Tackling psychosocial and capital constraints to alleviate poverty.

Many policies attempt to help extremely poor households build sustainable sources of income. Although economic interventions have predominated historically1,2, psychosocial support has attracted substantial interest3-5, particularly for its potential cost-effectiveness. Recent evidence has shown that multi-faceted 'graduation' programmes can succeed in generating sustained changes6,7. Here we show that a multi-faceted intervention can open pathways out of extreme poverty by relaxing capital and psychosocial constraints. We conducted a four-arm randomized evaluation among extremely poor female beneficiaries already enrolled in a national cash transfer government programme in Niger. The three treatment arms included group savings promotion, coaching and entrepreneurship training, and then added either a lump-sum cash grant, psychosocial interventions, or both the cash grant and psychosocial interventions. All three arms generated positive effects on economic outcomes and psychosocial well-being, but there were notable differences in the pathways and the timing of effects. Overall, the arms with psychosocial interventions were the most cost-effective, highlighting the value of including well-designed psychosocial components in government-led multi-faceted interventions for the extreme poor.

Defective T-cell response to COVID-19 vaccination in acute myeloid leukaemia and myelodysplastic syndromes.

Limited data exist on COVID-19 vaccination efficacy in patients with acute myeloid leukemia and myelodysplasia with excess blasts (AML/MDS-EB2). We report results from a prospective study, PACE (Patients with AML and COVID-19 Epidemiology). 93 patients provided samples post-vaccine 2 or 3 (PV2, PV3). Antibodies against SARS-COV-2 spike antigen were detectable in all samples. Neutralization of the omicron variant was poorer than ancestral variants but improved PV3. In contrast, adequate T-cell reactivity to SARS-COV-2 spike protein was seen in only 16/47 (34%) patients PV2 and 23/52 (44%) PV3. Using regression models, disease response (not in CR/Cri), and increasing age predicted poor T cell response.

Toward a science of delivering aid with dignity: Experimental evidence and local forecasts from Kenya.

How can governments and nonprofits design aid programs that afford dignity and facilitate beneficial outcomes for recipients? We conceptualize dignity as a state that manifests when the stigma associated with receiving aid is countered and recipients are empowered, both in culturally resonant ways. Yet materials from the largest cash transfer programs in Africa predominantly characterize recipients as needy and vulnerable. Three studies examined the causal effects of alternative aid narratives on cash transfer recipients and donors. In study 1, residents of low-income settlements in Nairobi, Kenya (N = 565) received cash-based aid accompanied by a randomly assigned narrative: the default deficit-focused "Poverty Alleviation" narrative, an "Individual Empowerment" narrative, or a "Community Empowerment" narrative. They then chose whether to spend time building business skills or watching leisure videos. Both empowerment narratives improved self-efficacy and anticipated social mobility, but only the "Community Empowerment" narrative significantly motivated recipients' choice to build skills and reduced stigma. Given the diverse settings in which aid is delivered, how can organizations quickly identify effective narratives in a context? We asked recipients to predict which narrative would best motivate skill-building in their community. In study 2, this "local forecasting" methodology outperformed participant evaluations and experimental pilots in accurately ranking treatments. Finally, study 3 confirmed that the narrative most effective for recipients did not undermine donors' willingness to contribute to the program. Together these studies show that responding to recipients' psychological and sociocultural realities in the design of aid can afford recipients dignity and help realize aid's potential.

Magnesium and calcium overaccumulate in the leaves of a schengen3 mutant of Brassica rapa.

Magnesium (Mg) and calcium (Ca) are essential mineral nutrients poorly supplied in many human food systems. In grazing livestock, Mg and Ca deficiencies are costly welfare issues. Here, we report a Brassica rapa loss-of-function schengen3 (sgn3) mutant, braA.sgn3.a-1, which accumulates twice as much Mg and a third more Ca in its leaves. We mapped braA.sgn3.a to a single recessive locus using a forward ionomic screen of chemically mutagenized lines with subsequent backcrossing and linked-read sequencing of second back-crossed, second filial generation (BC2F2) segregants. Confocal imaging revealed a disrupted root endodermal diffusion barrier, consistent with SGN3 encoding a receptor-like kinase required for normal formation of Casparian strips, as reported in thale cress (Arabidopsis thaliana). Analysis of the spatial distribution of elements showed elevated extracellular Mg concentrations in leaves of braA.sgn3.a-1, hypothesized to result from preferential export of excessive Mg from cells to ensure suitable cellular concentrations. This work confirms a conserved role of SGN3 in controlling nutrient homeostasis in B. rapa, and reveals mechanisms by which plants are able to deal with perturbed shoot element concentrations resulting from a "leaky" root endodermal barrier. Characterization of variation in leaf Mg and Ca accumulation across a mutagenized population of B. rapa shows promise for using such populations in breeding programs to increase edible concentrations of essential human and animal nutrients.

Venetoclax combined with low dose cytarabine compared to standard of care intensive chemotherapy for the treatment of favourable risk adult acute myeloid leukaemia (VICTOR): Study protocol for an international, open-label, multicentre, molecularly-guided randomised, phase II trial.

BACKGROUND: For patients with acute myeloid leukaemia (AML), the only potentially curative treatment is intensive chemotherapy (IC). This is highly toxic, particularly for patients > 60 years, potentially leading to prolonged hospitalisations requiring intensive supportive care, and sometimes treatment-related death. This also results in extensive healthcare costs and negatively impacts quality of life (QoL). Venetoclax with low-dose cytarabine (VEN + LDAC) is a novel, low-intensity treatment for AML patients who cannot receive IC. VEN + LDAC is given as an outpatient and toxicity appears significantly lower than with IC. Analysis of clinical trials performed to date are promising for patients with the genotype NPM1mutFLT3 ITDneg, where remission and survival rates appear comparable to those achieved with IC. METHODS: VICTOR is an international, two-arm, open-label, multi-centre, non-inferiority, randomised-controlled phase II trial to assess VEN + LDAC compared to standard of care (IC) as first-line treatment in older patients (initially aged ≥ 60 years) with newly diagnosed AML. The trial will recruit patients with a NPM1mutFLT3 ITDneg genotype; those with a favourable risk in relation to the experimental treatment. University of Birmingham is the UK co-ordinating centre, with national hubs in Aarhus University Hospital, Denmark, and Auckland District Health Board, New Zealand. The primary outcome is molecular event-free survival time where an event is defined as failure to achieve morphological complete response (CR) or CR with incomplete blood count recovery after two cycles of therapy; molecular persistence, progression or relapse requiring treatment change; morphological relapse, or; death. Secondary outcomes include cumulative resource use at 12- and 24-months, and QoL as assessed by EORTCQLQ-C30 and EQ-5D-3L at 3-, 6-, 12-, 18- and 24-months. The trial employs an innovative Bayesian design with target sample size of 156 patients aged > 60 years. DISCUSSION: The principle underpinning the VICTOR trial is that the chance of cure for patients in the experimental arm should not be compromised, therefore, an adaptive design with regular checks on accumulating data has been employed, which will allow for a staged expansion of the trial population to include younger patients if, and when, there is sufficient evidence of non-inferiority in older patients. TRIAL REGISTRATION: EudraCT: 2020-000,273-24; 21-Aug-2020. ISRCTN: 15,567,173; 08-Dec-2020.

Values and preferences of the general population in Indonesia in relation to rapid COVID-19 antigen self-tests: A cross-sectional survey.

OBJECTIVES: Home diagnostics are essential to assist members of the general population become active agents of case detection. In Indonesia, a country with an over-burdened healthcare system, individuals could use rapid SARS-CoV-2 antigen tests to self-detect COVID-19. To assess the general population's values and attitudes towards SARS-CoV-2 self-testing, a survey was conducted in mid-2021 in Jakarta and the provinces of Banten and North Sulawesi. METHODS: This was a quantitative survey that approached respondents in >600 randomly selected street-points in the three study geographies in July-August 2021. A 35-item questionnaire was used to collect data on key variables, such as likelihood to use a SARS-CoV-2 self-test, willingness to pay for a self-test device, and likely actions following a positive self-test result. Bivariate and multivariate regression analyses were performed. RESULTS: Of 630 respondents (318 were female), 15.53% knew about COVID-19 self-testing, while 62.70% agreed with the idea of people being able to self-test at home, unassisted, for COVID-19. If self-tests were available in Indonesia, >60% of respondents would use them if they felt it necessary and would undertake regular self-testing for example weekly if recommended. Upon receiving a positive self-test result, most respondents would communicate it (86.03%), request post-test counselling (80.79%), self-isolate (97.46%), and/or warn their close contacts (90.48%). CONCLUSIONS: The use of rapid SARS-CoV-2 antigen detection tests for self-testing appears acceptable to a majority of the Indonesian public, to learn whether they have COVID-19. Self-testing should be prioritised to complement to an over-burdened healthcare system by helping the public, asymptomatic individuals included, become agents of change in epidemiological surveillance of SARS-CoV-2 in their communities.

Fungicide Sensitivity of Colletotrichum Species Causing Bitter Rot of Apple in the Mid-Atlantic U.S.A.

Apple growers in the Mid-Atlantic region of the U.S.A. have reported increased losses to bitter rot of apple. We tested the hypothesis that this increase is because the Colletotrichum population has developed resistance to commonly used single-mode-of-action (single-MoA) fungicides. We screened 220 Colletotrichum isolates obtained from 38 apple orchards in the Mid-Atlantic region for resistance to 11 fungicides in Fungicide Resistance Action Committee (FRAC) groups 1, 7, 9, 11, 12, and 29. Eleven (5%) of these isolates were resistant to FRAC group 1 with confirmed ß-tubulin E198A mutations, and two (<1%) were also resistant to FRAC group 11 with confirmed cytochrome-b G143A mutations. Such low frequencies of resistant isolates indicate that fungicide resistance is unlikely to be the cause of any regional increase in bitter rot. A subsample of isolates was subsequently tested in vitro for sensitivity to every single-MoA fungicide registered for apple in the Mid-Atlantic U.S.A. (22 fungicides; FRAC groups 1, 3, 7, 9, 11, 12, and 29), and 13 fungicides were tested in field trials. These fungicides varied widely in efficacy both within and between FRAC groups. Comparisons of results from our in vitro tests with results from our field trials and other field trials conducted across the eastern U.S.A. suggested that EC25 values (concentrations that reduce growth by 25%) are better predictors of fungicide efficacy in normal field conditions than EC50 values. We present these results as a guideline for choosing single-MoA fungicides for bitter rot control in the Mid-Atlantic U.S.A.

Mu-Opioids Suppress GABAergic Synaptic Transmission onto Orbitofrontal Cortex Pyramidal Neurons with Subregional Selectivity.

The orbitofrontal cortex (OFC) plays a critical role in evaluating outcomes in a changing environment. Administering opioids to the OFC can alter the hedonic reaction to food rewards and increase their consumption in a subregion-specific manner. However, it is unknown how mu-opioid signaling influences synaptic transmission in the OFC. Thus, we investigated the cellular actions of mu-opioids within distinct subregions of the OFC. Using in vitro patch-clamp electrophysiology in brain slices containing the OFC, we found that the mu-opioid agonist DAMGO produced a concentration-dependent inhibition of GABAergic synaptic transmission onto medial OFC (mOFC), but not lateral OFC (lOFC) neurons. This effect was mediated by presynaptic mu-opioid receptor activation of local parvalbumin (PV+)-expressing interneurons. The DAMGO-induced suppression of inhibition was long lasting and not reversed on washout of DAMGO or by application of the mu-opioid receptor antagonist CTAP, suggesting an inhibitory long-term depression (LTD) induced by an exogenous mu-opioid. We show that LTD at inhibitory synapses is dependent on downstream cAMP/protein kinase A (PKA) signaling, which differs between the mOFC and lOFC. Finally, we demonstrate that endogenous opioid release triggered via moderate physiological stimulation can induce LTD. Together, these results suggest that presynaptic mu-opioid stimulation of local PV+ interneurons induces a long-lasting suppression of GABAergic synaptic transmission, which depends on subregional differences in mu-opioid receptor coupling to the downstream cAMP/PKA intracellular cascade. These findings provide mechanistic insight into the opposing functional effects produced by mu-opioids within the OFC.SIGNIFICANCE STATEMENT Considering that both the orbitofrontal cortex (OFC) and the opioid system regulate reward, motivation, and food intake, understanding the role of opioid signaling within the OFC is fundamental for a mechanistic understanding of the sequelae for several psychiatric disorders. This study makes several novel observations. First, mu-opioids induce a long-lasting suppression of inhibitory synaptic transmission onto OFC pyramidal neurons in a regionally selective manner. Second, mu-opioids recruit parvalbumin inputs to suppress inhibitory synaptic transmission in the mOFC. Third, the regional selectivity of mu-opioid action of endogenous opioids is due to the efficacy of mu-opioid receptor coupling to the downstream cAMP/PKA intracellular cascades. These experiments are the first to reveal a cellular mechanism of opioid action within the OFC.

Increased incidence of childhood mental disorders following exposure to early life infection.

Early life exposure to infectious diseases confers risk for adult psychiatric disorders but relatively few human population studies have examined associations with childhood mental disorder. Here we examined the effects of exposure to maternal infection during pregnancy, and child infectious diseases in early childhood (birth to age 4 years), in relation to first mental disorder diagnosis (age 5-13 years). The study sample comprised 71,841 children represented in a population cohort of children in New South Wales, Australia, followed from birth to early adolescence via linkage of administrative registers. Childhood exposure to infectious disease was determined during the prenatal period (i.e., maternal infection during gestation), and in early childhood (between birth and age 4 years) using the NSW Ministry of Health Admitted Patients data collection. Days to first diagnosis with a mental disorder was determined from recorded diagnoses between age 5-13 years in the NSW Ministry of Health's Admitted Patients, Emergency Department and Mental Health Ambulatory data collections. While crude hazard ratios for both prenatal infection and childhood infection exposures indicated significantly earlier diagnosis with mental disorders associated with both of these risk factors, only childhood infection exposure was associated with higher adjusted hazard ratios (aHR) for any diagnoses (aHR = 1.21, 95% CI = 1.11-1.32), externalising disorders (aHR = 1.45, 95% CI 1.18-1.79) and developmental disorders (aHR = 1.82, 95% CI 1.49-2.22) when the effects of maternal and early childhood (age < 5 years) mental disorders were taken into account. Exposure to infectious diseases during early childhood, but not prenatal infection exposure, appears to be associated with earlier diagnosis of mental disorders in childhood.

Lessons Learned from the Usability Evaluation of a Simulated Patient Dialogue System.

Simulated consultations through virtual patients allow medical students to practice history-taking skills. Ideally, applications should provide interactions in natural language and be multi-case, multi-specialty. Nevertheless, few systems handle or are tested on a large variety of cases. We present a virtual patient dialogue system in which a medical trainer types new cases and these are processed without human intervention. To develop it, we designed a patient record model, a knowledge model for the history-taking task, and a termino-ontological model for term variation and out-of-vocabulary words. We evaluated whether this system provided quality dialogue across medical specialities (n = 18), and with unseen cases (n = 29) compared to the cases used for development (n = 6). Medical evaluators (students, residents, practitioners, and researchers) conducted simulated history-taking with the system and assessed its performance through Likert-scale questionnaires. We analysed interaction logs and evaluated system correctness. The mean user evaluation score for the 29 unseen cases was 4.06 out of 5 (very good). The evaluation of correctness determined that, on average, 74.3% (sd = 9.5) of replies were correct, 14.9% (sd = 6.3) incorrect, and in 10.7% the system behaved cautiously by deferring a reply. In the user evaluation, all aspects scored higher in the 29 unseen cases than in the 6 seen cases. Although such a multi-case system has its limits, the evaluation showed that creating it is feasible; that it performs adequately; and that it is judged usable. We discuss some lessons learned and pivotal design choices affecting its performance and the end-users, who are primarily medical students.

The Gulf War Era Cohort and Biorepository: A Longitudinal Research Resource of Veterans of the 1990-1991 Gulf War Era.

The US Department of Veterans Affairs (VA) Gulf War Era Cohort and Biorepository (GWECB) is a nationally representative longitudinal cohort of US veterans who served during the 1990-1991 Gulf War era. The GWECB combines survey data, such as demographic, health behavior, and environmental exposure data; medical records; and a linked biorepository of blood specimens that can support a broad range of future research regarding health concerns unique to veterans of this era. To build this resource, the VA Cooperative Studies Program initiated a pilot study (2014-2016) to establish the GWECB and evaluate the processes required to build and maintain the resource. Participants (n = 1,275) consented to future sharing of their data and biospecimens for research purposes. Here we describe the pilot study, including recruitment and enrollment procedures, data collection and management, quality control, and challenges experienced. The GWECB data available to investigators under approved sharing mechanisms and the procedures for accessing them are extensively detailed. The study's consenting documents and a website link for the research survey are provided. Our hope is that new research drawing on the GWECB data and biospecimens will result in effective treatments and improved approaches to address the health concerns of Gulf War-era veterans.

Nursing Faculty Coaches: Uncovering a Hidden Resource for NCLEX-RN Success.

This article presents a nursing faculty department's strategy to empower nursing students identified as being at risk for not passing the National Council Licensure Examination for Registered Nurses (NCLEX-RN) on the first attempt while significantly increasing the nursing program's overall first-time NCLEX-RN pass rate. These students were identified as being at risk because of their low scores on standardized assessments with national norms predicting the likelihood of passing the NCLEX on the first attempt. This account details the NCLEX-RN Coaching Partnership as an exemplar to support nursing students' success through caring relationships with nursing faculty. Faculty coaches offered support, fostered confidence, and maintained accountability with the identified nursing students. The students provided positive feedback regarding the NCLEX-RN Coaching Partnership and ultimately attributed their passing to the coaching relationships. Seven of the eight identified students passed the examination on the first attempt; the overall program's first-time NCLEX-RN pass rate increased significantly from 78% to 90%.

Percutaneous Gastrostomy Device for the Treatment of Class II and Class III Obesity: Results of a Randomized Controlled Trial.

OBJECTIVES: The AspireAssist System (AspireAssist) is an endoscopic weight loss device that is comprised of an endoscopically placed percutaneous gastrostomy tube and an external device to facilitate drainage of about 30% of the calories consumed in a meal, in conjunction with lifestyle (diet and exercise) counseling. METHODS: In this 52-week clinical trial, 207 participants with a body-mass index (BMI) of 35.0-55.0 kg/m2 were randomly assigned in a 2:1 ratio to treatment with AspireAssist plus Lifestyle Counseling (n=137; mean BMI was 42.2±5.1 kg/m2) or Lifestyle Counseling alone (n=70; mean BMI was 40.9±3.9 kg/m2). The co-primary end points were mean percent excess weight loss and the proportion of participants who achieved at least a 25% excess weight loss. RESULTS: At 52 weeks, participants in the AspireAssist group, on a modified intent-to-treat basis, had lost a mean (±s.d.) of 31.5±26.7% of their excess body weight (12.1±9.6% total body weight), whereas those in the Lifestyle Counseling group had lost a mean of 9.8±15.5% of their excess body weight (3.5±6.0% total body weight) (P<0.001). A total of 58.6% of participants in the AspireAssist group and 15.3% of participants in the Lifestyle Counseling group lost at least 25% of their excess body weight (P<0.001). The most frequently reported adverse events were abdominal pain and discomfort in the perioperative period and peristomal granulation tissue and peristomal irritation in the postoperative period. Serious adverse events were reported in 3.6% of participants in the AspireAssist group. CONCLUSIONS: The AspireAssist System was associated with greater weight loss than Lifestyle Counseling alone.

Evaluation of the Destruction of the Harmful Cyanobacteria, Microcystis aeruginosa, with a Cavitation and Superoxide Generating Water Treatment Reactor.

Cyanobacterial/Harmful Algal Blooms are a major issue for lakes and reservoirs throughout the U.S.A. An effective destructive technology could be useful to protect sensitive areas, such as areas near water intakes. The study presented in this article explored the use of a reactor called the KRIA Water Treatment System. The reactor focuses on the injection of superoxide (O2 (-)), which is generated electrochemically from the atmosphere, into the water body. In addition, the injection process generates a significant amount of cavitation. The treatment process was tested in 190-L reactors spiked with water from cyanobacterial contaminated lakes. The treatment was very effective at destroying the predominant species of cyanobacteria, Microcystis aeruginosa, organic matter, and decreasing chlorophyll concentration. Microcystin toxin concentrations were also reduced. Data suggest that cavitation alone was an effective treatment, but the addition of superoxide improved performance, particularly regarding removal of cyanobacteria and reduction of microcystin concentration.

Impaired macrophage phagocytosis of bacteria in severe asthma.

BACKGROUND: Bacteria are frequently cultured from sputum samples of severe asthma patients suggesting a defect in bacterial clearance from the airway. We measured the capacity of macrophages from patients with asthma to phagocytose bacteria. METHODS: Phagocytosis of fluorescently-labelled polystyrene beads, Haemophilus influenzae or Staphylococcus aureus by broncholaveolar lavage alveolar macrophages (AM) and by monocyte-derived macrophages (MDM) from non-asthmatics, mild-moderate and severe asthmatic patients was assessed using fluorimetry. RESULTS: There were no differences in phagocytosis of polystyrene beads by AMs or MDMs from any of the subject groups. There was reduced phagocytosis of Haemophilus influenzae and Staphylococcus aureus in MDMs from patients with severe asthma compared to non-severe asthma (p < 0.05 and p < 0.01, respectively) and healthy subjects (p < 0.01and p < 0.001, respectively). Phagocytosis of Haemophilus influenzae and Staphylococcus aureus by AM was also reduced in severe asthma compared to normal subjects (p < 0.05). Dexamethasone and formoterol did not suppress phagocytosis of bacteria by MDMs from any of the groups. CONCLUSIONS: Persistence of bacteria in the lower airways may result partly from a reduced phagocytic capacity of macrophages for bacteria. This may contribute to increased exacerbations, airway colonization and persistence of inflammation.

Nursing Students' Experience of a Poverty Simulation and Its Impact on Empathy and Social Justice Awareness: A Descriptive Qualitative Study.

Holistic nursing practice requires an understanding of the constraints of poverty as one of the social determinants of health. Future nurses need to be change agents for social justice. A descriptive, qualitative study was conducted to explore students' experience of the Missouri Association for Community Action Poverty Simulation© (CAPS) and its impact on empathy and social justice awareness among a purposive sample of 56 sophomore baccalaureate nursing students at a public university in the Northeastern United States. Inductive thematic analysis was applied to data collected from a postparticipation reflection paper. Five themes emerged: (a) emotions, (b) personal history of poverty, (c) empathy, (d) rising advocacy, and (e) lessons learned. The results support that the CAPS simulation provides an experiential opportunity which impacts empathy and foundational attitudes to be a change agent for social justice. Recommendations include structured education about social determinants of health prior to the CAPS simulation, continued education throughout nursing curricula, and experiential opportunities to apply social justice skills before graduation.

An assessment of survey measures used across key epidemiologic studies of United States Gulf War I Era veterans.

Over the past two decades, 12 large epidemiologic studies and 2 registries have focused on U.S. veterans of the 1990-1991 Gulf War Era. We conducted a review of these studies' research tools to identify existing gaps and overlaps of efforts to date, and to advance development of the next generation of Gulf War Era survey tools. Overall, we found that many of the studies used similar instruments. Questions regarding exposures were more similar across studies than other domains, while neurocognitive and psychological tools were the most variable. Many studies focused on self-reported survey results, with a range of validation practices. However, physical exams, biomedical assessments, and specimen storage were not common. This review suggests that while research may be able to pool data from past surveys, future surveys need to consider how their design can yield data comparable with previous surveys. Additionally, data that incorporate recent technologies in specimen and genetic analyses would greatly enhance such survey data. When combined with existing data on deployment-related exposures and post-deployment health conditions, longitudinal follow-up of existing studies within this collaborative framework could represent an important step toward improving the health of veterans.

Neutron Reflectometry and Molecular Simulations Demonstrate HIV-1 Nef Homodimer Formation on Model Lipid Bilayers.

The HIV-1 Nef protein plays a critical role in viral infectivity, high-titer replication in vivo, and immune escape of HIV-infected cells. Nef lacks intrinsic biochemical activity, functioning instead through interactions with diverse host cell signaling proteins and intracellular trafficking pathways. Previous studies have established an essential role for Nef homodimer formation at the plasma membrane for most if not all its functions. Here we combined neutron reflectometry of full-length myristoylated Nef bound to model lipid bilayers with molecular simulations based on previous X-ray crystal structures of Nef homodimers. This integrated approach provides direct evidence that Nef associates with the membrane as a homodimer with its structured core region displaced from the membrane for partner protein engagement. Parallel studies of a dimerization-defective mutant, Nef-L112D, demonstrate that the helical dimerization interface present in previous crystal structures stabilizes the membrane-bound dimer. X-ray crystallography of the Nef-L112D mutant in complex with the SH3 domain of the Nef-associated host cell kinase Hck revealed a monomeric 1:1 complex instead of the 2:2 dimer complex formed with wild-type Nef. Importantly, the crystal structure of the Nef-L112D core and SH3 interface are virtually identical to the wild-type complex, indicating that this mutation does not affect the overall Nef fold. These findings support the intrinsic capacity of Nef to homodimerize at lipid bilayers using structural features present in X-ray crystal structures of dimeric complexes.

Comparison of success rate and intraocular pressure spikes between selective laser trabeculoplasty and micropulse laser trabeculoplasty in African American and Hispanic patients.

AIM: To examine the efficacy and safety of micropulse laser trabeculoplasty (MLT) versus selective laser trabeculoplasty (SLT) in a large cohort of primarily African American and Hispanic patients. METHODS: A single center retrospective comparative cohort review conducted at Cook County Health facilities that included patients with a diagnosis of open angle glaucoma or ocular hypertension who received an SLT or MLT procedure between January 2017 and May 2021. RESULTS: Totally 131 eyes of 99 patients were analyzed. The 77 eyes received SLT and 54 received MLT. Seven out of 77 eyes in the SLT group (9.1%) and 1 out of 54 eyes in the MLT group (1.9%) had an IOP spike (defined as > 5 mm Hg) at either 1h or 1wk after procedure (P=0.05, Chi-squared test with Haldane-Anscombe correction). The procedure failure rate at one year was 50% for SLT and 48% for MLT (P=0.31). CONCLUSION: MLT has a significantly lower incidence of pressure spikes and a similar treatment failure rate at 1-year post-procedure, demonstrating that it is a reasonable alternative compared to SLT.

Establishing an Antimicrobial Stewardship Program in Sierra Leone: A Report of the Experience of a Low-Income Country in West Africa.

Antimicrobial Resistance (AMR) is a growing global health challenge that threatens to undo gains in human and animal health. Prevention and control of AMR requires functional antimicrobial stewardship (AMS) program, which is complex and often difficult to implement in low- and middle-income countries. We aimed to describe the processes of establishing and implementing an AMS program at Connaught Hospital in Sierra Leone. The project involved the setting up of an AMS program, capacity building and performing a global point prevalence survey (GPPS) at Sierra Leone's national referral hospital. Connaught Hospital established a multidisciplinary AMS subcommittee in 2021 to provide AMS services such as awareness campaigns, education and training and review of guidelines. We performed a GPPS on 175 patients, of whom more than half (98, 56.0%) were prescribed an antibiotic: 63 (69.2%) in the surgical wards and 53 (51.2%) in the medical wards. Ceftriaxone (60, 34.3%) and metronidazole (53, 30.3%) were the most common antibiotics prescribed to patients. In conclusion, it is feasible to establish and implement an AMS program in low-income countries, where most hospitalized patients were prescribed an antibiotic.