoparticle (NP) stability and degradation in vivo is essential for the accurate evaluation of NP biodistribution in medical applications and for understanding their toxicological effects. Such determination is particularly challenging because NPs are extremely difficult to detect and quantify once distributed in a biological system. Radiolabelling with positron or gamma emitters and subsequent imaging studies using positron emission tomography (PET) or single-photon emission computerised tomography (SPECT) are some of the few valid alternatives. However, NPs that degrade or radionuclides that detach or are released from the NPs can cause artefact. Here, submicron-sized poly(lactide-co-glycolide) nanoparticles (PLGA-NPs) stabilised with bovine serum albumin (BSA) were dual radiolabelled using gamma emitters with different energy spectra incorporated into the core and coating. To label the core, 111In-doped iron oxide NPs were encapsulated inside PLGA-NPs during NP preparation, and the BSA coating was labelled by electrophilic substitution using 125I. After intravenous administration into rats, energy-discriminant SPECT resolved each radioisotope independently. Imaging revealed different fates for the core and coating, with a fraction of the two radionuclides co-localising in the liver and lungs for long periods of time after administration, suggesting that NPs are stable in these organs. Organ harvesting followed by gamma counting corroborated the SPECT results. The general methodology reported here represents an excellent alternative for visualising the degradation process of multi-labelled NPs in vivo and can be extended to a wide range of engineered NPs.


title: Single-port laparoscopic hepatectomy: technique, safety, and feasibility in a clinical case series.

text: BACKGROUND The recent use of single-port-access surgery in cholecystectomy and other abdominal surgeries has confirmed its safety and validity as a treatment option. However, few reports have described the use of complete single-port access surgeries in hepatectomy for neoplasms. METHODS The authors performed single-port laparoscopic hepatectomy (SLH) for eight patients (5 patients with hepatocellular carcinoma, 1 patient with metastatic liver tumor, 1 patient with endocrine liver tumor, and 1 patient with hemangioma). Furthermore, in terms of Child-Pugh classification, five patients were in category A, two in category B, and one in category C. The patients were eligible for SLH if they had solitary tumors measuring 3 cm or smaller on the caudal surface of the liver. The lesion was approached through a 20-mm supraumbilical incision using a single-port access device. RESULTS No patient experienced intraoperative complications that required additional port access and conversion to laparotomy. The operative time was 148 min (range, 141-235 min). The postoperative course of the patients was uneventful, and they were discharged an average of 6.2 days (range, 3-11 days) after the operation. Approximately 2 weeks after discharge, the patients experienced no wound pain or liver dysfunction. CONCLUSION The SLH technique is a safe and feasible procedure for a specific group of candidates, including patients with high-grade liver dysfunction.


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title: Thermal ablation of spinal osteoid osteomas close to neural elements: technical considerations.

text: OBJECTIVE The purpose of this study was to evaluate experience with and determine the efficacy and safety of thermal ablation in the management of spinal osteoid osteomas close to neural elements. MATERIALS AND METHODS The records of all patients with osteoid osteomas of the spine managed with thermal ablation at two academic centers from 1993 to 2008 were reviewed. RESULTS Seventeen patients (13 male patients, four female patients; mean age, 25.9 years) had lesions in the lumbar (seven patients), thoracic (six patients), cervical (three patients), and sacral (one patient) regions of the spine. Two lesions were in the vertebral body, one was within the dens, and the others were in the posterior elements. The mean lesion diameter was 8.8 mm, and the mean distance between the lesion and the closest neural element was 4.3 mm. The lesions were managed with laser (13 lesions) or radiofrequency (four lesions) ablation. Special thermal protection techniques involving the epidural injection of gas or cooled fluid were used. Pain levels were assessed immediately before the procedure and on the day after the procedure. Long-term follow-up findings were available for 11 patients. No complications were encountered, and all patients reported relief of pain. The 11 patients who participated in long-term follow-up reported continued relief of pain. CONCLUSION Percutaneous thermal ablation can be used to manage spinal osteoid osteomas close to the neural elements. Special thermal protection techniques may add a margin of safety.


Confronting the reality of COVID.


title: Etiological classification of depression based on the enzymes of tryptophan metabolism.

text: BACKGROUND Viewed in terms of input and output, the mechanisms of depression are still akin to a black box. However, there must be main pivots for diverse types of depression. From recent therapeutic observations, both the serotonin (5-HT) and kynurenine pathways of tryptophan metabolism may be of particular importance to improved understanding of depression. Here, I propose an etiological classification of depression, based on key peripheral and central enzymes of tryptophan metabolism. DISCUSSION Endogenous depression is caused by a larger genetic component than reactive depression. Besides enterochromaffin and mast cells, tryptophan hydroxylase 1 (TPH1), primarily expressed in the gastrointestinal tract, is also found in 5-hydroxytryptophan-producing cells (5-HTP cells) in normal intestinal enterocytes, which are thought to essentially shunt 5-HT production in 5-HT-producing cells. Genetic studies have reported an association between TPH1 and depression, or the responsiveness of depression to antidepressive medication. Therefore, it is possible that hypofunctional 5-HTP cells (reflecting TPH1 dysfunction) in the periphery lead to deficient brain 5-HT levels. Additionally,it has been reported that higher TPH2 expression in depressed suicides may reflect a homeostatic response to deficient 5-HT levels. Subsequently, endogenous depression may be caused by TPH1 dysfunction combined with compensatory TPH2 activation. Reactive depression results from life stresses and involves the hypothalamic-pituitary-adrenal axis, with resulting cortisol production inducing tryptophan 2,3-dioxygenase (TDO) activation. In secondary depression, caused by inflammation, infection, or oxidative stress, indoleamine 2,3-dioxygenase (IDO) is activated. In both reactive and secondary depression, the balance between 3-hydroxykynurenine (3-HK) and kynurenic acid may shift towards 3-HK production via kynurenine-3-monooxygenase (KMO) activation. By shifting the equilibrium position of key enzymes of tryptophan metabolism, the classical classification of depression can be reorganized, as below. Peripheral classification of depression by key enzymes: TPH1 dysfunction, TDO activation, IDO activation. Central classification: TPH2 activation, KMO activation. SUMMARY Etiological classification of depression expressed by peripheral (TPH1, TDO, IDO) and central (TPH2, KMO)enzymes of tryptophan metabolism may enable depression to be viewed as a clear box, with the inner components available for inspection and treatment.


title: Pediatric Life-Threatening Coronavirus Disease 2019 With Myocarditis.

text: We report the case of a pediatric life-threatening coronavirus disease 2019 who presented as myocarditis with heart failure. Clinicians should be aware of this severe presentation of the disease in children, possibly linked to an exaggerated inflammatory host immune response to severe acute respiratory syndrome coronavirus 2.


docid: gfizvpuu

title: Comparison of 2-Year Results of Roux-en-Y Gastric Bypass and Transit Bipartition with Sleeve Gastrectomy for Superobesity.

text: PURPOSE Although Roux-en-Y gastric bypass is a powerful procedure, achieving and maintaining significant weight loss remains challenging in superobese populations. Transit bipartition with sleeve gastrectomy is derived from biliopancreatic diversion with duodenal switch and might improve weight loss control. MATERIALS AND METHODS Two series of 71 primary laparoscopic Roux-en-Y gastric bypass (RYGB) and transit bipartition (TB) with a body mass index ≥ 50 kg/m2 were retrospectively compared after 2 years. Postoperative course, side effects, nutritional status, and weight outcomes were reviewed. Weight was expressed as BMI, percentage of excess BMI lost (%EBMIL), and percentage of total weight lost (%TWL). RESULTS The 2 groups were comparable for age and BMI of 51.9 ± 1.8 for RYGB and 51.6 ± 5 for TB. TB was longer to perform (92 vs 74 min, p ≤ 0.001) with a 30-day complication rate of 4.2% and 5.6%, but there was 1 death after RYGB. Weight loss was greater after TB compared with RYGB with %EBMIL of 85.3 ± 15.8% vs 73.9 ± 17.2% (p = 0.0002). One TB patient suffered from protein malnutrition but none after RYGB. After TB, 7% of the patients experienced > 3 stools a day and 1 patient required revision, while 3 patients had diarrhea after RYGB. Late reoperations were required for 7 and 1 patients after RYGB and TB. Comorbidity improvement was similar. CONCLUSION In a superobese population, TB appeared relatively safer compared with RYGB. It achieved a better weight loss at 2 years with a trend for more digestive side effects.


title: Outcomes of sleeve gastrectomy for morbid obesity: a safe and effective procedure?

text: BACKGROUND Sleeve gastrectomy is being performed with increasing frequency in Australia for the treatment of morbid obesity. The aims of this study were to show that sleeve gastrectomy can be performed safely with a low rate of complications and effective short to medium term weight loss. METHODS A retrospective review of prospectively collected data from a single surgeon series between 2006 and 2009. RESULTS A total of 185 patients were treated with laparoscopic sleeve gastrectomy (LSG) over a three-year period. The percentage excess weight loss (%EWL) was 47.2% at one year, 60.7% at two years and 66% at three years. There were no leaks; two staple line bleeds requiring reoperation via laparoscopy, one port site infection and one port site incisional hernia. There were no deaths. The average operating time was 111 min and the average hospital length of stay was 2.35 days. CONCLUSION Laparoscopic sleeve gastrectomy can be performed safely and with excellent weight loss. More long term follow up is required.


title: Effect of Aspiration Therapy on Obesity-Related Comorbidities: Systematic Review and Meta-Analysis.

text: Background/Aims Aspiration therapy (AT) involves endoscopic placement of a gastrostomy tube with an external device that allows patients to drain 30% of ingested calories after meals. Its efficacy for inducing weight loss has been shown. This study aimed to assess the effect of AT on obesity-related comorbidities. Methods A meta-analysis of studies that assessed AT outcomes was conducted through December 2018. Primary outcomes were changes in comorbidities at 1 year following AT. Secondary outcomes were the amount of weight loss at up to 4 years and pooled serious adverse events (SAEs). Results Five studies with 590 patients were included. At 1 year, there were improvements in metabolic conditions: mean difference (MD) in systolic blood pressure: -7.8 (-10.7 - -4.9) mm Hg; MD in diastolic blood pressure: -5.1 (-7.0 - 3.2) mm Hg; MD in triglycerides: -15.8 (-24.0 - -7.6) mg/dL; MD in high-density lipoprotein: 3.6 (0.7-6.6) mg/dL; MD in hemoglobin A1c (HbA1c): -1.3 (-1.8 - -0.8) %; MD in aspartate transaminase: -2.7 (-4.1 - -1.3) U/L; MD in alanine transaminase: -7.5 (-9.8 - -5.2) U/L. At 1 (n=218), 2 (n=125), 3 (n=46), and 4 (n=27) years, the patients experienced 17.8%, 18.3%, 19.1%, and 18.6% total weight loss (TWL), corresponding to 46.3%, 46.2%, 48.0%, and 48.7% excess weight loss (EWL) (p<0.0001 for all). Subgroup analysis of 2 randomized controlled trials (n=225) showed that AT patients lost more weight than did controls by 11.6 (6.5-16.7) %TWL and 25.6 (16.0-35.3) %EWL and experienced greater improvement in HbA1c and alanine transaminase by 1.3 (0.8-1.8) % and 9.0 (3.9-14.0) U/L. The pooled SAE rate was 4.1%. Conclusions Obesity-related comorbidities significantly improved at 1 year following AT. Additionally, a subgroup of patients who continued to use AT appeared to experience significant weight loss that persisted up to at least 4 years.


title: [Differences in the recognition of avian influenza risk between poultry farmers and the general population].

text: OBJECTIVES In this study, we aimed to compare the risk-recognition of avian influenza between poultry farmers and the general population. METHODS To obtain health-related data, including the participants' awareness of avian influenza, their recognition of potential infection, and their risk image, or their level of fear and understanding an anonymous self-reported questionnaire was administered. We measured the risk image on a 7-point scale, with 1 representing the lowest and 7 representing the highest risk image. Using their responses from 8 questions (4 per factor), We then calculated and averaged the scores to obtain the fear factor and unknown factor scores. RESULTS This questionnaire was completed by 310 of 1,000 (31.0%) members of the general population and 198 of 976 (20.3%) poultry farmers. The two groups differed significantly in terms of their overall awareness and understanding of severe acute respiratory syndrome (odds ratio=0.49 P=.003), with the general population scoring significantly lower than the poultry farmers. The risk image scores showed significant differences in fear factor (β=-0.89, P<.001) and unknown factor (β=0.74, P<.001), with the risk image for the fear factor being lower and that of the unknown factor being higher in the general population when compared with the poultry famers. CONCLUSION We found there to be a definite gap in the recognition of avian influenza between the two subject groups.


title: Persistent left sciatic artery eliminated need for revascularization in a 13-year-old with pseudoaneurysm of the superficial femoral artery.

text: Persistent sciatic artery (PSA) is an anatomical variation which is rare and most frequently diagnosed secondary to its clinical complications. The sciatic artery walls have a tendency to aneurysmal degeneration and may evolve to thrombosis or thromboembolism. This article reports the case of a 13-year-old male patient with left superficial femoral artery pseudoaneurysm after gunshot wound and complete PSA with in-line flow to the popliteal artery as incidental finding. The patient underwent coil embolization of the pseudoaneurysm with the sciatic artery left intact. The technical aspects are discussed and the literature on diagnosis and therapeutic approach of this anatomical variation is reviewed.


title: Teleneurology as a Solution for Outpatient Care During the COVID-19 Pandemic.

text: Background: The coronavirus disease of 2019 (COVID-19) pandemic and the need for social distancing have dramatically changed health care delivery. There is an urgent need to continue to deliver outpatient care for chronic neurological disease and teleneurology has the potential to fulfill this gap. Introduction: This study reports the implementation and utilization of teleneurology across all neurological subspecilities during the COVID-19 pandemic. Materials and Methods: This is a retrospective observational study that identified all in-person and teleneurology outpatient nonprocedural visits from January 5 to April 4, 2020, across neurological specialties at a single academic center. Visit volumes were assessed weekly and practice patterns were compared before and after March 15, 2020, as this was the date of a major statewide stay-at-home order in Ohio. Results: Before March 15 the mean in-person visit per week was 5129.4 and decreased to 866.7 after that date. The mean teleneurology visits per week increased from 209.1 to 2619.3 for the same time period. The overall teleneurology visit volume in the 3 weeks after March 15 increased by 533%. Discussion: In a relatively short time frame of 3 weeks, a single academic center was able to dramatically increase teleneurology visits to provide outpatient neurological care. Conclusions: This study demonostrates that teleneruology can be a solution for outpatient neurological care in the context of COVID-19. The increased utilization of teleneurology during this crisis has the potential to expand teleneurology and improve access to neurological care in the future outside the pandemic setting.


Advances in the methodology of co-ventilation during a disaster.


title: Developing policy options for SARS and SARS-like diseases - a Delphi study.

text: The objective of the SARSControl Delphi study was to develop options for national and international emerging infectious diseases policies. The aim of this paper is to present the results of the study, which gathered expert opinions on gaps and inconsistencies concerning preparedness and response planning for Severe Acute Respiratory Syndrome (SARS) and SARS-like diseases. The Delphi technique was employed, which comprised a pilot round, two written rounds and a face-to-face meeting. The Delphi panel consisted of 38 experts from 22 countries, who highlighted the necessity to test plans and stressed the importance of surveillance measures for the swift containment of communicable disease outbreaks and the inclusion of detailed triage plans in national pandemic plans. The experts also suggested a need to define criteria for testing pandemic preparedness plans at different regional levels. New policy alternatives were identified, such as the need for generic plans on pandemics and universal access to healthcare during an outbreak. The usefulness of some non-medical interventions, such as bans on travel, could not be established and need further research. Dissemination of the findings will help to bridge gaps and rectify inconsistencies in current pandemic planning and response strategies for SARS and SARS-like diseases, as well as add valuable knowledge towards the development of national and international emerging infectious disease policies.


title: Opioid and propofol pharmacodynamics modeling during brain mapping in awake craniotomy.

text: BACKGROUND Awake craniotomy (AC) is performed to identify cerebral language center. The challenge of anesthesia is to maintain a calm, comfortable, and cooperative patient during the mapping phase. Response surface models (RSMs) are multidrug modeling algorithms. In this pharmacodynamic study, we investigate the first use of RSM with bispectral index (BIS) to predict patient's response to name calling (RNC) and wakefulness (complete neurological tests) during AC. METHODS The study is performed in two phases. We prospectively enrolled 40 patients who received video-assisted thoracoscopic surgery (VATS) using propofol and fentanyl as the modeling group. Effect-site concentrations (Ce) and BIS values were recorded and a RSM is built from the data set. We verified the RSM retrospectively in AC patients, designated as the validation group. Corresponding BIS values were analyzed for RNC and wakefulness. RESULTS A total of 155 data sets of propofol Ce, fentanyl Ce, and BIS pairs were available for modeling. The range of propofol and fentanyl Ce were 0 to 9.95 μg/mL and 0 to 3.69 ng/mL, respectively. Observed BIS ranged from 21 to 98. The model identified an additive interaction between propofol and an opioid. RNC at BIS 64 is predicted by the model and 70 is required for wakefulness. CONCLUSION RSM built from VATS patients is verified with a separate group of AC patient. The BIS target advised for RSM-predicted wakefulness is 70. The model illustrates the timeline to wakefulness during AC under propofol and an opioid. It has implications in guiding, dosing, and estimation of time to wakefulness with propofol and an opioid.


How blood from coronavirus survivors might save lives.


title: A low-power bio-potential acquisition system with flexible PDMS dry electrodes for portable ubiquitous healthcare applications.

text: This work describes a bio-potential acquisition system for portable ubiquitous healthcare applications using flexible polydimethylsiloxane dry electrodes (FPDEs) and a low-power recording circuit. This novel FPDE used Au as the skin contact layer, which was made using a CO2 laser and replica method technology. The FPDE was revised from a commercial bio-potential electrode with a conductive snap using dry electrodes rather than wet electrodes that proposed reliable and robust attachment for the purpose of measurement, and attaching velcro made it wearable on the forearm for bio-potential applications. Furthermore, this study proposes a recording device to store bio-potential signal data and provides portability and low-power consumption for the proposed acquisition system. To acquire differential bio-potentials, such as electrocardiogram (ECG) signals, the proposed recording device includes a low-power front-end acquisition chip fabricated using a complementary metal-oxide-semiconductor (CMOS) process, a commercial microcontroller (MSP430F149), and a secure digital (SD) card for portable healthcare applications. The proposed system can obtain ECG signals efficiently and are comfortable to the skin. The power consumption of the system is about 85 mW for continuous working over a 3 day period with two AA batteries. It can also be used as a compact Holter ECG system.


title: Combinations of physical activity, sedentary time, and sleep duration and their associations with depressive symptoms and other mental health problems in children and adolescents: a systematic review.

text: BACKGROUND For optimal health benefits, the Canadian 24-Hour Movement Guidelines for Children and Youth (aged 5-17 years) recommend an achievement of high levels of physical activity (≥60 min of moderate-to-vigorous physical activity), low levels of sedentary behaviour (≤2 h of recreational screen time), and sufficient sleep (9-11 h for children or 8-10 h for adolescents) each day. The objective of this systematic review was to examine how combinations of physical activity, sedentary time, and sleep duration relate to depressive symptoms and other mental health indicators among children and adolescents. METHODS Literature was obtained through searching Medline, EMBASE, PsycINFO, and SportDiscus up to September 30, 2019. Peer-reviewed studies published in English or French were included if they met the following criteria: population (apparently healthy children and adolescents with a mean age of 5-17 years), intervention/exposure (combinations of physical activity, sedentary time, and sleep duration), and outcomes (depressive symptoms and other mental health indicators). A risk of bias assessment was completed for all included studies using the methods described in the Cochrane Handbook. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to assess the quality of evidence for each health indicator. Narrative syntheses were employed to describe the results due to high levels of heterogeneity across studies. RESULTS A total of 13 cross-sectional studies comprised in 10 papers met inclusion criteria. Data across studies involved 115,540 children and adolescents from 12 countries. Overall, the findings indicated favourable associations between meeting all 3 recommendations and better mental health indicators among children and adolescents when compared with meeting none of the recommendations. There was evidence of a dose-response gradient between an increasing number of recommendations met and better mental health indicators. Meeting the screen time and sleep duration recommendations appeared to be associated with more mental health benefits than meeting the physical activity recommendation. The quality of evidence reviewed was "very low" according to GRADE. CONCLUSIONS The findings indicate favourable associations between meeting all 3 movement behaviour recommendations in the 24-h guidelines and better mental health indicators among children and adolescents. There is a clear need for high-quality studies that use robust measures of all movement behaviours and validated measures of mental health to increase our understanding in this topic area.


title: Laparoscopic splenectomy for hereditary spherocytosis-preliminary report.

text: Splenectomy is considered standard surgical therapy in hereditary spherocytosis. The procedure is indicated in patients with severe anemia, recurrent hemolytic, and aplastic crises. The aim of the study was to assess treatment outcomes in patients with hereditary spherocytosis who underwent total or partial laparoscopic splenectomy. Fifteen patients aged 4-17 yr underwent laparoscopic splenectomy from 2009 to 2012. Partial and total splenectomies were performed (five and 10 children, respectively). Hematologic parameters, liver function tests, and splenic volume before and after the surgery were analyzed retrospectively. Total follow-up was 1-30 months. Hospitalization and operating time were similar in both groups. In partial splenectomy group, branches of splenic arteries gave better blood supply than short gastric vessels. In both groups, hematologic parameters were improved. Postoperative markedly elevated platelet count was maintained up to 6 months, and after that, platelet count gradually decreased to normal values. Bilirubin level was decreased in early postoperative period; however, it increased later to achieve levels lower than in preoperative period. No severe general infections were observed in both groups. Laboratory parameters (hemoglobin and bilirubin concentrations and RBC) after the surgery improved in all patients, and the effect was maintained during 12 months of follow-up. Platelet count increased significantly after the surgery and was maintained at high levels during the next 6 months. However, it returned to preoperative levels within a year after the surgery. Our study showed that partial splenectomy was not inferior to total splenectomy. However, full assessment requires longer follow-up and larger group of patients.


Nervous system: subclinical target of SARS-CoV-2 infection.


LAPAROSCOPIC SURGERY AND THE COVID-19 PANDEMIC: A WORD FROM A DIFFERENT HYMN SHEET.


title: Chinese herbs combined with Western medicine for severe acute respiratory syndrome (SARS).

text: BACKGROUND Severe acute respiratory syndrome (SARS) is an acute respiratory disease caused by a novel coronavirus, which first appeared in Foshan City, China on 22 December 2002. Chinese herbs were used in its treatment. OBJECTIVES To evaluate the possible effectiveness and safety of Chinese herbs combined with Western medicines versus Western medicines alone for SARS patients. SEARCH METHODS We searched CENTRAL 2012, Issue 3, MEDLINE (1966 to February Week 4, 2012), EMBASE (1990 to March 2012) and the Chinese Biomedical Literature (Issue 3, 2012). SELECTION CRITERIA Randomised controlled trials (RCTs) and quasi-RCTs of Chinese herbs combined with Western medicines versus Western medicines alone for patients diagnosed with SARS. DATA COLLECTION AND ANALYSIS Two review authors (XL, MZ) independently extracted trial data. We extracted dichotomous and continuous data with 95% confidence intervals (CI). For dichotomous data, we used risk ratio (RR). For continuous data, we calculated mean differences (MD). We calculated overall results based on the random-effects model if heterogeneity existed between studies. If no heterogeneity was detected between the studies, we used the fixed-effect model. We used the Z score and the Chi(2) test with significance being set at P < 0.05 to test heterogeneity. No severe adverse events were reported. MAIN RESULTS We included 12 RCTs and one quasi-RCT. A total of 640 SARS patients and 12 Chinese herbs were identified. We did not find Chinese herbs combined with Western medicines decreased mortality versus Western medicines alone. Two herbs may improve symptoms. Five herbs may improve lung infiltrate absorption. Four herbs may decrease the dosage of corticosteroids. Three herbs may improve the quality of life of SARS patients. One herb may shorten the length of hospital stay. AUTHORS' CONCLUSIONS Chinese herbs combined with Western medicines made no difference in decreasing mortality versus Western medicines alone. It is possible that Chinese herbs combined with Western medicines may improve symptoms, quality of life and absorption of pulmonary infiltration, and decrease the corticosteroid dosage for SARS patients. The evidence is weak because of the poor quality of the included trials. Long-term follow-up of these included trials is needed.


title: Inhibitors of SARS-3CLpro: virtual screening, biological evaluation, and molecular dynamics simulation studies.

text: SARS-CoV from the coronaviridae family has been identified as the etiological agent of Severe Acute Respiratory Syndrome (SARS), a highly contagious upper respiratory disease that reached epidemic status in 2002. SARS-3CL(pro), a cysteine protease indispensible to the viral life cycle, has been identified as one of the key therapeutic targets against SARS. A combined ligand and structure-based virtual screening was carried out against the Asinex Platinum collection. Multiple low micromolar inhibitors of the enzyme were identified through this search, one of which also showed activity against SARS-CoV in a whole cell CPE assay. Furthermore, multinanosecond explicit solvent simulations were carried out using the docking poses of the identified hits to study the overall stability of the binding site interactions as well as identify important changes in the interaction profile that were not apparent from the docking study. Cumulative analysis of the evaluated compounds and the simulation studies led to the identification of certain protein-ligand interaction patterns which would be useful in further structure based design efforts.


The Role of Scientific Publishing in the SARS-CoV-2 Pandemic.


title: Revised sleeve gastrectomy: another option for weight loss failure after sleeve gastrectomy.

text: INTRODUCTION Laparoscopic sleeve gastrectomy (LSG) is becoming a very common bariatric procedure, based on several advantages it carries over more complex bariatric procedures such as gastric bypass or duodenal switch (DS), and a better quality of life over gastric banding. However, in the long-term follow-up, weight loss failure and intractable severe reflux after primary LSG can necessitate further surgical interventions, and revisional sleeve gastrectomy (ReSG) can represent an option to correct these. METHODS From October 2008 to June 2013, 36 patients underwent an ReSG for progressive weight regain, insufficient weight, or severe gastroesophageal reflux in 'La Casamance' Private Hospital. All patients with weight loss failure after primary LSG underwent radiological evaluation. If Gastrografin swallow showed a huge unresected fundus or an upper gastric pouch dilatation, or if the computed tomography (CT) scan volumetry revealed a gastric tube superior to 250 cc, ReSG was proposed. RESULTS Thirty-six patients (34 women, two men; mean age 41.3 years) with a body mass index (BMI) of 39.9 underwent ReSG. Thirteen patients (36.1 %) had their original LSG surgery performed at another hospital and were referred to us for weight loss failure. Twenty-four patients (66.6 %) out of 36 had a history of gastric banding with weight loss failure. Thirteen patients (36.1 %) were super-obese (BMI > 50) before primary LSG. The LSG was realized for patients with morbid obesity with a mean BMI of 47.1 (range 35.4-77.9). The mean interval time from the primary LSG to ReSG was 34.5 months (range 9-67 months). The indication for ReSG was insufficient weight loss for 19 patients (52.8 %), weight regain for 15 patients (41.7 %), and 2 patients underwent ReSG for invalidating gastroesophageal reflux disease. In 24 cases the Gastrografin swallow results were interpreted as primary dilatation, and in the remaining 12 cases results were interpreted as secondary dilatation. The CT scan volumetry was realized in 21 cases, and it has revealed a mean gastric volume of 387.8 cc (range 275-555 cc). All 36 cases were completed by laparoscopy with no intraoperative incidents. The mean operative time was 43 min (range 29-70 min), and the mean hospital stay was 3.9 days (range 3-16 days). One perigastric hematoma was recorded. The mean BMI decreased to 29.2 (range 20.24-37.5); the mean percentage of excess weight loss was 58.5 % (±25.3) (p < 0.0004) for a mean follow-up of 20 months (range 6-56 months). CONCLUSIONS The ReSG may be a valid option for failure of primary LSG for both primary or secondary dilatation. Long-term results of ReSG are awaited to prove efficiency. Further prospective clinical trials are required to compare the outcomes of ReSG with those of Roux en Y Gastric Bypass or DS for weight loss failure after LSG.


title: The pathophysiology of acute pain: animal models.

text: PURPOSE OF REVIEW Trauma, surgery, and burns are three common clinical scenarios that are associated with significant acute pain. This review describes the pathophysiology of acute pain utilizing three preclinical models: surgery, burn, and fracture. RECENT FINDINGS In general, there is greater interest directed toward peripheral mediators of acute pain. Studies indicate that treatment against nerve growth factor, interleukins, and ischemic-like mediators may provide valuable avenues for treatment of acute pain. By targeting the periphery, analgesic therapies may have reduced side-effects. SUMMARY Peripheral mediators of acute pain can vary depending upon the type of injury. Treatment aimed toward those mediators specific to the injury may improve acute pain management in the future. It will be important to translate these findings into clinical trials in the future.


title: Click-chemistry-derived triazole ligands of arginine-glycine-aspartate (RGD) integrins with a broad capacity to inhibit adhesion of melanoma cells and both in vitro and in vivo angiogenesis.

text: A click chemistry approach was applied for the discovery of triazole-based arginine-glycine-aspartate (RGD) mimetics by Cu(I)-catalyzed 1,3-dipolar alkyne-azide coupling reaction, which showed binding affinity properties toward α(v)β(3)/α(v)β(5) integrins. Biological assays showed compound 18 capable of binding α(v)β(3) integrin with nanomolar affinity according to a two-sites model, and molecular modeling studies revealed a peculiar π-stacking interaction between the triazole ring and Tyr178 side chain. Accordingly, compound 18 inhibited the adhesion of integrin-expressing human melanoma cells to RGD-containing proteins of the extracellular matrix, such as vitronectin, fibronectin, and osteopontin, and also angiogenesis in in vitro and in vivo experimental models. The relevant biological effects exerted by compound 18 suggest its potential application as an antiangiogenic agent in the diagnosis and therapy of tumors where α(v)β(3) integrin expression is up-regulated.


title: Low concentration of heparin used for permanent catheters canal locking is effective and diminishes the risk of bleeding.

text: PURPOSE There is an increasing number of patients being dialyzed with permanent catheters (PC). In the majority of cases, heparin is used to maintain PC patency. This practice causes clotting disturbances due to heparin leakage and may predispose the patient to bleeding episodes. It has not been well studied whether lowering heparin concentration for canal locking decreases short-term bleeding complications after PC placement. METHODS This was a prospective single-center randomized open-label trial conducted in hemodialyzed patients undergoing PC insertion. Low concentration of heparin (LCH) 2,500 IU/ml versus high concentration of heparin (HCH) 5,000 IU/ml was randomly used for catheter lumens locking. The primary endpoint was the occurrence of bleeding within 24 h after catheter placement. The effects of clinical and laboratory data on bleeding events were analyzed as secondary endpoints. RESULTS Seventy-five patients (37 in LCH) were enrolled in the study. Only in the HCH group we found a significant prolongation of activated partial thromboplastin time (APTT) 2 h after PC placement (p < 0.001). There was a higher number of bleeding episodes in the HCH group (n = 16; 42.1%) than in the LCH group (n = 7; 18.9%) (χ(2) = 4.74; p = 0.029). In univariate analysis, assignment to HCH, baseline APTT, use of low molecular weight heparin, and femoral localization were associated with bleeding events. In multivariate analysis, the use of HCH (odds ratio [OR] 3.64; 95% confidence interval [95% CI] 1.10-12.05) and baseline APTT (OR 1.12; 95% CI 1.002-1.250) predicted bleeding after PC insertion. CONCLUSION LCH used for canals locking decreases bleeding events in the first 24 hours after permanent catheter placement, compared to HCH.


title: What factors explain the geographical range of mammalian parasites?

text: Free-living species vary substantially in the extent of their spatial distributions. However, distributions of parasitic species have not been comprehensively compared in this context. We investigated which factors most influence the geographical extent of mammal parasites. Using the Global Mammal Parasite Database we analysed 17 818 individual geospatial records on 1806 parasite species (encompassing viruses, bacteria, protozoa, arthropods and helminths) that infect 396 carnivore, ungulate and primate host species. As a measure of the geographical extent of each parasite species we quantified the number and area of world ecoregions occupied by each. To evaluate the importance of variables influencing the summed area of ecoregions occupied by a parasite species, we used Bayesian network analysis of a subset ( n = 866) of the parasites in our database that had at least two host species and complete information on parasite traits. We found that parasites that covered more geographical area had a greater number of host species, higher average phylogenetic relatedness between host species and more sampling effort. Host and parasite taxonomic groups had weak and indirect effects on parasite ecoregion area; parasite transmission mode had virtually no effect. Mechanistically, a greater number of host species probably increases both the collective abundance and habitat breadth of hosts, providing more opportunities for a parasite to have an expansive range. Furthermore, even though mammals are one of the best-studied animal classes, the ecoregion area occupied by their parasites is strongly sensitive to sampling effort, implying mammal parasites are undersampled. Overall, our results support that parasite geographical extent is largely controlled by host characteristics, many of which are subsumed within host taxonomic identity.


title: First outbreak with chimeric swine enteric coronavirus (SeCoV) on pig farms in Slovakia - lessons to learn.

text: This report describes the first disease outbreak caused by chimeric swine enteric coronavirus (SeCoV) on two pig farms in Slovakia in early 2015. The infection was introduced by import of two breeding boars which were placed in provisional quarantine in a unit not strictly separated from other healthy pigs in the same building. Subsequently, loss of appetite and diarrhoea were observed in both boars during the first three days in the isolation unit. The infection gradually spread to the farrowing area and throughout the farm in two weeks and later to another nearby farm. Yellow watery diarrhoea accompanied by dehydration and death was observed in piglets with a mortality ranging from 30 to 35%. In the absence of an available vaccine, the pregnant sows were dosed by mouth with a 10% suspension prepared from the intestine and faeces of infected piglets in warm water. Three weeks after dosing, new litters of piglets were born which remained healthy with no development of diarrhoea.


title: Long-term follow-up after robotic thymectomy for nonthymomatous myasthenia gravis.

text: BACKGROUND Thymectomy is recognized as a significant component in the treatment of myasthenia gravis. However, controversy exists as to the optimal surgical approach. This investigation summarizes our experience performing extended thymectomy using a robotic technique in a large group of patients with significant follow-up. METHODS Data collection for patients undergoing robotic thymectomy for nonthymomatous myasthenia gravis over a 6-year period was prospectively performed. Patients were assessed using the Myasthenia Gravis Foundation of America's quantitative disease severity score and the post intervention status classification. RESULTS During the study period, 75 patients underwent thymectomy by this method. Mean preoperative myasthenia gravis severity score was 2.7. Mean operative time was 113±46 minutes. Extubation in the operating room occurred in 73 (98%) patients. Mean intensive care stay and total hospital length of stay were 0.9 and 2.2 days respectively. Mean interval between surgery and return to work (or prethymectomy activities of daily living) was 15±6 days. Significant improvement of myasthenia gravis symptoms occurred in 65 (87%) patients with a mean follow-up of 45±14 months. CONCLUSIONS Robotic-assisted thymectomy is a safe and effective technique for patients with symptomatic myasthenia gravis. It allowed an extended thymectomy to be performed without the associated length of stay or recovery period of a transsternal approach while producing comparable rates of symptom improvement.


title: Defining human dendritic cell progenitors by multiparametric flow cytometry.

text: Human dendritic cells (DCs) develop from progressively restricted bone marrow (BM) progenitors: these progenitor cells include granulocyte, monocyte and DC progenitor (GMDP) cells; monocyte and DC progenitor (MDP) cells; and common DC progenitor (CDP) and DC precursor (pre-DC) cells. These four DC progenitors can be defined on the basis of the expression of surface markers such as CD34 and hematopoietin receptors. In this protocol, we describe five multiparametric flow cytometry panels that can be used as a tool (i) to simultaneously detect or phenotype the four DC progenitors, (ii) to isolate DC progenitors to enable in vitro differentiation or (iii) to assess the in vitro differentiation and proliferation of DC progenitors. The entire procedure from isolation of cells to flow cytometry can be completed in 3-7 h. This protocol provides optimized antibody panels, as well as gating strategies, for immunostaining of BM and cord blood specimens to study human DC hematopoiesis in health, disease and vaccine settings.


Don't rush to deploy COVID-19 vaccines and drugs without sufficient safety guarantees.


title: The effect of ambiguous data on phylogenetic estimates obtained by maximum likelihood and Bayesian inference.

text: Although an increasing number of phylogenetic data sets are incomplete, the effect of ambiguous data on phylogenetic accuracy is not well understood. We use 4-taxon simulations to study the effects of ambiguous data (i.e., missing characters or gaps) in maximum likelihood (ML) and Bayesian frameworks. By introducing ambiguous data in a way that removes confounding factors, we provide the first clear understanding of 1 mechanism by which ambiguous data can mislead phylogenetic analyses. We find that in both ML and Bayesian frameworks, among-site rate variation can interact with ambiguous data to produce misleading estimates of topology and branch lengths. Furthermore, within a Bayesian framework, priors on branch lengths and rate heterogeneity parameters can exacerbate the effects of ambiguous data, resulting in strongly misleading bipartition posterior probabilities. The magnitude and direction of the ambiguous data bias are a function of the number and taxonomic distribution of ambiguous characters, the strength of topological support, and whether or not the model is correctly specified. The results of this study have major implications for all analyses that rely on accurate estimates of topology or branch lengths, including divergence time estimation, ancestral state reconstruction, tree-dependent comparative methods, rate variation analysis, phylogenetic hypothesis testing, and phylogeographic analysis.


title: Hepatocyte spheroids as an alternative to single cells for transplantation after ex vivo gene therapy in mice and pig models.

text: BACKGROUND Autologous hepatocyte transplantation after ex vivo gene therapy is an alternative to liver transplantation for metabolic liver disease. Here we evaluate ex vivo gene therapy followed by transplantation of single-cell or spheroid hepatocytes. METHODS Pig and mouse hepatocytes were isolated, labeled with zirconium-89 and returned to the liver as single cells or spheroids. Biodistribution was evaluated through positron emission tomography-computed tomography. Fumarylacetoacetate hydrolase-deficient pig hepatocytes were isolated and transduced with a lentiviral vector containing the Fah gene. Animals received portal vein infusion of single-cell or spheroid autologous hepatocytes after ex vivo gene delivery. Portal pressures were measured and ultrasound was used to evaluate for thrombus. Differences in engraftment and expansion of ex vivo corrected single-cell or spheroid hepatocytes were followed through histologic analysis and animals' ability to thrive off 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione. RESULTS Positron emission tomography-computed tomography imaging showed spheroid hepatocytes with increased heterogeneity in biodistribution as compared with single cells, which spread more uniformly throughout the liver. Animals receiving spheroids experienced higher mean changes in portal pressure than animals receiving single cells (P < .01). Additionally, two animals from the spheroid group developed portal vein thrombi that required systemic anticoagulation. Immunohistochemical analysis of spheroid- and single-cell-transplanted animals showed similar engraftment and expansion rates of fumarylacetoacetate hydrolase-positive hepatocytes in the liver, correlating with similar weight stabilization curves. CONCLUSION Ex vivo gene correction of autologous hepatocytes in fumarylacetoacetate hydrolase-deficient pigs can be performed using hepatocyte spheroids or single-cell hepatocytes, with spheroids showing a more heterogeneous distribution within the liver and higher risks for portal vein thrombosis and increased portal pressures.


title: Epigenetic Dysregulation in Virus-Associated Neoplasms.

text: The oncoproteins of human tumor viruses regularly interact with the cellular epigenetic machinery. Such interactions alter the epigenome of the host cell and reprogram its gene expression pattern. Altered levels or redistribution of (cytosine-5)-DNA methyltransferases and changes in the cellular methylome were observed in Kaposi sarcoma-associated herpesvirus (KSHV), hepatitis B virus (HBV), hepatitis D virus (HDV), hepatitis C virus (HCV), and human papillomavirus (HPV) associated neoplasms and cell lines. Methylation-mediated silencing of cellular promoters was also noted in Merkel cell polyomavirus (MCPyV) positive Merkel cell carcinomas, and, as discussed elsewhere, in EBV-associated malignancies and adenovirus-induced rodent tumors as well. Promoter activation also occurred, either associated with DNA hypomethylation or with the induction of euchromatic histone modifications by viral oncoproteins. It is worthy to notice that HCV infection induced large, hypomethylated blocks of cellular chromatin, although the exact molecular mechanism remains to be elucidated. In hepatoma cells expressing HBx, the oncoprotein encoded by the HBV genome, demethylation of the repetitive satellite 2 sequences was observed, due to downregulation of the de novo DNA methyltransferase DNMT3B. Tax and HBZ, the oncoproteins of human T-cell lymphotropic virus type I (HTLV-I), can both activate and silence distinct cellular promoters by interacting with cellular enzymes involved in histone modification.


title: The role of thrombolysis in the clinical management of deep vein thrombosis.

text: The cornerstones of current management of deep vein thrombosis (DVT) are the routine use of anticoagulant therapy, graduated elastic compression stockings, and early ambulation. Thrombolytic therapy was previously reserved only for patients with life-, limb-, or organ-threatening complications. However, the postthrombotic syndrome has been increasingly recognized as a frequent and serious long-term complication of DVT. In parallel, endovascular thrombolytic methods have evolved considerably in recent years, prompting discussion and controversy as to whether they should be more liberally used. In some centers, pharmacomechanical catheter-directed thrombolysis is now routinely used in the treatment of acute iliofemoral DVT. Randomized trials are currently under way to determine when the use of pharmacomechanical catheter-directed thrombolysis is appropriate in patients presenting with acute proximal DVT.


docid: tpbljcxi

title: Anosmia in COVID-19 Associated with Injury to the Olfactory Bulbs Evident on MRI.

text: Patients with coronavirus disease 2019 (COVID-19) may have symptoms of anosmia or partial loss of the sense of smell, often accompanied by changes in taste. We report 5 cases (3 with anosmia) of adult patients with COVID-19 in whom injury to the olfactory bulbs was interpreted as microbleeding or abnormal enhancement on MR imaging. The patients had persistent headache (n = 4) or motor deficits (n = 1). This olfactory bulb injury may be the mechanism by which the Severe Acute Respiratory Syndrome coronavirus 2 causes olfactory dysfunction.


title: Expanding laparoscopic cholecystectomy to rural Mongolia.

text: BACKGROUND Although laparoscopic cholecystectomy was first introduced in Mongolia in 1994, the benefits of the laparoscopic approach have been largely unavailable to the majority of the population. The burden of gallbladder disease in Mongolia is significant. Despite the barriers to expanding laparoscopic surgery in Mongolia (lack of physical resources and adequate training opportunities, a difficult political situation, and an austere environment), the Health Sciences University of Mongolia (HSUM) began looking for ways to further the development of laparoscopy for the entire country, including the rural areas where half the population resides. METHODS Combined didactic and practical training courses lasting 2 weeks were developed collaboratively by a private nongovernmental organization and HSUM. The courses were taught at tertiary care centers in the capital city (Ulaanbaatar) and in a smaller, rural city (Erdenet), the regional northern referral center. Demographic data, preoperative diagnosis, ultrasound and operative findings, operative times, length of hospital stay, and intraoperative and postoperative complication rates were compared from 2007-2008 from hospitals in Ulaanbaatar and Erdenet. RESULTS A total of 36 surgeons participated in the training classes, and a total of 410 laparoscopic cholecystectomies were performed. Ultrasound was used as a diagnostic tool in all cases. There was no significant difference in intraoperative or postoperative complications between hospitals in the capital, where the procedures were performed by skilled laparoscopic surgeons, and in Erdenet, where the training courses first introduced laparoscopic cholecystectomy. Neither were there differences in complication rates between cases during the teaching and nonteaching periods. CONCLUSIONS Laparoscopic cholecystectomy can be expanded safely to the regional diagnostic referral centers in rural Mongolia through short-term training courses as a method to markedly improve access and outcomes for the 50% of the country previously denied the benefits of minimally invasive surgery.


docid: rluohllf

title: SARS-COV-2 in Ophthalmology: Current Evidence and Standards for Clinical Practice.

text: INTRODUCTION COVID-19 is caused by the coronavirus SARS-CoV-2. Ocular manifestations have been reported including conjunctivitis and retinal changes. Therefore, it is of the utmost importance to clarify eye involvement in COVID-19 in order to help with its diagnosis and to further prevent its transmission. The purpose of this review is to describe the structure and transmission of SARS-CoV-2, reported ocular findings and protection strategies for ophthalmologists. MATERIAL AND METHODS Literature search on PubMed for relevant articles using the keywords 'COVID-19', 'coronavirus', and 'SARS-CoV-2' in conjunction with 'ophthalmology' and 'eye'. Moreover, official recommendations of ophthalmological societies were reviewed. RESULTS Although the conjunctiva is directly exposed to extraocular pathogens, and the mucosa of the ocular surface and upper respiratory tract are connected by the nasolacrimal duct, the eye is rarely involved in human SARS-CoV-2 infection and the SARS-CoV-2 RNA positive rate by RT-PCR test in tears and conjunctival secretions from patients with COVID-19 is also extremely low. DISCUSSION The eye can be affected by SARS-CoV-2, which is supported by some reports of conjunctivitis and retinal changes, but its role in the spread of the disease is still unknown. CONCLUSION Given the current scarce evidence, more research is needed to clarify the relationship between SARS-CoV-2 and the eye.


docid: jlmtzadb

title: Hemodialysis tunneled central venous catheters: five-year outcome analysis.

text: BACKGROUND Tunneled central venous catheters (tCVCs) are considered inferior to arteriovenous fistulas (AVFs) and grafts in all nephrology guidelines. However, they are being increasingly used as hemodialysis vascular access. The purpose of this study was to document the natural history of tCVCs and determine the rate and type of catheter replacement. METHODS This was a prospective study of 141 patients who underwent hemodialysis with tCVCs between January 2008 and December 2012. The patients used 154 tCVCs. Standard protocols about management of tCVCs, according to European Renal Best Practice, were well established. All catheters were inserted in the internal jugular vein. Criteria for catheter removal were persistent bloodstream infection, detection of an outbreak of catheter-related bloodstream (CRBS) infections, or catheter dysfunction. Event rates were calculated per 1,000 catheter days; tCVC cumulative survival was estimated by Kaplan-Meier analysis. RESULTS Catheter replacement occurred in 15 patients (0.29 per 1,000 days); catheter dysfunction was the main cause of replacement (0.18 per 1,000 days), typically within 12 months of surgical insertion. A total of 53 CRBS events in 36 patients were identified (0.82 per 1,000 days); 17 organisms, most commonly Gram-positive pathogens, were isolated; 87% of CVC infections were treated by systemic antibiotics associated with lock therapy. tCVC cumulative survival was 91% at 1 year, 88% at 2 years and 85% at 4 years. CONCLUSIONS Our data show a high survival rate of tCVCs in hemodialysis patients, with low incidence of catheter dysfunction and CRBS events. These data justify tCVC use for hemodialysis vascular access, also as first choice, especially in patients with exhausted peripheral access and limited life expectancy.


title: The bumper technique for advancing a large profile microcatheter.

text: Operators commonly encounter difficulty maneuvering a microcatheter beyond the distal lip of wide neck aneurysms and aneurysms in challenging locations. Few techniques have been described to guide operators in these particular situations. In this case report of a 56-year-old woman with a 16 mm ophthalmic artery aneurysm, the microcatheter continually snagged the distal aneurysm lip, preventing delivery of a flow diverter into the distal parent vessel. In troubleshooting this obstacle, a second microguidewire was introduced alongside the microcatheter and was used to cover the distal lip of the aneurysm to prevent further snagging. The second guidewire successfully deflected the microcatheter into the distal vessel, a technique that we have aptly dubbed the 'bumper technique'.


title: Geriatric units at the beginning of the 2020 COVID-19 epidemic in France.

text: The COVID-19 epidemic that started in November in China became a national epidemic from March 16, 2020 with the declaration of population containment in order to reduce the spread of the virus in France. From March 17 to March 27, 2020, the monitoring unit of the French society of geriatrics and gerontology decided to conduct a survey to analyze the implementation of the mobilization of geriatric units, given that this epidemic had shown that it resulted in excess mortality mainly among the elderly. The survey was able to bring together the response of 34 services, nine of which were located in a high epidemic cluster zone. Dedicated acute geriatric units for patients infected with COVID-19 were present in eight facilities, only outside the cluster zones. Nine geriatric follow-up and rehabilitation services were dedicated, an additional telemedicine activity concerned 35% of the facilities, and family listening and tablet communication facilities concerned 36% of the facilities. This survey is a snapshot of an initial moment in the epidemic. It provides an opportunity to describe the context in which this epidemic occurred in terms of geriatric policy, and to assess the responsiveness and inventiveness of these services in meeting the needs of the elderly.


IST-3 stroke trial data available.


title: Interleukin-10 Modulation of Virus Clearance and Disease in Mice with Alphaviral Encephalomyelitis.

text: Alphaviruses are an important cause of mosquito-borne outbreaks of arthritis, rash, and encephalomyelitis. Previous studies in mice with a virulent strain (neuroadapted SINV [NSV]) of the alphavirus Sindbis virus (SINV) identified a role for Th17 cells and regulation by interleukin-10 (IL-10) in the pathogenesis of fatal encephalomyelitis (K. A. Kulcsar, V. K. Baxter, I. P. Greene, and D. E. Griffin, Proc Natl Acad Sci U S A 111:16053-16058, 2014, https://doi.org/10.1073/pnas.1418966111). To determine the role of virus virulence in generation of immune responses, we analyzed the modulatory effects of IL-10 on disease severity, virus clearance, and the CD4+ T cell response to infection with a recombinant strain of SINV of intermediate virulence (TE12). The absence of IL-10 during TE12 infection led to longer morbidity, more weight loss, higher mortality, and slower viral clearance than in wild-type mice. More severe disease and impaired virus clearance in IL-10-/- mice were associated with more Th1 cells, fewer Th2 cells, innate lymphoid type 2 cells, regulatory cells, and B cells, and delayed production of antiviral antibody in the central nervous system (CNS) without an effect on Th17 cells. Therefore, IL-10 deficiency led to more severe disease in TE12-infected mice by increasing Th1 cells and by hampering development of the local B cell responses necessary for rapid production of antiviral antibody and virus clearance from the CNS. In addition, the shift from Th17 to Th1 responses with decreased virus virulence indicates that the effects of IL-10 deficiency on immunopathologic responses in the CNS during alphavirus infection are influenced by virus strain.IMPORTANCE Alphaviruses cause mosquito-borne outbreaks of encephalomyelitis, but determinants of outcome are incompletely understood. We analyzed the effects of the anti-inflammatory cytokine IL-10 on disease severity and virus clearance after infection with an alphavirus strain of intermediate virulence. The absence of IL-10 led to longer illness, more weight loss, more death, and slower viral clearance than in mice that produced IL-10. IL-10 influenced development of disease-causing T cells and entry into the brain of B cells producing antiviral antibody. The Th1 pathogenic cell subtype that developed in IL-10-deficient mice infected with a less virulent virus was distinct from the Th17 subtype that developed in response to a more virulent virus, indicating a role for virus strain in determining the immune response. Slow production of antibody in the nervous system led to delayed virus clearance. Therefore, both the virus strain and the host response to infection are important determinants of outcome.


Covid-19: transforming healthcare will require collaboration and innovative policies.


title: Experience with thoracoscopic tracheal surgery in infants and children.

text: PURPOSE Complex thoracoscopic procedures in infants and children, such as tracheoesophageal fistula (TEF) repair and lung resection, have already been shown to be safe and efficacious in infants and children. This study evaluated the application of thoracoscopic techniques in more complex, unusual tracheal anomalies. METHODS From January 2002 to October 2008, 9 patients with more rare anatomic tracheal anomalies, between the thoracic inlet and the carina, were treated by thoracoscopy. Ages ranged from 5 months to 8 years and weights ranged from 5.4 to 8 years and from 5.9 to 42 kg. Pathology included 3 H-type TEFs, 2 recurrent TEFs following previous open repair of an esophageal atresia with fistula, resection of a giant tracheal pouch, and 3 tracheobronchi with associated abnormal lung parenchyma. RESULTS All procedures were successfully completed thoracoscopically. Operative times ranged from 60 to 130 minutes. Procedures included division and closure of the 3 H-type fistulas and 2 recurrent fistulas, resection of the tracheal pouch, 2 upper lobectomies, and resection of an aberrant upper lobe segment by segmentectomy. There were no operative or postoperative complications. Chest tubes were left in for an average of 1 day, and hospital stay averaged 2.2 days. CONCLUSIONS Thoracoscopy provides an excellent technique for approaching tracheal pathology from the level of the thoracic inlet to the carina. A thoracoscopic approach avoids the morbidity of a major thoracotomy and virigule or a major neck exploration while providing greater exposure, especially in the upper thorax.


title: Web Exclusive. Annals Graphic Medicine - Progress Notes: The Fog of COVID.

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title: Analysis of inter-system variability of systolic and diastolic intraventricular pressure gradients derived from color Doppler M-mode echocardiography.

text: Assessment of intraventricular pressure gradients (IVPG) using color Doppler M-mode echocardiography has gained increasing interest in the evaluation of cardiac function. However, standardized analysis tools for IVPG quantification are missing. We aimed to evaluate the feasibility, the test-retest observer reproducibility, and the inter-system variability of a semi-automated IVPG quantification algorithm. The study included forty healthy volunteers (50% were men). All volunteers were examined using two ultrasound systems, the Philips Epiq 7 and the General Electric Vivid 6. Left ventricular diastolic (DIVPG) and systolic (SIVPG) intraventricular pressure gradients were measured from the spatiotemporal distribution of intraventricular propagation flow velocities using color Doppler M-mode in standard apical views. There was good feasibility for both systolic and diastolic IVPG measurements (82.5% and 85%, respectively). Intra and inter-observer test-retest variability measured with the intraclass correlation coefficient were 0.98 and 0.93 for DIVPG respectively, and 0.95 and 0.89 for SIVPG respectively. The inter-system concordance was weak to moderate with Lin's concordance correlation coefficient of 0.59 for DIVPG and 0.25 for SIVPG. In conclusion, it is feasible and reproducible to assess systolic and diastolic IVPG using color Doppler M-mode in healthy volunteers. However, the inter-system variability in IVPG analysis needs to be taken into account, especially when using displayed data.


title: Concealment of Potential Exposure to COVID-19 and Its Impact on Outbreak Control: Lessons from the HIV Response.

text: Globally, more than 4 million people have been infected with COVID-19, and more than 300,000 deaths have been reported across 188 countries. Concealment of one's potential exposure to the virus has negative implications for the spread of COVID-19 across the socio-ecological spectrum, including the futility of contact-tracing efforts, exposure of frontline staff, and the spread of COVID-19 in the community. We draw lessons learned from HIV to discuss stigma and the attribution of blame surrounding the phenomenon of concealment of one's potential exposure to COVID-19 using a socio-ecological perspective. This article also illustrates the psychosocial aspect of the disease, and the negative repercussions of concealment of potential exposure on transmission in the community and to front-liners, healthcare resources, and outbreak containment.


The epic battle against coronavirus misinformation and conspiracy theories.


title: Evaluation of 177Lu-DOTA-sst2 antagonist versus 177Lu-DOTA-sst2 agonist binding in human cancers in vitro.

text: UNLABELLED Somatostatin receptor targeting of neuroendocrine tumors using radiolabeled somatostatin agonists is today an established method to image and treat cancer patients. However, in a study using an animal tumor model, somatostatin receptor antagonists were shown to label sst(2)- and sst(3)-expressing tumors in vivo better than agonists, with comparable affinity even though they are not internalized into the tumor cell. In the present study, we evaluated the in vitro binding of the antagonist (177)Lu-DOTA-pNO(2)-Phe-c (DCys-Tyr-DTrp-Lys-Thr-Cys) DTyrNH(2) ((177)Lu-DOTA-BASS) or the (177)Lu-DOTATATE agonist to sst(2)-expressing human tumor samples. METHODS Forty-eight sst(2)-positive human tumor tissue samples (9 ileal carcinoids, 10 pheochromocytomas, 7 breast carcinomas, 10 renal cell carcinomas, and 12 non-Hodgkin lymphomas) were analyzed by in vitro receptor autoradiography for the expression of sst(2), comparing the binding capacity of (177)Lu-DOTA-BASS and (177)Lu-DOTATATE in successive tissue sections. The autoradiograms were quantitated using an electronic autoradiography detection system. RESULTS In all cases, the radiolabeled antagonist bound to more receptor sites than did the agonist. The mean ratios of the antagonist (177)Lu-DOTA-BASS to the agonist (177)Lu-DOTATATE were 4.2 ± 0.5 in the 9 ileal carcinoids, 12 ± 3 in the 10 pheochromocytomas, 11 ± 4 in the 7 breast carcinomas, 5.1 ± 0.6 in the 10 renal cell carcinomas, and 4.8 ± 0.7 in the 12 non-Hodgkin lymphomas. CONCLUSION The present in vitro human data, together with previous in vivo animal tumor data, are strong arguments indicating that sst(2) antagonists may be worth testing in vivo in patients in a wide range of tumors including nonneuroendocrine tumors.


title: Results of laparoscopic repair of primary and recurrent incisional hernias at a single UK institution.

text: In this study incisional hernia repairs at a single UK institution between 1994 and 2008 were analyzed with respect to short-term and long-term results. Prospectively collected data were analyzed retrospectively to ascertain outcomes, complications, and recurrences. Two hundred and twenty-seven operations were performed with 35% of the operations being for recurrent hernias. A self-centering suture technique was used. Median operating time was 55 minutes. There were 8 conversions and median hospital stay was 1 night. There were 52 complications (23%) including 3 postoperative bleeds, 3 mesh infections, and 4 small bowel obstructions. Median postoperative follow-up was 53 months. There were 25 recurrences (11%) being detected, a median of 17 months after initial operation. In this large series, laparoscopic incisional hernia repair is safe and is associated with a short hospital stay. Recurrences after repair remain a concern prompting the development of strategies to try and minimize the likelihood of this occurring.


title: Retained Wireless Capsule Endoscope in a Girl with suspected Crohn's Disease.

text: Wireless capsule endoscopy (WCE) is one of the great milestones in the field of gastroenterology. It is versatile in image acquisition, painless and can reach parts of the small bowel not amenable to conventional endoscopy. The commonest complication with WCE is retention of the capsule. We report a case of retained capsule in a child who was being investigated for obscure gastrointestinal bleeding (OGIB). Operative intervention was required for its retrieval after two weeks of expectant management.


title: Suppression of somatosensory stimuli during motor planning may explain levels of balance and mobility after stroke.

text: The ability to actively suppress, or gate, irrelevant sensory information is required for safe and efficient walking in sensory-rich environments. Both motor attention and motor planning alter somatosensory evoked potentials (SEPs) in healthy adults. This study's aim was to examine the effect of motor attention on processing of irrelevant somatosensory information during plantar flexion motor planning after stroke. Thirteen healthy older adults and 11 individuals with stroke participated. Irrelevant tibial nerve stimulation was delivered while SEPs were recorded over Cz, overlaying the leg portion of the sensorimotor cortex at the vertex of the head. Three conditions were tested in both legs: (1) Rest, (2) Attend To, and (3) Attend Away from the stimulated limb. In conditions 2 and 3, relevant vibration cued voluntary plantar flexion movements of the stimulated (Attend To) or non-stimulated (Attend Away) leg. SEP amplitudes were averaged during motor planning per condition. Individuals with stroke did not show attention-mediated gating of the N40 component associated with irrelevant somatosensory information during motor planning. It may be that dysfunction in pathways connecting to area 3b explains the lack of attention-mediated gating of the N40. Also, attention-mediated gating during motor planning explained significant and unique variance in a measure of community balance and mobility combined with response time. Thus, the ability to gate irrelevant somatosensory information appears important for stepping in both older adults and after stroke. Our data suggest that therapies that direct motor attention could positively impact walking after stroke.


NO SIGNIFICANT EFFECT OF COVID-19 ON IMMUNOLOGICAL AND VIROLOGICAL PARAMETERS IN PATIENTS WITH HIV-1 INFECTION.


title: Assisted mechanical ventilation: the future is now!

text: Assisted ventilation is a highly complex process that requires an intimate interaction between the ventilator and the patient. The complexity of this form of ventilation is frequently underappreciated by the bedside clinician. In assisted mechanical ventilation, regardless of the specific mode, the ventilator's gas delivery pattern and the patient's breathing pattern must match near perfectly or asynchrony between the patient and the ventilator occurs. Asynchrony can be categorized into four general types: flow asynchrony; trigger asynchrony; cycle asynchrony; and mode asynchrony. In an article recently published in BMC Anesthesiology, Hodane et al. have demonstrated reduced asynchrony during assisted ventilation with Neurally Adjusted Ventilatory Assist (NAVA) as compared to pressure support ventilation (PSV). These findings add to the growing volume of data indicating that modes of ventilation that provide proportional assistance to ventilation - e.g., NAVA and Proportional Assist Ventilation (PAV) - markedly reduce asynchrony. As it becomes more accepted that the respiratory center of the patient in most circumstances is the most appropriate determinant of ventilatory pattern and as the negative outcome effects of patient-ventilator asynchrony become ever more recognized, we can expect NAVA and PAV to become the preferred modes of assisted ventilation!


title: Recombinant Chimpanzee Adenovirus Vaccine AdC7-M/E Protects against Zika Virus Infection and Testis Damage.

text: The recent outbreak of Zika virus (ZIKV) has emerged as a global health concern. ZIKV can persist in human semen and be transmitted by sexual contact, as well as by mosquitoes, as seen for classical arboviruses. We along with others have previously demonstrated that ZIKV infection leads to testis damage and infertility in mouse models. So far, no prophylactics or therapeutics are available; therefore, vaccine development is urgently demanded. Recombinant chimpanzee adenovirus has been explored as the preferred vaccine vector for many pathogens due to the low preexisting immunity against the vector among the human population. Here, we developed a ZIKV vaccine based on recombinant chimpanzee adenovirus type 7 (AdC7) expressing ZIKV M/E glycoproteins. A single vaccination of AdC7-M/E was sufficient to elicit potent neutralizing antibodies and protective immunity against ZIKV in both immunocompetent and immunodeficient mice. Moreover, vaccinated mice rapidly developed neutralizing antibody with high titers within 1 week postvaccination, and the elicited antiserum could cross-neutralize heterologous ZIKV strains. Additionally, ZIKV M- and E-specific T cell responses were robustly induced by AdC7-M/E. Moreover, one-dose inoculation of AdC7-M/E conferred mouse sterilizing immunity to eliminate viremia and viral burden in tissues against ZIKV challenge. Further investigations showed that vaccination with AdC7-M/E completely protected against ZIKV-induced testicular damage. These data demonstrate that AdC7-M/E is highly effective and represents a promising vaccine candidate for ZIKV control.IMPORTANCE Zika virus (ZIKV) is a pathogenic flavivirus that causes severe clinical consequences, including congenital malformations in fetuses and Guillain-Barré syndrome in adults. Vaccine development is a high priority for ZIKV control. In this study, to avoid preexisting anti-vector immunity in humans, a rare serotype chimpanzee adenovirus (AdC7) expressing the ZIKV M/E glycoproteins was used for ZIKV vaccine development. Impressively, AdC7-M/E exhibited exceptional performance as a ZIKV vaccine, as follows: (i) protective efficacy by a single vaccination, (ii) rapid development of a robust humoral response, (iii) durable immune responses, (iv) robust T cell responses, and (v) sterilizing immunity achieved by a single vaccination. These advantages of AdC7-M/E strongly support its potential application as a promising ZIKV vaccine in the clinic.


title: Inequalities and identity processes in crises: Recommendations for facilitating safe response to the COVID-19 pandemic.

text: Structural inequalities and identity processes are pivotal to understanding public response to COVID-19. We discuss how identity processes can be used to promote community-level support, safe normative behaviour, and increase compliance with guidance. However, we caution how government failure to account for structural inequalities can alienate vulnerable groups, inhibit groups from being able to follow guidance, and lead to the creation of new groups in response to illegitimate treatment. Moreover, we look ahead to the longitudinal impacts of inequalities during pandemics and advise government bodies should address identity-based inequalities to mitigate negative relations with the public and subsequent collective protest.


title: A prospective randomized comparison of traditional laparoendoscopic single-site surgery with needlescopic-assisted laparoscopic nephrectomy in the porcine model.

text: BACKGROUND AND PURPOSE Laparoendoscopic single-site (LESS) surgery produces virtually no scar but is technically challenging because of the loss of triangulation. The objective of this study is to compare classic transumbilical LESS nephrectomy with needlescopic-assisted laparoscopy (NAL) surgery. In doing so, we evaluated whether the addition of a single 2-mm subcostal port could restore triangulation while not jeopardizing recovery or cosmetic outcome in the porcine model. MATERIALS AND METHODS Ten female farm pigs were randomized to laparoscopic nephrectomy with either LESS or NAL. In LESS, a TriPort was placed through a single 2.5-cm umbilical incision. In NAL, 5- and 10-mm ports were placed in the umbilicus and a 2-mm port was placed in the midclavicular line. Preoperative, perioperative, and postoperative parameters were compared. Variables were analyzed with the Wilcoxon signed-rank test and two-tailed Fisher exact test. Cosmesis was evaluated objectively using the Vancouver Scar Scale and subjectively by a blinded dermatologist. A cost analysis was performed. RESULTS Estimated blood loss was minimal in both groups (28.8 mL in LESS and 9.4 mL in NAL). Operative time was significantly shorter in NAL (103 vs 150 min; P<0.001). There was no difference in complications (2 vs 1; P=0.500), objective cosmesis (3.9 vs 3.8; P>0.2), or subjective cosmesis (2 vs 3; P=0.500). The NAL protocol had significantly lower disposable equipment costs ($363 vs $1696). CONCLUSIONS The addition of a 2-mm subcostal port and the restoration of triangulation in the NAL protocol enable shorter operative times, increased surgeon comfort, improved technical ease, and lower costs while maintaining the scarless cosmesis of the traditional LESS protocol.


Recognition for contributions to feline infectious disease research.


title: Closed-loop fluid resuscitation: robustness against weight and cardiac contractility variations.

text: BACKGROUND Surgical patients present with a wide variety of body sizes and blood volumes, have large differences in baseline volume status, and may exhibit significant differences in cardiac function. Any closed-loop fluid administration system must be robust against these differences. In the current study, we tested the stability and robustness of the closed-loop fluid administration system against the confounders of body size, starting volume status, and cardiac contractility using control engineering methodology. METHODS Using an independently developed previously published hemodynamic simulation model that includes blood volumes and cardiac contractility, we ran a Monte-Carlo simulation series with variation in starting blood volume and body weight (phase 1, weight 35-100 kg), and starting blood volume and cardiac contractility (phase 2, contractility from 1500 [severe heart failure] to 6000 [hyperdynamic]). The performance of the controller in resuscitating to the target set point was evaluated in terms of milliliters of blood volume error from optimal, with <250 mL of error defined as "successful." RESULTS One thousand simulations were run for each of the 2 phases of the study. The phase 1 mean blood volume error ± SD from optimal was 25 ± 59 mL. The phase 2 mean blood volume error from optimal was -60 ± 89 mL. The lower 95% Clopper-Pearson binomial confidence interval for resuscitation to within 250 mL of optimal blood volume for phase 1 and 2 was 99.6% and 97.1%, respectively. CONCLUSION The results indicate that the controller is highly effective in targeting optimal blood and stroke volumes, regardless of weight, contractility or starting blood volume.


title: Relationship between brain computed tomography findings and bispectral index score in patients presenting with head trauma.

text: OBJECTIVE Head trauma is one of the most important emergency health problems both in the world and in our country. The objective in our study is to (i) state the correlation between the findings of bispectral index score (BIS) and computed tomography (CT), which are used to evaluate the level of consciousness of patients with isolated head trauma, and (ii) investigate objective results about the patient's level of consiousness/alertness according to the CT modality, which is used frequently. METHODS This prospective study was carried out between 03.01.2014 and 09.01.2014 in the emergency department of Fatih Sultan Mehmet Education and Research Hospital. The average BIS scores were correlated with the Glasgow Coma Scale (GCS) point, the Canadian CT Head Rule major and minor criteria, and the pathologic findings in CT imaging. The patients' demographic features, vital signs at admission, and arrival times at the hospital were investigated. RESULTS In our study, 64 (31.7%) patients were female, and 138 (68.3%) patients were male. The mean BIS scores were 84.99±11.20 (86.05) and 93.78±3.80 (95.05) in patients with and without CT pathologies, respectively. The correlation between CT pathology and BIS scores was statistically significant: BIS scores were lower in patients with CT pathologies (p=0.001; p<0.01). There was a statistically significant positive correlation between the BIS and GCS scores (45.6%) (p<0.05). CONCLUSION We showed that most head traumas occur after dangerous accidents, and according to the results, we can predict that males are more frequently affected than females. There was a statistically significant positive correlation between BIS scores and GCS points. In our study, the BIS scores were statistically significantly lower in patients with CT pathology than in patients without. We can predict that if the BIS score of the patient is low, then there will be the presence of pathology on CT imaging.


title: Viral etiology of acute respiratory infections with cough in infancy: a community-based birth cohort study.

text: BACKGROUND Acute respiratory infections (ARI) are a major cause of morbidity in infancy worldwide, with cough and wheeze being alarming symptoms to parents. We aimed to analyze in detail the viral aetiology of ARI with such symptoms in otherwise healthy infants, including rhinoviruses and recently discovered viruses such as human metapneumovirus (HMPV), coronavirus NL63 and HKU1, and human bocavirus (HBoV). METHODS We prospectively followed 197 unselected infants during their first year of life and assessed clinical symptoms by weekly standardized interviews. At the first ARI with cough or wheeze, we analyzed nasal swabs by sensitive individual real time polymerase chain reaction assays targeting 16 different respiratory viruses. RESULTS All 112 infants who had an ARI had cough, and 39 (35%) had wheeze. One or more respiratory viruses were found in 88 of 112 (79%) cases. Fifteen (17%) dual and 3 (3%) triple infections were recorded. Rhino- (23% of all viruses) and coronaviruses (18%) were most common, followed by parainfluenza viruses (17%), respiratory syncytial virus (RSV) (16%), HMPV (13%), and HBoV (5%). Together rhinoviruses, coronaviruses, HMPV, and HBoV accounted for 60% (65 of 109) of viruses. Although symptom scores and need for general practitioner (GP) consultations were highest in infants infected with RSV, they were similar in infants infected with other viruses. Viral shedding at 3 weeks occurred in 20% of cases. CONCLUSIONS Rhinoviruses, coronaviruses, HMPV, and HBoV are common pathogens associated with respiratory symptoms in otherwise healthy infants. They should be considered in the differential diagnosis of the aetiology of ARI in this age group.