Diversification of refugia types needed to secure the future of coral reefs subject to climate change.

Identifying locations of refugia from the thermal stresses of climate change for coral reefs and better managing them is one of the key recommendations for climate change adaptation. We review and summarize approximately 30 years of applied research focused on identifying climate refugia to prioritize the conservation actions for coral reefs under rapid climate change. We found that currently proposed climate refugia and the locations predicted to avoid future coral losses are highly reliant on  excess heat metrics, such as degree heating weeks. However, many existing alternative environmental, ecological, and life-history variables could be used to identify other types of refugia that lead to the desired diversified portfolio for coral reef conservation. To improve conservation priorities for coral reefs, there is a need to evaluate and validate the predictions of climate refugia with long-term field data on coral abundance, diversity, and functioning. There is also the need to identify and safeguard locations displaying resistance toprolonged exposure to heat waves and the ability to recover quickly after thermal exposure. We recommend using more metrics to identify a portfolio of potential refugia sites for coral reefs that can avoid, resist, and recover from exposure to high ocean temperatures and the consequences of climate change, thereby shifting past efforts focused on avoidance to a diversified risk-spreading portfolio that can be used to improve strategic coral reef conservation in a rapidly warming climate.

Diversificación de los tipos de refugio necesarios para asegurar el futuro de los arrecifes de coral sujetos al cambio climático Resumen Una de las principales recomendaciones para la adaptación al cambio climático es identificar los refugios de los arrecifes de coral frente al estrés térmico del cambio climático y mejorar su gestión. Revisamos y resumimos ∼30 años de investigación aplicada centrada en la identificación de refugios climáticos para priorizar las acciones de conservación de los arrecifes de coral bajo un rápido cambio climático. Descubrimos que los refugios climáticos propuestos actualmente y las ubicaciones que pueden evitarlos dependen en gran medida de métricas de exceso de calor, como las semanas de calentamiento en grados (SCG). Sin embargo, existen muchas variables alternativas de historia vital, ambientales y ecológicas que podrían utilizarse para identificar otros tipos de refugios que resulten en el acervo diversificado que se desea para la conservación de los arrecifes de coral. Para mejorar las prioridades de conservación de los arrecifes de coral, es necesario evaluar y validar las predicciones sobre refugios climáticos con datos de campo a largo plazo sobre abundancia, diversidad y funcionamiento de los corales. También es necesario identificar y salvaguardar lugares que muestren resistencia a la exposición climática prolongada a olas de calor y la capacidad de recuperarse rápidamente tras la exposición térmica. Recomendamos utilizar más métricas para identificar un acervo de posibles lugares de refugio para los arrecifes de coral que puedan evitar, resistir y recuperarse de la exposición a las altas temperaturas oceánicas y las consecuencias del cambio climático, para así desplazar los esfuerzos pasados centrados en la evitación hacia un acervo diversificado de riesgos que pueda utilizarse para mejorar la conservación estratégica de los arrecifes de coral en un clima que se calienta rápidamente.

Importance of Dipole Orientation in Electrostatic Aerosol Filtration.

Electrostatic charge is a major part of modern-day aerosol filtration media (e.g., N95 respirators and surgical facemasks) that has remained poorly understood due to its complicated physics. As such, charging a fibrous material has relied on empiricism in dire need of a mathematical foundation to further advance product design and optimization. In this concern, we have conducted a series of numerical simulations to improve our understanding of how an electrostatically charged fiber captures airborne particles and to quantify how the fiber's dipole orientation impacts its capture efficiency. Special attention was paid to the role of Coulomb and dielectrophoretic forces in the capture of particles of different charge polarities (e.g., particles having a Boltzmann charge distribution). Simulation results were compared with the predictions of the popular empirical correlations from the literature and discussed in detail. Predictions of the empirical correlations better agreed with the simulation results obtained for fibers with a dipole perpendicular to the flow direction rather than for fibers with a dipole parallel to the flow. This indicates that such empirical correlations are more suitable for filters charged via contact electrification (friction charging), where the dipoles are mostly perpendicular to the flow direction, and less suitable for corona-charged media, where the fiber dipoles are generally parallel to the flow direction.

Outcome of Three Dimensional Printed Functional Prostheses for Children with Upper Limb Deficiency in Nepal.

Background Children with congenital and traumatic upper limb amputation are undervalued in a low and middle-income country (LMIC) like Nepal. The use of a prosthetic hand can give them a feeling of self-reliance to perform their daily activities. However, prosthesis require periodic maintenance and replacement which could be a financial burden to some families. The e-Nable community has designed and developed three dimension printed prosthetic hands for children under 19 years old, and distributed them free of cost. Objective To explore the functionality of the three dimension printed prosthetic hands using semi-structured questionnaires and assess a series of daily tasks after three months prosthetic use. Method This descriptive cross-sectional study was conducted from July 2019 to June 2020, after receiving an ethical clearance from the Nepal Health Research Council (Registration number: 582/2019). Seventy six children (5-18 years old) who met the inclusion criteria were enrolled in this study. Data were collected using semistructured questionnaires, and observational methods to identify the benefits and drawbacks of the three dimensional prosthetic hands. Mean, standard deviation, and percentage were used to interpret the data. Result All participants could only lift light objects such as tray, tennis ball or a bottle of water. They had difficulty with those task that required complex movement and with lifting heavy objects. Moreover, only 47(61.8%) participants were completely satisfied with the prosthetic hand and the major reasons for dissatisfaction were tear of the rubber band or cord, and broken parts. Conclusion Participant were able to complete certain tasks using the e-Nable community three dimensional printed prosthetic hands.

Non-tuberculous Mycobacterium Rhinosinusitis in an Immunocompetent Patient.

Non-tuberculous mycobacteria (NTM) are slow-growing opportunistic pathogens that cause a variety of cutaneous, soft tissue, and pulmonary infections. On rare occasions, NTM causes chronic rhinosinusitis, with the majority of cases presenting in immunocompromised individuals. Other potential risk factors include the presence of foreign bodies, previous sinus surgery or chemoradiation, and use of contaminated water in sinus rinses. We report here a rare case of NTM rhinosinusitis in an otherwise immunocompetent 66-year-old female. The patient underwent functional endoscopic sinus surgery where intraoperative acid-fast bacteria cultures grew Mycobacterium abscessus. She received five weeks of broad-spectrum IV antibiotic therapy followed by three months of oral azithromycin, tigecycline, and linezolid. A one-year post-operative visit showed appropriate healing without crusting or visible infection. This case contributes to the small handful of documented presentations of NTM rhinosinusitis in immunocompetent patients. NTM should be considered when patients present with refractory rhinosinusitis as they may require extended courses of antibiotic treatment. Familiarity with risk factors can further expedite making a diagnosis, ensuring prompt initiation of treatment and relief of symptoms for patients.

An Unexpected Turn of Events in a Patient With Mitral Valve Endocarditis.

A variety of gram-positive infections can be treated with daptomycin. Daptomycin-induced acute eosinophilic pneumonia (DEP) is a rare adverse drug reaction with nonspecific clinical findings of dyspnea, dry cough, and fever. Although diagnostic criteria exist, prompt recognition is important to prevent rapid progression and respiratory failure. In this case, a 69-year-old female was initially admitted due to a prosthetic joint infection; however, her case was complicated by DEP.

Long-term outcomes of mesial temporal laser interstitial thermal therapy for drug-resistant epilepsy and subsequent surgery for seizure recurrence: a multi-centre cohort study.

BACKGROUND: Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive alternative to surgical resection for drug-resistant mesial temporal lobe epilepsy (mTLE). Reported rates of seizure freedom are variable and long-term durability is largely unproven. Anterior temporal lobectomy (ATL) remains an option for patients with MRgLITT treatment failure. However, the safety and efficacy of this staged strategy is unknown. METHODS: This multicentre, retrospective cohort study included 268 patients consecutively treated with mesial temporal MRgLITT at 11 centres between 2012 and 2018. Seizure outcomes and complications of MRgLITT and any subsequent surgery are reported. Predictive value of preoperative variables for seizure outcome was assessed. RESULTS: Engel I seizure freedom was achieved in 55.8% (149/267) at 1 year, 52.5% (126/240) at 2 years and 49.3% (132/268) at the last follow-up ≥1 year (median 47 months). Engel I or II outcomes were achieved in 74.2% (198/267) at 1 year, 75.0% (180/240) at 2 years and 66.0% (177/268) at the last follow-up. Preoperative focal to bilateral tonic-clonic seizures were independently associated with seizure recurrence. Among patients with seizure recurrence, 14/21 (66.7%) became seizure-free after subsequent ATL and 5/10 (50%) after repeat MRgLITT at last follow-up≥1 year. CONCLUSIONS: MRgLITT is a viable treatment with durable outcomes for patients with drug-resistant mTLE evaluated at a comprehensive epilepsy centre. Although seizure freedom rates were lower than reported with ATL, this series represents the early experience of each centre and a heterogeneous cohort. ATL remains a safe and effective treatment for well-selected patients who fail MRgLITT.

Efficacy of a filtered far-UVC handheld disinfection device in reducing the microbial bioburden of hospital surfaces.

BACKGROUND: The filtered far-UV-C (FFUV) handheld disinfection device is a small portable device that emits far UV-C at 222 nm. The objective of this study was to evaluate the device's ability to kill microbial pathogens on hospital surfaces and compare it to manual disinfection using germicidal sodium hypochlorite wipes. METHODS: A total of 344 observations (4 observations from 86 objects' surfaces) were sampled with 2 paired samples per surface: a pre- and a post-sodium hypochlorite and FFUV sample. The results were analyzed via a Bayesian multilevel negative binomial regression model. RESULTS: The estimated mean colony counts for the sodium hypochlorite control and treatment groups were 20.5 (95% uncertainty interval: 11.7-36.0) and 0.1 (0.0-0.2) colony forming units (CFUs), respectively. The FFUV control and treatment groups had mean colony counts of 22.2 (12.5-40.1) and 4.1 (2.3-7.2) CFUs. The sodium hypochlorite group and the FFUV group had an estimated 99.4% (99.0%-99.7%) and 81.4% (76.2%-85.7%) reduction in colony counts, respectively. CONCLUSIONS: The FFUV handheld device effectively reduced the microbial bioburden on surfaces in the health care setting. The major benefit of FFUV is likely seen when manual disinfection is not possible or when supplementing cleaners or disinfectants with the low-level disinfection properties.

Deep Brain Stimulator Infection by Oligella: A Case Report and Review of the Literature.

Oligella is a commensal bacteria genus of the human urinary tract that rarely precipitates clinical infections. We report the case of an asymptomatic 24-year-old male with a medical history of Tourette syndrome and the recent placement of deep brain stimulator leads, which were found to be co-infected with Oligella species during hardware implantation. This is the first reported case of a deep brain stimulator infection by Oligella, a potentially under-recognized and emerging opportunistic bacteria. We review the previously published cases of extra-genitourinary Oligella infections and detail the clinical management of this uncommon pathogen.

Dynamic odd-even effect in n-alkane systems: a molecular dynamics study.

Alternation in various properties of n-alkanes (CnH2n+2) as a function of carbon content (n) is termed 'odd-even effect'. Here, we report a comprehensive molecular dynamics simulation study on n-alkane systems carried out with n ranging between 3 (propane) and 8 (octane), examining the odd-even effect in melting point, density, intramolecular conformational ordering, translational and rotational motion. We observe an odd-even alternation in these properties, but with heptane (n = 7) exhibiting anomalous behavior for all except conformational ordering. Our simulations also show the presence of odd-even behavior in rotational and translational dynamics, below and above the melting point, respectively. The results highlight the role of both molecular shape and the variation in density and their interplay in the origins of the odd-even effect.

Polymicrobial Prosthetic Valve Endocarditis Due to Neisseria gonorrhoeae and Pseudomonas fluorescens in a Patient With Tetralogy of Fallot: A Case Report.

Disseminated gonococcal infections are rare clinical entities and a few progress to endocarditis. Endocarditis caused by Pseudomonasis even more infrequent, with the few reported cases associated with either intravenous drug use, prosthetic heart valves, or pacemakers. We report a case of a 25-year-old male patient with Tetralogy of Fallot presenting with anasarca and diagnosed with endocarditis due to Neisseria gonorrhoeae and Pseudomonas fluorescens. To our knowledge, this is the first case of tissue-proven infective endocarditis due to P. fluorescens with concomitant N. gonorrhoeae bacteremia. Clinical management of polymicrobial endocarditis in young adults includes obtaining a detailed sexual history, using multiple diagnostic methods to confirm endocarditis, and promptly initiating broad-spectrum antibiotic therapy.

Stride-level analysis of mouse open field behavior using deep-learning-based pose estimation.

Gait and posture are often perturbed in many neurological, neuromuscular, and neuropsychiatric conditions. Rodents provide a tractable model for elucidating disease mechanisms and interventions. Here, we develop a neural-network-based assay that adopts the commonly used open field apparatus for mouse gait and posture analysis. We quantitate both with high precision across 62 strains of mice. We characterize four mutants with known gait deficits and demonstrate that multiple autism spectrum disorder (ASD) models show gait and posture deficits, implying this is a general feature of ASD. Mouse gait and posture measures are highly heritable and fall into three distinct classes. We conduct a genome-wide association study to define the genetic architecture of stride-level mouse movement in the open field. We provide a method for gait and posture extraction from the open field and one of the largest laboratory mouse gait and posture data resources for the research community.

A machine-vision-based frailty index for mice.

Heterogeneity in biological aging manifests itself in health status and mortality. Frailty indices (FIs) capture health status in humans and model organisms. To accelerate our understanding of biological aging and carry out scalable interventional studies, high-throughput approaches are necessary. Here we introduce a machine-learning-based visual FI for mice that operates on video data from an open-field assay. We use machine vision to extract morphometric, gait and other behavioral features that correlate with FI score and age. We use these features to train a regression model that accurately predicts the normalized FI score within 0.04 ± 0.002 (mean absolute error). Unnormalized, this error is 1.08 ± 0.05, which is comparable to one FI item being mis-scored by 1 point or two FI items mis-scored by 0.5 points. This visual FI provides increased reproducibility and scalability that will enable large-scale mechanistic and interventional studies of aging in mice.

When cats need to see to step accurately?

Locomotion on complex terrains often requires vision. However, how vision serves locomotion is not well understood. Here, we asked when visual information necessary for accurate stepping is collected and how its acquisition relates to the step cycle. In cats of both sexes, we showed that a brief (200-400 ms) interruption of visual input can rapidly influence cat's walking along a horizontal ladder. Depending on the phase within the step cycle, a 200 ms period of darkness could be tolerated fully without any changes to the strides or could lead to minor increases of stride duration. The effects of 300-400 ms of visual input denial, which typically prolonged stances and/or swings, also depended on the phase of the darkness onset. The increase of the duration of strides was always shorter than the duration of darkness. We conclude that visual information for planning a swing is collected starting from the middle of the preceding stance until the beginning of the current swing. For a stance (and/or a swing of the other paw), visual information is collected starting from the end of the previous stance and until the middle of the current stance. Acquisition of visual information during these windows is not uniform but depends on the phase of the step cycle. Notably, both the extension of these windows and their non-homogeneity are closely related to the pattern of gaze behaviour in cats, described previously. This new knowledge will help to guide research and understanding of neuronal mechanisms of visuomotor integration and modulation of visual function by strides during locomotion. KEY POINTS: Cats, like humans, rely on vision to navigate in complex environments. In cats walking along a horizontally placed ladder, we show that visual information required for accurate stepping is collected in a non-uniform manner throughout the stride cycle. Brief denial of visual input during a swing prolongs the next stance of that forelimb. Denial of visual input during a stance prolongs this stance, as well as the next swing and stance. Denial during the first half of a stance has a greater effect than during the second half. The phase dependence of the use of vision for accurate stepping and the pattern of affected swings and stances are closely related to the previously described pattern of gaze behaviour in cats. This new knowledge opens new perspectives for research into neuronal mechanisms of visuomotor coordination and visual function during walking and for understanding related disorders.

Receptor Tyrosine Kinases ror1/2 and ryk Are Co-expressed with Multiple Wnt Signaling Components During Early Development of Sea Urchin Embryos.

AbstractA combination of receptors, co-receptors, and secreted Wnt modulators form protein complexes at the cell surface that activate one or more of the three different Wnt signaling pathways (Wnt/ß-catenin, Wnt/JNK, and Wnt/Ca2+). Two or more of these pathways are often active in the same cellular territories, forming Wnt signaling networks; however, the molecular mechanisms necessary to integrate information from these pathways in these situations are unclear in any in vivo model system. Recent studies have implicated two Wnt binding receptor tyrosine kinases, receptor tyrosine kinase-like orphan receptor (Ror) and related-to-receptor tyrosine kinase (Ryk), in the regulation of canonical and non-canonical Wnt signaling pathways, depending on the context; however, the spatiotemporal expression of these genes in relation to Wnt signaling components has not been well characterized in most deuterostome model systems. Here we use a combination of phylogenetic and spatiotemporal gene expression analyses to characterize Ror and Ryk orthologs in sea urchin embryos. Our phylogenetic analysis indicates that both ror1/2 and ryk originated as single genes from the metazoan ancestor. Expression analyses indicate that ror1/2 and ryk are expressed in the same domains of many Wnt ligands and Frizzled receptors essential for the specification and patterning of germ layers along the early anterior-posterior axis. In addition, both genes are co-expressed with Wnt signaling components in the gut, ventral ectoderm, and anterior neuroectoderm territories later in development. Together, our results indicate that Ror and Ryk have a complex evolutionary history and that their spatiotemporal expression suggests that they could contribute to the complexity of Wnt signaling in early sea urchin embryogenesis.

Efficacy and Safety of Acotiamide Versus Mosapride in Patients With Functional Dyspepsia Associated With Meal-Induced Postprandial Distress Syndrome: A Phase III Randomized Clinical Trial.

BACKGROUND:  Acotiamide is a novel prokinetic drug that acts by enhancing the release of acetylcholine and is used in the treatment of functional dyspepsia-postprandial distress syndrome (FD-PDS). Mosapride is indicated to FD-PDS as per the Rome III treatment guidelines. Mosapride 5 mg three times daily (TID) is approved by the Drugs Controller General of India (DCGI) for the treatment of FD-PDS. The objective of this study was to determine the efficacy and safety of Acotiamide in comparison with Mosapride on FD-PDS. METHODS: The 220 patients of either gender (aged 18-64 years) with active PDS included in the study were centrally randomized 1:1 to receive either 100 mg Acotiamide (test product) or 5 mg Mosapride (reference product) TID for four weeks. Responder rates for the overall treatment effect (OTE) at the end of four weeks were the primary efficacy endpoint. Secondary efficacy endpoints included the elimination rate of postprandial fullness, upper abdominal bloating, and early satiation. The study also evaluated the OTE at each week, individual symptom scores, and quality of life (QoL) assessed by the Short Form-Nepean Dyspepsia Index questionnaire (SF-NDI). The safety endpoints included assessments of treatment-emergent adverse events (TEAEs). RESULTS:  At the end of four weeks, the responders in the Acotiamide versus Mosapride group for OTE was 98% versus 93.27% in the per-protocol (PP) population. Among the intent to treat (ITT) population, the comparison of Acotiamide versus Mosapride stood at 95.15% versus 89.81%. Secondary efficacy endpoints were significantly improved with 100 mg TID Acotiamide, which was evident from the improvement in postprandial fullness (14.56%), upper abdominal bloating (15.53%), early satiation (10.68%), and QoL (13.7 ± 4.67). CONCLUSIONS:  Our study results demonstrated that Acotiamide is effective, safe, and well-tolerated and had significantly improved the QoL over a four-week treatment period in FD-PDS patients. The efficacy and safety profiles of Acotiamide were similar to Mosapride.

A systematic literature review on the prevalence and etiology of meningitis among critically ill and hospitalized patients in India.

BACKGROUND: In India, owing to multiple factors, such as insufficient laboratory capacity, poor reporting systems due to limited access to healthcare facilities and limited disease surveillance programmes, the actual disease burden of meningitis is unknown and may be largely under-reported. OBJECTIVE: A systematic literature review was performed to describe: (a) the prevalence of meningitis; and (b) its etiological pathogen across different regions, age groups and patients with comorbidities. METHOD: A systematic literature search was conducted between 1990 and 2020 using PubMed and Google Scholar databases to identify Indian studies reporting the prevalence rates and etiology of meningitis. A total of 51 studies were included in the final analysis. RESULTS: A total of 38 studies reported prevalence of meningitis and 21 studies reported data on the etiology of meningitis in India. These studies included mixed patient populations: (a) pyogenic meningitis; (b) meningitis in sick or hospitalized patients with tuberculosis, acute febrile encephalopathy syndrome, septicaemia, invasive pneumococcal disease or respiratory compromise; and (c) meningitis patients with comorbidities. The prevalence of confirmed bacterial meningitis in the pediatric population (0-14 years) ranged between 0.5% and 61.8%. A total of seven studies reported the prevalence of meningitis in patients of all age groups (0-75 years), with prevalence ranging between 8.68% and 78.85%. Cryptococcal meningitis was predominant in patients with positive HIV/AIDS, with a prevalence ranging between 2.09% and 53.1%. Streptococcus pneumoniae was found to be the predominant pathogen causing meningitis across different regions of India, with a frequency ranging from 4% to 61.8% in patients of all age groups. CONCLUSION: This systematic literature review displayed the possible range of frequency of bacterial meningitis pathogens across a wide variety of age groups in different regions of India. Further studies are warranted to monitor meningitis cases, which may facilitate the development of prevention and treatment strategies in India.

The connexin 43 carboxyl terminal mimetic peptide αCT1 prompts differentiation of a collagen scar matrix in humans resembling unwounded skin.

Phase II clinical trials have reported that acute treatment of surgical skin wounds with the therapeutic peptide alpha Connexin Carboxy-Terminus 1 (αCT1) improves cutaneous scar appearance by 47% 9-month postsurgery. While Cx43 and ZO-1 have been identified as molecular targets of αCT1, the mode-of-action of the peptide in scar mitigation at cellular and tissue levels remains to be further characterized. Scar histoarchitecture in αCT1 and vehicle-control treated skin wounds within the same patient were compared using biopsies from a Phase I clinical trial at 29-day postwounding. The sole effect on scar structure of a range of epidermal and dermal variables examined was that αCT1-treated scars had less alignment of collagen fibers relative to control wounds-a characteristic that resembles unwounded skin. The with-in subject effect of αCT1 on scar collagen order observed in Phase I testing in humans was recapitulated in Sprague-Dawley rats and the IAF hairless guinea pig. Transient increase in histologic collagen density in response to αCT1 was also observed in both animal models. Mouse NIH 3T3 fibroblasts and primary human dermal fibroblasts treated with αCT1 in vitro showed more rapid closure in scratch wound assays, with individual cells showing decreased directionality in movement. An agent-based computational model parameterized with fibroblast motility data predicted collagen alignments in simulated scars consistent with that observed experimentally in human and the animal models. In conclusion, αCT1 prompts decreased directionality of fibroblast movement and the generation of a 3D collagen matrix postwounding that is similar to unwounded skin-changes that correlate with long-term improvement in scar appearance.

Systematic Literature Review on Burden of Clostridioides difficile Infection in India.

BACKGROUND: Owing to limited diagnostic facilities and surveillance protocols, there is a paucity on the prevalence data of Clostridioides difficile infections (CDIs) in developing countries such as India. OBJECTIVE: The aims of these studies are (1) to determine the prevalence of CDI in India, (2) to understand the risk factors of CDI, and (3) to determine the impact of different diagnostic methods on reported CDI rates. METHOD: A systematic literature search was conducted using PubMed and Google Scholar database to identify Indian studies reporting the prevalence of CDI. A total of 31 studies, published between 1990 and 2020 were included in the final analysis. A chi-square test was used to determine statistically significant association between prevalence rates, accuracy of different diagnosis methods, and antibiotic usage rates of CDI. RESULTS: The prevalence of CDI was in the range of 3.4% to 18%, and the difference between regional prevalence of CDI was statistically significant (P < .001). The use of antibiotics, hospital stay, comorbidities, recent surgery, and the use of proton-pump inhibitors was considered as risk factors for the development of CDI. Compared to other regions, the rate of antibiotic usage was significantly higher in North India (P < .001). Among different diagnostic methods, C. difficile detection was significantly higher with enzyme-linked immunosorbent assay (18.02%) versus other multiple testing methods used (P < .001). CONCLUSION: There is a significant burden of CDI across the country. Further surveillance studies are required to monitor changes in prevalence of CDI, risk factors, and accuracy of diagnosis methods for a better understanding of the disease burden in India.