title: Investigations of selected historically important syndromic outbreaks: impact and lessons learned for public health preparedness and response.

text: Public health readiness has increased at all jurisdictional levels because of increased sensitivity to threats. Since 2001, with billions of dollars invested to bolster the public health system's capacity, the public expects that public health will identify the etiology of and respond to events more rapidly. However, when etiologies are unknown at the onset of the investigation but interventions must be implemented, public health practitioners must benefit from past investigations' lessons to strengthen preparedness for emerging threats. We have identified such potentially actionable lessons learned from historically important public health events that occurred primarily as syndromes for which the etiological agent initially was unknown. Ongoing analysis of investigations can advance our capability to recognize and investigate syndromes and other problems and implement the most appropriate interventions.


title: Into the eye of the cytokine storm.

text: The cytokine storm has captured the attention of the public and the scientific community alike, and while the general notion of an excessive or uncontrolled release of proinflammatory cytokines is well known, the concept of a cytokine storm and the biological consequences of cytokine overproduction are not clearly defined. Cytokine storms are associated with a wide variety of infectious and noninfectious diseases. The term was popularized largely in the context of avian H5N1 influenza virus infection, bringing the term into popular media. In this review, we focus on the cytokine storm in the context of virus infection, and we highlight how high-throughput genomic methods are revealing the importance of the kinetics of cytokine gene expression and the remarkable degree of redundancy and overlap in cytokine signaling. We also address evidence for and against the role of the cytokine storm in the pathology of clinical and infectious disease and discuss why it has been so difficult to use knowledge of the cytokine storm and immunomodulatory therapies to improve the clinical outcomes for patients with severe acute infections.


title: Advances in endovascular aneurysm management: coiling and adjunctive devices.

text: Endovascular coil embolisation continues to evolve and remains a valid modality in managing ruptured and unruptured cerebral aneurysms. Technological advances in coil properties, adjunctive devices and interventional techniques continue to improve long-term aneurysm occlusion rates. This review elaborates on the latest advances in next-generation endovascular coils and adjunctive coiling techniques for treating cerebral aneurysms.


title: Single-port laparoscopic adrenalectomy for a right-sided aldosterone-producing adenoma: a case report.

text: INTRODUCTION Single-port laparoscopic adrenalectomy is one of the most interesting surgical advances. Here, we evaluate the safety and feasibility of single-port laparoscopic adrenalectomy as treatment for a right-sided aldosterone-producing adenoma. CASE PRESENTATION A 39-year-old Japanese woman presented with hypertension and hypokalemia. Abdominal computed tomography and an endocrinological workup revealed a 19mm right adrenal tumor with primary aldosteronism. Our patient was informed of the details of the surgical procedure and our efforts to reduce the number of incisions needed - ideally, to a single incision - when removing her adrenal gland. A single-port laparoscopic adrenalectomy was attempted. A multichannel port was inserted through a 2.5cm umbilical incision. A 5mm flexible laparoscope, articulating laparoscopic dissector and tissue sealing device were the primary tools used in the operation. The right liver lobe was evaluated using a percutaneous instrument, providing good visualization of the operative field surrounding her right adrenal gland. The single-port laparoscopic adrenalectomy was successfully completed without any intraoperative complications. The operating time was 76 minutes, and her blood loss was 5mL. Oral intake was resumed on the first postoperative day, and the length of her hospital stay was three days. Her postoperative course was uneventful with no morbidity within one month of follow-up, and our patient had excellent cosmetic results. CONCLUSIONS Single-port laparoscopic adrenalectomy is a safe and feasible procedure for patients with a right-sided adrenal tumor when performed by a surgeon experienced in laparoscopic and adrenal surgery. However, more surgical experience using this technique is required to confirm our initial impressions.


Association between Numbers of "Imported Cases" and "Reported Cases in a Source Country" of COVID-19: January to April 2020 in Japan.


title: Prognostic Hemostasis Biomarkers in Acute Ischemic Stroke.

text: Objectives- The prediction of patients at risk for poor clinical outcome after acute ischemic stroke remains challenging. An imbalance of coagulation factors may play an important role in progression and prognosis of these patients. In this systematic review, we assessed the current literature on hemostasis biomarkers and the association with poor clinical outcome in acute ischemic stroke. Approach and Results- A systematic search of Embase, Medline, Cochrane Library, Web of Science, and Google Scholar was performed on studies reporting on hemostasis biomarkers and clinical outcome after acute ischemic stroke. Studies were considered eligible if blood samples were collected within 72 hours after symptom onset. Additionally, clinical outcome should be assessed using a disability score (Barthel Index or modified Rankin scale). Methodological quality of included studies was assessed with an adapted version of the Quality Assessment of Diagnostic Accuracy Studies questionnaire. A total of 80 articles were read full text, and 41 studies were considered eligible for inclusion, reporting on 37 different hemostasis biomarkers. No single biomarker appeared to be effective in predicting poor clinical outcome in acute ischemic stroke patients. Conclusions- Based on current literature, no clear recommendations can be provided on which hemostasis biomarkers are a predictor of clinical outcome after acute ischemic stroke. However, some biomarkers show promising results and need to be further investigated and validated in large populations with clear defined study designs.


title: Emerging studies of human HIV-specific antibody repertoires.

text: There has been an explosion of interest in the human B cell response to HIV infection of late. Recent advances in techniques for isolation of human antibodies and antibody secreting cell lines have facilitated a rapid expansion in the number of antibodies available for study. Early analysis of these repertoires reveals interesting features of the HIV-specific antibody response. HIV-specific repertoires exhibit a high level of clonality in circulating cells, and high levels of somatic mutations within the antibody variable gene segments. It appears that many if not most antibodies in circulation bind to virus envelope conformations that are found only in complex oligomeric structures on virion particles or virus-like particles. The rapid isolation of large panels of novel human neutralizing antibodies promises to reveal new insights into the fundamental principles underlying antibody-mediated neutralization of HIV.


title: Electrical stimulation induces differentiation of human cardiosphere-derived cells (hCDCs) to committed cardiomyocyte.

text: Logistic complexities of heart transplantation embossed the necessity of utilizing novel methods, which enable heart regeneration. Human cardiosphere-derived cells (hCDCs) are taken into consideration as a promising cell resource in cell therapy in recent years. In this study, we designed an electrochemical stimulation system, which sends square pulses to the hCDCs and records their electrical response. Morphology, viability and differentiation of hCDCs are monitored at certain time courses of the treatment. Differentiating hCDCs aligned perpendicularly with respect to the direction of applied electric current, and obtained a spindle-like morphology, while they remained viable. At the same time, specific cardiac marker genes including GATA4, cTnT and α-MHC showed a considerable up-regulation. Our findings confirm that hCDCs differentiate to committed cardiomyocytes when hCDCs receive an electrical energy of 0.06 - 0.12 Wh. This amount of electrical energy could be applied to the stem cells using versatile electrical stimulation patterns via commercially available devices.


title: Management of neonates after postpartum discharge and all children in the ambulatory setting during the coronavirus disease 2019 pandemic.

text: PURPOSE OF REVIEW The present coronavirus disease 2019 (COVID-19) pandemic has created additional challenges with an increased number of presumed healthy, full-term newborns being discharged at 24 h after delivery. Short lengths of stay raise the possibility of mother-infant dyads being less ready for discharge, defined as at least one of the three informants (i.e., mother, pediatrician, and obstetrician) believing that either the mother and/or infant should stay longer than the proposed time of discharge. This public health crisis has reduced the number of in-person well child visits, negatively impacting vaccine receipt, and anticipatory guidance. RECENT FINDINGS Extra precautions should be taken during the transition period between postpartum discharge and follow-up in the ambulatory setting to ensure the safety of all patients and practice team members. This should include restructuring office flow by visit type and location, limiting in-person visits during well infant exams, instituting proper procedures for personal protective equipment and for cleaning of the office, expanding telehealth capabilities for care and education, and prioritizing universal vaccinations and routine screenings. SUMMARY Based on current limited evidence, this report provides guidance for the postdischarge management of newborns born to mothers with confirmed or suspected disease in the ambulatory setting as well as prioritizing universal immunizations and routine screenings during the COVID-19 pandemic.


title: MicroRNA-126 Regulates Angiogenesis and Neurogenesis in a Mouse Model of Focal Cerebral Ischemia.

text: Studies demonstrate that microRNA-126 plays a critical role in promoting angiogenesis. However, its effects on angiogenesis following ischemic stroke are unclear. Here, we explored the effect of microRNA-126-3p and microRNA-126-5p on angiogenesis and neurogenesis after brain ischemia. We demonstrated that both microRNA (miRNA)-126-3p and microRNA-126-5p increased the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) compared with the scrambled miRNA control (p < 0.05). Transferring microRNA-126 into a mouse middle cerebral artery occlusion model via lentivirus, we found that microRNA-126 overexpression increased the number of CD31+/BrdU+ (5-bromo-2'-deoxyuridine-positive) proliferating endothelial cells and DCX+/BrdU+ neuroblasts in the ischemic mouse brain, improved neurobehavioral outcomes (p < 0.05), and reduced brain atrophy volume (p < 0.05) compared with control mice. Western blot results showed that AKT and ERK signaling pathways were activated in the lentiviral-microRNA-126-treated group (p < 0.05). Both PCR and western blot results demonstrated that tyrosine-protein phosphatase non-receptor type 9 (PTPN9) was decreased in the lentiviral-microRNA-126-treated group (p < 0.05). Dual-luciferase gene reporter assay also showed that PTPN9 was the direct target of microRNA-126-3p and microRNA-126-5p in the ischemic brain. We demonstrated that microRNA-126-3p and microRNA-126-5p promoted angiogenesis and neurogenesis in ischemic mouse brain, and further improved neurobehavioral outcomes. Our mechanistic study further showed that microRNA-126 mediated angiogenesis through directly inhibiting its target PTPN9 and activating AKT and ERK signaling pathways.


title: A multidisciplinary, minimally invasive approach combining lacrimoscopy and fluoroscopically guided stenting for management of nasolacrimal apparatus obstruction in dogs.

text: OBJECTIVE To describe and evaluate outcomes of a multidisciplinary, minimally invasive approach combining lacrimoscopy and fluoroscopically guided stenting for management of nasolacrimal apparatus (NLA) obstruction in dogs. DESIGN Prospective, nonrandomized clinical trial. ANIMALS 16 client-owned dogs with confirmed NLA obstruction. PROCEDURES Dogs underwent CT contrast dacryocystorhinography, rhinoscopy, and lacrimoscopy. Whenever possible, the NLA was stented, typically with fluoroscopic guidance. RESULTS Median duration of clinical signs prior to treatment was 3.2 months (range, 0.2 to 14 months). Causes of NLA obstruction were a foreign body (n = 5), dacryocystitis (4), stenosis secondary to fibrosis (3), granulation tissue (1), or granulation tissue in association with a small foreign body (1); a cause was not identified in 2 dogs. Stents were placed in 14 of 16 (88%) dogs for a median duration of 5.6 weeks (range, 1.3 to 9.4 weeks). Stenting was not possible in 2 dogs with stenosis of the NLA secondary to granulation tissue or fibrosis. Owners of all 16 dogs reported at least 60% clinical improvement with median improvement rated as 95%, and owners of 8 dogs reporting complete resolution of signs. Two dogs required antimicrobial administration because of dacryocystitis that persisted after stent removal; a foreign body was not found in either dog. CONCLUSIONS AND CLINICAL RELEVANCE Overall clinical response and owner-rated improvement for dogs with NLA obstruction that underwent lacrimoscopy and fluoroscopically guided stenting were high, especially given that these dogs had failed to respond to conventional treatment.


title: Mechanism of PM2.5-induced human bronchial epithelial cell toxicity in central China.

text: Exposure to PM2.5 has been linked to respiratory disorders, yet knowledge of the molecular mechanism is limited. Here, PM2.5 was monitored and collected in central China, and its cytotoxicity mechanism on human bronchial epithelial cells (BEAS-2B) was investigated. With the average concentration of 109 ± 69 μg/m3, PM2.5 was rich in heavy metals and organic pollutants. After exposure to PM2.5, the viability of BEAS-2B cells decreased, where 510 dysregulated genes were predicted to induce necroptosis via inhibiting ATP synthesis through the oxidative phosphorylation signaling pathway. Cellular experiments demonstrated that the content of ATP was downregulated, while the expression of RIP3, a necroptosis indicator, was upregulated. Besides, four enzymes in charge of ATP synthesis were downregulated, including ATP5F, NDUF, COX7A, and UQCR, while two genes of RELA and CAPN1 responsible for necroptosis were upregulated. Furthermore, N-acetylcysteine was applied as an enhancer for ATP synthesis, which reversed the downregulation of ATP5F, NDUF, and COX7A, and consequently alleviated the elevation of RELA, CAPN1, and RIP3. In conclusion, PM2.5 exposure downregulates ATP5F, NDUF, COX7A, and UQCR, and that inhibits ATP synthesis via the oxidative phosphorylation signaling pathway, which subsequently upregulates RELA and CAPN1 and ultimately leads to necroptosis of BEAS-2B cells.


MedEdPublish.


title: Establishment of conventional PCR and real-time PCR assays for accurate, rapid and quantitative authentication of four mistletoe species.

text: Adulterants in processed food and herbal medicines reduce their safety, quality control, or pharmacological efficacy. Four mistletoe species, including Viscum coloratum, inhabit Korea. Leaves and branches of V. coloratum, defined as edible or medicinal mistletoe species in Korean, are used to prepare Korean herbal medicines as well as leached tea. However, other mistletoe species including Taxillus sutchuenensis var. duclouxii, Korthalsella japonica, and Loranthus tanakae are frequently distributed as authentic V. coloratum in Korean markets because of similarities in the branches morphology and Korean names of these species with V. coloratum. Although herbal medicines and food products prepared from the other mistletoe species are inauthentic, they are sold at high prices because of the rarity of these species. Thus, it is important to distinguish between authentic and inauthentic adulterant mistletoe species. In this study, we developed species-specific primer, based on matK sequences, suitable for both conventional PCR and real time PCR (qPCR) assay. These assays allowed rapid discrimination among all four mistletoe species. Moreover, qPCR assay enabled the detection of trace amounts of adulterant mistletoe species in V. coloratum samples. Furthermore, we used these assays to monitor commercial mistletoe products distributed in Korean markets. Our data suggest that these methods would serve as a reliable genetic tool to prevent adulteration and standardize the quality of commercial V. coloratum products.


title: Persistent posterior seroma after laparoscopic repair of ventral abdominal wall hernias with expanded polytetrafluoroethylene mesh: prevalence, independent predictors and detached tacks : Retrospective review.

text: PURPOSE A persistent seroma located posterior to a mesh (PPS) remains a little known complication after laparoscopic ventral hernia repair (LVHR). The aim of this large case series was to analyse the prevalence and clinical course as well as identify related factors and independent predictors of PPS. METHODS All 1288 adult patients who underwent a LVHR with an expanded polytetrafluoroethylene mesh (ePTFE) between January 2003 and July 2014 were reviewed. Those who underwent an abdominal computed tomography (CT) scan more than 3 months afterwards (n = 166) were included and their scans were analysed. The primary outcome measure was the prevalence of a PPS and its characteristics. The secondary outcome measures were identification of significantly related factors and independent predictors of PPS. RESULTS A PPS was observed in 14 of 166 analysed CT scans (8.4%). Eleven patients were symptomatic; conservative treatment (wait-and-see policy) was successful in eight. Three underwent relaparoscopy with removal of a thick neoperitoneum. Several instances of tack and/or mesh detachment were identified on CT scans and during relaparoscopy. Independent predictors were: > 3 trocars (RR 5.0, 95% CI 1.6-15.8) and use of a mesh larger than > 300 cm2 (RR 9.9, 95% CI 1.9-51.2). CONCLUSIONS A PPS is a relatively common complication after LVHR with an ePTFE mesh of usually larger hernias. A "wait-and-see" approach seems justified in most cases. Some require laparoscopic excision of the thick neoperitoneum. A PPS can cause tack and mesh detachment but the clinical consequences are unclear. Recurrences have not been observed in this series.


title: MicroRNA transcriptome analysis in chicken kidneys in response to differing virulent infectious bronchitis virus infections.

text: Infectious bronchitis virus (IBV) can cause a highly contagious and acute respiratory disease in poultry. MicroRNAs (miRNAs) have emerged as a class of crucial regulators for gene expression and are involved in the regulation of virus defence and immunological processes. To understand miRNA regulation in chickens in response to IBV infection, high-throughput sequencing was performed to compare the small RNA libraries from the kidneys of chicken infected with SCK2, SCDY2 and LDT3-A. By comparing these data to healthy chickens, a total of 58 differentially expressed (DE) miRNAs were identified. The DE miRNAs were further classified into five miRNA expression patterns (up or down regulation compared to control). Using Gene Ontology (GO) enrichment prediction, the DE miRNAs were shown to be mostly associated with metabolic processes, catalytic activities, gene expression, binding activities and immune responses. Seven highly expressed miRNAs (gga-miR-30d, gga-miR-1454, gga-miR-7b, gga-miR-215-5p, gga-miR-1a-3p, gga-miR-3538 and gga-miR-2954) were selected for miRNA-mRNA conjoint analysis. Furthermore, the miRNAs inversely correlated with the corresponding target gene mRNAs. These seven miRNAs were considered to play an important role in IBV-host interactions and the differing virulence of IBV strains. This is the first demonstration that infection with different virulent IBVs elicits different expression of miRNAs in chicken kidneys; this expression also seems to be associated with the virulence of IBV. These results are significant for the study of immune responses to infection with different virulent IBVs mediated by miRNAs as well as the interaction between the chicken host and IBV.


title: Use of stapling devices for safe cholecystectomy in acute cholecystitis.

text: Many techniques are described for the ligation of a difficult cystic duct (CD). The aim of this study is to assess the effectiveness and safety of stapling of a difficult CD in acute cholecystitis using Endo-GIA. From January 2008 to June 2012, 1441 patients with cholelithiasis underwent laparoscopic cholecystectomy (LC) at the Department of General Surgery, Haydarpasa Numune Education and Research Hospital. Of these, 19 (0.62%) were identified as having a difficult CD and were ligated using an Endo-GIA stapler. All patients were successfully treated with a laparoscopic approach. The length of hospital stay was 3.4 days. There were umbilical wound infections in 4 patients (21%). The length of follow-up ranged from 1.0 to 50.4 months. In conclusion, Endo-GIA is a safe and easy treatment method for patients with a dilated and difficult CD. The cystic artery should be isolated and ligated if possible before firing the Endo-GIA stapler. If isolation and stapling are not possible, fibrin sealant can be applied to avoid bleeding. The vascular Endo-GIA can be applied in a large CD, but for acute cholecystitis with an edematous CD, the Endo-GIA roticulator 4.8 or 3.5 stapler is preferred.


title: Training in neurology: Flexibility and adaptability of a neurology training program at the epicenter of COVID-19.

text: OBJECTIVE To outline changes made to a neurology residency program in response to coronavirus disease 2019 (COVID-19). METHODS In early March 2020, the first cases of COVID-19 were announced in the United States. New York City quickly became the epicenter of a global pandemic, and our training program needed to rapidly adapt to the increasing number of inpatient cases while being mindful of protecting providers and continuing education. Many of these changes unfolded over days, including removing residents from outpatient services, minimizing the number of residents on inpatient services, deploying residents to medicine services and medical intensive care units, converting continuity clinic patient visits to virtual options, transforming didactics to online platforms only, and maintaining connectedness in an era of social distancing. We have been able to accomplish this through daily virtual meetings among leadership, faculty, and residents. RESULTS Over time, our program has successfully rolled out initiatives to service the growing number of COVID-related inpatients while maintaining neurologic care for those in need and continuing our neurologic education curriculum. CONCLUSION It has been necessary and feasible for our residency training program to undergo rapid structural changes to adapt to a medical crisis. The key ingredients in doing this successfully have been flexibility and teamwork. We suspect that many of the implemented changes will persist long after the COVID-19 crisis has passed and will change the approach to neurologic and medical training.


Managing clinical trials for covid-19: the importance of ethics committees.


title: Open tension-free hernioplasty using a novel lightweight self-gripping mesh: medium-term experience from two institutions.

text: PURPOSE The process of mesh fixation and the potential risk of associated chronic pain are always surgeon's main concerns in hernia surgery. A wide variety of lightweight mesh models are currently available on the market to overcome some of these problems showing good preliminary results, but no data representing the medium- or long-term results. The present study aims to report the clinical outcomes of two institutional series of patients who underwent hernia repair using a partially absorbable auto adherent mesh (Parietene™ Progrip™--PP). METHODS A prospective analysis was performed including unselected patients with primary groin hernia who underwent a standardized Lichtenstein procedure using the PP mesh at two tertiary institutions. RESULTS During the 2-year study period, 181 patients (167 males; 14 females) with a median age of 63 years (19-85 years) were operated on at both centers. Short-term complications occurred in 27 patients (15%), the most commonly seen being urinary retention (6%) followed by hematoma (5%) and acute orchitis (2%). With a median follow-up of 17 months (12-29 months), 4 patients (2%) had a feeling of a foreign body in the groin, and 7 (4%) developed chronic pain. A total of four patients (2%) developed recurrence. CONCLUSIONS In our experience, the use of the PP mesh for hernioplasties offers a potential benefit not only in the short-term period but also in a medium-term follow-up with low recurrence and late chronic pain rates. However, this particular mesh does not fully prevent all complications and chronic pain and recurrent hernias have been reported for the first time.


title: Insights from COVID-19 cluster containment in Bhilwara District, Rajasthan.

text: Background In March 2020, a healthcare professional from a renowned private hospital, in the textile city of Bhilwara, Rajasthan, reported clustering of cases of pneumonia amongst doctors and paramedical staff suspected to be due to COVID-19. The basis of suspicion was clinico-eco-epidemiologic-radiological findings as, by that time, about 20 COVID19 cases were reported from the state of Rajasthan including a big Italian group of tourists who travelled extensively in Rajasthan, including Udaipur city. Objectives The current study presents the field experience of the Central and the State Rapid Response Teams (RRTs) in the cluster containment at Bhilwara. Methods: The information regarding the sociodemographic profile of the cases was provided by the Senior Medical Officer In-charge. The containment strategy was modeled under 6 pillars. Google Maps was used for preparing spot map. Results Immediate public health actions of cluster containment including contact tracing, quarantine, and isolation were initiated using epidemiological approach of mapping the cluster and taking care of reservoir of infection by the District Public Health Team supported by Multidisciplinary Rapid Response Team. This was supplemented by strict enforcement of lock down in the District taking care of daily need of the community by the leadership of administration with very strong intersectoral co-ordination (locally called "ruthless containment"). Conclusion The forthcoming challenge resides in re-establishment of inter-district and inter-state travel, which can become a risk of re-entry of the new cases, which needs to be taken care of, with the help of stringent administrative measures and screening at all points of entry. The team in Bhilwara needs to remain vigilant to pick up any imported cases early before local transmission establishes.


title: Effect of Axonal Trauma on Nerve Regeneration in Side-to-side Neurorrhaphy: An Experimental Study.

text: BACKGROUND Side-to-side (STS) neurorrhaphy can be performed distally to ensure timely end-organ innervation. It leaves the distal end of the injured nerve intact for further reconstruction. Despite encouraging clinical results, only few experimental studies have been published to enhance the regeneration results of the procedure. We examined the influence of different size epineural windows and degree of axonal injury of STS repair on nerve regeneration and donor nerve morbidity. METHODS Three clinically relevant repair techniques of the transected common peroneal nerve (CPN) were compared. Group A: 10-mm long epineural STS windows; group B: 2-mm long windows and partial axotomy to the donor tibial nerve; and group C: 2-mm long windows with axotomies to both nerves. Regeneration was followed by the walk track analysis, nerve morphometry, histology, and wet muscle mass calculations. RESULTS The results of the walk track analysis were significantly better in groups B and C compared with group A. The nerve fiber count, total fiber area, fiber density, and percentage of the fiber area values of CPN of the group C were significantly higher when compared with group A. The wet mass ratio of the CPN-innervated anterior tibial muscle was significantly higher in group C compared with group A. The wet mass ratio of the tibial nerve-innervated gastrocnemial muscle was higher in group A compared with the other groups. CONCLUSIONS All three variations of the STS repair technique showed nerve regeneration. Deliberate donor nerve axotomy enhanced nerve regeneration. A larger epineural window did not compensate the effect of axonal trauma on nerve regeneration.


title: Selective laser trabeculoplasty (SLT) performed by optometrists for patients with glaucoma and ocular hypertension: a scoping review protocol.

text: Introduction In the UK, the National Institute for Health and Clinical Excellence are amending guidelines to support use of selective laser trabeculoplasty (SLT) as a first-line treatment for patients with glaucoma and ocular hypertension. The procedure is quick, effective in lowering intraocular pressure, cost-effective for the National Health Service and offers an equivalent safety profile to other therapies. The procedure is typically performed by an ophthalmologist; however, there is potential for suitably trained non-medical professionals to deliver the therapy. This scoping review will identify service delivery models where SLT is delivered by non-medical professionals worldwide, with a focus on optometrists. Methods and analysis A systematic search of the following databases will be conducted: CINAHL; MEDLINE Complete; Embase; HMIC and Ovid Emcare. For inclusion, studies must examine healthcare models of SLT delivery by optometrists and describe one of the following outcomes: training procedures; clinical effectiveness; safety and cost-effectiveness. A search of grey literature will be conducted via professional societies; national health departments; medicine regulatory bodies; charities and conference proceedings. Two reviewers will independently screen titles, abstracts and full-texts articles, followed by charting of data. This evidence synthesis will summarise findings narratively, supplemented with tables and descriptive statistics. Ethics and dissemination The review focuses on published articles and therefore ethical approval is not required. The findings will be relevant to key stakeholders including health service managers, policymakers, clinicians and patients. The findings of this review will be disseminated through peer-reviewed publications, conference presentations and summary reports for key stakeholders.


title: Robotic cylindrical abdominoperineal resection with transabdominal levator transection.

text: PURPOSE The extralevator approach to abdominoperineal resection is an emerging surgical option for patients with low rectal cancer. This technique involves a wide excision of the levator muscles that could reduce the high incidence of circumferential margin positivity associated with conventional abdominoperineal resections. We present our technique of robotic cylindrical abdominoperineal resection where the daVinci robot is used to perform a controlled transection of the levator muscles transabdominally under direct visualization. METHODS Five patients with rectal adenocarcinoma within 5 cm of the anal verge underwent robot-assisted cylindrical abdominoperineal resection. Safety, feasibility, immediate postoperative outcomes, and pathological adequacy of the specimen were assessed. RESULTS The procedure was successfully completed in all 5 patients without any intraoperative complications, robot-associated morbidity, or conversion to the open approach. The mean operative time and length of hospital stay were 343 minutes and 5.8 days. An intact mesorectal envelope and negative circumferential margin was achieved in all cases. All specimens had a cylindrical shape. CONCLUSIONS Robotic assistance enables the transabdominal transection of the levator muscles in cylindrical abdominoperineal resection, with acceptable perioperative and pathological outcomes. Further studies are essential to objectively define the safety, efficacy, and long-term results of this new technique.


title: Inhibition of Human Metapneumovirus Binding to Heparan Sulfate Blocks Infection in Human Lung Cells and Airway Tissues.

text: UNLABELLED Human metapneumovirus (HMPV), a recently discovered paramyxovirus, infects nearly 100% of the world population and causes severe respiratory disease in infants, the elderly, and immunocompromised patients. We previously showed that HMPV binds heparan sulfate proteoglycans (HSPGs) and that HMPV binding requires only the viral fusion (F) protein. To characterize the features of this interaction critical for HMPV binding and the role of this interaction in infection in relevant models, we utilized sulfated polysaccharides, heparan sulfate mimetics, and occluding compounds. Iota-carrageenan demonstrated potent anti-HMPV activity by inhibiting binding to lung cells mediated by the F protein. Furthermore, analysis of a minilibrary of variably sulfated derivatives of Escherichia coli K5 polysaccharide mimicking the HS structure revealed that the highly O-sulfated K5 polysaccharides inhibited HMPV infection, identifying a potential feature of HS critical for HMPV binding. The peptide dendrimer SB105-A10, which binds HS, reduced binding and infection in an F-dependent manner, suggesting that occlusion of HS at the target cell surface is sufficient to prevent infection. HMPV infection was also inhibited by these compounds during apical infection of polarized airway tissues, suggesting that these interactions take place during HMPV infection in a physiologically relevant model. These results reveal key features of the interaction between HMPV and HS, supporting the hypothesis that apical HS in the airway serves as a binding factor during infection, and HS modulating compounds may serve as a platform for potential antiviral development. IMPORTANCE Human metapneumovirus (HMPV) is a paramyxovirus that causes respiratory disease worldwide. It has been previously shown that HMPV requires binding to heparan sulfate on the surfaces of target cells for attachment and infection. In this study, we characterize the key features of this binding interaction using heparan sulfate mimetics, identify an important sulfate modification, and demonstrate that these interactions occur at the apical surface of polarized airway tissues. These findings provide insights into the initial binding step of HMPV infection that has potential for antiviral development.


title: The Role of Punctuated Evolution in the Pathogenicity of Influenza Viruses.

text: Influenza is an acute respiratory disease caused by influenza viruses. Evolutionarily, all influenza viruses are zoonoses, arising in the animal reservoir and spilling over into the human population. Several times a century, one of these zoonotic events results in a new influenza virus lineage becoming established in humans and circulating for years or decades as an endemic strain. The worldwide pandemic that occurs shortly after the nascent virus becomes established can have a profound impact on morbidity and mortality. Because influenza viruses continually evolve and the illness they engender can vary considerably based on characteristics of the strain, the weather, other circulating or endemic pathogens, as well as the number of susceptible hosts, the impact of each season on human health is unpredictable. Over time, the general pattern is for pandemic strains to adapt and gradually take on characteristics of seasonal strains with lower virulence and a diminished synergism with bacterial pathogens. Study of this punctuated evolution yields a number of insights into the overall pathogenicity of influenza viruses.


title: A critical role for proinflammatory behavior of smooth muscle cells in hemodynamic initiation of intracranial aneurysm.

text: BACKGROUND Intracranial aneurysm initiation is poorly understood, although hemodynamic insult is believed to play an important role in triggering the pathology. It has recently been found in a rabbit model that while macrophages are absent during hemodynamic aneurysm initiation, matrix metalloproteinases (MMPs) are elevated and co-localize with smooth muscle cells (SMCs). This study investigates whether SMCs play a mechanistic role in aneurysm initiation triggered by hemodynamics. METHODS Aneurysmal damage was induced at the basilar terminus via bilateral common carotid artery ligation in rabbits (n = 45, plus 7 sham controls). 16 ligated rabbits were treated with doxycycline to inhibit MMPs, 7 received clodronate liposomes to deplete circulating monocytes, and the rest received no drug. Effects of the treatments on aneurysm development were assessed histologically 5 days and 6 months after ligation. MMP production and expression of inflammatory markers by SMCs was monitored by immunohistochemistry and in situ hybridization. RESULTS Treatment with doxycycline attenuated aneurysmal development examined at 5 days and 6 months, suggesting that MMPs contribute to aneurysm initiation. However, systemic depletion of macrophages did not decrease MMPs or suppress aneurysmal development. Immunofluorescence showed that during aneurysm initiation MMP-2 and MMP-9 were distributed in SMCs, and in situ hybridization indicated that they were transcribed by SMCs. In regions of early aneurysmal lesion, SMCs exhibited decreased expression of smooth muscle actin and increased NF-κB and MCP-1 expressions. CONCLUSIONS During aneurysm initiation triggered by hemodynamics, SMCs rather than macrophages are responsible for MMP production that is critical for aneurysmal lesion development. These SMCs exhibit proinflammatory behavior.


title: Prioritizing candidate disease genes by network-based boosting of genome-wide association data.

text: Network "guilt by association" (GBA) is a proven approach for identifying novel disease genes based on the observation that similar mutational phenotypes arise from functionally related genes. In principle, this approach could account even for nonadditive genetic interactions, which underlie the synergistic combinations of mutations often linked to complex diseases. Here, we analyze a large-scale, human gene functional interaction network (dubbed HumanNet). We show that candidate disease genes can be effectively identified by GBA in cross-validated tests using label propagation algorithms related to Google's PageRank. However, GBA has been shown to work poorly in genome-wide association studies (GWAS), where many genes are somewhat implicated, but few are known with very high certainty. Here, we resolve this by explicitly modeling the uncertainty of the associations and incorporating the uncertainty for the seed set into the GBA framework. We observe a significant boost in the power to detect validated candidate genes for Crohn's disease and type 2 diabetes by comparing our predictions to results from follow-up meta-analyses, with incorporation of the network serving to highlight the JAK-STAT pathway and associated adaptors GRB2/SHC1 in Crohn's disease and BACH2 in type 2 diabetes. Consideration of the network during GWAS thus conveys some of the benefits of enrolling more participants in the GWAS study. More generally, we demonstrate that a functional network of human genes provides a valuable statistical framework for prioritizing candidate disease genes, both for candidate gene-based and GWAS-based studies.


COVID-19 Research in Brief: 9 May to 15 May, 2020.


title: [Application of pulmonary ultrasound in the diagnosis of COVID-19 pneumonia in neonates].

text: Objective: To investigate the application of pulmonary ultrasound in the diagnosis of neonatal COVID-19. Methods: In this retrospective study, the clinical data of 5 infants, who were admitted to the Department of Neonatology in Wuhan Children's Hospital from 31(st) January to 25(th) February 2020, were collected. Bedsides pulmondary ultrasound was conducted on admission, during the hospitalization, and before discharge, the result were compared with the chest X-ray or CT done at the same time. Results: Among the 5 cases who aged 1-18 days, 3 were male. The main clinical manifestations were respiratory and gastrointestinal symptoms. The pulmonary ultrasonography on admission showed abnormal pleural line and pulmonary edema of different severity in all 5 cases, presented as increase and fusion of B-line, and pulmonary interstitial syndrome; among them, one case also had a small-range consolidation. The chest CT on admission showed no obvious parenchymal infiltration in 2 cases, small strip or patchy high-density shadow in 2 cases, and ground glass change in one case. The re-examination of ultrosound during the hospitalization and at discharge showed improvement in all cases and were consistent with the chest X-ray taken at the same time. Conclusions: The main changes on the pulmonary ultrasonography in neonates with COVID-19 pneumonia are increase and fusion of B-line, abnormal pleural line, and alveolar interstitial syndrome, and may coexist with small range of pulmonary consolidation. The sensitivity of pulmonary ultrasound is higher than that of chest X-ray and CT in the diagnosis of pulmonary edema, and could be used in monitoring and evaluation of the disease.


title: Development of reverse transcription recombinase polymerase amplification assay for avian influenza H5N1 HA gene detection.

text: The 2006 outbreaks of H5N1 avian influenza in Egypt interrupted poultry production and caused staggering economic damage. In addition, H5N1 avian influenza viruses represent a significant threat to public health. Therefore, the rapid detection of H5 viruses is very important in order to control the disease. In this study, a qualitative reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of hemagglutinin gene of H5 subtype influenza viruses was developed. The results were compared to the real-time reverse transcription polymerase chain reaction (RT-PCR). An in vitro transcribed RNA standard of 970 nucleotides of the hemagglutinin gene was developed and used to determine the assay sensitivity. The developed H5 RT-RPA assay was able to detect one RNA molecule within 7 min, while in real-time RT-PCR, at least 90 min was required. H5 RT-RPA assay did not detect nucleic acid extracted from H5 negative samples or from other pathogens producing respiratory manifestation in poultry. The clinical performance of the H5 RT-RPA assay was tested in 30 samples collected between 2014 and 2015; the sensitivity of H5 RT-RPA and real-time RT-PCR was 100%. In conclusion, H5 RT-RPA was faster than real-time RT-PCR and easily operable in a portable device. Moreover, it had an equivalent sensitivity and specificity.


Intermittent high dosage oxygen treats COVID-19 infection: the Chinese studies.


title: Clinical trial design principles and endpoint definitions for transcatheter mitral valve repair and replacement: part 2: endpoint definitions: A consensus document from the Mitral Valve Academic Research Consortium.

text: Mitral regurgitation (MR) is one of the most prevalent valve disorders and has numerous aetiologies, including primary (organic) MR, due to underlying degenerative/structural mitral valve (MV) pathology, and secondary (functional) MR, which is principally caused by global or regional left ventricular remodelling and/or severe left atrial dilation. Diagnosis and optimal management of MR requires integration of valve disease and heart failure specialists, MV cardiac surgeons, interventional cardiologists with expertise in structural heart disease, and imaging experts. The introduction of trans- catheter MV therapies has highlighted the need for a consensus approach to pragmatic clinical trial design and uniform endpoint definitions to evaluate outcomes in patients with MR. The Mitral Valve Academic Research Consortium is a collaboration between leading academic research organizations and physician-scientists specializing in MV disease from the United States and Europe. Three in-person meetings were held in Virginia and New York during which 44 heart failure, valve, and imaging experts, MV surgeons and interventional cardiologists, clinical trial specialists and statisticians, and representatives from the U.S. Food and Drug Administration considered all aspects of MV pathophysiology, prognosis, and therapies, culminating in a 2-part document describing consensus recommendations for clinical trial design (Part 1) and endpoint definitions (Part 2) to guide evaluation of transcatheter and surgical therapies for MR. The adoption of these recommendations will afford robustness and consistency in the comparative effectiveness evaluation of new devices and approaches to treat MR. These principles may be useful for regulatory assessment of new transcatheter MV devices, as well as for monitoring local and regional outcomes to guide quality improvement initiatives.


title: Prospective analysis of the pattern and risk for severe vital sign changes during percutaneous radiofrequency ablation of the liver under opioid analgesia.

text: OBJECTIVE The aims of this study were to evaluate the pattern of vital sign changes and to elucidate significant risk factors for severe cardiovascular inhibition caused by percutaneous hepatic radiofrequency ablation (RFA). SUBJECTS AND METHODS A total of 102 patients (male-to-female ratio, 73:29; age range, 35-85 years; mean age, 58.1 years) with 119 malignant hepatic tumors were enrolled and analyzed prospectively. The patients underwent percutaneous RFA with IV infusion of opioid analgesics. Changes in blood pressure (BP) and heart rate (HR) and the occurrence of significant cardiovascular inhibition (BP or HR < 70% of baseline) were monitored during the procedure. Respiratory rate and skin body temperature were recorded before and after the procedure. RESULTS Whereas the mean BP was elevated (36%, 43/119) or depressed (36%, 43/119) with a similar frequency, the HR was predominantly depressed (56%, 66/119) during the procedure. The BP and HR were stable in only 18% cases (21/119), respectively. The respiratory rate showed no significant change (p = 0.521) after RFA; however, body temperature decreased (p < 0.001) after RFA. Although significant cardiovascular inhibition occurred in 41 cases (35%), all of the cases could be managed successfully and the technical success rate was 100% (119/119). Among the risk factors analyzed, old age (B = -0.003, p = 0.019) was significant for systolic BP depression, and contact of the RFA zone with the central portal vein (B = -0.096, p = 0.014) and female sex (B = -0.078, p = 0.033) were significant risk factors for HR depression as determined by multivariate analysis. CONCLUSION Changes in BP and HR, especially bradycardia, are common during percutaneous RFA of hepatic lesions. Significant risk factors for severe cardiovascular inhibition include contact of the RFA zone with the branches of the central portal vein, old age, and female sex.


title: Assay sensitivity and study features in neuropathic pain trials: an ACTTION meta-analysis.

text: OBJECTIVE Our objective was to identify patient, study, and site factors associated with assay sensitivity in placebo-controlled neuropathic pain trials. METHODS We examined the associations between study characteristics and standardized effect size (SES) in a database of 200 publicly available randomized clinical trials of pharmacologic treatments for neuropathic pain. RESULTS There was considerable heterogeneity in the SESs among the examined trials. Univariate meta-regression analyses indicated that larger SESs were significantly associated with trials that had 1) greater minimum baseline pain inclusion criteria, 2) greater mean subject age, 3) a larger percentage of Caucasian subjects, and 4) a smaller total number of subjects. In a multiple meta-regression analysis, the associations between SES and minimum baseline pain inclusion criterion and age remained significant. CONCLUSIONS Our analyses have examined potentially modifiable correlates of study SES and shown that a minimum pain inclusion criterion of 40 or above on a 0 to 100 scale is associated with a larger SES. These data provide a foundation for investigating strategies to improve assay sensitivity and thereby decrease the likelihood of falsely negative outcomes in clinical trials of efficacious treatments for neuropathic pain.


docid: bnejroie

title: Testing strategy for SARS-CoV-2 in the paediatric emergency department.


title: A Prospective Blinded Study of Endoscopic Ultrasound Elastography in Liver Disease: Towards a Virtual Biopsy.

text: BACKGROUND/AIMS Liver biopsy has traditionally been used for determining the degree of fibrosis, however there are several limitations. Endoscopic ultrasound (EUS) real-time elastography (RTE) is a novel technology that uses image enhancement to display differences in tissue compressibility. We sought to assess whether liver fibrosis index (LFI) can distinguish normal, fatty, and cirrhotic liver tissue. METHODS A total of 50 patients undergoing EUS were prospectively enrolled. RTE of the liver was performed to synthesize the LFI in each patient. Univariate and multivariable analyses were performed. Chi-square and t-tests were performed for categorical and continuous variables, respectively. A p-value of <0.05 was considered significant. RESULTS Abdominal imaging prior to endoscopic evaluation suggested normal tissue, fatty liver, and cirrhosis in 26, 16, and 8 patients, respectively. Patients with cirrhosis had significantly increased mean LFI compared to the fatty liver (3.2 vs. 1.7, p<0.001) and normal (3.2 vs. 0.8, p<0.001) groups. The fatty liver group showed significantly increased LFI compared to the normal group (3.8 vs. 1.4, p<0.001). Multivariable regression analysis suggested that LFI was an independent predictor of group features (p<0.001). CONCLUSIONS LFI computed from RTE images significantly correlates with abdominal imaging and can distinguish normal, fatty, and cirrhotic-appearing livers; therefore, LFI may play an important role in patients with chronic liver disease.


docid: crsqtwxq

title: Treatment of Intra- and Extracranial Aneurysms Using the Flow-Redirection Endoluminal Device: Multicenter Experience and Follow-Up Results.

text: BACKGROUND AND PURPOSE Flow diversion emerged as a crucial treatment option for intracranial aneurysms. We report a multicenter retrospective analysis of the safety and efficacy in the treatment of intracranial aneurysms with the Flow-Redirection Endoluminal Device (FRED) flow diverter, a dual-layer flow-modulation device. MATERIALS AND METHODS All intracranial aneurysms treated with the FRED between March 2013 and February 2016 at 4 neurovascular centers were included. Angiographic and clinical results were retrospectively analyzed, including all follow-up examinations. Aneurysms were unruptured in 44 cases, whereas 8 treatments were due to an acute SAH from the target aneurysm. RESULTS Successful implantation of the FRED was possible in 96.2% (50/52) of cases. At 3-month follow-up, complete occlusion was determined in 58.1% (25/43) and near-complete in 25.6% (11/43). At 12-month follow-up, aneurysm occlusion was complete in 75.0% (27/36) and near-complete in 22.2% (8/36). The overall acute and late thromboembolic and hemorrhagic complication rate was 17.3% (9/52), with a permanent treatment-related morbidity and mortality of 4.0% (2/50) and 2.0% (1/50), respectively, to date. CONCLUSIONS The FRED device offers an effective tool in the treatment of intracranial aneurysms. The dual-layer design promotes contemporary and stable long-term occlusion rates. Sufficient device expansion should be documented by angiographic CT. Further studies might help to identify a more optimal antiplatelet regimen to avoid thromboembolic complications during the follow-up period.


title: Comparison of combination therapies in the management of hepatocellular carcinoma: transarterial chemoembolization with radiofrequency ablation versus microwave ablation.

text: PURPOSE To compare retrospectively the outcomes and complications of transcatheter arterial chemoembolization with drug-eluting embolic agents combined with radiofrequency (RF) ablation or microwave (MW) ablation in treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS From 2003-2011, 89 patients with HCC received a combination therapy-transcatheter arterial chemoembolization plus RF ablation in 38 patients and transcatheter arterial chemoembolization plus MW ablation in 51 patients. Local tumor response, tumor progression-free survival (PFS), overall PFS, overall survival (OS), and complications were compared. Overall PFS and OS were compared between the two treatment groups in multivariate analysis controlling for Child-Pugh class, Barcelona Clinic Liver Classification stage, and index tumor size. RESULTS Complete local tumor response was achieved in 37 (80.4%) of the tumors treated with transcatheter arterial chemoembolization plus RF ablation and 49 (76.6%) of the tumors treated with transcatheter arterial chemoembolization plus MW ablation (P = .67). The median tumor PFS and overall PFS were 20.8 months and 9.3 months (P = .72) for transarterial chemoembolization plus RF ablation and 21.8 months and 9.2 months for transarterial chemoembolization plus MW ablation (P = .32). The median OS of the transcatheter arterial chemoembolization plus RF ablation group was 23.3 months, and the median OS of the transcatheter arterial chemoembolization plus MW ablation group was 42.6 months, with no significant difference in the survival experience between the two groups (log-rank test, P = .10). In the multivariate analysis, Barcelona Clinic Liver Classification stage was the only factor associated with overall PFS and OS. One patient in the transcatheter arterial chemoembolization plus RF ablation cohort (3%) and two patients in the transcatheter arterial chemoembolization plus MW ablation cohort (4%) required prolonged hospitalization (< 48 h) for pain management after the procedure (P = 1.00). CONCLUSIONS Based on similar safety and efficacy outcomes, both combination therapies, transcatheter arterial chemoembolization plus RF ablation and transcatheter arterial chemoembolization plus MW ablation, are effective treatments for HCC.


title: A Teenager with Congenital Heart Defect and Covid-19.

text: A 16 year-old girl with history of treated congenital mitral valve disease and signs of respiratory infection was admitted to our pediatric cardiology department. She was tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite her severe preexisting cardiac conditions with pulmonary hypertension, atrial arrhythmias and mitral valve stenosis, the infection did not lead to any cardiac or pulmonary deterioration. In adults, cardiac comorbidities are known risk-factors for a severe course of Covid-19 infections. This case illustrates that in children even severe cardiac disease is not necessarily associated with a severe course of Covid-19.


title: The wire anchor loop traction (WALT) maneuver.

text: Crossing the neck of large complex intracranial aneurysms for the purposes of stent deployment can be challenging using standard over the wire techniques. We describe a novel yet simple technique for straightening out the loop formed within a large intracranial aneurysm, which is often required in order to cross the aneurysm neck into the distal branch. Both the microcatheter and microwire are initially introduced into the distal vasculature, followed by withdrawal of the microwire to a point parallel to the distal exiting branch. The microcatheter and microwire are then gently withdrawn and a series of maneuvers to gradually reduce the loop is performed, obviating the need for distal purchase in the form of a stent, balloon, or coil, which have previously been described to maintain distal purchase.


title: From SARS-CoV to SARS-CoV-2: The response and challenge of forensic infectious disease autopsy.

text: Abstract


title: Human small intestine is capable of restoring barrier function after short ischemic periods.

text: AIM To assess intestinal barrier function during human intestinal ischemia and reperfusion (IR). METHODS In a human experimental model, 6 cm of jejunum was selectively exposed to 30 min of ischemia (I) followed by 30 and 120 min of reperfusion (R). A sham procedure was also performed. Blood and tissue was sampled at all-time points. Functional barrier function was assessed using dual-sugar absorption tests with lactulose (L) and rhamnose (R). Plasma concentrations of citrulline, an amino acid described as marker for enterocyte function were measured as marker of metabolic enterocytes restoration. Damage to the epithelial lining was assessed by immunohistochemistry for tight junctions (TJs), by plasma marker for enterocytes damage (I-FABP) and analyzed by electron microscopy (EM) using lanthanum nitrate as an electrondense marker. RESULTS Plasma L/R ratio's were significantly increased after 30 min of ischemia (30I) followed by 30 min of reperfusion (30R) compared to control (0.75 ± 0.10 vs 0.20 ± 0.09, P < 0.05). At 120 min of reperfusion (120R), ratio's normalized (0.17 ± 0.06) and were not significantly different from control. Plasma levels of I-FABP correlated with plasma L/R ratios measured at the same time points (correlation: 0.467, P < 0.01). TJs staining shows distortion of staining at 30I. An intact lining of TJs was again observed at 30I120R. Electron microscopy analysis revealed disrupted TJs after 30I with paracellular leakage of lanthanum nitrate, which restored after 30I120R. Furthermore, citrulline concentrations closely paralleled the histological perturbations during intestinal IR. CONCLUSION This study directly correlates histological data with intestinal permeability tests, revealing that the human gut has the ability of to withstand short episodes of ischemia, with morphological and functional recovery of the intestinal barrier within 120 min of reperfusion.


docid: nwdklhss

title: A novel design for steerable instruments based on laser-cut nitinol.

text: OBJECTIVE Omnidirectional articulated instruments enhance dexterity. In neurosurgery, for example, the simultaneous use of 2 instruments through the same endoscopic shaft remains a difficult feat. It is, however, very challenging to manufacture steerable instruments of the requisite small diameter. We present a new technique to produce such instruments by means of laser cutting. Only 3 coaxial tubes are used. The middle tube has a cutting pattern that allows the steering forces to be transmitted from the proximal to the distal end. In this way the steering part is concealed in the wall of the tube. Large diameter articulated instruments such as for laparoscopy might benefit from the excellent tip stability provided by the same economical technology. METHOD Coaxial nitinol tubes are laser-cut with a Rofin Stent Cutter in a specific pattern. The 3 tubes are assembled by sliding them over one another, forming a single composite tube. In a surgical simulator, the neurosurgical microinstruments and laparoscopic needle drivers were evaluated on surgical convenience. RESULTS Simultaneous use of 2 neurosurgical instruments (1.5 mm diameter) through the same endoscopic shaft proved to be very intuitive. The tip of the steerable laparoscopic instruments (10 mm diameter) could resist a lateral force of more than 20 N. The angle of motion for either instrument was at least 70° in any direction. CONCLUSIONS A new design for steerable endoscopic instruments is presented. It allows the construction in a range from microinstruments to 10-mm laparoscopic devices with excellent tip stability.


Regional coordination and bottom-up response of general practitioners in Belgium and the Netherlands.


title: Multi-modal Framework for Image-guided Trans-oral Surgery with Intraoperative Imaging and Deformation Modeling.

text: Treatment of throat cancers have improved due to minimally-invasive trans-oral approaches. Surgeons rely on preoperative imaging to guide their resection; however, large tissue deformations occur during trans-oral procedures due to placement of necessary retractors and laryngoscopes which hinders the surgeon's ability to accurately assess tumor extent and location of critical structures. We propose an image-guided framework utilizing intraoperative imaging and deformation modeling to improve surgeon accuracy and confidence. A CT-compatible laryngoscopy system previously developed was evaluated in this framework. Intraoperative images were acquired during laryngoscopy; force-sensing capabilities were enabled in the laryngoscope; and tracking of the scope and anatomic features was trialed. Tissue deformation and displacement were quantified and determined to be extensive, with values <; 4.6 cm in the tongue, <; 1.8 cm in bony structures, and <; 108.9 cm3 in airway volume change. Surgical navigation using intraoperative imaging and tracking was evaluated. Preliminary assessment of deformation modeling showed potential to supplement intraoperative imaging. Future work will involve streamlined integration of the components of this framework.


title: Virus and Immune-Mediated Encephalitides: Epidemiology, Diagnosis, Treatment, and Prevention.

text: Virus encephalitis remains a major cause of acute neurological dysfunction and permanent disability among children worldwide. Although some disorders, such as measles encephalomyelitis, subacute sclerosing panencephalitis, and varicella-zoster virus-associated neurological conditions, have largely disappeared in resource-rich regions because of widespread immunization programs, other disorders, such as herpes simplex virus encephalitis, West Nile virus-associated neuroinvasive disease, and nonpolio enterovirus-induced disorders of the nervous system, cannot be prevented. Moreover, emerging viral disorders pose new, potential threats to the child's nervous system. This review summarizes current information regarding the epidemiology of virus encephalitis, the diagnostic methods available to detect central nervous system infection and identify viral pathogens, and the available treatments. The review also describes immune-mediated disorders, including acute disseminated encephalomyelitis and N-methyl-D-aspartate receptor antibody encephalitis, conditions that mimic virus encephalitis and account for a substantial proportion of childhood encephalitis.


title: A review of antibody-based therapeutics targeting G protein-coupled receptors: an update.

text: Introduction: G protein-coupled receptors (GPCRs) play key roles in many biological functions and are linked to many diseases across all therapeutic areas. As such, GPCRs represent a significant opportunity for antibody-based therapeutics.Areas covered: The structure of the major GPCR families is summarized in the context of choice of antigen source employed in the drug discovery process and receptor biology considerations which may impact on targeting strategies. An overview of the therapeutic GPCR-antibody target landscape and the diversity of current therapeutic programs is provided along with summary case studies for marketed antibody drugs or those in advanced clinical studies. Antibodies in early clinical studies and the emergence of next-generation modalities are also highlighted.Expert opinion: The GPCR-antibody pipeline has progressed significantly with a number of technical developments enabling the successful resolution of some of the challenges previously encountered and this has contributed to the growing interest in antibody-based therapeutics addressing this target class.


title: Biodegradable implants for sustained drug release in the eye.

text: The safety and effectiveness of systemic and topical medical therapies for ocular disorders are limited due to poor ocular drug uptake, nonspecificity to target tissues, systemic side effects, and poor adherence to therapy. Intravitreal injections can enhance ocular drug delivery, but the need for frequent retreatment and potential injection-related side effects limit the utility of this technique. Sustained-release drug delivery systems have been developed to overcome these limitations; such systems can achieve prolonged therapeutic drug concentrations in ocular target tissues while limiting systemic exposure and side effects and improving patient adherence to therapy. A critical factor in the development of safe and effective drug delivery systems has been the development of biocompatible polymers, which offer the versatility to tailor drug release kinetics for specific drugs and ocular diseases. Ocular implants include nonbiodegradable and biodegradable designs, with the latter offering several advantages. The polymers most commonly used in biodegradable delivery systems are synthetic aliphatic polyesters of the poly-α-hydroxy acid family including polylactic acid, polyglycolic acid, and polylactic-co-glycolic acid. The characteristics of these polymers for medical applications as well as the pharmacological properties, safety, and clinical effectiveness of biodegradable drug implants for the treatment of ocular diseases are reviewed herein.


title: Laparoscopic splenectomy and azygoportal disconnection with intraoperative splenic blood salvage.

text: BACKGROUND Intraoperative blood salvage can reduce or avoid perioperative allogeneic blood transfusion. Salvaging the blood in the portal hypertension-induced enlarged spleen becomes an issue of concern during devascularization surgery because an enlarged spleen accommodates a large red cell pool. We report 20 cases of laparoscopic splenectomy and azygoportal disconnection and present the advantages of the use of intraoperative splenic blood salvage during the procedure. METHODS A total of 20 cirrhotic patients with esophagogastric variceal bleeding refractory to treatment with β-blockers and endoscopic therapy were studied. Laparoscopic splenectomy with azygoportal disconnection was performed. During the procedure, an intraoperative autologous blood salvage device recovered the splenic blood. The perioperative data were recorded from various viewpoints. RESULTS The operative time was 3.1 ± 0.3 h and the blood loss was 70.5 ± 32.5 ml. The weight of the excised and morcellated spleen was 826.0 ± 155.1 g. The volume of autotransfused blood was 541.0 ± 150.4 ml. No patient received a perioperative allogeneic blood transfusion. There were no significant complications either intraoperatively or postoperatively. The hemoglobin value increased from 9.3 ± 0.8 to 11.5 ± 1.1 g/dl at postoperative day 1 (p < 0.01). During a postoperative follow-up period of 18.0 ± 9.0 months for 18 patients, neither esophageal variceal bleeding nor encephalopathy recurred. CONCLUSION Laparoscopic splenectomy with azygoportal disconnection is a feasible, effective, and safe surgical method for the treatment of bleeding portal hypertension. Intraoperative splenic blood salvage can avoid the risk associated with allogeneic transfusion during the procedure, with an advantage of significantly increased postoperative hemoglobin levels.


title: COVID-19 and "natural" experiments arising from physical distancing: a hypothetical case study from chronobiology.

text: With countless "natural" experiments triggered by the COVID-19-associated physical distancing, one key question comes from chronobiology: "When confined to homes, how does the reduced exposure to natural daylight arising from the interruption of usual outdoor activities plus lost temporal organization ordinarily provided from workplaces and schools affect the circadian timing system (the internal 24 h clock) and, consequently, health of children and adults of all ages?" Herein, we discuss some ethical and scientific facets of exploring such natural experiments by offering a hypothetical case study of circadian biology.


title: Incidental finding of malignancy in patients preoperatively evaluated for aneurysm wall pathology using PET/CT.

text: Preoperative positron emission tomography/computed tomography (PET/CT) was performed in 26 consecutive patients considered fit for aneurysm repair. Besides information on aneurysm wall pathology, PET/CT identified 6 patients with concomitant malignancy. As a result of this coincidental finding, the operation was postponed in 2 patients and cancelled in 1. Although previous studies have shown that PET/CT might affect patient selection based on aneurysm wall inflammation, our preliminary results show a big impact on patient management as a result of the sensitivity of PET/CT for detecting malignancy. Future larger studies are warranted to investigate the effect and cost effectiveness of routine PET/CT in abdominal aortic aneurysm (AAA) patients.


Covid-19: Two thirds of people contacted through tracing did not fully cooperate, pilot scheme finds.


Covid-19: what do trainees need to know?


Cluster of chalazia in nurses using eye protection while caring for critically ill patients with COVID-19 in intensive care.


title: Results of endovascular treatment of middle cerebral artery aneurysms after first giving consideration to clipping.

text: BACKGROUND Middle cerebral artery (MCA) aneurysms are among the more challenging aneurysms for endovascular treatment. We report a contemporary 5-year experience with endovascular therapy for MCA aneurysms at a high-volume neurovascular center. METHODS Review of prospectively maintained intracranial aneurysm database. RESULTS Between 2005 and 2009, 148 patients underwent treatment of 149 MCA aneurysms at our hospital, of which 33 patients with 34 aneurysms underwent endovascular therapy. Among these 33 patients, 14 presented with subarachnoid hemorrhage. Eleven patients were treated with stent-assisted coiling, 1 with balloon-assisted coiling, and the remainder with coiling alone. Three patients required repeat endovascular treatment. There were 7 periprocedural complications, including intraprocedural aneurysm rupture resulting in death in 2 patients. Two patients died at later dates from remote aneurysm rehemorrhage. Average follow-up of remaining patients was 17.1 months radiographically, and 20.3 months clinically. Average modified Rankin scale (mRS) score at last follow up was 2.09, with 17 patients with mRS 0/1 and 5 patients with mRS 2. Fifteen patients showed evidence of radiographic residual at last follow up: 13 were simple neck residuals. Unruptured status and saccular aneurysms were associated with mRS 0/1 outcome (each p < 0.05). CONCLUSIONS At our hospital, MCA aneurysms are being treated with endovascular techniques, but in a minority of patients. Despite the rate of residual neck remnants, few retreatments were necessary and few rehemorrhages occurred. The periprocedural complication rate was not insignificant; therefore, in more recent years and at present, most MCA aneurysms are considered for clipping first at our center.


docid: ymxuvolo

title: Influenza A (H1N1): outbreak management in a dialysis unit and clinical outcomes of infection in chronic hemodialysis patients.

text: INTRODUCTION Chronic hemodialysis (HD) patients are considered to be at high risk for infection. Here, we describe the clinical outcomes of chronic HD patients with influenza A (H1N1) infection and the strategies adopted to control an outbreak of influenza A in a dialysis unit. METHODS Among a total of 62 chronic HD patients, H1N1 infection was identified in 12 (19.4%). Of the 32 staff members, four (12.5%) were found to be infected with the H1N1 virus. Outcomes included symptoms at presentation, comorbidities, occurrence of hypoxemia, hospital admission, and clinical evaluation. Infection was confirmed by real-time reverse transcriptase polymerase chain reaction. RESULTS The 12 patients who had H1N1 infection did not differ significantly from the other 50 non-infected patients with respect to age, sex, dialysis vintage, dialysis modality, or proportion of comorbidities. Obesity was higher in the H1N1-infected group (41.5 vs. 4%, p<0.002). The most common symptoms were fever (92%), cough (92%), and rhinorrhea (83%). Early empirical antiviral treatment with oseltamivir was started in symptomatic patients and infection control measures, including the intensification of contact-reduction measures by the staff members, antiviral chemoprophylaxis to asymptomatic patients undergoing HD in the same shift of infected patients, and dismiss of staff members suspected of being infected, were implemented to control the spread of infection in the dialysis unit. CONCLUSION The clinical course of infection with H1N1 in our patients was favorable. None of the patients developed severe disease and the strategies adopted to control the outbreak were successful.


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

text: OBJECTIVE To determine the frequency of enteropathogens in cats entering an animal shelter with normal feces or diarrhea. DESIGN Cross-sectional study. ANIMALS 100 cats evaluated at an open-admission municipal animal shelter in Florida. PROCEDURES Fecal samples collected within 24 hours after admission from 50 cats with normal feces and 50 cats with diarrhea were tested by fecal flotation, antigen testing, PCR assay, and electron microscopy for selected enteropathogens. RESULTS 12 enteropathogens were identified. Cats with diarrhea were no more likely to be infected with ≥ 1 (84%) enteropathogens than were cats with normal feces (84%). Only feline coronavirus was significantly more prevalent in cats with diarrhea (58%) than in cats with normal feces (36%). Other enteropathogens identified in cats with and without diarrhea included Clostridium perfringens enterotoxin A (42% and 50%, respectively), Cryptosporidium spp (10% and 20%, respectively), Giardia spp (20% and 8%, respectively), Cystoisospora spp (14% and 10%, respectively), hookworms (10% and 18%, respectively), ascarids (6% and 16%, respectively), Salmonella spp (6% and 4%, respectively), astrovirus (8% and 2%, respectively), feline panleukopenia virus (4% and 4%, respectively), calicivirus (0% and 2%, respectively), and Spirometra spp (0% and 2%, respectively). CONCLUSIONS AND CLINICAL RELEVANCE In the present study, cats entered the shelter with a variety of enteropathogens, many of which are pathogenic or zoonotic. Most infections were not associated with diarrhea or any specific risk factors such as signalment, source, or body condition, making it difficult to predict which cats were most likely to be infected. It is not possible to test all shelter cats for all possible infections, so practical guidelines should be developed to treat routinely for the most common and important enteropathogens.


title: Modulation of TNF-alpha-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-alpha production and facilitates viral entry.

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) is a high-risk infectious pathogen. In the proposed model of respiratory failure, SARS-CoV down-regulates its receptor, angiotensin-converting enzyme 2 (ACE2), but the mechanism involved is unknown. We found that the spike protein of SARS-CoV (SARS-S) induced TNF-alpha-converting enzyme (TACE)-dependent shedding of the ACE2 ectodomain. The modulation of TACE activity by SARS-S depended on the cytoplasmic domain of ACE2, because deletion mutants of ACE2 lacking the carboxyl-terminal region did not induce ACE2 shedding or TNF-alpha production. In contrast, the spike protein of HNL63-CoV (NL63-S), a CoV that uses ACE2 as a receptor and mainly induces the common cold, caused neither of these cellular responses. Intriguingly, viral infection, judged by real-time RT-PCR analysis of SARS-CoV mRNA expression, was significantly attenuated by deletion of the cytoplasmic tail of ACE2 or knock-down of TACE expression by siRNA. These data suggest that cellular signals triggered by the interaction of SARS-CoV with ACE2 are positively involved in viral entry but lead to tissue damage. These findings may lead to the development of anti-SARS-CoV agents.


title: Who are the Most At-Risk Older Adults in the COVID-19 Era? It's Not Just Those in Nursing Homes.

text: COVID-19 has taken a terrible toll on the nursing home population. Yet, there are five times the number of seniors living in the community who are also extremely vulnerable because they suffer from respiratory illnesses. Using the 2018 wave of the Health and Retirement Study we analyze this group of roughly 7 million seniors living in the community and find that they have multiple risk factors that make them particularly exposed. We also show how current strategies for protecting this population may be exacerbating risks and suggest concrete steps for better protecting this group.


title: In situ cleavage of baculovirus occlusion-derived virus receptor binding protein P74 in the peroral infectivity complex.

text: Proteolytic processing of viral membrane proteins is common among enveloped viruses and facilitates virus entry. The Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) occlusion-derived virus (ODV) protein P74 is part of a complex of essential peroral infectivity factors (PIFs). Here we report that P74 is efficiently cleaved into two fragments of about equal size by an occlusion body (OB) endogenous alkaline protease during ODV release when AcMNPV OBs are derived from larvae. The cleavage is specific for P74, since the other known peroral infectivity factors in the same complex (PIF1, PIF2, and PIF3) were not cleaved under the same conditions. P74 cleavage was not observed in OBs produced in three different insect cell lines, suggesting a larval host origin of the responsible protease. P74 in OBs produced in larvae of two different host species was cleaved into fragments with the same apparent molecular mass, indicating that the virus incorporates a similar alkaline protease from different hosts. Coimmunoprecipitation analysis revealed that the two P74 subunit fragments remain associated with the recently discovered PIF complex. We propose that under in vivo ODV infection conditions, P74 undergoes two sequential cleavage events, the first one being performed by an ODV-associated host alkaline protease and the second carried out by trypsin in the host midgut.


title: Virucidal, antiviral and immunomodulatory activities of β-escin and Aesculus hippocastanum extract.

text: OBJECTIVES β-Escin, one of the constituents of Aesculus hippocastanum L. (Hippocastanaceae) seed extract (AH), inhibits NF-κB activation, which plays an important role in HSV-1 replication. The aim was to examine the antiherpetic activity of β-escin and AH, as well as their effect on the activation of NF-κB and AP-1 and cytokine secretion in epithelial cells and macrophages. METHODS Cell viability was evaluated using MTT assay, and antiviral and virucidal activity was determined by plaque assay. The effect on NF-κB and AP-1 signalling pathways activation was determined by a luciferase reporter assay, and cytokine production was measured by ELISA. KEY FINDINGS β-Escin and AH had virucidal and anti-HSV-1 activities, and the antiviral activity was discovered for other enveloped viruses (VSV and Dengue). Moreover, β-escin and AH significantly reduced NF-κB and AP-1 activation and cytokine production in macrophages stimulated with HSV-1 and TLRs ligands. However, an enhanced activation of these pathways and an increase in the levels of pro-inflammatory cytokines in β-escin and AH-treated HSV-1-infected epithelial cells were found. CONCLUSIONS This study demonstrates virucidal and broad-spectrum antiviral activities for β escin and AH. Besides, β-escin and AH modulate cytokine production depending on the stimuli (viral or non-viral) and the cell type under study.


BET 1: Lopinavir-ritonavir and COVID-19.


title: Association between length of hospital stay and implementation of discharge planning in acute psychiatric inpatients in Japan.

text: BACKGROUND Japan has introduced an acute psychiatric care unit to the public healthcare insurance program, but its requirement of a shorter length of stay could lead to discharges without proper discharge planning. The aim of this study was to examine the association between the implementation of discharge planning and the length of stay of acute psychiatric inpatients in Japan. METHODS This retrospective cross-sectional study included 449 patients discharged from the 'psychiatric emergency ward' of 66 hospitals during a two-week period from March 7 to 20, 2011. The assigned nurse or nursing assistant for each patient provided information on the implementation of discharge planning in the hospital stay. RESULTS Approximately one quarter of the 449 patients (n = 122) received no support for coordination with post-discharge community care resources. The 122 patients who had received no support for community care coordination had a significantly lower mean age at admission, a shorter length of stay, and a higher rate of either no follow-up or unidentified post-discharge outpatient service than the other 327 patients. Multilevel linear regression analysis demonstrated a significantly greater length of stay among patients who were older, those who had a primary diagnosis of schizophrenia, those who were admitted compulsorily, those who received hospital outpatient services, and those who received community care coordination support from the assigned nurse or nursing assistant. The implementation of support for community care coordination did not indicate a significant association with these factors, which have been related to an increased risk of psychiatric readmission. CONCLUSION Patients to whom the assigned nurse or nursing assistant provided support on community care coordination experienced a significantly greater length of hospital stay. The implementation of support for community care coordination did not indicate a significant association with these factors, which have been related to an increased risk of psychiatric readmission. The mental health policy should increase focus on discharge planning in the acute psychiatric setting to enhance a link between psychiatric inpatient care and post-discharge community care resources.


title: Criterion-based laparoscopic training reduces total training time.

text: INTRODUCTION The benefits of criterion-based laparoscopic training over time-oriented training are unclear. The purpose of this study is to compare these types of training based on training outcome and time efficiency. METHODS During four training sessions within 1 week (one session per day) 34 medical interns (no laparoscopic experience) practiced on two basic tasks on the Simbionix LAP Mentor virtual-reality (VR) simulator: 'clipping and grasping' and 'cutting'. Group C (criterion-based) (N = 17) trained to reach predefined criteria and stopped training in each session when these criteria were met, with a maximum training time of 1 h. Group T (time-based) (N = 17) trained for a fixed time of 1 h each session. Retention of skills was assessed 1 week after training. In addition, transferability of skills was established using the Haptica ProMIS augmented-reality simulator. RESULTS Both groups improved their performance significantly over the course of the training sessions (Wilcoxon signed ranks, P < 0.05). Both groups showed skill transferability and skill retention. When comparing the performance parameters of group C and group T, their performances in the first, the last and the retention training sessions did not differ significantly (Mann-Whitney U test, P > 0.05). The average number of repetitions needed to meet the criteria also did not differ between the groups. Overall, group C spent less time training on the simulator than did group T (74:48 and 120:10 min, respectively; P < 0.001). Group C performed significantly fewer repetitions of each task, overall and in session 2, 3 and 4. CONCLUSIONS Criterion-based training of basic laparoscopic skills can reduce the overall training time with no impact on training outcome, transferability or retention of skills. Criterion-based should be the training of choice in laparoscopic skills curricula.


Diabetic Medicine in lock-down.


title: Transvaginal uterine evisceration during labor in a Bengal queen.

text: Case summary A 2.5-year-old Bengal queen was admitted with a 12-h history of a mass protruding from the vulva during labor. At that time, three healthy kittens had already been delivered. Physical examination identified the mass as a portion of the uterus that was eviscerated without eversion of the mucosa. Exploratory laparotomy revealed a vaginal vault rupture with a large portion of the uterus herniated through the tear and eviscerated through the vulva. Ovariohysterectomy was performed, and a dead fetus was removed with the uterus. Reconstruction of the vaginal rupture required careful dissection and urethral catheterization. The queen recovered without complications. Relevance and novel information Uterine evisceration through a vaginal tear is a very rare condition that sometimes is erroneously referred to as 'prolapse'. Uterine prolapse and uterine evisceration may have similar presenting signs; however, proper identification and surgical correction is key when the uterus is eviscerated. This case highlights the importance of differentiating these two conditions and of rapid identification and surgical intervention for successful patient survival.


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title: A Snapshot of Elective Oncological Surgery in Italy During COVID-19 Emergency: Pearls, Pitfalls, and Perspectives.

text: OBJECTIVE To analyze the impact of COVID-19 emergency on elective oncological surgical activity in Italy. SUMMARY OF BACKGROUND DATA COVID-19 emergency shocked national health systems, subtracting resources from treatment of other diseases. Its impact on surgical oncology is still to elucidate. METHODS A 56-question survey regarding the oncological surgical activity in Italy during the COVID-19 emergency was sent to referral centers for hepato-bilio-pancreatic, colorectal, esophago-gastric, and sarcoma/soft-tissue tumors. The survey portrays the situation 5 weeks after the first case of secondary transmission in Italy. RESULTS In total, 54 surgical Units in 36 Hospitals completed the survey (95%). After COVID-19 emergency, 70% of Units had reduction of hospital beds (median -50%) and 76% of surgical activity (median -50%). The number of surgical procedures decreased: 3.8 (interquartile range 2.7-5.4) per week before the emergency versus 2.6 (22-4.4) after (P = 0.036). In Lombardy, the most involved district, the number decreased from 3.9 to 2 procedures per week. The time interval between multidisciplinary discussion and surgery more than doubled: 7 (6-10) versus 3 (3-4) weeks (P < 0.001). Two-third (n = 34) of departments had repeat multidisciplinary discussion of patients. The commonest criteria to prioritize surgery were tumor biology (80%), time interval from neoadjuvant therapy (61%), risk of becoming unresectable (57%), and tumor-related symptoms (52%). Oncological hub-and-spoke program was planned in 29 departments, but was active only in 10 (19%). CONCLUSIONS This survey showed how surgical oncology suffered remarkable reduction of the activity resulting in doubled waiting-list. The oncological hub-and-spoke program did not work adequately. The reassessment of healthcare systems to better protect the oncological path seems a priority.


title: Efficacy of iodine-treated biocidal filter media against bacterial spore aerosols.

text: AIMS To assess the effectiveness of iodine-treated biocidal filter media against bacterial spore aerosols. METHODS AND RESULTS Bacillus subtilis spores were aerosolized and introduced into a filtration system. Both treated and untreated filters exhibited high viable removal efficiency (>99.996%) with negligible variation in pressure drop during the entire experiment. The viability of collected spores on the filter was investigated by enumeration of spores extracted from the filter by vortexing. At room temperature and low relative humidity (RH), the survival fraction of the treated filter was significantly lower than that of the untreated filter (P-value < 0.05). Meanwhile, at room temperature and high RH and at high temperature and high RH, the survival fractions on the treated medium were statistically the same as the untreated control at room temperature and low RH. CONCLUSIONS Both treated and untreated filters achieved excellent viable removal efficiency for spores. The pressure drop of the treated filter was not affected by the iodine treatment. The viability of collected bacterial spores was decreased because of the exertion of iodine disinfectant. SIGNIFICANCE AND IMPACT OF THE STUDY The evaluation demonstrates that the iodine-treated filter is a viable medium for respiratory protection against infectious spore aerosols. The results warrant further evaluation of smaller biological agents, which exhibit higher penetration.


title: Recommendations to Leverage the Palliative Nursing Role During COVID-19 and Future Public Health Crises.

text: With the daily number of confirmed COVID-19 cases and associated deaths rising exponentially, social fabrics on a global scale are being worn by panic, uncertainty, fear, and other consequences of the health care crisis. Comprising more than half of the global health care workforce and the highest proportion of direct patient care time than any other health professional, nurses are at the forefront of this crisis. Throughout the evolving COVID-19 pandemic, palliative nurses will increasingly exercise their expertise in symptom management, ethics, communication, and end-of-life care, among other crucial skills. The literature addressing the palliative care response to COVID-19 has surged, and yet, there is a critical gap regarding the unique contributions of palliative nurses and their essential role in mitigating the sequelae of this crisis. Thus, the primary aim herein is to provide recommendations for palliative nurses and other health care stakeholders to ensure their optimal value is realized and to promote their well-being and resilience during COVID-19 and, by extension, in anticipation of future public health crises.


The successful retrieval of a broken guide wire from the diagonal branch of the left anterior descending coronary artery complicated by partial stent rolling.


title: The compelling arguments for the need for microvascular investigation in COVID-19 critical patients.

text: The burden of pandemic COVID-19 is growing worldwide, as the continuous increases of contagion. Only 10-15% of the entire infected population has the necessity of intensive care unit (ICU) treatments. But, this relatively low rate of patients has absorbed almost the whole availability of ICU during few days, becoming at least in Italy, an emergency for the national health system. In COVID-19 ICU patients massive aggression of lung with severe pulmonary failure, as well as kidney and liver injuries, heart, brain, bowel and spleen damages with lymph nodes necrosis and even cutaneous manifestations have been observed. Moreover, increased levels of cytokines so-called "cytokines storm (CS), and overt intravascular disseminated coagulation have been also reported. The hypercoagulation and CS would speculate about a microvascular dysfunction. Unfortunately, no specific observations have been performed on microcirculatory dysfunction in COVID-19 patients. Hence the presumed pathophysiological pathways and models about a microvascular involvement can be gathered by sepsis models studies. But despite this lack of evidence, the COVID-19 has emphasized the compelling need for microcirculation monitoring at the bedside in ICU patients.


title: Contemporary endovascular and open aneurysm treatment in the era of flow diversion.

text: Clinical outcomes have improved considerably over the last decade for patients with ruptured and unruptured aneurysms. Modern endovascular techniques, such as flow diversion, are associated with high aneurysm occlusion rates and have become a popular treatment modality for many types of aneurysms. However, the safety and effectiveness of flow diversion has not yet been established in trials comparing it with traditional aneurysm treatments. Moreover, there are some types of aneurysms that may not be appropriate for endovascular coiling, such as wide-necked aneurysms located at branch points of major vessels, large saccular aneurysms with multiple efferent arteries, dolichoectatic aneurysms, large aneurysms with mass effect, when there are technical complications with endovascular treatment, when patients cannot tolerate or have contraindications to antiplatelet therapy or in the setting of a subarachnoid haemorrhage. For these cases, open cerebrovascular surgery remains important. This review provides a discussion on the current trends and evidence for both flow diversion and open cerebrovascular surgery for complex aneurysms that may not be suitable for coiling. We emphasise a continued important role for surgical treatment in certain situations.


Covid-19 mass testing facilities could end the epidemic rapidly.


title: On the Way to Close the Loop in Information Logistics: Data from the Patient - Value for the Patient.

text: OBJECTIVE To summarize recent research and to propose a selection of best papers published in 2017 in the field of Clinical Information Systems (CIS). METHOD Each year a systematic process is carried out to retrieve articles and to select a set of best papers for the CIS section of the International Medical Informatics Association (IMIA) Yearbook of Medical Informatics. The query aiming at identifying relevant publications in the field of CIS was refined by the section editors during the last years. For three years now, the query is stable. It comprises search terms from the Medical Subject Headings (MeSH) thesaurus as well as additional free text search terms from PubMed and Web of Science®. The retrieved articles were categorized in a multi-pass review carried out by the two section editors. The final selection of candidate papers was then peer-reviewed by Yearbook editors and external reviewers. Based on the review results, the best papers were then selected by the IMIA Yearbook editorial board. Text mining, and term co-occurrence mapping techniques were used to get an overview on the content of the retrieved articles. RESULTS The query was carried out in mid-January 2018, yielding a consolidated result set of 2,255 articles which had been published in 939 different journals. Out of them, 15 papers were nominated as candidate best papers and four of them were finally selected as best papers in the CIS section. Again, the content analysis of the articles revealed the broad spectrum of topics which is covered by CIS research. CONCLUSIONS Modern clinical information systems serve as backbone for a very complex, trans-institutional information logistics process. Data that is produced by, documented in, shared via, organized in, presented by, and stored within clinical information systems is more and more reused for multiple purposes. We found a lot of examples showing the benefits of such data reuse with various novel approaches implemented to tackle the challenges of this process. We also found that the patient moves in the focus of interest of CIS research. So the loop of information logistics begins to close: data from the patients is used to produce value for the patients.


title: Evolution of laparoscopic liver resection at Singapore General Hospital: a nine-year experience of 195 consecutive resections.

text: INTRODUCTION We aimed to analyse the changing trends, safety and outcomes associated with the adoption of laparoscopic liver resection (LLR) at a single centre. METHODS A retrospective review of patients who underwent LLR from 2006 to 2014 at our institution was performed. To explore the evolution of LLR, the study was divided into three equal consecutive time periods (Period 1: 2006-2008, Period 2: 2009-2011, and Period 3: 2012-2014). RESULTS Among 195 patients who underwent LLR, 24 (12.3%) required open conversions, 68 (34.9%) had resection of tumours in the difficult posterosuperior segments and 12 (6.2%) underwent major (≥ 3 segments) hepatectomies. Median operation time was 210 (range 40-620) minutes and median postoperative stay was 4 (range 1-26) days. Major postoperative morbidity (> Grade II) occurred in 11 (5.6%) patients and 90-day/in-hospital mortality was 1 (0.5%). During the study, the number of LLRs performed showed an increasing trend (Period 1: n = 22; Period 2: n = 19; Period 3: n = 154). Other statistically significant trends were: (a) increase in malignant neoplasms resected; (b) increase in resections of difficult posterosuperior segments; (c) longer median operation time; and (d) decrease in open conversion rates. CONCLUSION Over the study period, the number of LLRs increased rapidly. LLR was increasingly performed for malignant neoplasms and lesions located in the difficult posterosuperior segments, resulting in longer operation times. However, open conversion rates decreased, and there was no change in postoperative morbidity and other perioperative outcomes.


title: Highly Selective Phosphatidylinositol 4-Kinase IIIβ Inhibitors and Structural Insight into Their Mode of Action.

text: Phosphatidylinositol 4-kinase IIIβ is a cellular lipid kinase pivotal to pathogenesis of various RNA viruses. These viruses hijack the enzyme in order to modify the structure of intracellular membranes and use them for the construction of functional replication machinery. Selective inhibitors of this enzyme are potential broad-spectrum antiviral agents, as inhibition of this enzyme results in the arrest of replication of PI4K IIIβ-dependent viruses. Herein, we report a detailed study of novel selective inhibitors of PI4K IIIβ, which exert antiviral activity against a panel of single-stranded positive-sense RNA viruses. Our crystallographic data show that the inhibitors occupy the binding site for the adenine ring of the ATP molecule and therefore prevent the phosphorylation reaction.