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Abstract Introduction In low‐ and middle‐income countries (LMICs), which are disproportionately affected by the HIV epidemic and manage limited resources, optimized implementation strategies are needed to enhance the efficiency of the HIV response. Assessing strategy usage to date could identify research gaps and inform future implementation efforts. We conducted a systematic review to describe the features and distributions of published implementation strategies attempting to improve HIV treatment service delivery and outcomes. Methods We searched PubMed, Embase, and CINAHL and screened abstracts and full texts published between 1 January 2014 and 27 August 2021, for English‐language studies conducted in LMICs that described the implementation of HIV intervention and reported at least one HIV care cascade outcome, ranging from HIV testing to viral suppression. Implementation strategies were inductively specified, characterized by unique combinations of actor, action and action target, and summarized based on existing implementation strategy taxonomies. All strategies included in this study were independently reviewed to ensure accuracy and consistency. Results We identified 44,126 abstracts and reviewed 1504 full‐text manuscripts. Among 485 included studies, 83% were conducted in sub‐Saharan Africa; the rest were conducted in South‐East Asia and Western Pacific (12%), and the Americas (8%). A total of 7253 unique implementation strategies were identified, including changing health service delivery (48%) and providing capacity building and support strategies (34%). Healthcare providers and researchers led 59% and 28% of the strategies, respectively. People living with HIV and their communities (62%) and healthcare providers (38%) were common strategy targets. Strategies attempting to change governance, financial arrangements and implementation processes were rarely reported. Discussion We identified a range of published implementation strategies that addressed HIV cascade outcomes, though some key gaps exist. We may need to expand the application of implementation strategies to ensure that all stakeholders are meaningfully involved to support equitable implementation efforts across the geographic regions and target populations, and to optimize implementation outcomes. Conclusions Some health service delivery and capacity building and support strategies have been most commonly used to date. Future research and implementation may incorporate a more diverse range of strategies and detailed reporting on their usage to inform improved HIV responses globally.

Abstract Background Acute kidney injury (AKI) is a known complication of COVID-19 and is associated with an increased risk of in-hospital mortality. Unbiased proteomics using biological specimens can lead to improved risk stratification and discover pathophysiological mechanisms. Methods Using measurements of ~4000 plasma proteins in two cohorts of patients hospitalized with COVID-19, we discovered and validated markers of COVID-associated AKI (stage 2 or 3) and long-term kidney dysfunction. In the discovery cohort (N = 437), we identified 413 higher plasma abundances of protein targets and 30 lower plasma abundances of protein targets associated with COVID-AKI (adjusted p

Abstract Predicting COVID-19 severity is difficult, and the biological pathways involved are not fully understood. To approach this problem, we measured 4701 circulating human protein abundances in two independent cohorts totaling 986 individuals. We then trained prediction models including protein abundances and clinical risk factors to predict COVID-19 severity in 417 subjects and tested these models in a separate cohort of 569 individuals. For severe COVID-19, a baseline model including age and sex provided an area under the receiver operator curve (AUC) of 65% in the test cohort. Selecting 92 proteins from the 4701 unique protein abundances improved the AUC to 88% in the training cohort, which remained relatively stable in the testing cohort at 86%, suggesting good generalizability. Proteins selected from different COVID-19 severity were enriched for cytokine and cytokine receptors, but more than half of the enriched pathways were not immune-related. Taken together, these findings suggest that circulating proteins measured at early stages of disease progression are reasonably accurate predictors of COVID-19 severity. Further research is needed to understand how to incorporate protein measurement into clinical care.

Abstract Background Approximately 7% of all reported tuberculosis (TB) cases each year are recurrent, occurring among people who have had TB in the recent or distant past. TB recurrence is particularly common in India, which has the largest TB burden worldwide. Although patients recently treated for TB are at high risk of developing TB again, evidence around effective active case finding (ACF) strategies in this population is scarce. We will conduct a hybrid type I effectiveness-implementation non-inferiority randomized trial to compare the effectiveness, cost-effectiveness, and feasibility of two ACF strategies among individuals who have completed TB treatment and their household contacts (HHCs). Methods We will enroll 1076 adults (≥ 18 years) who have completed TB treatment at a public TB unit (TU) in Pune, India, along with their HHCs (averaging two per patient, n = 2152). Participants will undergo symptom-based ACF by existing healthcare workers (HCWs) at 6-month intervals and will be randomized to either home-based ACF (HACF) or telephonic ACF (TACF). Symptomatic participants will undergo microbiologic testing through the program. Asymptomatic HHCs will be referred for TB preventive treatment (TPT) per national guidelines. The primary outcome is rate per 100 person-years of people diagnosed with new or recurrent TB by study arm, within 12 months following treatment completion. The secondary outcome is proportion of HHCs

To determine the rate of parental stress within a pediatric ophthalmology population, parents in an urban or suburban community pediatric ophthalmology clinic were administered the Parental Stress Index Short Form survey. Demographic information and parental depression or anxiety data were collected and analyzed using an independent sample t-test and chi-squared analysis. Stress measures were recorded as percentiles. One hundred and twenty-one surveys revealed the following mean percentiles: Total Stress, 45.9 ± 22.4; Parental Distress (PD), 49.7 ± 19.8; and Parent Child Dysfunctional Interaction (P-CDI), 45.1 ± 23.6. The PD percentiles of the non-married parents, those with positive parental depression or anxiety scores, and those with a high school diploma or less were 55.9 ± 18.5 versus 45.2 ± 19.6, p < 0.01; 55.2 ± 18.6 versus 46.7 ± 19.9, p < 0.05; and 56.8 ± 18.2 versus 47.0 ± 19.8, p < 0.01, respectively. The parents with a high school diploma or less in a suburban environment demonstrated higher PD/P-CDI scores versus those of an urban population. Those with median household incomes (MHI) below USD 60,000 in both the total and suburban populations showed higher PD scores. There is no significant difference in parental stress between the pediatric ophthalmology patients and the general population. The parents who are unmarried, depressed, have a high school degree or less, or an MHI below USD 60,000 experience significantly higher stress levels.

BackgroundAccess to drug resistant testing for tuberculosis (TB) remains a challenge in high burden countries. Recently, the World Health Organization approved the use of several moderate complexity automated nucleic acid amplification tests (MC-NAAT) that have performance profiles suitable for placement in a range of TB laboratory tiers to improve drug susceptibility tests (DST) coverage.MethodsWe conducted cost analysis of two MC-NAATs with different testing throughput: Lower Throughput (LT, < 24 tests per run) and Higher Throughput (HT, upto 90+ tests per run) for placement in a hypothetical laboratory in a resource limited setting. We used per-test cost as the main indicator to assess 1) drivers of cost by resource types and 2) optimized levels of annual testing volumes for the respective MC-NAATs.ResultsThe base-case per test cost of $18.52 (range: $13.79 - $40.70) for LT test and $15.37 (range: $9.61 - $37.40) for HT test. Per test cost estimates were most sensitive to the number of testing days per week, followed by equipment costs and TB-specific workloads. In general, HT NAATs were cheaper at all testing volume levels, but at lower testing volumes (less than 2,000 per year) LT tests can be cheaper if the durability of the testing system is markedly better and/or procured equipment costs are lower than that of HT NAAT.ConclusionAssuming equivalent performance and infrastructural needs, placement strategies for MC-NAATs need to be prioritized by laboratory system's operational factors, testing demands, and costs.

Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.

We investigate the Pt thickness dependence of spin–orbit torques (SOTs) in Co/Pt layers grown on single crystalline SrTiO3 and LaAlO3 and amorphous SiO2 substrates. We measure the SOT-induced effective damping-like fields and spin Hall magnetoresistances of the Co/Pt (tPt) samples, where tPt varies from 0.5 to 5.5 nm. We find that the Co/Pt layers grown on the single crystalline substrates show weaker thickness dependence of the SOT than the samples on the SiO2 substrate, which cannot be explained by the conventional bulk spin Hall effect in the Pt layer. This indicates that there is a non-negligible interfacial SOT originating from the Pt/substrate interface, which is more pronounced for thinner Pt. These results provide a way to design SOT material structures with enhanced SOT efficiency by incorporating interfacial SOT.

Acinetobacter species are Gram-negative coccobacilli found to cause a multitude of infections. However, they are a rare cause of bacteremia with Acinetobacter radioresistens accounting for less than 10 % of Acinetobacter infections. In this report, we describe a patient presenting with acute encephalopathy, fever, and hypoxia who was initially found to have bilateral perihilar and lower lobar peribronchial thickening on chest x-ray. Two sets of blood cultures obtained on admission were positive for Acinetobacter radioresistens and Enterococcus casseliflavus and one set of blood cultures returned positive for Leclercia adecarboxylata although believed to be a skin contaminant. Susceptibilities confirmed all bacteria were pan-sensitive. The patient was also found to have an aortic valve vegetation which was not amenable to surgical intervention. He was treated with 42 days of daptomycin and cefepime. At present, co-infection with Acinetobacter radioresistens and Enterococcus casseliflavus with manifestations of polymicrobial endocarditis has never been reported. Though this co-infection was pan-sensitive, there is an increasing rate of resistance to commonly used, broad-spectrum antibiotics such as β-lactams, which will continue to pose a challenge between balancing treatment and antibiotic stewardship.

The current-induced spin–orbit torque in single-layer ferromagnetic CoFeB thin films is quantitatively investigated by using in-plane harmonic Hall measurements. After the subtraction of thermal contributions such as the anomalous and ordinary Nernst effects, the obtained overall spin–orbit torque is successfully decomposed into damping-like (DL) and field-like (FL) terms. The DL and FL torques exhibit opposite trends of ferromagnetic layer thickness dependence before saturation, giving rise to distinctively different spin torque efficiencies: the DL torque efficiency shows a strong thickness dependence, while the FL torque efficiency is almost independent of the thickness. Such a result shows strong evidence that the DL torque originates from a spin-Hall-like charge-spin conversion in the ferromagnet, while the FL torque stems from interfacial effects such as the Rashba–Edelstein effect. With both DL and FL torques quantified in the single-layer CoFeB, our results exhibit an important step toward the understanding of nontrivial spin–orbit torques in single-layer ferromagnetic thin films.

Development of a rapid approach for universal microbial detection is required in the healthcare, food and environmental sectors to aid with medical intervention, food safety and environmental protection. This research investigates the use of enzymatic hydrolysis of a substrate by a microorganism to generate a volatile organic compound (VOC). One such enzyme activity that can be used in this context is nitroreductase as such activity is prevalent across a range of microorganisms. A study was developed to evaluate a panel of 51 microorganisms of clinical interest for their nitroreductase activity. Two enzyme substrates, nitrobenzene and 1-fluoro-2-nitrobenzene, were evaluated for this purpose with evolution, after incubation, of the VOCs aniline and 2-fluoroaniline, respectively. Detection of the VOCs was done using headspace-solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) with obtained limits of quantitation (LOQ) of 0.17 and 0.03 µg/mL for aniline and 2-fluoroaniline, respectively. The results indicated that both enzyme substrates were reduced by the same 84.3% of microorganisms producing the corresponding volatile anilines which were detected using HS-SPME-GC-MS. It was found that nitroreductase activity could be detected after 6–8 h of incubation for the selected pathogenic bacteria investigated. This approach shows promise as a rapid universal microbial detection system.

Household air pollution from solid fuel cooking causes millions of deaths each year and contributes to climate change. These emissions can be reduced if households transition to cleaner cooking fuels such as LPG or biogas, yet emission measurements during actual use are limited. Six LPG and 57 biogas cooking event emissions were measured during typical cooking practices in Nepal. Emission factors are reported for elemental carbon (EC), organic carbon (OC), particulate matter (PM2.5), and carbon monoxide (CO) and compared to measurements from wood stoves in the same households. Biogas cooking emission factors were 7.4 ± 10.9 mg MJ−1 for PM2.5 and 0.2 ± 0.3 mg MJ−1 for EC on a fuel energy basis, and were not significantly different from LPG stoves (9.5 ± 6.8 mg MJ−1 for PM2.5 and 0.3 ± 0.3 mg MJ−1 for EC, p > 0.05). Wood stoves emitted 50 times more PM2.5 than biogas on a fuel energy basis and 230 times more EC. EC emissions were about 3% of total particle emissions from biogas and LPG stoves. Most PM2.5 emissions from gas stoves were attributed to food frying and stove ignition (90%), not the gas fuel (10%), implying that there is a limit to emission reductions that can be achieved with improved fuels.

Introduction Unintentional toxic ingestions are a common occurrence in the pediatric population, and it is therefore important for resident physicians to learn to both recognize and effectively manage these events. Seizures caused by isoniazid overdose are a well-described clinical entity for which pyridoxine serves as an effective antidote. We developed a pediatric simulation case using a high-fidelity patient simulator to engage learners in a case of status epilepticus in a toddler caused by accidental isoniazid ingestion. Methods The learning objectives of this activity are for participants to recognize that toxic ingestion has occurred, execute appropriate initial management of status epilepticus, and administer pyridoxine as an antidote. Equipment and personnel needed for this activity include a high-fidelity patient simulator, simulated medical supplies, a patient simulator operator, and one actor. Results This simulated case debuted among resident physicians at a simulation competition event within the emergency medicine residency program of an academic medical center. Feedback elicited after the event included a high proportion of respondents agreeing that the cases used were “sufficiently complex” and “relevant for my clinical practice.” Discussion Despite some barriers to effective implementation, this simulation case was well received and may serve as a valuable educational tool for training resident physicians to effectively manage toxic ingestions. The effectiveness of this simulation in accomplishing its specific learning objectives was not formally assessed, but participant evaluations suggest that it was well received by its target audience.

The Neuron Restrictive Silencer Factor (NRSF) is the well-known master transcriptional repressor of the neuronal phenotype. Research to date has shown that it is an important player in the growth and development of the nervous system. Its role in the maturation of neural precursor cells to adult neurons has been well characterized in stem cell models. While much has been characterized from a developmental perspective, research is revealing that NRSF plays a role in various neurological diseases, ranging from neurodegenerative, neuropsychiatric, to cancer. Dysregulation of NRSF activity disrupts downstream gene expression that is responsible for neuronal cell homeostasis in several models that contribute to pathologic states. Interestingly, it is now becoming apparent that the dysregulation of NRSF contributes to neurological disease through epigenetic mechanisms. Although NRSF itself is a transcription factor, its major effectors are chromatin modifiers. At the level of epigenetics, changes in NRSF activity have been well characterized in models of neuropathic pain and epilepsy. Better understanding of the epigenetic basis of brain diseases has led to design and use of small molecules that can prevent NRSF from repressing gene expression by neutralizing its interactions with its chromatin remodelers. This review will address the basic function of NRSF and its cofactors, investigate their mechanisms, then explore how their dysfunction can cause disease states. This review will also address research on NRSF as a therapeutic target and delve into new therapeutic strategies that focus on disrupting NRSF’s ability to recruit chromatin remodelers.

Abstract Palliative medicine has been identified as the new frontier in emergency medicine (EM). For many, the union of these two fields is counterintuitive. However, it is not uncommon for terminally ill patients either actively contemplating or already enrolled in hospice to present to the Emergency Department (ED). Thus, it is essential that ED providers develop the skills to appropriately care for this patient demographic. Given the unfamiliarity of this territory, simulation offers a protected environment for both learners and educators to launch training endeavors. This case is based on actual patient encounters at the University of Wisconsin Hospital and Clinics (UWHC). The case is that of a complicated geriatric patient with metastatic cancer who presents with a left hip fracture in the setting of a fall; the patient progressively decompensates while in the ED due to an acute massive pulmonary embolism. As part of an intradepartmental simulation contest, the case was presented to two separate teams of EM faculty members as a formative assessment. Residents and other faculty members observed either team complete the 10− to 15-minute case via video monitoring and then voted to determine which team advanced to the final round of simulation. Another period of 20-30 minutes was allotted for debriefing. The effectiveness of this simulation case in meeting the educational objectives was gathered in the context of the entire simulation series, which included feedback from both simulation participants and simulation observers. The simulation case presented here created a unique opportunity to engage both EM residents and faculty at the UWHC in the practice of basic palliative medicine skills.

Understanding how fuels and stoves are used to meet a diversity of household needs is an important step in addressing the factors leading to continued reliance on polluting devices, and thereby improving household energy programs. In Nepal and many other countries dependent on solid fuel, efforts to mitigate the impacts of residential solid fuel use have emphasized cooking while focusing less on other solid fuel dependent end-uses. We employed a four-season fuel assessment in a cohort of 110 households residing in two elevation regions of the Far-Western Development Region (Province 7) of Nepal. Household interviews and direct fuel weights were used to assess seasonality in fuel consumption and its association with stoves that met cooking and non-cooking needs. Per-capita fuel consumption in winter was twice that of other measured seasons, on average. This winter increase was attributed to greater prevalence of use and fuel consumption by supplemental stoves, not the main cooking stove. End-use profiles showed that fuel was used in supplemental stoves to meet the majority of non-meal needs in the home, notably water heating and preparation of animal food. This emphasis on fuels, stoves, and the satisfaction of energy needs—rather than just stoves or fuels—leads to a better understanding of the factors leading to device and fuel choice within households.

High serum resistin levels have been associated with kidney dysfunction. Most of these studies have been carried out in individuals with severe kidney impairment, diabetes, cardiovascular disease and related treatments. Thus, the observed association might have been influenced by these confounders. Our aim was to study the relationship between serum resistin, urinary albumin/creatinine ratio (ACR) and glomerular filtration rate (GFR) in a family-based sample, the Gargano Family Study (GFS) of 635 non diabetic, untreated Whites.A linear mixed effects model and bivariate analyses were used to evaluate the phenotypic and genetic relations between serum resistin and both ACR and eGFR. All analyses were adjusted for sex, age, age squared, BMI, systolic blood pressure, smoking habits and physical exercise.After adjustments, resistin levels were slightly positively associated with ACR (β±SE = 0.049±0.023, p = 0.035) and inversely related to eGFR (β±SE = -1.43±0.61, p = 0.018) levels. These associations remained significant when either eGFR or ACR were, reciprocally, added as covariates. A genetic correlation (ρg = -0.31±0.12; adjusted p = 0.013) was observed between resistin and eGFR (but not ACR) levels.Serum resistin levels are independently associated with ACR and eGFR in untreated non-diabetic individuals. Serum resistin and eGFR share also some common genetic background. Our data strongly suggest that resistin plays a role in modulating kidney function.