title: Interferon Regulatory Factor 1 Protects against Chikungunya Virus-Induced Immunopathology by Restricting Infection in Muscle Cells.

text: The innate immune system protects cells against viral pathogens in part through the autocrine and paracrine actions of alpha/beta interferon (IFN-α/β) (type I), IFN-γ (type II), and IFN-λ (type III). The transcription factor interferon regulatory factor 1 (IRF-1) has a demonstrated role in shaping innate and adaptive antiviral immunity by inducing the expression of IFN-stimulated genes (ISGs) and mediating signals downstream of IFN-γ. Although ectopic expression experiments have suggested an inhibitory function of IRF-1 against infection of alphaviruses in cell culture, its role in vivo remains unknown. Here, we infected Irf1 -/- mice with two distantly related arthritogenic alphaviruses, chikungunya virus (CHIKV) and Ross River virus (RRV), and assessed the early antiviral functions of IRF-1 prior to induction of adaptive B and T cell responses. IRF-1 expression limited CHIKV-induced foot swelling in joint-associated tissues and prevented dissemination of CHIKV and RRV at early time points. Virological and histological analyses revealed greater infection of muscle tissues in Irf1 -/- mice than in wild-type mice. The antiviral actions of IRF-1 appeared to be independent of the induction of type I IFN or the effects of type II and III IFNs but were associated with altered local proinflammatory cytokine and chemokine responses and differential infiltration of myeloid cell subsets. Collectively, our in vivo experiments suggest that IRF-1 restricts CHIKV and RRV infection in stromal cells, especially muscle cells, and that this controls local inflammation and joint-associated swelling.IMPORTANCE Interferon regulatory factor 1 (IRF-1) is a transcription factor that regulates the expression of a broad range of antiviral host defense genes. In this study, using Irf1 -/- mice, we investigated the role of IRF-1 in modulating pathogenesis of two related arthritogenic alphaviruses, chikungunya virus and Ross River virus. Our studies show that IRF-1 controlled alphavirus replication and swelling in joint-associated tissues within days of infection. Detailed histopathological and virological analyses revealed that IRF-1 preferentially restricted CHIKV infection in cells of nonhematopoietic lineage, including muscle cells. The antiviral actions of IRF-1 resulted in decreased local inflammatory responses in joint-associated tissues, which prevented immunopathology.


title: Hybrid vaginal MA-NOS sleeve gastrectomy: technical note on the procedure in a patient.

text: BACKGROUND Standard sleeve gastrectomy for the morbidly obese is feasible and safe using the hybrid transvaginal minilaparoscopic-assisted natural orifice surgery (MA-NOS) with available laparoscopic/endoscopic instruments and technology as illustrated by this technical report on a female patient. METHODS The intervention was a transvaginal sleeve gastrectomy in a 67-year-old woman who was hypertensive, noninsulin-dependent with diabetes with morbid obesity (BMI, 37). Operative field view was maintained at all times with a gastroscope introduced through a transvaginal trocar. The surgeon positioned himself at the right side of the patient using a 2-mm needle port/mini-grasper placed in the left upper quadrant for traction of the greater curvature of the stomach. A 12-mm umbilical trocar was used as the port for insertion of the LigaSure device used for division of the short gastric vessels and the Endo-GIA stapler for creation of the gastric tube. The first assistant used a second mini-grasper for liver retraction and stomach positioning. The resected stomach was retrieved through the vagina. There were no intraoperative complications. The operative time was 150 minutes. RESULTS The advantages of minimally invasive surgery seemed to be enhanced with this hybrid laparoscopic approach. Postoperative course was uneventful. All component steps of a laparoscopic sleeve gastrectomy (LSG) were reproduced. The patient was discharged on the third postoperative day. CONCLUSIONS Transvaginal hybrid MA-NOS sleeve gastrectomy is both feasible and safe. The hybrid technique ensured safety during the performance of the procedure. MA-NOS is a potential option to avoid abdominal incisions and related complications for the laparoscopic resection of large intra-abdominal organs. Combined hybrid laparoscopic NOS for humans is currently a safe and reliable approach for major surgery through the NOS approach in female patients. Hybrid surgery allows controlled implementation of NOS techniques in clinical practice, providing a stepwise progression to the pure NOS approach once the appropriate technology has been developed. Additionally, it is the best way to stimulate the active development and evaluation of the underpinning technologies and instruments for these novel endoscopic surgical approaches. Appropriate clinical indications for these new procedures are yet to be defined. LSG is associated with short-term excess weight loss and resolution of comorbidities comparable to those obtained with other restrictive procedures. The performance of sleeve gastrectomy is an option in selected patients undergoing bariatric surgical treatment, particularly in the super obese and those who are considered high risk because of comorbid disease.


docid: jerxafkr

title: The differences in histological changes among pulmonary vessels divided with an energy device.

text: OBJECTIVES Histological changes after division of the pulmonary artery (PA) and the pulmonary vein (PV) using a vessel-sealing device are not fully understood. The goal of the present study was to clarify histologically and immunohistochemically how division with the device affects the wall layers of the pulmonary vasculature. METHODS This prospective cohort study analysed outcomes of 20 patients who underwent anatomical lung resection. After a single proximal ligation, the PA and the PV (diameter 2-7 mm) were divided using a LigaSure Blunt Tip (LSB). Histological findings and thermal damage were evaluated in vascular specimens from resected lungs. RESULTS The PA has a well-developed media with rich elastic fibres and a thin adventitia, whereas the PV has a thinner media and a thicker adventitia with abundant collagen fibres. Vascular division of the PAs and PVs appeared complete to the naked eye. However, in all divided PAs, the area adjacent to the sealed zone comprised only adventitia and thin disrupted media. Additionally, thermal energy generated by the LSB resulted in a wide area of thermal necrosis over the histologically fragile region in all cases. Conversely, the wall layers of all divided PVs were completely fused without disruption. Thermal spread and disruption did not significantly differ between small (2-4 mm) and large (5-7 mm) PAs [187 (150-253) vs 236 (190-275) μm, P = 0.22; 180 (138-200) vs 210 (161-305) μm, P = 0.22]. Histological changes differed significantly between the pulmonary vessels after division using the LSB. CONCLUSIONS Surgeons should consider that dividing the pulmonary vessels with a vessel-sealing device might have more histological impact on the layers of the wall of the PA than on those of the PV, although it remains unclear whether these findings constitute a clinical risk.


title: Nitrogenous subcutaneous emphysema caused by spray application of fibrin glue during retroperitoneal laparoscopic surgery.

text: We report a case of a patient treated by retroperitoneoscopic partial nephrectomy who developed nitrogenous subcutaneous emphysema (SCE) as a complication. The use of a nitrogen gas-pressured fibrin tissue adhesive applied as a spray caused excessively increased pressure in the closed retroperitoneal space and resulted in widespread SCE with protracted clinical course. To the best of our knowledge, this is the first report of nitrogenous SCE associated with pneumoperitoneum. The clinical significance of nitrogenous SCE is emphasized, and the risks associated with the use of fibrin glue as a spray during laparoscopic surgery are discussed.


docid: ogvrxbnz

title: Perioperative management of shock in two fontan patients with plastic bronchitis.

text: Plastic bronchitis is potentially a life-threatening complication of long-standing surgically palliated single ventricle congenital heart disease. Patients can present with hypoxia requiring urgent bronchoscopy for removal of bronchial casts. Perioperative care for these patients is challenging and anesthesia is associated with significant cardiac risk. As more surgically corrected single ventricle patients survive to adulthood, these patients are expected to present more frequently. This report details the perioperative management of 2 Fontan patients with hypoxia and significant plastic bronchitis disease burden.


Covid-19: Over 300 Italian doctors and scientists call for more testing.


'We need to be alert': Scientists fear second coronavirus wave as China's lockdowns ease.


title: Identifying process and outcome indicators of successful transitions from child to adult mental health services: protocol for a scoping review.

text: INTRODUCTION A significant proportion of youth need to transition from child and adolescent mental health services (CAMHS) to adult mental health services (AMHS); however, the transition process is not well understood and often experienced poorly by youth. In the effort to design and evaluate standards of practice for transitions, there is a need to identify key elements of a successful transition. The objectives of this scoping review are to: (1) identify definitions of successful transitions from CAMHS to AMHS; and (2) identify indicators that have been used to measure CAMHS-AMHS transition care processes and quality, and outcomes. METHODS We will search 8 electronic bibliographic databases from 1980 to 2016 (eg, Medline, EMBASE, PsycINFO), professional associations, policy documents, and other grey literature to identify relevant material. We will include experimental, quasi-experimental, observational studies, and non-research studies (guidelines, narrative reviews, policy documents) examining the transition from CAMHS to AMHS. 2 raters will independently screen each retrieved title and abstract for eligibility using the study inclusion criteria (level 1), and then will independently assess full-text articles to determine if these meet the inclusion criteria (level 2). Data extraction will be completed and results will be synthesised both quantitatively and qualitatively. ETHICS AND DISSEMINATION The results of the scoping review will be used to develop a set of indicators that will be prioritised and evaluated in a Delphi consensus study. This will serve as a foundation for the development of the first instrument to assess the quality and success of CAMHS-AMHS transitions. Ethics approval is not required for this scoping study.


title: Effectiveness of workplace interventions in rehabilitating musculoskeletal disorders and preventing its consequences among workers with physical and sedentary employment: systematic review protocol.

text: BACKGROUND Musculoskeletal disorders (MSDs) are the leading cause of work disability and sickness absence worldwide. The prevalence of MSDs increases with age, consequently challenging sustainable employability among the growing ageing workforce. Knowledge of feasible and efficient workplace-based interventions to rehabilitate MSD or prevent its consequences is therefore warranted. This systematic review will evaluate the effectiveness of workplace-based interventions on MSDs and its consequences among adult workers with physical and sedentary work tasks, respectively. METHODS We will search the following bibliographic databases: PubMed (including the database 'MEDLINE') and Web of Science Core Collection (including the databases 'Science Citation Index Expanded', 'Social Sciences Citation Index' and 'Arts & Humanities Citation Index'). Manual searches will also be performed. We will include randomised controlled trials (RCTs) and non-RCTs reported in English in which (1) participants are adult workers with MSD, (2) interventions are aiming at rehabilitating pain symptoms of MSD or preventing the consequences of MSD and (3) interventions are initiated and/or carried out at the workplace. The review will adhere to the 'Preferred Reporting Items for Systematic reviews and Meta-Analyses' (PRISMA) guidelines for reporting systematic reviews and the Institute for Work and Health (IWH) guidelines for workplace-based interventions. For the primary evaluation of the review, the quality assessment and evidence synthesis will conform to the IWH guidelines. Secondary evaluation will include a meta-analysis (unless the included studies do not allow this due to heterogeneity) and employ the risk of bias domains recommended by Cochrane along with the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach on the studies with pain intensity as an outcome. DISCUSSION This systematic review will provide knowledge on effective workplace-based interventions among physical and sedentary workers with MSD. RCTs are considered the most powerful experimental design in clinical trials, but solely including these may be too restrictive to understand effective workplace-based interventions where randomised and carefully controlled trials (RCTs) are not always possible. In order to maximize practical relevance, the selection process will, therefore, include both RCTs and non-RCTs and the quality assessment and evidence synthesis will conform to IWH guidelines focusing on developing practical guidelines for stakeholders. The result of this work will form the basis for industry-specific evidence-based recommendations on effective workplace-based interventions for rehabilitation of MSDs and its consequences that will later be operationalised into concrete and user-friendly practical tools for workplaces. SYSTEMATIC REVIEW REGISTRATION International Prospective Register of Systematic Reviews (PROSPERO) number CRD42018116752 .


title: What will it take to eliminate drug-resistant tuberculosis?

text: Drug-resistant tuberculosis (DR-TB) is challenging to diagnose, treat, and prevent, but this situation is slowly changing. If the world is to drastically reduce the incidence of DR-TB, we must stop creating new DR-TB as an essential first step. The DR-TB epidemic that is ongoing should also be directly addressed. First-line drug resistance must be rapidly detected using universal molecular testing for resistance to at least rifampin and, preferably, other key drugs at initial TB diagnosis. DR-TB treatment outcomes must also improve dramatically. Effective use of currently available, new, and repurposed drugs, combined with patient-centered treatment that aids adherence and reduces catastrophic costs, are essential. Innovations within sight, such as short, highly effective, broadly indicated regimens, paired with point-of-care drug susceptibility testing, could accelerate progress in treatment outcomes. Preventing or containing resistance to second-line and novel drugs is also critical and will require high-quality systems for diagnosis, regimen selection, and treatment monitoring. Finally, earlier detection and/or prevention of DR-TB is necessary, with particular attention to airborne infection control, case finding, and preventive therapy for contacts of patients with DR-TB. Implementing these strategies can overcome the barrier that DR-TB represents for global TB elimination efforts, and could ultimately make global elimination of DR-TB (fewer than one annual case per million population worldwide) attainable. There is a strong cost-effectiveness case to support pursuing DR-TB elimination; however, achieving this goal will require substantial global investment plus political and societal commitment at national and local levels.


title: Differences in Glycoprotein Complex Receptor Binding Site Accessibility Prompt Poor Cross-Reactivity of Neutralizing Antibodies between Closely Related Arenaviruses.

text: The glycoprotein complex (GPC) of arenaviruses, composed of stable signal peptide, GP1, and GP2, is the only antigen correlated with antibody-mediated neutralization. However, despite strong cross-reactivity of convalescent antisera between related arenavirus species, weak or no cross-neutralization occurs. Two closely related clade B viruses, Machupo virus (MACV) and Junín virus (JUNV), have nearly identical overall GPC architecture and share a host receptor, transferrin receptor 1 (TfR1). Given structural and functional similarities of the GP1 receptor binding site (RBS) of these viruses and the recent demonstration that the RBS is an important target for neutralizing antibodies, it is not clear how these viruses avoid cross-neutralization. To address this, MACV/JUNV chimeric GPCs were assessed for interaction with a group of α-JUNV GPC monoclonal antibodies (MAbs) and mouse antisera against JUNV or MACV GPC. All six MAbs targeted GP1, with those that neutralized JUNV GPC-pseudovirions competing with each other for RBS binding. However, these MAbs were unable to bind to a chimeric GPC composed of JUNV GP1 containing a small disulfide bonded loop (loop 10) unique to MACV GPC, suggesting that this loop may block MAbs interaction with the GP1 RBS. Consistent with this loop causing interference, mouse anti-JUNV GPC antisera that solely neutralized pseudovirions bearing autologous GP1 provided enhanced neutralization of MACV GPC when this loop was removed. Our studies provide evidence that loop 10, which is unique to MACV GP1, is an important impediment to binding of neutralizing antibodies and contributes to the poor cross-neutralization of α-JUNV antisera against MACV.IMPORTANCE Multiple New World arenaviruses can cause severe disease in humans, and some geographic overlap exists among these viruses. A vaccine that protects against a broad range of New World arenaviruses is desirable for purposes of simplicity, cost, and broad protection against multiple National Institute of Allergy and Infectious Disease-assigned category A priority pathogens. In this study, we sought to better understand how closely related arenaviruses elude cross-species neutralization by investigating the structural bases of antibody binding and avoidance. In our studies, we found that neutralizing antibodies against two New World arenaviruses, Machupo virus (MACV) and Junín virus (JUNV), bound to the envelope glycoprotein 1 (GP1) with JUNV monoclonal antibodies targeting the receptor binding site (RBS). We further show that altered structures surrounding the RBS pocket in MACV GP1 impede access of JUNV-elicited antibodies.


title: Angioplasty for renal artery stenosis in pediatric patients: an 11-year retrospective experience.

text: PURPOSE Studies of long-term percutaneous transluminal angioplasty (PTA) results have been less extensive in children than in adults. The authors sought to evaluate the outcomes of PTA for pediatric renovascular hypertension. MATERIALS AND METHODS The authors retrospectively evaluated 19 hypertensive children (ages 2-18 years) who underwent renal PTA from 1997-2009. Angiograms were reviewed in consensus to characterize lesions. This information was correlated with data from chart review to determine clinical outcomes. RESULTS Seven patients had neurofibromatosis type 1 (NF1), and 12 had fibromuscular dysplasia (FMD); one was lost to follow-up. Technical success was achieved in 29 of 32 lesions (91%). Cure of hypertension was achieved in seven of 18 patients (39%) and improvement in three (17%). There was a failed hypertension response in eight (44%): two with refractory stenosis, four with recurrent stenosis, and two with no response despite technical success. PTA was repeated in five children, all with failed response. Cure or improvement was seen in five of seven patients with NF1 and five of 11 with FMD. Most (nine of ten) patients with cure/improvement had single lesions or discrete lesions ≤ 10 mm. Residual stenosis < 10% was associated with cure/improvement (P = .0395). Three of five with bilateral and two of two with intraparenchymal disease demonstrated failure. The percentage of initial stenosis and presence of ostial lesions, aneurysms, or collaterals were not predictive of clinical response to PTA (P > .05). Cutting balloons were used after failure to efface with conventional balloons in seven patients and was successful in five of seven. CONCLUSIONS Despite a high rate of technical success, PTA provided a clinical benefit in a smaller majority of children. This study characterizes the utility of pediatric renal angioplasty and suggests criteria that may be prognostic of patient response.


title: Complications following 573 percutaneous renal radiofrequency and cryoablation procedures.

text: PURPOSE To review complications related to percutaneous renal tumor ablation. MATERIALS AND METHODS Prospectively collected data related to renal radiofrequency (RF) ablation and cryoablation procedures performed from May 2000 through November 2010 were reviewed. This included 573 renal ablation procedures performed in 533 patients to treat 633 tumors. A total of 254 RF ablation and 311 cryoablation procedures were performed; eight patients underwent simultaneous RF ablation and cryoablation. The mean age of patients at the time of the procedure was 70 years (range, 24-93 y), and 382 of 573 procedures (67%) were performed in male patients. Complications were recorded according to the Clavien-Dindo classification scheme. Duration of hospitalization was also documented. RESULTS Of the 573 procedures, 63 produced complications (11.0% overall complication rate). There were 66 reported complications, of which 38 (6.6% of total procedures) were Clavien-Dindo grade II-IV major complications; there were no deaths. Major complication rates did not differ statistically (P = .15) between cryoablation (7.7%; 24 of 311) and RF ablation (4.7%; 12 of 254). Of the complications related to cryoablation, bleeding and hematuria were most common. Bleeding during cryoablation was associated with advanced age, increased tumor size, increased number of cryoprobes, and central position (P < .05). Of those treated with RF ablation, nerve and urothelial injury were most common. Mean hospitalization duration was 1 day for RF ablation and cryoablation. CONCLUSIONS Complications related to percutaneous renal ablation are infrequent. Recognition of potential complications and associated risk factors can allow optimization of periprocedural care.


title: Inhibition of vaccinia virus replication by two small interfering RNAs targeting B1R and G7L genes and their synergistic combination with cidofovir.

text: In view of the threat of the potential use of variola virus in a terrorist attack, considerable efforts have been performed to develop new antiviral strategies against orthopoxviruses. Here we report on the use of RNA interference, either alone or in combination with cidofovir, as an approach to inhibit orthopoxvirus replication. Two selected small interfering RNAs (siRNAs), named siB1R-2 and siG7L-1, and a previously reported siRNA, i.e., siD5R-2 (which targets the viral D5R mRNA), were evaluated for antiviral activity against vaccinia virus (VACV) by plaque reduction and virus yield assays. siB1R-2 and siG7L-1, administered before or after viral infection, reduced VACV replication by more than 90%. Also, these two siRNAs decreased monkeypox virus replication by 95% at a concentration of 1 nM. siB1R-2 and siG7L-1 were demonstrated to specifically silence their corresponding transcripts, i.e., B1R and G7L mRNAs, without induction of a beta interferon response. Strong synergistic effects were observed when siB1R-2, siG7L-1, or siD5R-2 was combined with cidofovir. In addition, the antiviral activities of these three siRNAs were evaluated against VACV resistant to cidofovir and other acyclic nucleoside phosphonates. siG7L-1 and siD5R-2 remained active against four of five VACV mutants, while siB1R-2 showed activity against only one of the mutants. Our results showed that siRNAs are potent inhibitory agents in vitro, not only against wild-type VACV but also against several cidofovir-resistant VACV. Furthermore, we showed that a combined therapy using siRNA and cidofovir may be useful in the treatment of poxvirus infections.


title: Two-phase anaerobic co-digestion of food waste and sewage sludge.

text: The feasibility and performance of food waste and sewage sludge co-digestion were investigated to gain insight into their resource utilization. In this study, two-phase anaerobic digestion (TPAD) was operated under a total solids mixing ratio of 1:1 and different sludge retention times (SRTs). Results show that an acidogenic reactor with a 5-day SRT obtained the highest acidification efficiency, and its acetic acid content was dominant. The organic removal rate of a methanogenic reactor (MR) with a 20-day SRT and its corresponding TPAD system with a 25-day SRT were both the highest among the MRs and TPAD systems. Volatile solids and total chemical oxygen demand average removal efficiencies of the TPAD system with a 25-day SRT reached 64.7 and 60.8%, respectively. The MR with a 30-day SRT obtained the minimum ratio of volatile fatty acid to alkalinity (0.12). The methane content generated from the different MRs fluctuated at around 70%. All of the above results can provide reference for future research.


title: The recruitment of extra-intestinal cells to the injured mucosa promotes healing in radiation enteritis and chemical colitis in a mouse parabiosis model.

text: Mucosal healing occurs through migration and proliferation of cells within injured epithelium, yet these processes may be inadequate for mucosal healing after significant injury where the mucosa is denuded. We hypothesize that extra-intestinal cells can contribute to mucosal healing after injury to the small and large intestine. We generated parabiotic pairs between wild-type and tdTomato mice, which were then subjected to radiation-induced enteritis and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. We now show that as compared with singleton mice, mice with a parabiotic partner were protected against intestinal damage as revealed by significantly reduced weight loss, reduced expression of pro-inflammatory cytokines, reduced enterocyte apoptosis, and improved crypt proliferation. Donor cells expressed CD45-, Sca-1+, c-kit+, and CXCR4+ and accumulated around the injured crypts but did not transdifferentiate into epithelia, suggesting that extra-intestinal cells play a paracrine role in the healing response, while parabiotic pairings with Rag1-/- mice showed improved healing, indicating that adaptive immune cells were dispensable for mucosal healing. Strikingly, ablation of the bone marrow of the donor parabionts removed the protective effects. These findings reveal that the recruitment of extra-intestinal, bone marrow-derived cells into the injured intestinal mucosa can promote mucosal healing, suggesting novel therapeutic approaches for severe intestinal disease.


title: Mechanical thrombectomy for acute stroke in childhood: how much does restricted diffusion matter?

text: Mechanical thrombectomy holds promise for children with large cerebral arterial occlusions, although there are few reports in this population. We report a case of retrievable stent-assisted mechanical thrombectomy in a 5-year-old with basilar artery occlusion, despite late presentation and extensive initial diffusion-weighted imaging (DWI) restriction. This resulted in successful Thrombolysis in Cerebral Infarction 2B reperfusion and excellent clinical outcome. At 6-week follow-up he was completely back to baseline with no residual deficits (pediatric stroke outcome measure=0, modified Rankin scale=0). At 3-month follow-up the patient has not had any recurrent stroke or concern for stroke-like symptoms. We review the literature on mechanical thrombectomy and DWI changes in acute stroke in early to middle childhood (<12 years old).


title: New procedures for uterine prolapse.

text: Traditionally, vaginal hysterectomy and Manchester repair were the surgical approaches to treating uterine prolapse; however, both are associated with a relatively high subsequent vaginal vault recurrence. Laparoscopic uterine suspension is a new way of maintaining uterine support. Many women are keen to keep their uterus for a variety of reasons, including maintaining reproductive capability and the belief that the uterus, cervix, or both, may play a part of their gender identity. Non-removal of the uterus may retain functional (e.g. bowel, bladder and sexual) benefits. Therefore, the concept of uterine preservation for pelvic-organ prolapse has been of interest to pelvic-floor surgeons for many decades. In this review, we provide an overview of the available evidence on treating uterine prolapse surgically. We describe techniques to support the vault during hysterectomy, and examine the evidence for uterine-sparing surgery. Comparative outcomes for vaginal, abdominal and laparoscopic routes will be made.


title: Comparison of prenatal and postnatal treatments of spina bifida in Poland--a non-randomized, single-center study.

text: OBJECTIVE The aim of this study was a comparison of the outcomes of intrauterine myelomeningocele (MMC) repairs (IUMR) in type II Chiari malformation (II CM) fetuses with clinical data of newborns and infants operated on postnatally. METHODS The study group (SG) comprised 46 pregnant women whose type II CM children underwent IUMR, while 47 pregnant women whose type II CM children were operated on postnatally constituted the control group (CG). A total of 24 SG and 20 CG patients reached the endpoint of the study. RESULTS High incidence of prelabor rupture of membranes (24 (52.2%), CI: 3.74 (1.69-8.26) (p < 0.001) was noted in the group of prenatal surgeries as compared to controls. The need for ventriculoperitoneal shunt implantation was statistically significantly lower (p < 0.008) in the group of children after IUMR as compared to controls (5 (27.8%) and 16 (80%), respectively, CI: 0.35 (0.16-0.75). None of the postnatally treated CG children can walk without adaptive equipment. In contrast, two children from the SG (2 (11.1%) CI: 1.86 (1.00-3.48) p < 0.05) are able to walk independently. CONCLUSIONS Prenatal MMC closure significantly lowers further adverse evolution of the II CM. Further studies are needed, especially on preventive measures for preterm labor and iatrogenic preterm prelabor rupture of membranes (iPPRM) in the postoperative course of IUMR.


title: Design and evaluation of sifuvirtide, a novel HIV-1 fusion inhibitor.

text: Enfuvirtide (T20) is the first and only HIV-1 fusion inhibitor approved for clinical use, but it can easily induce drug resistance limiting its practical application. A novel anti-HIV peptide, termed sifuvirtide, was designed based on the three-dimensional structure of the HIV-1 gp41 fusogenic core conformation. Here we report its in vitro anti-HIV potency, its mechanism of action, as well as the results from Phase Ia clinical studies. We demonstrated that sifuvirtide inhibited HIV-1-mediated cell-cell fusion in a dose-dependent manner and exhibited high potency against infections by a wide range of primary and laboratory-adapted HIV-1 isolates from multiple genotypes with R5 or X4 phenotypes. Notably, sifuvirtide was also highly effective against T20-resistant strains. Unlike T20, sifuvirtide could efficiently block six-helix bundle formation in a dominant negative fashion. These results suggest that sifuvirtide has a different mechanism of action from that of T20. Phase Ia clinical studies of sifuvirtide (FS0101) in 60 healthy individuals demonstrated good safety, tolerability, and pharmacokinetic profiles. A single dose regimen (5, 10, 20, 30, and 40 mg) by subcutaneous injection once daily at abdominal sites was well tolerated without serious adverse events. Pharmacokinetic studies of single and multiple administration of sifuvirtide showed that its decay half-lives were 20.0 +/- 8.6 h and 26.0 +/- 7.9 h, respectively. In summary, sifuvirtide has potential to become an ideal fusion inhibitor for treatment of HIV/AIDS patients, including those with HIV-1 strains resistant to T20.


Curbing Youth E-cigarette Use Must Remain a Priority.


title: Is intraoperative neural monitoring necessary for exploration of the superior laryngeal nerve?

text: BACKGROUND We aimed to evaluate the contribution of intraoperative neuromonitoring to the visual and functional identification of the external branch of the superior laryngeal nerve and the effect on postoperative voice changes. METHODS The prospective data of 221 patients (183 women, 38 men) who underwent thyroid operation with intraoperative neuromonitoring for exploration of the external branch of the superior laryngeal nerve were evaluated retrospectively. The surface endotracheal tube-based Medtronic NIM3 (Medtronic, Jacksonville, FL) intraoperative neuromonitoring device was used. The function of the external branch of the superior laryngeal nerve was evaluated by cricothyroid muscle twitch. Additionally, the contribution of the external branch of the superior laryngeal nerve to vocal cord adduction was evaluated using electromyographic records. RESULTS A total of 374 (95.2%) of 393 external branch of the superior laryngeal nerves were identified; 145 (36.9%) external branch of the superior laryngeal nerves were identified visually before being stimulated with a probe, and 130 (33.1%) external branch of the superior laryngeal nerves were identified visually after being identified with a probe. Although 99 (25.2%) external branch of the superior laryngeal nerves were identified with a probe, they were not visualized. Intraoperative neuromonitoring provided meaningful contributions to visual (P = .001) and functional (P = .001) identification of the external branch of the superior laryngeal nerve. Positive electromyographic responses were recorded from 257 external branch of the superior laryngeal nerves (68.7%). After the patients with recurrent laryngeal nerve palsy were excluded, voice changes were detected in 6 (3.3%) of 184 patients with identified external branch of the superior laryngeal nerves and 3 (20%) of 15 patients in whom at least 1 external branch of the superior laryngeal nerve could not be identified with intraoperative neuromonitoring. CONCLUSION Intraoperative neuromonitoring provided an important contribution to the visual and functional identification of the external branch of the superior laryngeal nerve. Intraoperative neuromonitoring is a helpful adjunct for identifying the external branch of the superior laryngeal nerve.


title: A new method for the radiochemical purity measurement of ¹¹¹In-pentetreotide.

text: OBJECTIVES AND METHODS The recommended method for the measurement of radiochemical purity (RCP) of ¹¹¹In-labelled pentetreotide is thin-layer chromatography with a silica gel as the stationary phase and a 0.1 N sodium citrate solution (pH 5) as the mobile phase. According to the supplier's instructions, the mobile phase must be prepared before the test is carried out, and the recommended stationary phase is off-market. We propose a new method for RCP measurement in which the mobile phase is acid citrate dextrose, solution A, which does not need to be prepared beforehand, and thin-layer chromatography is performed with a silica gel-impregnated glass fibre sheet as the stationary phase. We used both methods to measure the percentages of radiopharmaceutical and impurities. RESULTS The range of RCP values obtained was 98.0-99.9% (mean=99.3%) by the standard method and 98.1-99.9% (mean=99.2%) by the new method. We observed no differences between the RCP values of both methods (P=0.070). CONCLUSION The proposed method is suitable for RCP testing because it yields results that are in good agreement with those of the standard method and because it is easier to perform as the mobile-phase solution need not be prepared in advance.


title: Development of a Taqman RT-PCR assay for the detection and quantification of negatively stranded RNA of human enteroviruses: evidence for false-priming and improvement by tagged RT-PCR.

text: Human enteroviruses are among the most common viruses infecting humans. These viruses are known to be able to infect a wide range of tissues and are believed to establish persistent infections. Enteroviruses are positive-sense single-stranded RNA viruses whose replication involves the synthesis of negative strand intermediates. Therefore, the specific detection of negatively stranded viral RNA in tissues or cells is a reliable marker of active enteroviral replication. The present report presents the development of a real-time RT-PCR allowing the specific detection and quantification of negatively stranded viral RNA. Since it was known that specific amplification of single-stranded RNA can be made difficult by false-priming events leading to false-positive or overestimated results, the assay was developed by using a tagged RT primer. This tagged RT-PCR was shown to be able to amplify specifically negative RNA of enteroviruses grown in cell cultures by preventing the amplification of cDNAs generated by false-priming.


title: Intraoperative tissue oxygenation and postoperative outcomes after major non-cardiac surgery: an observational study.

text: BACKGROUND The relationship between tissue oxygen saturation (StO(2)) and serious postoperative complications remains unclear. We tested the hypothesis that perioperative in patients undergoing major non-cardiac surgery is inversely related to serious surgical outcomes. METHODS We enrolled 124 patients, ASA physical status ≤IV, having elective major non-cardiac surgeries with general anaesthesia. An InSpectra Model 650 StO(2) monitor (Hutchinson Technology, Hutchinson, MN, USA) was used to measure at the thenar eminence throughout surgery and for two postoperative hours. Our primary outcome was a composite of 30 day mortality and serious in-hospital complications. The secondary outcome was an a priori subset of the primary composite outcome representing infectious and wound-healing complications. Multivariable logistic regression was used to evaluate the associations between our primary and secondary outcomes and time-weighted average (TWA) and minimum . RESULTS Patients were 61 (12), mean (SD) yr old. The minimum was inversely associated with our primary composite outcome (P=0.02). The estimated odds ratio (97.5% CI) of having any major postoperative morbidity was 0.82 (0.67, 1.00) for a 5% increase in the minimum . In contrast, TWA was not significantly associated with major postoperative morbidity (P=0.35). Furthermore, neither TWA (P=0.65) nor minimum (P=0.70) was significantly associated with wound complications. CONCLUSIONS Minimum perioperative peripheral tissue oxygenation predicted a composite of major complications and mortality from major non-cardiac surgery. This is an observational association and whether clinical interventions to augment tissue oxygenation will improve outcomes remains to be determined.


title: A preliminary study of silver sodium zirconium phosphate polyurethane foam wound dressing on wounds of the distal aspect of the forelimb in horses.

text: OBJECTIVE To determine if application of silver sodium zirconium phosphate polyurethane semi-occlusive foam (SPF) dressing would improve measures of wound healing and decrease bacterial contamination compared with a non-adherent, absorbent dressing applied to wounds created on the distal aspect of the equine limb. STUDY DESIGN Controlled randomized experimental study. ANIMALS Adult Quarter Horse and Thoroughbred horses (n = 5). METHODS One 6.25 cm(2) wound was created on the dorsomedial aspect of the proximal metacarpus on each forelimb. A SPF dressing was applied to 1 randomly assigned limb as a treatment and a non-adherent, absorbent dressing was applied to the opposite limb as control. Bandages were changed every 3 days for 60 days. Granulation tissue was scored every 3 days, wound area measured every 6 days, and wound bed was cultured every 12 days. RESULTS SPF-treatment wounds had significantly decreased wound area and decreased granulation tissue scores when evaluated <30 days and over the 60 day study, although complete wound healing times were not significantly different. Bacteria were cultured from all wounds at varying times throughout the study. CONCLUSIONS The SPF wound dressing improved some measures of wound healing compared with the control dressing, most significantly during the first 30 days. This suggests that the SPF wound dressing may be useful in the early management of wounds on the equine lower limb. Further studies using the SPF dressing are needed to characterize the temporal and cellular effects on wound healing and evaluate this dressing in a clinical environment.


title: Canadian Stroke Best Practice Recommendations: Hyperacute Stroke Care Guidelines, Update 2015.

text: The 2015 update of the Canadian Stroke Best Practice Recommendations Hyperacute Stroke Care guideline highlights key elements involved in the initial assessment, stabilization, and treatment of patients with transient ischemic attack (TIA), ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and acute venous sinus thrombosis. The most notable change in this 5th edition is the addition of new recommendations for the use of endovascular therapy for patients with acute ischemic stroke and proximal intracranial arterial occlusion. This includes an overview of the infrastructure and resources required for stroke centers that will provide endovascular therapy as well as regional structures needed to ensure that all patients with acute ischemic stroke that are eligible for endovascular therapy will be able to access this newly approved therapy; recommendations for hyperacute brain and enhanced vascular imaging using computed tomography angiography and computed tomography perfusion; patient selection criteria based on the five trials of endovascular therapy published in early 2015, and performance metric targets for important time-points involved in endovascular therapy, including computed tomography-to-groin puncture and computed tomography-to-reperfusion times. Other updates in this guideline include recommendations for improved time efficiencies for all aspects of hyperacute stroke care with a movement toward a new median target door-to-needle time of 30 min, with the 90th percentile being 60 min. A stronger emphasis is placed on increasing public awareness of stroke with the recent launch of the Heart and Stroke Foundation of Canada FAST signs of stroke campaign; reinforcing the public need to seek immediate medical attention by calling 911; further engagement of paramedics in the prehospital phase with prehospital notification to the receiving emergency department, as well as the stroke team, including neuroradiology; updates to the triage and same-day assessment of patients with transient ischemic attack; updates to blood pressure recommendations for the hyperacute phase of care for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. The goal of these recommendations and supporting materials is to improve efficiencies and minimize the absolute time lapse between stroke symptom onset and reperfusion therapy, which in turn leads to better outcomes and potentially shorter recovery times.


Focal Cerebral Arteriopathy in a COVID-19 Pediatric Patient.


Using socioeconomics to counter health disparities arising from the covid-19 pandemic.


title: Homologs of aminoacyl-tRNA synthetases acylate carrier proteins and provide a link between ribosomal and nonribosomal peptide synthesis.

text: Aminoacyl-tRNA synthetases (aaRSs) are ancient and evolutionary conserved enzymes catalyzing the formation of aminoacyl-tRNAs, that are used as substrates for ribosomal protein biosynthesis. In addition to full length aaRS genes, genomes of many organisms are sprinkled with truncated genes encoding single-domain aaRS-like proteins, which often have relinquished their canonical role in genetic code translation. We have identified the genes for putative seryl-tRNA synthetase homologs widespread in bacterial genomes and characterized three of them biochemically and structurally. The proteins encoded are homologous to the catalytic domain of highly diverged, atypical seryl-tRNA synthetases (aSerRSs) found only in methanogenic archaea and are deprived of the tRNA-binding domain. Remarkably, in comparison to SerRSs, aSerRS homologs display different and relaxed amino acid specificity. aSerRS homologs lack canonical tRNA aminoacylating activity and instead transfer activated amino acid to phosphopantetheine prosthetic group of putative carrier proteins, whose genes were identified in the genomic surroundings of aSerRS homologs. Detailed kinetic analysis confirmed that aSerRS homologs aminoacylate these carrier proteins efficiently and specifically. Accordingly, aSerRS homologs were renamed amino acid:[carrier protein] ligases (AMP forming). The enzymatic activity of aSerRS homologs is reminiscent of adenylation domains in nonribosomal peptide synthesis, and thus they represent an intriguing link between programmable ribosomal protein biosynthesis and template-independent nonribosomal peptide synthesis.


title: Postoperative effects of laparoscopic sleeve gastrectomy in morbid obese patients with type 2 diabetes.

text: BACKGROUND Laparoscopic Sleeve Gastrectomy has become one of the most popular bariatric surgery types and helps treating not only obesity but also endocrinological diseases related to obesity. Therefore we aimed to evaluate the effects of laparoscopic sleeve gastrectomy on the treatment of type 2 diabetes. METHODS All patients, who underwent morbid obesity surgery during 2013-2014 and had a HbA1c >6 % were included in this prospective study. Demographical data, usage of oral antidiabetic drugs or insulin were recorded, and laboratory findings as HbA1c and fasting plasma glucose were evaluated preoperatively and postoperatively at the 6th and 12th months. Diabetes remission criteria were used to assess success of the surgical treatment. RESULTS Totally 88 patients were included in this study. 55 patients were using oral antidiabetic drugs and 33 patients were using insulin. At the 6th month complete remission was observed in 80 (90.9 %), partial remission in 3 (3.4 %) and persistent diabetes in 5 (5.6 %) patients. At the 12th month complete remission was observed in 84 (95.4 %), partial remission in 1 (1.1 %) and persistent diabetes in 3 (3.4 %) patients. CONCLUSIONS This study indicated that laparoscopic sleeve gastrectomy surgery achieved a complete remission of diabetes in 95.4 % patients having type 2 diabetes during a 1 year fallow up period. However, complete remission of type 2 diabetes has been reported as 80 % during long term fallow up in the literature. In our opinion this rate may change with longer follow up periods and studies involving more patients suffering type 2 diabetes.


docid: evdvghkk

title: Identification of patient venous thromboembolism risk across the continuum of care.

text: Venous thromboembolism (VTE) complications are the leading cause of preventable in-hospital mortality and morbidity in the United States. Initiatives by the National Quality Forum, the Joint Commission, and the Surgical Care Improvement Project aim to improve the prevention of VTE and emphasize the need to recognize the risk of the condition in hospitalized patients. In clinical practice, individual risk assessment using a validated scoring system provides patients with the best care in the prevention of VTE. This is accomplished by a weighted scoring of risk factors, selection of the most appropriate prevention strategy for patients at risk, and regular risk review across the continuum of care. All hospitals should have a local, written, care pathway which assesses inpatient risk of VTE as early as possible upon admission and identifies members of the health care team responsible for applying risk assessment. Venous thromboembolism risk should be regularly reassessed for any changes in the level of risk, with extended out-of-hospital prophylaxis considered for patients with continued risk factors, such as prolonged immobility or illness, treated at home, or in a long-term care facility. Finally, a mandatory alert system requiring the clinician to address the issue of prophylaxis before any orders are carried out by the nursing staff is one way to protect all hospitalized patients.


Persistence of viral RNA in stool samples from patients recovering from covid-19.


title: A systematic review of the effectiveness of employer-led interventions for drug misuse.

text: AIMS Employers in the United States incur substantial costs associated with substance use disorders. Our goal was to examine the effectiveness of employer-led interventions to reduce the adverse effects of drug misuse in the workplace. METHODS We conducted a systematic review of studies that evaluated the effectiveness of recommended workplace interventions for opioids and related drugs: employee education, drug testing, employee assistance programs, supervisor training, written workplace drug-free policy, and restructuring employee health benefit plans. We searched PubMed MEDLINE, EMBASE (embase.com), PsycINFO (Ebsco), ABI Inform Global, Business Source Premier, EconLit, CENTRAL, Web of Science (Thomson Reuters), Scopus (Elsevier), Proquest Dissertations, and Epistemonikos from inception through May 8, 2019, with no date or language restrictions. We included randomized controlled trials, quasi-experimental studies, and cross-sectional studies with no language or date restrictions. The Downs and Black questionnaire was used to assess the quality of included studies. The results were reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. RESULTS In all, 27 studies met our inclusion criteria and were included in the systematic review. Results were mixed, with each intervention shown to be effective in at least one study, but none showing effectiveness in over 50% of studies. Studies examining the impact of interventions on workplace injuries or accidents were more commonly reported to be effective. Although four studies were randomized controlled trials, the quality of all included studies was "fair" or "poor." CONCLUSIONS Despite the opioid epidemic, high-quality studies evaluating the effectiveness of employer-led interventions to prevent or reduce the adverse effects of substance use are lacking. Higher quality and mixed methods studies are needed to determine whether any of the interventions are generalizable and whether contextual adaptations are needed. In the meantime, there is a reason to believe that commonly recommended, employer-led interventions may be effective in some environments.


title: A bench study of the effects of leak on ventilator performance during noninvasive ventilation.

text: BACKGROUND During noninvasive ventilation (NIV), leak around the mask may cause inadequate ventilatory support or patient-ventilator asynchrony such as auto-triggering. Some NIV ventilators may be better than others at compensating for leak. METHODS We bench studied 3 NIV ventilators (Vision, Carina, and Trilogy100) and 2 ICU ventilators (Puritan Bennett 840 and Evita XL) to assess how they coped with 2 leak levels and zero leak during NIV. With a 2-bellows-in-a-box lung model we simulated spontaneous breathing with tidal volumes of 300 mL and 500 mL, at pressure support of 0 and 10 cm H(2)O and PEEP of 5 and 10 cm H(2)O. We affixed the airway opening of the lung model to the mouth of a mannequin head and secured a mask on the mannequin face. We created a medium leak and a large leak with different size holes, and measured PEEP in the presence of leak. We also measured the actual pressure-support values and calculated the deviations from the set pressure-support value and the pressure-time product (PTP) of the airway opening pressure below and above baseline. RESULTS With the medium leak only the Vision and Carina maintained the set PEEP and pressure support. With the large leak the pressure support was decreased with all the tested ventilators. With the larger leak and pressure support of 10 cm H(2)O the PTP below baseline for triggering increased with 2 ventilators, and the PTP above baseline for supporting the patient's inspiratory effort decreased with all 5 ventilators. The larger tidal volume increased the PTP below baseline with all 5 ventilators and at all leak sizes. CONCLUSIONS Some of the ventilators compensated for leak better than others. With the larger leak none of the ventilators maintained the set PEEP or pressure support.


title: ABCD: Update of the 2009 guidelines on prevention and management of feline infectious diseases.

text: OVERVIEW In this article, the ABCD guidelines published in the JFMS Special Issue of July 2009 (Volume 11, Issue 7, pages 527-620) are updated by including previously unavailable and novel information. For a better picture, the reader is advised to consult that issue before focusing on the novel features.


title: Otitis and meningoencephalitis associated with infectious coryza ( Avibacterium paragallinarum) in commercial broiler chickens.

text: Infectious coryza, caused by Avibacterium paragallinarum, is an acute respiratory disease of poultry that can result in substantial morbidity, mortality, and economic losses. In March 2017, the Turlock branch of the California Animal Health and Food Safety laboratory system encountered an unusual clinical and pathologic presentation of infectious coryza in 6 live, 29-d-old, commercial broiler chickens that were submitted for diagnostic investigation. Antemortem evaluation revealed severe neurologic signs, including disorientation, torticollis, and opisthotonos. Swollen head-like syndrome and sinusitis were also present. Histologically, severe sinusitis, cranial osteomyelitis, otitis media and interna, and meningoencephalitis were noted, explaining the clinical signs described. A. paragallinarum was readily isolated from the upper and lower respiratory tract, brain, and cranial bones. Infectious bronchitis virus (IBV) was also detected by PCR, and IBV was isolated in embryonated chicken eggs. Based on sequencing analysis, the IBV appeared 99% homologous to strain CA1737. A synergistic effect between A. paragallinarum and IBV, resulting in exacerbation of clinical signs and increased mortality, may have occurred in this case. A. paragallinarum should be considered among the possible causes of neurologic signs in chickens. Appropriate media should be used for bacterial isolation, and the role of additional contributing factors and/or complicating agents should be investigated in cases of infectious coryza.


title: Mechanical thrombectomy using the Solitaire stent in a left main coronary artery: A novel approach to coronary thrombus retrieval.

text: The Solitaire stent is a self-expanding nitinol, fully retrievable stent that was originally designed for applications in cerebral circulation. Expanded indications for its use in mechanical embolectomy during acute ischemic stroke have proven safe and effective. Herein, we describe a novel use of this stent to perform a mechanical thrombectomy of a large left main coronary artery thrombus. © 2016 Wiley Periodicals, Inc.


title: ImmunoSPECT and immunoPET of IGF-1R expression with the radiolabeled antibody R1507 in a triple-negative breast cancer model.

text: UNLABELLED The insulinlike growth factor 1 receptor (IGF-1R) is a new target for the treatment of breast cancer. Patients with breast cancer lesions that express IGF-1R may benefit from treatment with anti-IGF-1R antibodies. Therefore, the aim of the present study was to develop a noninvasive, in vivo imaging method, using radiolabeled antibodies, to visualize IGF-1R expression. METHODS R1507 is a monoclonal antibody directed against the IGF-1R. In vitro, the affinity and internalization kinetics of (111)In-R1507 were determined using the IGF-1R-expressing triple-negative breast cancer cell line SUM149. In vivo, the pharmacodynamics of (111)In-R1507 and (125)I-R1507 were determined in mice with subcutaneous SUM149 tumors. (111)In-R1507 SPECT and (89)Zr-R1507 PET images of mice with subcutaneous SUM149 tumors were acquired at 1, 3, and 7 d after injection. RESULTS (111)In-R1507 (concentration required to inhibit binding by 50%, 0.1 nM) was slowly internalized by SUM149 cells. (111)In-R1507 specifically and efficiently accumulated in the SUM149 xenografts: the tumor uptake was 20 percentage injected dose per gram (%ID/g), 33 %ID/g, and 31 %ID/g at 1, 3, and 7 d after injection, respectively. (125)I-R1507 accumulated in the tumor less efficiently. Small-animal SPECT and small-animal PET of mice clearly visualized the subcutaneous SUM149 xenograft, with increasing contrast at later time points. CONCLUSION (111)In-R1507 and (89)Zr-R1507 are new tracers to noninvasively determine IGF-1R expression in vivo in breast cancer xenografts using SPECT and PET. In the future, these techniques may enable patient selection for IGF-1R-targeted therapy.


title: Endovascular management of carotid artery dissections with the use of new generation stents and protection systems.

text: Dissection of the internal carotid artery (ICA) is a rare disease, but in young patients is responsible for about 20% of cerebral events. We presented three different cases of ICA dissection, including one iatrogenic and two spontaneous ones, which were successfully managed endovascularly, with the use of different techniques, different protection devices and stents. In this article, the clinical management and details of procedures were described.


title: Rewarming from therapeutic hypothermia induces cortical neuron apoptosis in a swine model of neonatal hypoxic-ischemic encephalopathy.

text: The consequences of therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy are poorly understood. Adverse effects from suboptimal rewarming could diminish neuroprotection from hypothermia. Therefore, we tested whether rewarming is associated with apoptosis. Piglets underwent hypoxia-asphyxia followed by normothermic or hypothermic recovery at 2 hours. Hypothermic groups were divided into those with no rewarming, rewarming at 0.5 °C/hour, or rewarming at 4 °C/hour. Neurodegeneration at 29 hours was assessed by hematoxylin and eosin staining, TUNEL assay, and immunoblotting for cleaved caspase-3. Rewarmed piglets had more apoptosis in motor cortex than did those that remained hypothermic after hypoxia-asphyxia. Apoptosis in piriform cortex was greater in hypoxic-asphyxic, rewarmed piglets than in naive/sham piglets. Caspase-3 inhibitor suppressed apoptosis with rewarming. Rapidly rewarmed piglets had more caspase-3 cleavage in cerebral cortex than did piglets that remained hypothermic or piglets that were rewarmed slowly. We conclude that rewarming from therapeutic hypothermia can adversely affect the newborn brain by inducing apoptosis through caspase mechanisms.


docid: ekidsypj

title: Autonomic testing for prediction of competition performance in Paralympic athletes.

text: While we now appreciate that autonomic dysfunction can impact wheelchair rugby performance, this is currently not being assessed during classification, largely due to lack of a standardized and evidence-based strategy to assess autonomic function. Our aim, therefore, was to establish the optimal autonomic testing protocol that best predicts cardiovascular capacity during competition by comprehensively examining autonomic function in elite wheelchair rugby athletes with cervical SCI and thereby enhance the standardized classification. Twenty-six individuals with cervical SCI (C4-C8; AIS A, B, C) participated in this study during the 2015 Parapan American Games in Toronto, Canada. Clinic autonomic testing included: sympathetic skin responses, baseline hemodynamics, orthostatic challenge test, and cold-pressor tests. Further, we completed standard motor/sensory assessments and obtained each participants' International Wheelchair Rugby Federation classification. These clinic metrics were correlated to in-competition heart rate monitoring obtained during competition. The current study provides novel evidence that the change in systolic blood pressure during an orthostatic challenge test predicts approximately 50% of the in-competition peak heart rate (P<.001). Conversely, International Wheelchair Rugby Federation classification was poorly associated with in-competition peak heart rate (R2 =.204; P<.05). Autonomic testing provides deep insight regarding preserved autonomic control after SCI that is associated with performance in elite wheelchair rugby athletes. As such, incorporating assessments of cardiovascular capacity in classification will help to ensure a level playing field and may obviate the need for practices such as boosting to gain an advantage due to poor cardiovascular control.


title: Icariin Protects against Glucocorticoid-Induced Osteonecrosis of the Femoral Head in Rats.

text: BACKGROUND/AIMS Glucocorticoid (GC)-related osteonecrosis of the femoral head (ONFH) is a common complication following administration of steroids to treat many diseases. Our previous study demonstrated that icariin (ICA) might have a beneficial effect on the bone marrow mesenchymal stem cells (BMSCs) of patients with steroid-associated osteonecrosis. In this study, we investigated the underlying mechanisms of ICA associated with the potential enhancement of osteogenesis and anti-adipogenesis in GC-related ONFH. METHODS In vitro cell proliferation was evaluated by CCK-8 assay. Alizarin red S and alkaline phosphatase (ALP) activity were used to measure osteogenic differentiation, while adipogenic differentiation was revealed by oil red O staining and TG content assay. The expression level of osteogenesis-associated genes and PPARγ was evaluated by RT-qPCR, western blotting and immunofluorescence. A total of 30 female SD rats were randomly separated into three groups: a control group, a methylprednisolone (MPS) group and a MPS + ICA group. Serum ALP and TG (triglyceride), micro-CT scanning, histological and immunohistochemical analyses were performed in the animal model. RESULTS In the in vitro study, ICA promoted proliferation, improved osteogenic differentiation and suppressed adipogenic differentiation of BMSCs treated with MPS. The group treated with MPS and 10-6 M ICA expressed higher levels of Runx2, ALP, bone morphogenetic protein (BMP) 2, and OC and lower expression of PPARγ than the MPS group. In the in vivo study, ICA prevented bone loss in a rat model of GC-related ONFH as shown by micro-CT scanning, histological and immunohistochemical analyses. CONCLUSIONS ICA is an effective compound for promoting bone repair and preventing or delaying the progression of GC-associated ONFH in rats. This effect can be explained by its ability to improve the balance between adipogenesis and osteogenesis, indicating that ICA is an effective candidate for management of GC-associated ONFH.


title: Impact of structural features on dynamic breathing resistance of healthcare face mask.

text: In order to provide an overall evaluation and characterization of the comfort sensation and performance of face mask related to breathing resistance for healthcare in fog and haze weather, and address the influence of structural features on breathing resistance properties, an experimental set-up was developed, which was able to continuously change the direction and rate of air flow and the breathing frequency to simulate the dynamic breathing process during the actual wearing of face mask. The dynamic changes of airflow rate and the breathing resistance were acquired by a virtual instrument (VI) system and a microelectronics system. Six evaluation indices were defined for the dynamic performance and comfort sensation of face mask, derived from the source data of dynamic breathing resistance. Twelve types of face masks from different department stores with different features such as shape, respiratory valve, brand, main materials and protection level were tested using the experimental set-up. The one-way ANOVA analysis was carried out to identify the significance of the differences of the indices among the test masks. The results showed that each evaluation index was significantly different (P < 0.05) among different test masks. The change rate of breathing resistance could be obtained using the dynamic measurement of breathing resistance and could be applied for the dynamic performance evaluation of face mask compared with the static measurement of breathing resistance under constant airflow rate. The influences of structural features such as respiratory valve, shape and main materials on breathing resistance were evaluated and analyzed. The face masks with respiratory valve had lower change rate of breathing resistance. Moreover, the cup type mask had lower change rate of breathing resistance than the folding mask. Furthermore, the cotton mask had lower change rate of breathing resistance than the nonwoven fabric mask.


title: Compensatory enlargement of the left main coronary artery: insights from the PROSPECT study.

text: OBJECTIVES Glagov proposed that remodeling delayed development of significant coronary artery stenoses until plaque occupied, on average, 40% of arterial area (40% plaque burden). The aim of the current study was to confirm the previously proposed concept of coronary remodeling as first described by Glagov who studied postmortem left main coronary arteries (LMCAs). METHODS Using the in-vivo intravascular ultrasound data from the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study, we evaluated 552 LMCAs in 552 patients. RESULTS External elastic membrane cross-sectional areas (CSAs) increased in proportion to the increase in plaque and media CSAs (r=0.61, P<0.0001), especially when the plaque burden was 20% or lower (r=0.88, P<0.0001). For more advanced atherosclerosis (>40% plaque burden), there was an inverse relationship between lumen CSA and plaque burden (r=-0.57, P<0.0001), whereas this relationship was weak in the presence of less than 40% plaque burden. The frequency of virtual histology derived thin-cap fibroatheroma increased with increasing plaque burden. In contrast, the frequency of pathological intimal thickening decreased. CONCLUSION The previously proposed remodeling concept of Glagov was validated in vivo in the PROSPECT study patients. In addition, the present study suggested that plaque phenotype worsened with increasing LMCA plaque growth.


title: Considerations in Applying a New Stent Retriever in Pediatric Endovascular Cerebral Thrombectomy for Acute Ischemic Stroke.

text: Acute ischemic stroke (AIS) in children has been difficult to diagnose, treat and study, due to atypical clinical presentation, imaging challenges and the rarity of large-vessel embolic occlusion as the etiology of acute neurological change in children. With endovascular thrombectomy showing success in randomized trials of adult AIS, the technique is increasingly being extrapolated to pediatric stroke. However, there is little evidence regarding the safety or efficacy of applying in children these devices developed and tested in adults. There is concern about a vessel-to-device size mismatch that may result in a different complication and benefit profile than typically seen. We report on the successful application in pediatric stroke of a newer-generation, smaller stent retriever, designed to be delivered through relatively smaller and more navigable microcatheters than the prior generation of this device.


title: How to reduce the likelihood of coronavirus-19 (CoV-19 or SARS-CoV-2) infection and lung inflammation mediated by IL-1.

text: SARS-CoV-2, also referred to as CoV-19, is an RNA virus which can cause severe acute respiratory diseases (COVID-19), with serious infection of the lower respiratory tract followed by bronchitis, pneumonia and fibrosis. The severity of the disease depends on the efficiency of the immune system which, if it is weak, cannot stem the infection and its symptoms. The new CoV-19 spreads in the population at a rate of 0.8-3% more than normal flu and mostly affects men, since immune genes are more expressed on the X chromosome. If CoV-19 would spread with a higher incidence rate (over 10%), and affect the people who live in closed communities such as islands, it would cause many more deaths. Moreover, people from the poorest classes are most at risk because of lack of health care and should be given more assistance by the competent authorities. To avoid the aggravation of CoV-19 infection, and the collapse of the health system, individuals should remain at home in quarantine for a period of approximately one month in order to limit viral transmission. In the case of a pandemic, the severe shortage of respirators and protective clothing, due to the enormous demand and insufficient production, could lead the CoV-19 to kill a large number of individuals. At present, there is no drug capable of treating CoV-19 flu, the only therapeutic remedies are those aimed at the side effects caused by the virus, such as inflammation and pulmonary fibrosis, recognized as the first causes of death. One of the COVID-19 treatments involves inhaling a mixture of gaseous hydrogen and oxygen, obtaining better results than with oxygen alone. It was also noted that individuals vaccinated for viral and/or bacterial infectious diseases were less likely to become infected. In addition, germicidal UV radiation "breaks down" the oxygen O2 which then aggregate into O3 (ozone) molecules creating the ozone layer, capable of inhibiting viral replication and improving lung respiration. All these precautions should be taken into consideration to lower the risk of infection by CoV-19. New anti-viral therapies with new drugs should also be taken into consideration. For example, microbes are known to bind TLR, inducing IL-1, a pleiotropic cytokine, highly inflammatory, mediator of fever and fibrosis. Therefore, drugs that suppress IL-1 or IL-1R, also used for the treatment of rheumatoid arthritis are to be taken into consideration to treat COVID-19. We strongly believe that all these devices described above can lead to greater survival and. therefore, reduction in mortality in patients infected with CoV-19.


title: Pepsin detection in patients with laryngopharyngeal reflux before and after fundoplication.

text: BACKGROUND Some patients with gastroesophageal reflux disease (GERD) suffer from laryngopharyngeal reflux (LPR). There is no reliable diagnostic test for LPR as there is for GERD. We hypothesized that detection of pepsin (a molecule only made in the stomach) in laryngeal epithelium or sputum should provide evidence for reflux of gastric contents to the larynx, and be diagnostic of LPR. We tested this hypothesis in a prospective study in patients with LPR symptoms undergoing antireflux surgery (ARS). METHODS Nine patients undergoing ARS for LPR symptoms were studied pre- and postoperatively using a clinical symptom questionnaire, laryngoscopy, 24-h pH monitoring, biopsy of posterior laryngeal mucosa, and sputum collection for pepsin Western blot assay. RESULTS The primary presenting LPR symptom was hoarseness in six, cough in two, and globus sensation in one patient. Pepsin was detected in the laryngeal mucosa in eight of nine patients preoperatively. There was correlation between biopsy and sputum (+/+ or -/-) in four of five patients, both analyzed preoperatively. Postoperatively, pH monitoring improved in all but one patient and normalized in five of eight patients. Eight of nine patients reported improvement in their primary LPR symptom (six good, two mild). Only one patient (who had negative preoperative pepsin) reported no response to treatment of the primary LPR symptom. Postoperatively, pepsin was detected in only one patient. CONCLUSIONS Pepsin is often found on laryngeal epithelial biopsy and in sputum of patients with pH-test-proven GERD and symptoms of LPR. ARS improves symptoms and clears pepsin from the upper airway. Detection of pepsin improves diagnostic accuracy in patients with LPR.


title: Minimally invasive surgery for gastric cancer in UK: current status and future perspectives.

text: The aim of this study is to review the literature and report the various minimally invasive methods used to treat gastric cancer in the UK and compare it with worldwide practice. Published randomised studies, non-randomised studies and case series reporting the use of minimal invasive approach to treat gastric cancer were retrieved from the search of standard medical electronic databases and their outcomes were highlighted suggesting their effectiveness. Several randomised, controlled trials and meta-analyses have proven the clinical and oncological safety of the laparoscopic gastrectomy for gastric cancer. Similarly, robot-assisted gastrectomy, EMR (endoscopic mucosal resection) and ESD (endoscopic sub-mucosal dissection) have also been proven feasible and safe to treat gastric cancer of various stages in prospective and retrospective comparative studies. However, UK based studies on minimally invasive surgery to treat gastric cancer is scarce and the paucity of trials led to uncertain outcomes. Laparoscopic gastrectomy, robot-assisted gastrectomy, EMR and ESD are feasible procedures in terms of clinical and oncological safety but mainly being practiced in Asian countries with high prevalence of stomach cancer. The UK based practice is still small and limited but the introduction of MIGOCS and STOMACH trial might help to widen the application of this technique.


title: Introduction of Cobas Liat Influenza A/B for rapid point-of-care diagnosis of influenza infection in an acute trust.

text: Background We aimed to evaluate the impact of a new molecular point-of-care test (POCT), the Cobas Liat Influenza A/B for rapid diagnosis of influenza within 20 min, on the operational workflow of the Trust, accurate diagnosis and potential cost savings during the winter of 2017-2018. Methods A retrospective cohort study was conducted on all patients aged > 18 years tested for flu A/B by laboratory PCR in January 2017 and by POCT in January 2018. Results From 21 December 2017 to 30 April 2018, a total of 1375 POCTs were performed with a total of 479 (35%) influenza-positive cases. Results demonstrated that 1046 (76%) suspected cases did not require isolation or were able to be discharged from Emergency Department (ED), once other risks had been ruled out. We particularly looked into the differences between the month of January 2017 (before POCT) and the month of January 2018. Discussion Results demonstrate that influenza POCT had a positive impact on the Trust regarding prompt patient diagnosis and treatment, discharge decisions, improvement of patient bed management by avoiding unnecessary patient isolation and reducing bay closures, and significant reduction in length of stay in both positive and negative cases. Estimated cost savings were significant.


title: Twenty percent of a representative sample of patients taking bupropion have abnormal, asymptomatic electroencephalographic findings.

text: The risk of dose-dependent seizures is a safety issue with bupropion hydrochloride. To evaluate the presence of specific electroencephalographic (EEG) waveforms, 210 adult subjects taking stable doses of bupropion hydrochloride were recruited to undergo 2 EEGs in a prospective, single-center cohort study. The occurrence of spike waves, sharp waves, and focal slowing was recorded and assessed with a continuation ratio logit model for polytomous responses. This model showed that there was a relationship between sex and the incidence of these waveforms, such that the odds of female subjects having sharp waves was increased by a factor of 2.53 (P = 0.05) when compared with male subjects and controlled for both age and dose. Similarly, female subjects were 2.45 (P = 0.09) times more likely than males to have focal slowing on EEG. Overall, 19.8% (39/197) of this representative population was found to have abnormal, asymptomatic EEG findings. The presence of these waveforms in individuals taking a medication known to lower the seizure threshold may be a risk factor for developing seizures.


title: Positive psychological impact of treating victims of politically motivated violence among hospital-based health care providers.

text: BACKGROUND Health care personnel treating victims of politically motivated violence are at risk for traumatic stress symptoms. Few studies have assessed the positive psychological impact of politically motivated violence on health care workers. In this study, the level of positive psychological impact among health care workers with recurrent exposure to victims of politically motivated violence was examined. METHODS A validated questionnaire survey of health care personnel treating victims of politically motivated violence during 2000-2005 in two hospital settings was conducted. Positive psychological impact was assessed by the Posttraumatic Growth Inventory and traumatic stress symptoms were assessed using the Revised Posttraumatic Stress Disorder Inventory. Subjects included physicians (surgeons and anesthesiologists), nurses, and psychotherapists. RESULTS The rate of response to the mail-in questionnaires was 68.3% (n = 138). The sample consisted of 70 physicians, 37 nurses, and 31 hospital-based psychotherapists. Positive psychological impact was noted for the entire sample and among all professions. Traumatic stress symptoms predicted positive psychological impact for the entire sample and for each profession, and there was a curvilinear relationship between traumatic stress symptoms and positive psychological impact. Women experienced greater levels of positive psychological impact. CONCLUSIONS Hospital-based health care providers treating victims of politically motivated violence experience both positive and negative psychological impact. Individuals who are more traumatized by their experience are more likely to also have a positive psychological impact.


title: Metagenomic detection methods in biopreparedness outbreak scenarios.

text: In the field of diagnostic microbiology, rapid molecular methods are critically important for detecting pathogens. With rapid and accurate detection, preventive measures can be put in place early, thereby preventing loss of life and further spread of a disease. From a preparedness perspective, early detection and response are important in order to minimize the consequences. During the past 2 decades, advances in next-generation sequencing (NGS) technology have changed the playing field of molecular methods. Today, it is within reach to completely sequence the total microbiological content of a clinical sample, creating a metagenome, in a single week of laboratory work. As new technologies emerge, their dissemination and capacity building must be facilitated, and criteria for use, as well as guidelines on how to report results, must be established. This article focuses on the use of metagenomics, from sample collection to data analysis and to some extent NGS, for the detection of pathogens, the integration of the technique in outbreak response systems, and the risk-based evaluation of sample processing in routine diagnostics labs. The article covers recent advances in the field, current debate, gaps in research, and future directions. Examples of metagenomic detection, as well as possible applications of the methods, are described in various biopreparedness outbreak scenarios.


title: A response surface model approach for continuous measures of hypnotic and analgesic effect during sevoflurane-remifentanil interaction: quantifying the pharmacodynamic shift evoked by stimulation.

text: BACKGROUND The authors studied the interaction between sevoflurane and remifentanil on bispectral index (BIS), state entropy (SE), response entropy (RE), Composite Variability Index, and Surgical Pleth Index, by using a response surface methodology. The authors also studied the influence of stimulation on this interaction. METHODS Forty patients received combined concentrations of remifentanil (0 to 12 ng/ml) and sevoflurane (0.5 to 3.5 vol%) according to a crisscross design (160 concentration pairs). During pseudo-steady-state anesthesia, the pharmacodynamic measures were obtained before and after a series of noxious and nonnoxious stimulations. For the "prestimulation" and "poststimulation" BIS, SE, RE, Composite Variability Index, and Surgical Pleth Index, interaction models were applied to find the best fit, by using NONMEM 7.2.0. (Icon Development Solutions, Hanover, MD). RESULTS The authors found an additive interaction between sevoflurane and remifentanil on BIS, SE, and RE. For Composite Variability Index, a moderate synergism was found. The comparison of pre- and poststimulation data revealed a shift of C50SEVO for BIS, SE, and RE, with a consistent increase of 0.3 vol%. The Surgical Pleth Index data did not result in plausible parameter estimates, neither before nor after stimulation. CONCLUSIONS By combining pre- and poststimulation data, interaction models for BIS, SE, and RE demonstrate a consistent influence of "stimulation" on the pharmacodynamic relationship between sevoflurane and remifentanil. Significant population variability exists for Composite Variability Index and Surgical Pleth Index.


title: Prospective clinical trial of factors predicting the early development of incisional hernia after midline laparotomy.

text: BACKGROUND Information-based scoring systems predictive of outcomes of midline laparotomy are needed; these systems can support surgical decisions with the aim of improving patient outcomes and quality of life, and reducing the risk of secondary surgical procedures. STUDY DESIGN All study subjects were followed for a minimum of 6 months after operation. Numerous demographic, clinical, treatment, and outcomes-related perioperative factors were recorded to determine statistical association with the primary end point: incisional hernia development. The first analysis was designed to establish the statistical model (scoring system) for estimating the risk of incisional hernia within 6 months of midline laparotomy. Univariate and multivariate analyses were performed. A simple additive model was constructed using stepwise logistic and linear regression. The second part of the study analysis was validation of the scoring systems developed initially. RESULTS A logistic linear minimum regression model was developed based on four covariates independently predictive of incisional hernia: Body mass index (BMI) > 24.4kg/m(2); fascial suture to incision ratio (SIR) < 4.2; deep surgical site, deep space, or organ infection (SSI); and time to suture removal or complete epithelialization >16 days (TIME). The hernia risk scoring system equation [p(%) = 32(SIR) + 30(SSI) + 9(TIME) + 2(BMI)] provided accurate estimates of incisional hernia according to stratified risk groups based on total score: low (0 to 5 points), 1.0%; moderate (6 to 15 points), 9.7%; increased (16 to 50 points), 30.2%; and markedly increased (>50 points), 73.1%. CONCLUSIONS A statistically valid, straightforward, and clinically useful predictive model was developed for estimating the risk of incisional hernia within 6 months of midline laparotomy. Prospective independent validation of this model appears indicated.


title: Intracranial aneurysms: review of current treatment options and outcomes.

text: Intracranial aneurysms are present in roughly 5% of the population, yet most are often asymptomatic and never detected. Development of an aneurysm typically occurs during adulthood, while formation and growth are associated with risk factors such as age, hypertension, pre-existing familial conditions, and smoking. Subarachnoid hemorrhage, the most common presentation due to aneurysm rupture, represents a serious medical condition often leading to severe neurological deficit or death. Recent technological advances in imaging modalities, along with increased understanding of natural history and prevalence of aneurysms, have increased detection of asymptomatic unruptured intracranial aneurysms (UIA). Studies reporting on the risk of rupture and outcomes have provided much insight, but the debate remains of how and when unruptured aneurysms should be managed. Treatment methods include two major intervention options: clipping of the aneurysm and endovascular methods such as coiling, stent-assisted coiling, and flow diversion stents. The studies reviewed here support the generalized notion that endovascular treatment of UIA provides a safe and effective alternative to surgical treatment. The risks associated with endovascular repair are lower and incur shorter hospital stays for appropriately selected patients. The endovascular treatment option should be considered based on factors such as aneurysm size, location, patient medical history, and operator experience.


title: A Randomized Controlled Trial Assessing the Effect of a Continuous Subcutaneous Infusion of Local Anesthetic Following Elective Surgery to the Great Toe.

text: Local anesthetic use for wound infusions, single injection, and continuous nerve blocks for postoperative analgesia is well established. No study has investigated the effect of a continuous block of the saphenous and superficial peroneal nerves at the level of the ankle joint following first ray surgery. A double blind randomized controlled trial was designed. One hundred patients with hallux valgus and rigidus requiring surgical correction were recruited and randomized to receive a postoperative continuous infusion at the ankle of normal saline or ropivacaine for 24 hours. Pain scores were recorded on postoperative days 1 and 7. There were more females than males. Follow-up was 100%. There were no significant differences in demographic data between the 2 randomized groups. There was no significant difference between the absolute visual analog scale scores on day 1 (P = .14) and day 7 (P = .16); nor was there a significant difference in reduction in scores between days 1 and 7 (P = .70). This study has shown no benefit to postoperative analgesia with the use of a continuous infusion of ropivacaine at the ankle. We, therefore, cannot currently recommend its use in the way described. Further studies may still identify a role for continuous local anesthetic infusions at the ankle to improve postoperative analgesia. LEVELS OF EVIDENCE Level I : Prospective randomised control trial.


title: Fibromyalgia and arthritides.

text: Fibromyalgia (FM) is a chronic pain syndrome that affects at least 2% of the adult population. It is characterised by widespread pain, fatigue, sleep alterations and distress, and emerging evidence suggests a central nervous system (CNS) malfunction that increases pain transmission and perception. FM is often associated with other diseases that act as confounding and aggravating factors, such as rheumatoid arthritis (RA), spondyloarthritides (SpA), osteoarthritis (OA) and thyroid disease. Mechanism-based FM management should consider both peripheral and central pain, including effects due to cerebral input and that come from the descending inhibitory pathways. Rheumatologists should be able to distinguish primary and secondary FM, and need new guidelines and instruments to avoid making mistakes, bearing in mind that the diffuse pain of arthritides compromises the patients' quality of life.


Sixty seconds on . . . reorganising the NHS.


docid: rswexkbg

title: Abdominal radiology in the era of the Interventional Radiology/Diagnostic Radiology certificate.


title: Self-fixating mesh for the Lichtenstein procedure--a prestudy.

text: INTRODUCTION Secure fixation of the mesh in groin hernia repair is essential to avoid mesh dislocation. The fixation, however, is also thought to be a source of chronic postoperative pain. We tested the new self-fixating mesh Parietene progrip vs. traditional suture fixating Lichtenstein repair in a double-blinded randomized study evaluating postoperative pain and the use of analgesics. METHODS Fifty patients were randomized into two groups: Patients of group A (24 patients) were operated with the new self-fixating Parietene progrip mesh without fixation sutures and patients of group B (26 patients) were operated with the traditional Lichtenstein repair. Postoperative course including pain and the use of analgesics were monitored. Patients were reinvestigated after 6 months regarding pain score and the amount of analgesics used during this interval. Primary end point was pain on the first operative day. RESULTS The visual analog scale pain score showed at the first postoperative day a significantly lower level in group A than in group B (mean 17.9 vs. 32.3 mm, p = 0.03). Additionally, the cumulative dose of postoperatively required analgesics was lower in group A than in group B. The operative time in group A was significantly shorter than in group B. Six months after the operation, a trend toward a lower pain score was observed in group A, but this did not reach statistical significance. CONCLUSIONS This is the first randomized study to show a beneficial effect of the new self-fixating mesh on pain score. According to our investigations, operative time is reduced, which is a considerable fact with regard to economic aspects as well as the beneficial aspects for the patients. A study with a larger cohort of patients should be conducted to confirm the promising results of this exploratory study.


title: Toward a translationally independent RNA-based synthetic oscillator using deactivated CRISPR-Cas.

text: In synthetic circuits, CRISPR-Cas systems have been used effectively for endpoint changes from an initial state to a final state, such as in logic gates. Here, we use deactivated Cas9 (dCas9) and deactivated Cas12a (dCas12a) to construct dynamic RNA ring oscillators that cycle continuously between states over time in bacterial cells. While our dCas9 circuits using 103-nt guide RNAs showed irregular fluctuations with a wide distribution of peak-to-peak period lengths averaging approximately nine generations, a dCas12a oscillator design with 40-nt CRISPR RNAs performed much better, having a strongly repressed off-state, distinct autocorrelation function peaks, and an average peak-to-peak period length of ∼7.5 generations. Along with free-running oscillator circuits, we measure repression response times in open-loop systems with inducible RNA steps to compare with oscillator period times. We track thousands of cells for 24+ h at the single-cell level using a microfluidic device. In creating a circuit with nearly translationally independent behavior, as the RNAs control each others' transcription, we present the possibility for a synthetic oscillator generalizable across many organisms and readily linkable for transcriptional control.


title: Bench tests of simple, handy ventilators for pandemics: performance, autonomy, and ergonomy.

text: BACKGROUND It has been pointed out that in the wake of a virulent flu strain, patients with survivable illness will die from lack of resources unless more ventilators are made available. Numerous disaster-type ventilators are available, but few evaluations have been performed. OBJECTIVE To compare simple, lightweight, and handy ventilators that could be used in the initial care of patients with respiratory distress. METHODS We bench-tested 4 volume-cycled ventilators (Carevent ALS, EPV100, Pneupac VR1, and Medumat Easy) and 2 pressure-cycled ventilators (Oxylator EMX and VAR-Plus). We studied their general physical characteristics, sonometry, gas consumption, technical performance, ergonomy, and user-friendliness. With a test lung we assessed performance at F(IO(2)) of 0.50 and 1.0, set compliance of 30, 70, and 120 mL/cm H(2)O, and set resistance of 5, 10, and 20 cm H(2)O/L/s. To study user-friendliness and ergonomy we conducted, in randomized order, 7 or 8 objective, quantitative tests and 2 subjective tests. RESULTS Compliance and resistance strongly affected tidal volume with the pressure-cycled ventilators (from 418 ± 49 mL to 1,377 ± 444 mL with the VAR-Plus, at the lowest pressure level), whereas the volume-cycled ventilators provided a consistent tidal volume in the face of changing test lung characteristics. CONCLUSIONS We are concerned that the pressure-cycled ventilators did not provide a consistent tidal volume, and under certain conditions the volume delivered would be unsafe (too large or too small). Most of the volume-cycled ventilators proved to be technically efficient and reliable. Their reliability, portability, and ease of use could make them valuable in natural disasters and mass-casualty events.


title: Mortality after total hip replacement surgery: A systematic review.

text: Total hip replacement causes a short-term increase in the risk of mortality. It is important to quantify this and to identify modifiable risk factors so that the risk of post-operative mortality can be minimised. We performed a systematic review and critical evaluation of the current literature on the topic. We identified 32 studies published over the last 10 years which provide either 30-day or 90-day mortality data. We estimate the pooled incidence of mortality during the first 30 and 90 days following hip replacement to be 0.30% (95% CI 0.22 to 0.38) and 0.65% (95% CI 0.50 to 0.81), respectively. We found strong evidence of a temporal trend towards reducing mortality rates despite increasingly co-morbid patients. The risk factors for early mortality most commonly identified are increasing age, male gender and co-morbid conditions, particularly cardiovascular disease. Cardiovascular complications appear to have overtaken fatal pulmonary emboli as the leading cause of death after hip replacement. Cite this article: Bone Joint Res 2014;3:175-82.


title: Granulomas in Crohn's disease: does progression through the bowel layers affect presentation or predict recurrence?

text: AIM The aim of the study was to correlate the presence and pattern of distribution of granulomas in resected specimens to clinical characteristics and outcome in patients undergoing surgery for Crohn's disease. METHOD Patients with Crohn's disease who underwent surgical resection between 2001 and 2007 were identified. Pathology slides were reviewed for the presence, number and location of granulomas in four representative slides from each specimen. RESULTS Two-hundred and seven patients were identified. At a mean follow up of 14 months, 39 patients had a recurrence, 22 (57%) of whom underwent reoperation. Ninety-four (45%) patients had granulomas present in the surgical specimen. Patients with granulomas were younger (P<0.001), had a lower preoperative body mass index (P=0.037), were more likely to be female (P=0.017) and were more likely to have extra-intestinal manifestations (P=0.026) or perianal disease (P=0.012). Sites of disease and procedures performed were similar in both groups. Disease recurrence and reoperative rates were similar in both groups, as were length of stay and morbidity rates. The average number of granulomas present in each sampled pathology slide was 7.2, and there was no correlation between number of granulomas and disease severity. No link was found between the depth of involvement of the granulomas and fistulizing or stricturing disease. CONCLUSION Granulomas were associated with increased extra-intestinal manifestations and perianal disease, a lower body mass index and younger or female patients. There was no correlation between the presence of granulomas and disease progression or recurrence rates during the short follow-up period of this study.


title: Utilization pattern and side effect profile of oral anticonceptives: A community-based cross-sectional study among Saudi women.

text: BACKGROUND The rapid change in the socio-demographic pattern and changing beliefs toward fertility and birth spacing have resulted in a notable increase in the use of oral anticonceptives in the Saudi Arabian community. However, information on the current utilization of oral anticonceptives and attitudes toward their use remains sparse. OBJECTIVE The present study evaluated the utilization pattern of oral anticonceptives, attitude toward pill use, and incidence of side effects among Saudi women. SETTING The study was conducted in a community setting in Jazan, Kingdom of Saudi Arabia. METHODS Eligible Saudi women routinely using oral anticonceptive pills were invited to participate in this prospective, cross-sectional survey. Data were collected using a standardized, pretested, semi-structured questionnaire. Jazan was selected as it recorded the highest number of women using contraceptives in Saudi Arabia. MAIN OUTCOME MEASURE The pattern of pill utilization, attitude toward pill use, and incidence of side effects. RESULTS A total of 496 women consented to participate in this study. Most of the respondents (87.5%) were using or had used oral anticonceptives for birth control. In nearly half (49.2%) of participants, oral pills were advised by a gynaecologist, and approximately two-thirds (69.0%) were using or had used combined oral anticonceptives. Nearly two-thirds (63.1%) of respondents preferred pills over other contraception methods due to their ease of use. More than one-third (39.3%) of participants agreed that oral pills are safe. Approximately half (53.2%) of participants were aware that a missed pill must be taken immediately after recalling that a dose was missed. A total of 69.6% of participants experienced at least one side effect, of which mood swings (61.1%), weight gain or increase appetite (42.2%), decreased libido (34.1%), and nausea (31.2%) were most common. CONCLUSION Saudi women had a high acceptance rate for oral anticonceptives as a legitimate method to prevent unintended pregnancy. This was associated with a modest degree of understanding about their risks and benefits. Pharmacists should provide up-to-date information and counsel patients about the use and side effects of oral anticonceptives.