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Disasters around the world have adversely affected every aspect of life and panic-health of stranded persons is one such category. An effective and on-time evacuation from disaster-affected areas can avoid any panic-related health problems of the stranded persons. Although the nature of disasters differ in terms of how they occur, the evacuation of stranded persons faces approximately same set of issues related to the communication, time-sensitive computation and energy efficiency of the devices operated in the disaster-affected areas. In this paper, a cyber physical system (CPS) is proposed that takes into account various challenges of the disaster evacuation, so an efficient on-time and orderly evacuation of stranded panicked persons could be realized. The system employs fog-assisted mobile and UAV devices for time-sensitive computation services, data relaying and energy-aware computation. The system uses a fog-assisted two-factor energy-aware computation approach using data reduction, which enables the energy-efficient data reception and transmission (DRecTrans) operations at the fog nodes and compensates to extend the period for other functionalities. The data reduction at fog devices employs Novel Events Identification (NEI) and Principal Component Analysis (PCA) for detecting consecutive duplicate traffic and data summarization of high dimensional data, respectively. The proposed system operates in two spaces: physical and cyber. Physical space facilitates real-world data acquisition and information sharing with the concerned stakeholders (stranded persons, evacuation teams and medical professionals). The cyber space houses various data-analytics layers and comprises of two subspaces: fog and cloud. The fog space helps in providing real-time panic-health diagnostic and alert services and enables the optimized energy consumption of devices operate in disaster-affected areas, whereas the cloud space facilitates the monitoring and prediction of panic severity of the stranded persons, using a conditional probabilistic model and seasonal auto regression integrated moving average (SARIMA), respectively. Cloud space also facilitates the disaster mapping for converging the evacuation map to the actual situation of the disaster-affected area, and geographical population analysis (GPA) for the identification of the panic severity-based critical regions. The performance evaluation of the proposed CPS acknowledges its Logistic Regression-based panic-well being determination and real-time alert generation efficiency. The simulated implementation of NEI and PCA depicts the fog-assisted energy efficiency of the DRecTrans operations of the fog nodes. The performance evaluation of the proposed CPS also acknowledges the prediction efficiency of the SARIMA and disaster mapping accuracy through GPA. The proposed system also discusses a case study related to the pandemic disaster of coronavirus disease 2019 (COVID-19), where the system can help in panic-based selective testing of the persons, and preventing panic due to distressing period of COVID-19 outbreak. [ABSTRACT FROM AUTHOR]

Background. Recurrent Clostridioides difficile infections (rCDI) are a global public health threat. To reduce rCDI, microbiotarestoring therapies are needed, particularly standardized, easy-to-administer formulations. Methods. This phase I open-label trial assessed the safety, efficacy in preventing rCDI recurrence, and intestinal microbiome effects of RBX7455, a room temperature-stable, orally administered investigational live biotherapeutic. Adult participants with 1 or more prior episodes of rCDI received: 4 RBX7455 capsules twice daily for 4 days (group 1); 4 RBX7455 capsules twice daily for 2 days (group 2); or 2 RBX7455 capsules twice daily for 2 days (group 3). For all groups, the first dose was administered in clinic, with remaining doses selfadministered at home. Adverse events were monitored during and for 6 months after treatment. Treatment success was defined as rCDI prevention through 8 weeks after treatment. Participants’ microbiome composition was assessed prior to and for 6 months after treatment. Results. Nine of 10 group 1 patients (90%), 8 of 10 group 2 patients (80%), and 10 of 10 group 3 patients (100%) were recurrencefree at the 8-week endpoint with durability to 6 months. Seventy-five treatment-emergent adverse events were observed in 27 participants with no serious investigational product-related events. Prior to treatment, participants’ microbiomes were dissimilar from the RBX7455 composition with decreased Bacteroidia- and Clostridia-class bacteria, whereas after treatment, responders’ microbiomes showed increased Bacteroidia and Clostridia. Conclusions. Three dosing regimens of RBX7455 were safe and effective at preventing rCDI. Responders’ microbiomes converged toward the composition of RBX7455. These results support its continued clinical evaluation. [ABSTRACT FROM AUTHOR]

Objective Sexually transmitted infections because of Neisseria gonorrhoeae (NG) and/or Chlamydia trachomatis (CT) remain a major public health problem. Although the literature describes the population-based epidemiology of CT/NG, it does not appear to contain reference points for the statistical analyses of specimen positivity rates by nucleic acid testing (NAT) with polymerase chain reaction (PCR) that would be collected by a laboratory following best laboratory and regulatory practice. For facilities that diagnose NG and CT by a real-time PCR assay, an understanding of the expected specimen positivity rate of gonorrhea and chlamydia would be helpful for monitoring the assay for quality assurance. Therefore, on behalf of the Michael J. Crescenz Veteran Affairs Medical Center (VAMC), we present this novel quality assurance study on its CT/NG specimen positivity rates conducted by NAT with PCR. Methods Quality assurance/improvement quarterly data from April 1, 2012 to September 30, 2019 were reviewed to obtain both the test volume of PCR for CT/NG and the number of positive test results at the VAMC to collate and perform statistical analyses. Testing had been performed using the Abbott m2000 RealTime System (Abbott Park, IL). Results A total of 22,709 PCR tests for CT/NG had been performed on the veteran population; of these, 502 tests were positive for NG and 744 were positive for CT. Quarterly percentage rates ranged from 1.67% to 5.30% for CT and from 1.00% to 3.25% for NG, with average rates of 3.35% and 2.22% for CT and NG, respectively. Conclusion The establishment of an expected rate of specimen positivity of CT/NG by NAT with PCR at the VAMC is a significant novel reference point in the quality assurance (QA) literature and provides a benchmark that aids tremendously in QA for the microbiology/molecular laboratory. [ABSTRACT FROM AUTHOR]

Objective This study aimed to describe and validate a novel ultrasound-guided intercostal peripheral nerve stimulator implantation technique. Methods The fifth to tenth ribs on both sides of an unembalmed cadaveric specimen were localized using a 15–6-MHz linear array transducer, counting distally from T-1 bilaterally. A single interventionist then implanted 12 peripheral nerve stimulators on the fifth through tenth ribs, six MicroLeads on the left side and six StimRouters on the right side, using an in-plane lateral to medial approach to the inferior border of the corresponding rib. After all the stimulators were implanted, their location was confirmed using fluoroscopy. Gross anatomic dissection was later performed for each of the stimulators placed, and the distance of the lead from the intercostal nerve and pleura was noted. Results All leads were noted in an accurate position in the plane between the inner and innermost intercostal muscle, without any intrapleural placement. The distance of the leads from the intercostal nerves was on average 2.3 mm and 1.1 mm for MicroLead and StimRouter, respectively. Conclusions To our knowledge, this study is the first to determine the feasibility of ultrasound-guided peripheral nerve stimulator placement in close proximity to the pleura. All the stimulator leads were accurately placed using our ultrasound-guided technique and were within 0.5–3 mm from the intercostal nerve. Although this technique might prove technically challenging, the use of ultrasound for intercostal peripheral nerve stimulator implantation appears feasible and warrants further investigation to establish this as an acceptable technique for patients. [ABSTRACT FROM AUTHOR]

Introduction: In patients with prior myocardial infarction (MI), cardiac rehabilitation (CR) has been shown to reduce all-cause mortality, cardiac mortality, and risk of recurrent MI. Medically supervised cardiac rehab has challenges such as increased patient and center cost, patient transportation issues, patient time commitment, and increased need for resources. Home-based cardiac rehabilitation (HBCR) is an innovative alternative to medically supervised CR which can help to address some of the aforementioned issues. HBCR has been shown to have similar patient outcomes when compared to medically supervised CR; however, implantation efforts and experiences within Veteran Affair (VA) facilities were limited. Thus, we sought to describe our implementation efforts and outcomes of HBCR at our VA medical center, since our VA medical center does not offer an on-site medically supervised CR program.Materials and Methods: The project was not reviewed by our institutional review board as this quality improvement project was determined by our VA medical service chief to not qualify as human subjects research. Veterans eligible for CR in our VA medical system were enrolled in a 12-week HBCR program. Veterans performed exercise training at home with equipment provided at no cost. In addition, participating veterans received nutrition counseling, smoking cessation encouragement, stress management, and psychosocial consultation through weekly telephone calls performed by registered nurses. Progress was measured using Life's Simple 7, Duke Activity status index, 6-minute walk test, and Short Form Health Survey (SF-36) before and after HBCR. Medical records were monitored for death, MI, and readmission to the hospital for CHF within the VA medical system for 1 year after the program was complete. SAS and R were used for data input and analysis.Results: Data from 213 veterans were available for analysis and 136 of these veterans completed the HBCR program; the 95 veterans who did not complete the program either declined enrollment, discontinued follow-up with this program, or failed to actively participate and thus were removed from the program. Veterans who completed the 12-week HBCR program reported significant improvement, when compared before and after HBCR program, in Simple 7, Duke Activity status index metabolic equivalent of tasks, 6-minute walk test, SF-36 physical functioning, SF-36 bodily pain, and SF-36 vitality. Overall survival and recurrent MIs were similar between the veterans who completed and the veterans who did not complete the HBCR program in the 1 year follow-up. Hospital admission for heart failure in the 1-year follow-up was lower among veterans who completed the HBCR program when compared to the veterans who did not complete the HBCR program.Conclusions: HBCR is an effective alternative to facility-based CR. Veterans who completed the program showed improvement in physical capacity and functional status. Compared to those who were eligible but did not complete the program, hospitalization for heart failure was reduced after completing HBCR. [ABSTRACT FROM AUTHOR]

Motivation Despite conservation in general architecture of promoters and protein–DNA interaction interface of RNA polymerases among various prokaryotes, identification of promoter regions in the whole genome sequences remains a daunting challenge. The available tools for promoter prediction do not seem to address the problem satisfactorily, apparently because the biochemical nature of promoter signals is yet to be understood fully. Using 28 structural and 3 energetic parameters, we found that prokaryotic promoter regions have a unique structural and energy state, quite distinct from that of coding regions and the information for this signature state is in-built in their sequences. We developed a novel promoter prediction tool from these 31 parameters using various statistical techniques. Results Here, we introduce SEProm, a novel tool that is developed by studying and utilizing the in-built structural and energy information of DNA sequences, which is applicable to all prokaryotes including archaea. Compared to five most recent, diverged and current best available tools, SEProm performs much better, predicting promoters with an ' F -value' of 82.04 and 'Precision' of 81.08. The next best ' F -value' was obtained with PromPredict (72.14) followed by BProm (68.37). On the basis of 'Precision' value, the next best 'Precision' was observed for Pepper (75.39) followed by PromPredict (72.01). SEProm maintained the lead even when comparison was done on two test organisms (not involved in training for SEProm). Availability and implementation The software is freely available with easy to follow instructions (www.scfbio-iitd.res.in/software/TSS%5fPredict.jsp). Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Background Visual impairment in developing countries has both social and economic impact on individuals and communities. Understanding the subjective visual functioning of populations will allow for local policymakers to identify the need for optometric or ophthalmic services in their communities. Methods The authors surveyed 644 adult patients in Mwanza, Tanzania at three clinics (Buzuruga, Mwananchi and Kisesa) using a modified Visual Functioning Questionnaire 25. Responses were categorized into General health, General vision, Ocular pain, Near activities, Distance activities, Social function, Mental health, Role difficulties, Color vision, Peripheral vision and Dependency. Results Patients at Buzuruga reported the lowest scores on most subscales. Of 100 employed patients, 37% claimed to have at least some difficulty in performing job duties due to their eyesight. At Kisesa, 146 (246/221) patients (66.1%) had never had an eye exam, compared with 134/227 (59.0%) at Buzuruga and 69/173 (39.9%) at Mwananchi (p<0.01). Common reasons for not seeing an eye doctor were the perceived expense and lack of vision problems. Conclusions Due to regional differences in visual functioning in Mwanza, a national effort for vision health cannot be entirely successful without addressing the individualized needs of local communities. Reducing the cost of vision care appointments may expand vision health care utilization in Mwanza. [ABSTRACT FROM AUTHOR]

Background Although fecal microbiota transplant has been used to prevent recurrent Clostridioides difficile infection (rCDI), documented pathogen transmissions highlight inherent safety risks of minimally processed stool. We describe manufacturing processes for fecal microbiota spores, live (VOWST; VOS, formerly SER-109), a microbiota-based oral therapeutic of Firmicutes spores. Methods Bacterial inactivation kill curves were obtained after ethanol exposure for 4 model organisms spiked into process intermediates. Results Bacterial log reduction factors ranged from 6.5 log10 to 7.4 log10 and lysis of spiked organisms occurred rapidly within 30 seconds. Conclusions These experiments demonstrate substantial and rapid inactivation of representative organisms, supporting the potential benefit of VOS manufacturing processes to mitigate risk. [ABSTRACT FROM AUTHOR]

Purpose. Results of a study to test the hypothesis that taking niacin simultaneously with different forms of aspirin would reduce the occurrence of niacin-induced flushing are reported. Methods. Traditionally, taking enteral absorbed aspirin 30 minutes before a niacin dose has been shown to reduce flushing by 30-50% relative to nonuse of aspirin. The objective of the study was to evaluate the efficacy of enteral absorbed and orally dissolved aspirin, taken at the same time as niacin, in reducing the frequency of moderate-to-severe flushing. In a prospective, double-blind, placebo-controlled crossover trial, healthy adult male and female volunteers were asked to take aspirin or a placebo (both agents were taken in both orally dissolved and swallowed formulations) immediately before niacin administration. Subjects then self-evaluated flushing symptoms on a validated scale. Results. Simultaneous administration of swallowed aspirin and niacin reduced moderate-to-severe flushing events by a mean of 36.1%, from 2.35 to 1.5 events per subject (p = 0.003), relative to event rates with use of niacin alone. In a subset of subjects who had experienced moderate-to-severe flushing symptoms despite taking swallowed aspirin, flushing in response to subsequent niacin use was decreased by 20.5% (p = 0.05) with coadministration of orally dissolved aspirin and by 18.0% with a regimen containing both orally dissolved and swallowed aspirin (p = 0.03). Conclusion. Novel regimens of niacin and aspirin, including orally dissolved aspirin, were effective in reducing niacin-induced flushing in a small sample of healthy adult volunteers. [ABSTRACT FROM AUTHOR]

Background Young people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) (PLWA) are at risk for HIV stigma. Methods The HIV/AIDS Stigma Instrument for PLWA was administered to 36 young PLWA across six clinics in Bandung, Indonesia, to assess the fear of contagion (FC), verbal abuse (VA), social isolation (SI), workplace stigma (WS), health care neglect (HCN) and negative self-perception (NSP). Results The median scores for FC, VA, SI, WS and HCN were all 0 while the median score for NSP was 4. In the last 3 months approximately 45% of surveyed PLWA felt they did not deserve to live and 64% felt completely worthless. Conclusions While these results are preliminary, access to mental health services should be a priority in the clinics that provide antiretroviral therapies. [ABSTRACT FROM AUTHOR]

Background. Patients with recurrent Clostridium difficile infection (CDI) have a ≥ 60% risk of relapse, as conventional therapies do not address the underlying gastrointestinal dysbiosis. This exploratory study evaluated the safety and efficacy of bacterial spores for preventing recurrent CDI. Methods. Stool specimens from healthy donors were treated with ethanol to eliminate pathogens. The resulting spores were fractionated and encapsulated for oral delivery as SER-109. Following their response to standard-of-care antibiotics, patients in cohort 1 were treated with SER-109 on 2 consecutive days (geometric mean dose, 1.7 x 109 spores), and those in cohort 2 were treated on 1 day (geometric mean dose, 1.1 x 108 spores). The primary efficacy end point was absence of C. difficile-positive diarrhea during an 8-week follow-up period. Microbiome alterations were assessed. Results. Thirty patients (median age, 66.5 years; 67% female) were enrolled, and 26 (86.7%) met the primary efficacy end point. Three patients with early, self-limiting C. difficile-positive diarrhea did not require antibiotics and tested negative for C. difficile at 8 weeks; thus, 96.7% (29 of 30) achieved clinical resolution. In parallel, gut microbiota rapidly diversified, with durable engraftment of spores and no outgrowth of non-spore-forming bacteria found after SER-109 treatment. Adverse events included mild diarrhea, abdominal pain, and nausea. Conclusions. SER-109 successfully prevented CDI and had a favorable safety profile, supporting a novel microbiome-based intervention as a potential therapy for recurrent CDI. [ABSTRACT FROM AUTHOR]

We used an in silico approach to survey and compare microsatellites in transcript sequences of four sequenced members of genus Fusarium. G + C content of transcripts was found to be positively correlated with the frequency of SSRs. Our analysis revealed that, in all the four transcript sequences studied, the occurrence, relative abundance and density of microsatellites varied and was not influenced by transcript sizes. No correlation between relative abundance and transcript sizes was observed. The relative abundance and density of microsatellites were highest in the transcripts of Fusarium solani when compared with F. graminearum, F. verticillioides and F. oxysporum. The maximum frequency of SSRs among all four sequence sets was of trinucleotide repeats (67.8%), whereas the dinucleotide repeat represents <1%. Among all classes of repeats, 36.5% motifs were found conserved within Fusarium species. In order to study polymorphism within Fusarium isolates, 11 polymorphic genic-SSR markers were developed. Of the 11 markers, 5 were from F. oxysporum and remaining 6 belongs to F. solani. SSR markers from F. oxysporum were found to be more polymorphic (38%) as compared to F. solani (26%). Eleven polymorphic markers obtained in this study clearly demonstrate the utility of newly developed SSR markers in establishing genetic relationships among different isolates of Fusarium. [ABSTRACT FROM AUTHOR]

The article focuses on Fecal Microbiota Transplantation. Topics discussed include Microbiota-based therapies are generally considered safe and are the cornerstone of management of patients with recurrent Clostridioides difficile infection, with high success rates to prevent future recurrences; and Health screening for stool donors who participate in studies and clinical practice of microbiome-based therapies have evolved.

In the article, the author discusses the developments in the study of microbiome-based therapies for the treatment of diseases associated with dysbiotic microbiome. Among the accomplishments is the use of fecal microbiota transplantation (FMT) to manage recurrent Clostridioides difficile infection. Also cited are how the use of antimicrobials increased the life expectancy of humans and the evolution of pathobionts to develop resistance to antibiotics.

Objectives A vast number of blinding diseases have genetic aetiologies and may be treated by molecular based therapies such as antisense oligonucleotides or short interfering RNA. However, treatment success of ocular gene therapy is highly dependent on efficient delivery of such molecules. Key findings The majority of clinical studies for ocular gene therapy utilize viral vectors. While these have proven highly efficient, they show limited loading capacity and pose significant safety risks owing to their oncogenic and immunogenic effects. Non-viral gene carriers have emerged as a promising alternative with dendrimers providing great potential for gene therapy because of their size, shape and high density of modifiable surface groups. However, while dendrimers have been used extensively for drug and gene delivery to other organs, only a few studies have been reported on the eye. Summary This review focuses on the development of dendrimers for gene delivery with special emphasis on ocular gene therapy. Different synthesis approaches and types of dendrimers are discussed. Ocular gene therapy targets are highlighted with an overview of current clinical studies. The use of dendrimers in ocular gene delivery in comparison to liposomes and nanoparticles is also discussed. Finally, future prospects of tailored multifunctional dendrimers for ocular gene therapy are highlighted. [ABSTRACT FROM AUTHOR]

Clostridium difficile incidence in children increased significantly from 1991 through 2009. The majority of cases were community-acquired. Severe infection was more common in hospital-acquired than community-acquired cases. There were fewer treatment failures with vancomycin compared to metronidazole.Background. The incidence of Clostridium difficile infection (CDI) is increasing, even in populations previously thought to be at low risk, including children. Most incidence studies have included only hospitalized patients and are thus potentially influenced by referral or hospitalization biases.Methods. We performed a population-based study of CDI in pediatric residents (aged 0–18 years) of Olmsted County, Minnesota, from 1991 through 2009 to assess the incidence, severity, treatment response, and outcomes of CDI.Results. We identified 92 patients with CDI, with a median age of 2.3 years (range, 1 month–17.6 years). The majority of cases (75%) were community-acquired. The overall age- and sex-adjusted CDI incidence was 13.8 per 100 000 persons, which increased 12.5-fold, from 2.6 (1991–1997) to 32.6 per 100 000 (2004–2009), over the study period (P < .0001). The incidence of community-acquired CDI was 10.3 per 100 000 persons and increased 10.5-fold, from 2.2 (1991–1997) to 23.4 per 100 000 (2004–2009) (P < .0001). Severe, severe-complicated, and recurrent CDI occurred in 9%, 3%, and 20% of patients, respectively. The initial treatment in 82% of patients was metronidazole, and 18% experienced treatment failure. In contrast, the initial treatment in 8% of patients was vancomycin and none of them failed therapy.Conclusions. In this population-based cohort, CDI incidence in children increased significantly from 1991 through 2009. Given that the majority of cases were community-acquired, estimates of the incidence of CDI that include only hospitalized children may significantly underestimate the burden of disease in children. [ABSTRACT FROM AUTHOR]

Background. Mycobacterium tuberculosis, the causative agent of tuberculosis, has a remarkable ability to usurp its host's innate immune response, killing millions of infected people annually. One approach to manage infection is prevention through the use of natural agents. In this regard, stem bromelain (SBM), a pharmacologically active member of the sulfhydryl proteolytic enzyme family, obtained from Ananas comosus and possessing a remarkable ability to induce the innate and acquired immune systems, is important.Methods. We evaluated SBM's ability to induce apoptosis and free-radical generation in macrophages. We also studied antimycobacterial properties of SBM and its effect on foamy macrophages.Results. SBM treatment of peritoneal macrophages resulted in the upregulation of proapoptotic proteins and downregulation of antiapoptotic proteins. Additionally, SBM treatment activated macrophages, curtailed the levels of free glutathione, and augmented the production of hydrogen peroxide, superoxide anion, peroxynitrite, and nitric oxide. SBM cleaves CD36 and reduced the formation of foam cells, the hallmark of M. tuberculosis infection. These conditions created an environment for the increased clearance of M. tuberculosis.Conclusions. Together these data provide a mechanism for antimycobacterial activity of SBM and provide important insights for the use of cysteine proteases as immunomodulatory agents. [ABSTRACT FROM PUBLISHER]

Fusarium oxysporum is a ubiquitous species complex of soil-borne plant pathogens comprising of many different formae speciales, each characterized by a high degree of host specificity. In the present investigation, we surveyed microsatellites in the available express sequence tags and transcript sequences of three formae speciales of F. oxysporum viz. melonis ( Fom), cucumerium ( Foc), and lycopersici ( Fol). The relative abundance and density of microsatellites were higher in Fom when compared with Foc and Fol. Thirty microsatellite primers were designed, ten from each forma specialis, for genetic characterization of F. oxysporum isolates belonging to five formae speciales. Of the 30 primers, only 14 showed amplification. A total of 28 alleles were amplified by 14 primers with an average of two alleles per marker. Eight markers showed 100% polymorphism. The markers were found to be more polymorphic (47%) in Fol as compared to Fom and Foc; however, polymorphic information content was the maximum (0.899) in Foc SSR-3. Nine polymorphic markers obtained in this study clearly demonstrate the utility of newly developed markers in establishing genetic relationships among different isolates of F. oxysporum. [ABSTRACT FROM AUTHOR]

An editorial is presented on Clostridium difficile infection (CDI). Topics include patients with diarrhoea and the positive test for C. difficile has presumed to have active infection, the diarrhoea does not respond to C. difficile treatment, does that mean the chosen agent being ineffective and an alternative treatment for CDI has initiated, and investigators have been searching for a test to make this distinction.

Acute infection with Epstein–Barr virus (EBV) causes fever, fatigue and pharyngitis. Renal involvement in systemic EBV infections typically manifests as acute tubular necrosis or tubulointerstitial nephritis. Rarely, EBV infection causes nephrotic syndrome due to minimal change disease. A 22-year-old male with infectious mononucleosis (IM) presented with nephrotic syndrome. Renal biopsy showed minimal change disease with diffuse foot process effacement of the podocytes. Treatment with methylprednisone led to rapid and complete clinical remission. Minimal change nephropathy is a very rare manifestation of EBV infection and should be considered in patients with IM and proteinuria. [ABSTRACT FROM PUBLISHER]

Introduction: Measurement of coagulation assay is pivotal all across in different specialties in field of medicine. We compared prothrombin time, activated prothrombin time and fibrinogen from fresh blood samples drawn into glass vs. plastic tubes. There was a recent recall of glass tubes nationwide from a leading manufacture. This type of situation imposes difficult scenario and put labs in a dilemma whether to use plastic tubes in place of glass tubes. Also the literature is extremely sparse in reference to the use of plastic tubes and shows inconsistence results. Hence, there is a need for further studies. To handle this scenario of the recall, the quality assurance project was performed at CMC Philadelphia VA Medical Center. Method: We collected 65 venous blood samples into 4.5 mL glass tubes and 2.7 mL plastic tubes from mix population patients with and without anticoagulant therapy. After centrifugation we used Diagnostic Stago instrument with Stago reagents for this testing. Mean and standard deviation (SD) were used to verify the adequacy of the analytic ranges in the study and to summarize results. Results: In our results, there was no statistically significance difference observed in prothrombin time, activated partial thromboplastin time, and fibrinogen results. We used Bland-Altman plot for determination of results comparison. Bland-Altman plot shows good correlation between two methods, and their regression shows excellent correlation of r values between 0.98 and 1.00. There is no indication of bias between the methods. Conclusion: Our study shows that the plastic tubes can be safely and successfully used for the coagulation studies in place of glass tubes. [ABSTRACT FROM AUTHOR]

The article discusses the BEST-CLI International Collaborative, which aims to improve care and outcomes for patients with chronic limb-threatening ischemia (CLTI) globally. The article highlights the increasing prevalence of peripheral arterial disease (PAD) and the need for evidence-based treatment strategies for CLTI. The BEST-CLI trial, funded by the National Heart, Lung, and Blood Institute, compared open surgery and endovascular therapy for CLTI patients. The article also mentions the BASIL-2 trial, which compared different revascularization strategies for CLTI. The BEST-CLI International Collaborative seeks to interpret the trial results, identify gaps in CLTI care, disseminate evidence-based medicine, and identify future research priorities. The text discusses the findings of a survey conducted among vascular specialists from 22 countries regarding the treatment of chronic limb-threatening ischemia (CLTI). The survey revealed wide disparities in the management of CLTI, including variations in patient demographics, diagnostic classification, treatment approaches, and costs. The text emphasizes the need for global education and collaboration to promote best practices in CLTI treatment and ensure equal access to evidence-based care. It also highlights the importance of considering local contexts and health economics when implementing treatment strategies. Additionally, the text mentions the potential of new technologies to improve revascularization outcomes and the importance of training programs to enhance physician skills in CLTI interventions. The text discusses the evolution of new technology in caring for patients with critical limb-threatening ischemia (CLTI) and emphasizes the importance [Extracted from the article]

A letter to the editor in response to the article "Current status of Clostridium difficile infection epidemiology," published in a previous issue of the periodical is presented.

Background: Published guidelines call for prolonged courses of intravenous (iv) antibiotics for the treatment of MRSA bloodstream infection (BSI) to ensure eradication of deep foci and decrease relapse risk. Sequential iv-to-oral antibiotic therapy has been successfully applied to other serious infections but has not been evaluated for MRSA BSI.Objectives: To compare outcomes in adults completing MRSA BSI therapy with oral versus parenteral antibiotics in the outpatient setting [oral outpatient antibiotic therapy (OOAT) versus outpatient parenteral antibiotic therapy (OPAT)].Methods: This was a single-centre, retrospective, cohort study between 2008 and 2018. The primary outcome was 90 day clinical failure (MRSA BSI recurrence, deep-seated MRSA infection or all-cause mortality). Analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW).Results: A total of 492 patients were included (70 OOAT, 422 OPAT). In general, OOAT patients had characteristics consistent with a lower risk of poor outcomes; however, after IPTW key prognostic factors were balanced. In IPTW-adjusted analysis, there was non-significant reduction in the rate of 90 day clinical failure in the OOAT group compared with the OPAT group [adjusted HR (aHR) 0.379, 95% CI 0.131-1.101]. In analyses restricted to pre-specified subgroups defined by index infection complexity and comorbidity burden, findings were consistent with the main analysis. Furthermore, OOAT patients had a significantly reduced rate of 90 day hospital readmission (aHR 0.603, 95% CI 0.388-0.937).Conclusions: We provide preliminary evidence that selected patients with MRSA BSI may have at least equivalent clinical outcomes with OOAT versus OPAT and provide support to ongoing and future studies evaluating oral antibiotics for MRSA BSI. [ABSTRACT FROM AUTHOR]

Background Published guidelines call for prolonged courses of intravenous (iv) antibiotics for the treatment of MRSA bloodstream infection (BSI) to ensure eradication of deep foci and decrease relapse risk. Sequential iv-to-oral antibiotic therapy has been successfully applied to other serious infections but has not been evaluated for MRSA BSI. Objectives To compare outcomes in adults completing MRSA BSI therapy with oral versus parenteral antibiotics in the outpatient setting [oral outpatient antibiotic therapy (OOAT) versus outpatient parenteral antibiotic therapy (OPAT)]. Methods This was a single-centre, retrospective, cohort study between 2008 and 2018. The primary outcome was 90 day clinical failure (MRSA BSI recurrence, deep-seated MRSA infection or all-cause mortality). Analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW). Results A total of 492 patients were included (70 OOAT, 422 OPAT). In general, OOAT patients had characteristics consistent with a lower risk of poor outcomes; however, after IPTW key prognostic factors were balanced. In IPTW-adjusted analysis, there was non-significant reduction in the rate of 90 day clinical failure in the OOAT group compared with the OPAT group [adjusted HR (aHR) 0.379, 95% CI 0.131–1.101]. In analyses restricted to pre-specified subgroups defined by index infection complexity and comorbidity burden, findings were consistent with the main analysis. Furthermore, OOAT patients had a significantly reduced rate of 90 day hospital readmission (aHR 0.603, 95% CI 0.388–0.937). Conclusions We provide preliminary evidence that selected patients with MRSA BSI may have at least equivalent clinical outcomes with OOAT versus OPAT and provide support to ongoing and future studies evaluating oral antibiotics for MRSA BSI. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study is to evaluate the development of a 1-wk screening campaign and efforts towards the implementation of a sustainable system that addresses cervical cancer in Mwanza, Tanzania with a screen-and-treat model utilizing visual inspection of the cervix with acetic acid (VIA) and cryotherapy. Methods: In partnership with CureCervicalCancer (CCC), a non-profit organization based in Los Angeles, CA, USA, 11 medical students at the University of California, Irvine School of Medicine established a model for sustainable human papillomavirus screening practices in Mwanza, Tanzania. This study both quantitatively and qualitatively assesses the successes and limitations of the program model. Results: During the 5-day training, a total of 614 women attended the screenings and 556 women were screened with VIA, of whom 10.6% (n=59) were VIA positive and 89.4% (n=499) were VIA negative. Of those who were VIA positive, 83.1% (n=49) received cryotherapy while 16.9% (n=10) did not due to suspicion of advanced cancer (n=7), refusal to receive cryotherapy (n=2) or pregnancy (n=1). Conclusions: The screen-and-treat model for the identification and treatment of precancerous cervical lesions is an effective public health intervention with the potential to impact women by providing the tools and education needed by local healthcare professionals. However, limitations common to resource-poor settings, such as continuity of funding, loss to follow-up and transportation costs, remain barriers to sustainability. [ABSTRACT FROM AUTHOR]

Herein, we investigated the extent of gender disparity among dermatologists awarded Canadian Institutes of Health Research (CIHR) grants. Https://doi.org/10.1093/bjd/ljad192 DearEditor, Grant-awarding organizations are uniquely positioned to confer funding that is associated with improved research quality and career advancement of the recipient.[1] Unfortunately, evidence suggests that disproportionate amounts of research funding are awarded to males compared with females, furthering gender disparities in academic research.[2] Between 2015 and 2019, although American females comprised 51% of full-time dermatology faculty, they accounted for only 39.1% of total funding, receiving $121.3 million less than male colleagues.[2] Whether a similar trend occurs in the Canadian context remains unknown. [Extracted from the article]

Aim This study was aimed to determine antimicrobial and antiviral activity of a novel lanthipeptide from a Brevibacillus sp. for disinfectant application. Methods and results The antimicrobial peptide (AMP) was produced by a bacterial strain AF8 identified as a member of the genus Brevibacillus representing a novel species. Whole genome sequence analysis using BAGEL identified a putative complete biosynthetic gene cluster involved in lanthipeptide synthesis. The deduced amino acid sequence of lanthipeptide named as brevicillin, showed >30% similarity with epidermin. Mass determined by MALDI-MS and Q-TOF suggested posttranslational modifications like dehydration of all Ser and Thr amino acids to yield Dha and Dhb, respectively. Amino acid composition determined upon acid hydrolysis is in agreement with core peptide sequence deduced from the putative biosynthetic gene bvrAF8. Biochemical evidence along with stability features ascertained posttranslational modifications during formation of the core peptide. The peptide showed strong activity with 99% killing of pathogens at 12 μg ml−1 within 1 minute. Interestingly, it also showed potent anti-SARS-CoV-2 activity by inhibiting ∼99% virus growth at 10 μg ml−1 in cell culture-based assay. Brevicillin did not show dermal allergic reactions in BALB/c mice. Conclusion This study provides detailed description of a novel lanthipeptide and demonstrates its effective antibacterial, antifungal and anti-SARS-CoV-2 activity. [ABSTRACT FROM AUTHOR]

Background ageing is an important risk factor for a variety of human pathologies. Biological age (BA) may better capture ageing-related physiological changes compared with chronological age (CA). Objective we developed a deep learning (DL) algorithm to predict BA based on retinal photographs and evaluated the performance of our new ageing marker in the risk stratification of mortality and major morbidity in general populations. Methods we first trained a DL algorithm using 129,236 retinal photographs from 40,480 participants in the Korean Health Screening study to predict the probability of age being ≥65 years ('RetiAGE') and then evaluated the ability of RetiAGE to stratify the risk of mortality and major morbidity among 56,301 participants in the UK Biobank. Cox proportional hazards model was used to estimate the hazard ratios (HRs). Results in the UK Biobank, over a 10-year follow up, 2,236 (4.0%) died; of them, 636 (28.4%) were due to cardiovascular diseases (CVDs) and 1,276 (57.1%) due to cancers. Compared with the participants in the RetiAGE first quartile, those in the RetiAGE fourth quartile had a 67% higher risk of 10-year all-cause mortality (HR = 1.67 [1.42–1.95]), a 142% higher risk of CVD mortality (HR = 2.42 [1.69–3.48]) and a 60% higher risk of cancer mortality (HR = 1.60 [1.31–1.96]), independent of CA and established ageing phenotypic biomarkers. Likewise, compared with the first quartile group, the risk of CVD and cancer events in the fourth quartile group increased by 39% (HR = 1.39 [1.14–1.69]) and 18% (HR = 1.18 [1.10–1.26]), respectively. The best discrimination ability for RetiAGE alone was found for CVD mortality (c-index = 0.70, sensitivity = 0.76, specificity = 0.55). Furthermore, adding RetiAGE increased the discrimination ability of the model beyond CA and phenotypic biomarkers (increment in c-index between 1 and 2%). Conclusions the DL-derived RetiAGE provides a novel, alternative approach to measure ageing. [ABSTRACT FROM AUTHOR]

Background Observational data suggest ceftaroline may be effective for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI), but comparative data with standard of care are limited. This analysis compares the outcomes of MRSA BSI treated with ceftaroline or daptomycin. Methods Multicenter, retrospective, observational cohort study of adult patients with MRSA BSI from 2010 to 2017. Patients treated with ≥72 hours of ceftaroline or daptomycin were included. Those clearing BSI before study drug and those with a pneumonia source were excluded. The primary outcome was composite treatment failure, defined as 30-day mortality, BSI duration ≥7 days on study drug, and 60-day MRSA BSI recurrence. Inverse probability of treatment weighted risk difference in composite failure between daptomycin and ceftaroline groups was computed and 15% noninferiority margin applied. Results Two hundred seventy patients were included; 83 ceftaroline and 187 daptomycin. Ceftaroline was noninferior to daptomycin with respect to composite failure (39% daptomycin, 32.5% ceftaroline; weighted risk difference, 7.0% [95% confidence interval, –5.0% to 19.0%]). No differences between treatment groups was observed for 30-day mortality or other secondary efficacy outcomes. Creatine phosphokinase elevation was significantly more common among daptomycin patients (5.3% vs 0%, P =.034). Rash was significantly more common among ceftaroline patients (10.8 vs 1.1%, P =.001). Conclusions No difference in treatment failure or mortality was observed between MRSA BSI treated with ceftaroline or daptomycin. These data support future study of ceftaroline as a primary MRSA BSI treatment and current use of ceftaroline when an alternative to vancomycin and daptomycin is required. [ABSTRACT FROM AUTHOR]

Chandipura virus ( CHPV), alike other pathogens, exploits the cellular infrastructure of their hosts through complex network of interactions for successful infection. CHPV being a recently emerged pediatric encephalitic virus, the mechanisms involved in the establishment of viral persistence are still ill defined. Because the protein interface between CHPV and its host provides one means by which the virus invades and seize control of their human host machinery, the authors in this study have employed computational methods to create a network of putative protein-protein interactions between CHPV and its human host to shed light on the hitherto less-known CHPV biology. On the basis of the 2105 potential interactions predicted among 1650 human proteins and the five proteins of CHPV, the authors decipher the probable mode by which the virus manipulates the biological pathways of its host toward its own end and replicates while evading the immune system. Identification of such conserved set of putative interactions that allow the virus to take control of the host has the potential to deepen our understanding of the virus-specific remodeling processes of the host cell and illuminate new arenas of disease intervention. [ABSTRACT FROM AUTHOR]

The past five decades have witnessed the unprecedented contribution of arboviral diseases towards global morbidity and disability. It is primarily attributed due to unplanned urbanization, population explosion and globalization. Out of these, dengue is considered the most important arboviral disease because of its predominant growth in the past. The presented study explores the immense potential of Internet of things (IoT), fog and cloud computing for providing technology-based healthcare solutions for dengue virus (DENV) infection. In this paper, a hierarchical healthcare computing system for controlling DENV infection using fog–cloud-assisted IoT is proposed. This system provides a real-time remote diagnosis of DENV infection in individuals and monitors and predicts their health sensitivity during its infection period. The system uses fog computing to diagnose the DENV infection status of the individuals using |$k$| -means clustering and generates immediate diagnostic alerts to individuals, at the fog layer. Furthermore, the system uses cloud computing to monitor and predict the probabilistic health sensitivity of the DENV-infected individuals using Bayesian belief network and artificial neural network, respectively, at the cloud layer. The prediction of health sensitivity in the proposed system helps the infected individuals and healthcare agencies in determining the health vulnerability of DENV-infected individuals and preventing severe or permanent health losses in the future. The proposed system is experimentally evaluated using well-defined approaches, which conform to its validity and applicability. The results obtained from the experimental evaluations of the proposed system acknowledge the performance superiority and high efficiency of the system in delivering DENV-related healthcare services in real time. [ABSTRACT FROM AUTHOR]

Background Fecal microbiota transplantation (FMT) is highly effective for preventing recurrent Clostridioides difficile infection (CDI). Durability (no recurrence despite additional risk factor exposure) of FMT protection is largely unknown. We studied the durability of FMT in patients with recurrent CDI. Methods We conducted a retrospective study of adults undergoing FMT for recurrent CDI. Data collected included demographics, CDI risk factors (comorbidities, healthcare exposure, non-CDI antibiotic use, acid suppressant medications), and future CDI episodes. Durable response to FMT was defined as lack of CDI episodes within 1 year post-FMT despite risk factor exposure. Results Overall, 460 patients were included (median age, 57 years [18–94]; 65.2% female). Comorbidities included chronic liver disease, 12.8% (n = 59); cancer, 11.7% (n = 54); chronic kidney disease, 3.9% (n = 18); and inflammatory bowel disease, 21.9% (n = 101). Overall, 31.3% (n = 144) received antibiotics, 21.7% (n = 100) received acid suppressants, and 76.8% (n = 350) had healthcare exposure after FMT. Of 374 patients with risk factor exposure, 78.1% (95% confidence interval [CI], 72.7%–84.0%) had durable response to FMT at 1 year. On multivariable analysis, antibiotic use was independently associated with decreased durability of FMT (hazard ratio, 0.27; 95% CI,.15–.49; P  < .001). Conclusions The majority of patients had a durable response to FMT despite exposure to CDI risk factors. Antibiotic exposure after FMT independently predicted loss of durability of FMT. Larger studies are needed to define predictors of durable response in patients with and without exposure to antibiotics. [ABSTRACT FROM AUTHOR]

While neuro-cognitive work examining aggression has examined patients with conditions at increased risk for aggression or individuals self-reporting past aggression, little work has attempted to identify neuro-cognitive markers associated with observed/recorded aggression. The goal of the current study was to determine the extent to which aggression by youth in the first three months of residential care was associated with atypical responsiveness to threat stimuli. This functional MRI study involved 98 (68 male; mean age = 15.96 [sd = 1.52]) adolescents in residential care performing a looming threat task involving images of threatening and neutral human faces or animals that appeared to be either loom or recede. Level of aggression was negatively associated with responding to looming stimuli (irrespective of whether these were threatening or neutral) within regions including bilateral inferior frontal gyrus, right inferior parietal lobule, right superior/middle temporal gyrus and a region of right uncus proximal to the amygdala. These data indicate that aggression level is associated with a decrease in responsiveness to a basic threat cue-looming stimuli. Reduced threat responsiveness likely results in the individual being less able to represent the negative consequences that may result from engaging in aggression, thereby increasing the risk for aggressive episodes. [ABSTRACT FROM AUTHOR]

Background Recurrent Clostridioides difficile infection (rCDI) is associated with loss of microbial diversity and microbe-derived secondary bile acids, which inhibit C. difficile germination and growth. SER-109, an investigational microbiome drug of donor-derived, purified spores, reduced recurrence in a dose-ranging, phase (P) 1 study in subjects with multiple rCDIs. Methods In a P2 double-blind trial, subjects with clinical resolution on standard-of-care antibiotics were stratified by age (< or ≥65 years) and randomized 2:1 to single-dose SER-109 or placebo. Subjects were diagnosed at study entry by PCR or toxin testing. Safety, C. difficile–positive diarrhea through week 8, SER-109 engraftment, and bile acid changes were assessed. Results 89 subjects enrolled (67% female; 80.9% diagnosed by PCR). rCDI rates were lower in the SER-109 arm than placebo (44.1% vs 53.3%) but did not meet statistical significance. In a preplanned analysis, rates were reduced among subjects ≥65 years (45.2% vs 80%, respectively; RR, 1.77; 95% CI, 1.11–2.81), while the <65 group showed no benefit. Early engraftment of SER-109 was associated with nonrecurrence (P <.05) and increased secondary bile acid concentrations (P <.0001). Whole-metagenomic sequencing from this study and the P1 study revealed previously unappreciated dose-dependent engraftment kinetics and confirmed an association between early engraftment and nonrecurrence. Engraftment kinetics suggest that P2 dosing was suboptimal. Adverse events were generally mild to moderate in severity. Conclusions Early SER-109 engraftment was associated with reduced CDI recurrence and favorable safety was observed. A higher dose of SER-109 and requirements for toxin testing were implemented in the current P3 trial. Clinical Trials Registration NCT02437487, https://clinicaltrials.gov/ct2/show/NCT02437487?term=SER-109&draw= 2&rank=4. [ABSTRACT FROM AUTHOR]

Bilateral visual impairment includes participants with visual impairment in one eye and visual impairment/blindness in the other eye. e Presence of any existing cataract or any history of cataract surgery in either eye (Modified Wisconsin Cataract Grading System). f Among diabetic individuals. g VTDR, vision-threatening diabetic retinopathy. Bilateral visual impairment includes participants with visual impairment in one eye and visual impairment/blindness in the other eye. d Based on the WHO definition, visual impairment was defined as VA<20/60 to 20/400. The overall age-adjusted BCVA prevalence of bilateral blindness (VA< 20/200, based on the better-seeing eye) and VI (VA< 20/40 to 20/200, based on the better-seeing eye) was 0.3% [95% confidence interval (CI) 0.2-0.4] and 4.2% (95% CI 3.8- 4.5), respectively. Globally, blindness and visual impairment (VI) are estimated to affect 36 million and 400 million people, respectively. [Extracted from the article]

Background Mounting evidence suggests the addition of a β-lactam (BL) to daptomycin (DAP) results in synergistic in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA) and bolsters the innate immune response to infection. This study's objective was to provide clinical translation to these experimental data and determine if DAP+BL combination therapy results in improved clinical outcomes compared with treatment with DAP alone in patients with MRSA bloodstream infections (BSIs). Methods This was a retrospective, comparative cohort study conducted at 2 academic medical centers between 2008 and 2018. Adults with MRSA BSI treated with DAP for ≥72 hours and initiated ≤5 days of culture collection were included. Patients who received a BL for ≥24 hours and initiated ≤24 hours of DAP comprised the DAP+BL group. The primary outcome was composite clinical failure (60-day all-cause mortality and/or 60-day recurrence). Analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW). Results A total of 229 patients were included (72 DAP+BL and 157 DAP). In unadjusted and IPTW-adjusted analyses, DAP+BL was associated with significantly reduced odds of clinical failure (odds ratio [OR], 0.362; 95% confidence interval [CI],.164–.801; adjusted OR, 0.386; 95% CI,.175–.853). Adjusted analyses restricted to prespecified subgroups based on infection complexity and baseline health status were consistent with the main analysis. Conclusions The addition of a BL to DAP was associated with improved clinical outcomes in patients with MRSA BSI. This study provides support to ongoing and future studies evaluating the impact of combination therapy for invasive MRSA infections. Patients treated with daptomycin plus a β-lactam for MRSA bloodstream infection had lower odds of composite clinical failure defined as 60-day all-cause mortality and/or 60-day recurrence compared with patients treated with daptomycin monotherapy after adjusting for confounding variables using inverse probability of treatment weighting. [ABSTRACT FROM AUTHOR]

Background Fecal microbiota transplantation (FMT) is highly effective for treating recurrent Clostridium difficile infection (CDI) in observational studies (>90%), but cure rates in clinical trials are lower. We performed a systematic review and meta-analysis to assess the efficacy of FMT for recurrent CDI in open-label studies and clinical trials. Methods A systematic search from January 1978 to March 2017 was performed to include clinical trials of FMT for CDI. We analyzed CDI resolution by calculating weighted pooled rates (WPRs). Results Thirteen trials were included, comprising 610 patients with CDI treated with single FMT. Overall, 439 patients had clinical cure (WPR, 76.1%; 95% confidence interval (CI), 66.4%–85.7%). There was significant heterogeneity among studies (I 2 = 91.35%). Cure rates were lower in randomized trials (139/216 patients; WPR, 67.7%; 95% CI, 54.2%–81.3%) than in open-label studies (300/394 patients; WPR, 82.7%; 71.1%–94.3%) (P <.001). Subgroup analysis by FMT delivery modality showed lower cure rates with enema than colonoscopy (WPR, 66.3% vs 87.4%; P <.001) but no difference between colonoscopy and oral delivery (WPR, 87.4% vs 81.4%; P =.17). Lower rates were seen for studies including both recurrent and refractory CDI than for those including only recurrent CDI (WPR, 63.9% vs 79%; P <.001). Conclusions FMT was associated with lower cure rates in randomized trials than in open-label and in observational studies. Colonoscopy and oral route are more effective than enema for stool delivery. The efficacy also seems to be higher for recurrent than for refractory CDI. [ABSTRACT FROM AUTHOR]

Background Despite advancements, recurrent Clostridium difficile infections (CDI) remain an urgent public health threat with insufficient response rates to currently approved antibiotic therapies. Microbiota-based treatments appear effective, but rigorous clinical trials are required to optimize dosing strategies and substantiate long-term safety. Methods This randomized, double-blind, placebo-controlled phase 2B trial enrolled adults with 2 or more CDI recurrences to receive: 2 doses of RBX2660, a standardized microbiota-based drug (group A); 2doses of placebo (group B); or 1 dose of RBX2660 followed by 1 dose of placebo (group C). Efficacy was defined as prevention of recurrent CDI for 8 weeks following treatment. Participants who had a recurrence within 8 weeks were eligible to receive up to 2 open-label RBX2660 doses. The primary endpoint was efficacy for group A compared to group B. Secondary endpoints included the efficacy of group C compared to group B, combined efficacy in the blinded and open-label phases, and safety for 24 months. Results The efficacy for groups A, B, and C were 61%, 45%, and 67%, respectively. The primary endpoint was not met (P =.152). One RBX2660 dose (group C) was superior to placebo (group B; P =.048), and the overall efficacy (including open-label response) for RBX2660-treated participants was 88.8%. Adverse events did not differ significantly among treatment groups. Conclusions One, but not 2, doses of RBX2660 was superior to placebo in this randomized, placebo-controlled trial. These data provide important insights for a larger phase 3 trial and continued clinical development of RBX2660. Clinical Trials Registration NCT02299570. [ABSTRACT FROM AUTHOR]

Background. The choice of antibiotics for systemic infections in patients with a high risk of Clostridium difficile infection (CDI) remains a clinical practice dilemma. Although some studies suggest that tetracyclines may be associated with a lower risk of CDI than other antibiotics, other results are conflicting. We conducted a systematic review and metaanalysis of studies that assessed the risk of CDI with tetracyclines compared to other antibiotics. Methods. We conducted a systematic search of Medline, Embase, and Web of Science from January 1978 through December 2016 to include studies that assessed the association between tetracycline use and risk of CDI. Weighted summary estimates were calculated using generalized inverse variance with a random-effects model using RevMan 5.3. Study quality was assessed using the Newcastle-Ottawa scale. Results. Six studies (4 case control, 2 cohort) with patient recruitment between 1993 and 2012 were included. Metaanalysis using a random-effects model, demonstrated that tetracyclines were associated with a decreased risk of CDI (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.47-0.81; P < .001). There was significant heterogeneity, with an I2 of 53% with no publication bias. Subgroup analysis of studies that evaluated the risk of CDI with doxycycline alone also demonstrated a decreased risk of CDI (OR, 0.55; 95% CI, 0.40-0.75; P < .001). Conclusions. Metaanalyses of existing studies suggest that tetracyclines may be associated with a decreased risk of CDI compared with other antimicrobials. It may be reasonable to use tetracyclines whenever appropriate to decrease CDI associated with antibiotic use. [ABSTRACT FROM AUTHOR]

The adaptation of CRISPR/SpCas9 technology to mammalian cell lines is transforming the study of human functional genomics. Pooled libraries of CRISPR guide RNAs (gRNAs) targeting human protein-coding genes and encoded in viral vectors have been used to systematically create gene knockouts in a variety of human cancer and immortalized cell lines, in an effort to identify whether these knockouts cause cellular fitness defects. Previous work has shown that CRISPR screens are more sensitive and specific than pooled-library shRNA screens in similar assays, but currently there exists significant variability across CRISPR library designs and experimental protocols. In this study, we reanalyze 17 genome-scale knockout screens in human cell lines from three research groups, using three different genome-scale gRNA libraries. Using the Bayesian Analysis of Gene Essentiality algorithm to identify essential genes, we refine and expand our previously defined set of human core essential genes from 360 to 684 genes. We use this expanded set of reference core essential genes, CEG2, plus empirical data from six CRISPR knockout screens to guide the design of a sequence-optimized gRNA library, the Toronto KnockOut version 3.0 (TKOv3) library. We then demonstrate the high effectiveness of the library relative to reference sets of essential and nonessential genes, as well as other screens using similar approaches. The optimized TKOv3 library, combined with the CEG2 reference set, provide an efficient, highly optimized platform for performing and assessing gene knockout screens in human cell lines. [ABSTRACT FROM AUTHOR]