Deworming and micronutrient status by community open defecation prevalence: An observational study using nationally representative data from India, 2016-2018.

BACKGROUND: Micronutrient deficiencies are widespread in India. Soil-transmitted helminth (STH) infections are acquired by interaction with soil and water contaminated by human feces and lead to blood loss and poor micronutrient absorption. The current recommendation for control of STH-related morbidity is targeted deworming, yet little is known about the effectiveness of deworming on micronutrient status in varying sanitation contexts. Ranging between 1% and 40% prevalence across Indian states, open defecation (OD) remains high despite India's investments at elimination by promoting community-wide sanitation. This variation provides an opportunity to study the relationship between deworming, micronutrient status, and OD at-scale. METHODS AND FINDINGS: Cross-sectional datasets that were representative for India were obtained the Comprehensive National Nutrition Survey in 2016 to 2018 (n = 105,060 individuals aged 1 to 19 years). Consumption of deworming medication was described by age and community OD level. Logistic regression models were used to examine the relationship between deworming, cluster OD, and their interactions, with anemia and micronutrient deficiencies (iron, zinc, vitamin A, folate, and vitamin B12), controlling for age, sex, wealth, diet, and seasonality. These regression models further allowed us to identify a minimum OD rate after which deworming becomes ineffective. In sensitivity analyses, the association between deworming and deficiencies were tested in subsamples of communities classified into 3 OD levels based on statistical tertiles: OD free (0% of households in the community practicing OD), moderate OD (>0% and <30%), or high OD (at least 30%). Average deworming coverage and OD prevalence in the sample were 43.4% [IQR 26.0, 59.0] and 19.1% [IQR 0, 28.5], respectively. Controlling for other determinants of nutritional status, adolescents living in communities with higher OD levels had lower coverage of deworming and higher prevalence of anemia, zinc, vitamin A, and B12 deficiencies. Compared to those who were not dewormed, dewormed children and adolescents had lower odds of anemia (adjusted odds ratio 0.72, (95% CI [0.67, 0.78], p < 0.001) and deficiencies of iron 0.78, (95% CI [0.74, 0.82], p < 0.001) and folate 0.69, (95% CI [0.64,0.74], p<0.001)) in OD free communities. These protective effects remained significant for anemia but diminished for other micronutrient deficiencies in communities with moderate or high OD. Analysis of community OD indicated a threshold range of 30% to 60%, above which targeted deworming was no longer significantly associated with lower anemia, iron, and folate deficiency. The primary limitations of the study included potential for omitted variables bias and inability to capture longitudinal effects. CONCLUSIONS: Moderate to high rates of OD significantly modify the association between deworming and micronutrient status in India. Public health policy could involve sequencing interventions, with focus on improving deworming coverage in communities that have achieved minimum thresholds of OD and re- triggering sanitation interventions in high OD communities prior to deworming days, ensuring high coverage for both. The efficacy of micronutrient supplementation as a complementary strategy to improve nutritional outcomes alongside deworming and OD elimination in this age group needs further study.

Medication errors in emergency departments: a systematic review and meta-analysis of prevalence and severity.

BACKGROUND: Medication errors significantly compromise patient safety in emergency departments. Although previous studies have investigated the prevalence of these errors in this setting, results have varied widely. AIM: The aim was to report pooled data on the prevalence and severity of medication errors in emergency departments, as well as the proportion of patients affected by these errors. METHOD: Systematic searches were conducted in Embase, PubMed, and the Cochrane Library from database inception until June 2023. Studies provided numerical data on medication errors within emergency departments were eligible for inclusion. Random-effects meta-analysis was employed to pool the prevalence of medication errors, the proportion of patients experiencing these errors, and the error severity levels. Heterogeneity among studies was assessed using the I2 statistic and Cochran's Q test. RESULTS: Twenty-four studies met the inclusion criteria. The meta-analysis gave a pooled prevalence of medication errors in emergency departments of 22.6% (95% Confidence Interval [CI] 19.2-25.9%, I2 = 99.9%, p < 0.001). The estimated proportion of patients experiencing medication errors was 36.3% (95% CI 28.3-44.3%, I2 = 99.8%, p < 0.001). Of these errors, 42.6% (95% CI 5.0-80.1%) were potentially harmful but not life-threatening, while no-harm errors accounted for 57.3% (95% CI 14.1-100.0%). CONCLUSION: The prevalence of medication errors, particularly those potentially harmful, underscores potential safety issues in emergency departments. It is imperative to develop and implement effective interventions aimed at reducing medication errors and enhancing patient safety in this setting.

Dengue virus serotypes and related factors in children with dengue hemorrhagic fever in Southern Vietnam.

INTRODUCTION: After the Coronavirus Disease 2019 pandemic, a high number of cases and severe dengue in children were reported in some provinces in the south of Vietnam. This study aimed to determine the distribution of dengue virus serotypes and their correlation with demographic factors, disease severity, clinical manifestations, and laboratory findings. METHODOLOGY: This study employed a cross-sectional design. Ninety-six dengue-infected children admitted to Can Tho Children's Hospital between October 2022 and March 2023 were included. Confirmation of dengue infection was achieved through the real-time polymerase chain reaction (RT-PCR). RESULTS: Among the identified serotypes, DENV-2 accounted for the highest proportion (71.87%), followed by DENV-1 (23.96%), and DENV-4 (4.17%). DENV-3 was not detected. No significant demographic, disease severity, or laboratory differences were observed among the identified dengue serotypes. However, DENV-2 was associated with a higher occurrence of mucous membrane hemorrhages and gastrointestinal bleeding compared to other serotypes. CONCLUSIONS: Although DENV-2 was the most prevalent serotype responsible for dengue in children in southern Vietnam, it did not lead to more severe cases compared to other serotypes. This finding is crucial for evaluating the illness's prognosis.

γ-Secretase Modulator BPN15606 Reduced Aß42 and Aß40 and Countered Alzheimer-Related Pathologies in a Mouse Model of Down Syndrome.

OBJECTIVES: Due to increased gene dose for the amyloid precursor protein (APP), elderly adults with Down syndrome (DS) are at a markedly increased risk of Alzheimer's disease (AD), known as DS-AD. How the increased APP gene dose acts and which APP products are responsible for DS-AD is not well understood, thus limiting strategies to target pathogenesis. As one approach to address this question, we used a novel class of γ-secretase modulators that promote γ-site cleavages by the γ-secretase complex, resulting in lower levels of the Aß42 and Aß40 peptides. METHODS: Ts65Dn mice, which serve as a model of DS, were treated via oral gavage with 10 mg/kg/weekday of BPN15606 (a potent and novel pyridazine-containing γ-secretase modulators). Treatment started at 3 months-of-age and lasted for 4 months. RESULTS: Demonstrating successful target engagement, treatment with BPN15606 significantly decreased levels of Aß40 and Aß42 in the cortex and hippocampus; it had no effect on full-length APP or its C-terminal fragments in either 2 N or Ts65Dn mice. Importantly, the levels of total amyloid-ß were not impacted, pointing to BPN15606-mediated enhancement of processivity of γ-secretase. Additionally, BPN15606 rescued hyperactivation of Rab5, a protein responsible for regulating endosome function, and normalized neurotrophin signaling deficits. BPN15606 treatment also normalized the levels of synaptic proteins and tau phosphorylation, while reducing astrocytosis and microgliosis, and countering cognitive deficits. INTERPRETATION: Our findings point to the involvement of increased levels of Aß42 and/or Aß40 in contributing to several molecular and cognitive traits associated with DS-AD. They speak to increased dosage of the APP gene acting through heightened levels of Aß42 and/or Aß40 as supporting pathogenesis. These findings further the interest in the potential use of γ-secretase modulators for treating and possibly preventing AD in individuals with DS. ANN NEUROL 2024.

Use it or Lose it: Predictors of Compliance and Satisfaction With Postoperative Nasal Stent Therapy After Primary Cleft Lip Repair.

OBJECTIVE: Postoperative nasal stents (NSs) are used to improve esthetic outcomes after primary or secondary cleft lip repair (CLR). Prior studies have utilized anthropometric measurements or physician assessment to determine the efficacy of NS, but data on caregiver-reported outcomes is limited. This study aims to assess caregiver compliance and satisfaction with postoperative NS. METHODS: The authors designed a survey to collect parent-reported postoperative NS usage outcomes. Parents of infants with cleft lip (CL) who used postoperative NS after primary CLR were approached through social media to complete the survey. Data were analyzed to determine factors impacting compliance, satisfaction, and parent-reported outcomes. RESULTS: Eighty-five parents completed the questionnaire, and 60% reported noncompliance with NS. Parents with male children (odds ratio: 5.08, P = 0.019) and patients with incomplete CL (odds ratio: 5.72, P = 0.006) were more likely to be non-compliant with NS for over a week. Complete CL and use of presurgical molding therapy were each associated with better overall experience with postoperative NS (P = 0.002 and P = 0.037), higher appearance ratings (P = 0.005 and P = 0.0008), and greater satisfaction with nostril shape after surgery (P = 0.016 and P = 0.001). CONCLUSIONS: Despite limited literature related to caregiver-reported outcomes after postoperative NS for primary CLR, the authors' results align with what has been published regarding this topic. These results can help guide surgeons in counseling patients preoperatively. Larger, multi-institutional studies are needed to better delineate and address factors associated with compliance and satisfaction after NS therapy.

Perturbation-Specific Transcriptional Mapping facilitates unbiased target elucidation of antibiotics.

The rising prevalence of antibiotic resistance threatens human health. While more sophisticated strategies for antibiotic discovery are being developed, target elucidation of new chemical entities remains challenging. In the post-genomic era, expression profiling can play an important role in mechanism-of-action (MOA) prediction by reporting on the cellular response to perturbation. However, the broad application of transcriptomics has yet to fully fulfill its promise of transforming target elucidation. We developed an unbiased strategy for MOA prediction, called Perturbation-Specific Transcriptional Mapping (PerSpecTM), in which large-throughput expression profiling of wild-type or hypomorphic mutants depleted for essential targets, enables a reference-based strategy to associate similar perturbations, whether small molecule or genetic, based on the principle that similar perturbations will elicit similar transcriptional responses. We applied this approach to rapidly elucidate the MOAs of three new molecules with activity against the important bacterial pathogen Pseudomonas aeruginosa by mapping their expression profiles to those generated for a reference set of antimicrobial compounds with known MOA. Meanwhile, we also show that small molecule inhibition can be mapped to genetic depletion of essential targets by CRISPRi by PerSpecTM, thus demonstrating proof-of-concept that correlations between expression profiles of small molecule and genetic perturbations can predict MOA when no chemical entities exist to serve as a reference. Empowered by PerSpecTM and its leveraging of reference transcriptional profiles for known small molecule or genetic perturbations, this work lays the foundation for an unbiased, readily scalable, systematic reference-based strategy for MOA elucidation that could transform antibiotic discovery efforts. Significance Statement: In an era of increasing antibiotic resistance, new antibiotics are critically needed. However, MOA elucidation remains a challenging step in antibiotic discovery and thus a major bottleneck. Building on the principle that molecules with similar MOAs elicit similar transcriptional responses, we have now developed a highly scalable strategy for MOA prediction in the important bacterial pathogen Pseudomonas aeruginosa based on correlations between the expression profiles of new molecules and known perturbations, either small molecule inhibition by known antibiotics or transcriptional repression of essential targets by CRISPRi. By rapidly assigning MOA to three new molecules with anti-pseudomonal activity, we provide proof-of-concept for a rapid, comprehensive, systematic, reference-based approach to MOA prediction, with the potential to transform antibiotic discovery efforts.

Subgaleal and Epidural Hematomas Secondary to Calvarial Infarcts: An Uncommon Presentation of Sickle Cell Disease.

We present the case of a 13-year-old male with sickle cell disease (SCD) who presented to the emergency department with a severe headache secondary to calvarial infarcts with associated epidural and subgaleal hematomas. This case was complicated by external compression of the superior sagittal sinus by the hematomas as seen on magnetic resonance imaging. Management included supportive treatment of pain and swelling. This case emphasizes skull infarctions with associated hematomas as a possible differential diagnosis for patients with SCD presenting with headaches and scalp swellings.

Correlation of Orthognathic Surgical Movements to Perception of Facial Appearance in Patients With Cleft Lip and Palate.

STUDY DESIGN: Cephalometric scans were compared before and after surgery to assess the degree of correction. Correlations between skeletal movements and survey outcomes were determined using multivariate regression analysis. OBJECTIVE: This study aims to identify relationships between subjective observer-reported improvements in esthetics and emotional appearance with specific surgical movements. METHODS: Ten patients at a single tertiary institution (average age: 18.1 ± 0.8), 9 males and 1 female, underwent orthognathic repair and had comprehensive cephalometric records. Standardized anterior posterior and lateral pre and postoperative photographs of patients were included in a survey to clinicians to assess noncognitive domains on a Likert Scale (1-10). CLEFT-Q was administered to gauge patient satisfaction in categories of appearance, speech, and quality of life. RESULTS: Per clinicians, multiple domains increased including facial attractiveness (4.1 ± 0.7 versus 7.3 ± 0.7, P < 0.001), friendliness (4.5 ± 0.4 versus 7.3 ± 0.5, P < 0.001), confidence (4.1 ± 0.4 versus 7.1 ± 0.4, P < 0.001), and recommendation for surgery decreased (8.9 ± 0.1 versus 3.6 ± 0.5, P < 0.001). Speech distress decreased with increased SNA and convexity, whereas Psychological and Social scores decreased with an increased ANB. Functional eating and drinking scores increased with maxillary depth. CONCLUSIONS: Orthognathic surgery improves many noncognitive domains in patients with cleft lip and palate as assessed by both patients and clinicians on all aspects of facial attractiveness and perception. These findings demonstrate objective bases of skeletal adjustments for perceived improvements in facial appearance and emotion.

High-Pressure Polymorphism in Silver Ferrite Delafossite, AgFeO2.

The delafossites are a class of layered metal oxides that are notable for being able to exhibit optical transparency alongside an in-plane electrical conductivity, making them promising platforms for the development of transparent conductive oxides. Pressure-induced polymorphism offers a direct method for altering the electrical and optical properties in this class, and although the copper delafossites have been studied extensively under pressure, the silver delafossites remain only partially studied. We report two new high-pressure polymorphs of silver ferrite delafossite, AgFeO2, that are stabilized above ∼6 and ∼14 GPa. In situ X-ray diffraction and vibrational spectroscopy measurements are used to examine the structural changes across the two phase transitions. The high-pressure structure between 6 and 14 GPa is assigned as a monoclinic C2/c structure that is analogous to the high-pressure phase reported for AgGaO2. Nuclear resonant forward scattering reveals no change in the spin state or valence state at the Fe3+ site up to 15.3(5) GPa.

Opportunities and barriers to pediatric antimicrobial stewardship by community pharmacists.

Community Pharmacists (CPs) are easily accessible and can advocate for appropriate use of antibiotics in children. Semi-structured interviews were conducted with 47 CPs and 46 parents/caregivers. Both groups expressed challenges to intervening when antibiotics have already been prescribed and highlighted the need for more support for CPs to make informed decisions.

Investigation of Urinary Metabolites of Organophosphate Esters in Hanoi, Vietnam: Assessment Exposure and Estimated Daily Intake.

In recent years, organophosphate esters (OPEs) have become one of the most common additives in various consumer products worldwide, therefore the exposure and impact of OPEs on human health are drawing a lot of attention. In this study, three metabolites of OPEs including bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPhP) and diethyl phosphate (DEP) were investigated in first-morning void urine samples taken from a population (age range: 3-76 years old) in Hanoi, Vietnam. The most dominant urinary OPE metabolite was DEP with the geometric mean of specific gravity adjust (SG-adjusted) concentration were 1960 ng mL-1 and detected frequency (DF) of 98%. Followed by DPhP (8.01 ng mL-1, DF: 100%) and BDCIPP (2.18 ng mL-1, DF: 51%). The results indicated that gender and age might have associations with the OPE metabolites variation in urine samples. The levels of OPE metabolites in urine samples from females were slightly higher than in males. An increase in age seems to have an association with a decrease in DPhP levels in urine. Exposure doses of parent OPEs were evaluated from the unadjusted urinary concentration of corresponding OPE metabolite. The estimated exposure doses of triethyl phosphate (TEP) (mean: 534,000 ng kg-1 d-1) were significantly higher than its corresponding reference dose, suggesting the high potential risk from the current exposure doses of TEP to human health. The results of this work provided the initial information on the occurrence of three OPE metabolites in urine from Hanoi, Vietnam and estimated exposure dose of corresponding parent OPEs.

Classification and application of metal-based nanoantioxidants in medicine and healthcare.

Antioxidants play an important role in the prevention of oxidative stress and have been widely used in medicine and healthcare. However, natural antioxidants have several limitations such as low stability, difficult long-term storage, and high cost of large-scale production. Along with significant advances in nanotechnology, nanomaterials have emerged as a promising solution to improve the limitations of natural antioxidants because of their high stability, easy storage, time effectiveness, and low cost. Among various types of nanomaterials exhibiting antioxidant activity, metal-based nanoantioxidants show excellent reactivity because of the presence of an unpaired electron in their atomic structure. In this review, we summarize some novel metal-based nanoantioxidants and classify them into two main categories, namely chain-breaking and preventive antioxidant nanomaterials. In addition, the applications of antioxidant nanomaterials in medicine and healthcare are also discussed. This review provides a deeper understanding of the mechanisms of metal-based nanoantioxidants and a guideline for using these nanomaterials in medicine and healthcare.

Utilizing surface plasmon resonance as a novel method for monitoring in-vitro P-glycoprotein efflux.

P-glycoprotein (Pgp) is known for its dichotomous roles as both a safeguarding efflux transporter against xenobiotics and as a catalyst for multidrug resistance. Given the susceptibility of numerous therapeutic compounds to Pgp-mediated resistance, compliance with Food and Drug Administration (FDA) guidelines mandates an in-depth in vitro transport assay during drug development. This study introduces an innovative transport assay that aligns with these regulatory imperatives but also addresses limitations in the currently established techniques. Using Pgp-reconstituted liposomes and employing surface plasmon resonance (SPR), this study developed a distinct method of measuring the relative transport rates of Pgp substrates in a controlled microenvironment. The Pgp substrates selected for this study-quinidine, methadone, and desipramine-resulted in transport ratios that corroborate with trends previously observed. To assess the kinetics of Pgp-mediated transport, the results were analyzed by fitting the data to both currently proposed Pgp substrate translocation models-the vacuum cleaner and flippase models. While the resulting kinetic analysis in this study lends support predominantly to the vacuum cleaner model, this study most notably developed a novel method of assessing Pgp-mediated transport rates and real-time kinetics using surface plasmon resonance.

Shared genetic risk between major orofacial cleft phenotypes in an African population.

Nonsyndromic orofacial clefts (NSOFCs) represent a large proportion (70%-80%) of all OFCs. They can be broadly categorized into nonsyndromic cleft lip with or without cleft palate (NSCL/P) and nonsyndromic cleft palate only (NSCPO). Although NSCL/P and NSCPO are considered etiologically distinct, recent evidence suggests the presence of shared genetic risks. Thus, we investigated the genetic overlap between NSCL/P and NSCPO using African genome-wide association study (GWAS) data on NSOFCs. These data consist of 814 NSCL/P, 205 NSCPO cases, and 2159 unrelated controls. We generated common single-nucleotide variants (SNVs) association summary statistics separately for each phenotype (NSCL/P and NSCPO) under an additive genetic model. Subsequently, we employed the pleiotropic analysis under the composite null (PLACO) method to test for genetic overlap. Our analysis identified two loci with genome-wide significance (rs181737795 [p = 2.58E-08] and rs2221169 [p = 4.5E-08]) and one locus with marginal significance (rs187523265 [p = 5.22E-08]). Using mouse transcriptomics data and information from genetic phenotype databases, we identified MDN1, MAP3k7, KMT2A, ARCN1, and VADC2 as top candidate genes for the associated SNVs. These findings enhance our understanding of genetic variants associated with NSOFCs and identify potential candidate genes for further exploration.

Field and laboratory investigation of highly pathogenic avian influenza H5N6 and H5N8 in Quang Ninh province, Vietnam, 2020 to 2021.

BACKGROUND: Avian influenza (AI) is a contagious disease that causes illness and death in poultry and humans. High pathogenicity AI (HPAI) H5N6 outbreaks commonly occur in Quang Ninh province bordering China. In June 2021, the first HPAI H5N8 outbreak occurred at a Quang Ninh chicken farm. OBJECTIVES: This study examined the risk factors associated with HPAI H5N6 and H5N8 outbreaks in Quang Ninh. METHODS: A retrospective case-control study was conducted in Quang Ninh from Nov 2021 to Jan 2022. The cases were households with susceptible poultry with two or more clinical signs and tested positive by real-time reverse transcription polymerase chain reaction. The controls were households in the same village as the cases but did not show clinical symptoms of the disease. Logistic regression models were constructed to assess the risk factors associated with HPAI outbreaks at the household level. RESULTS: There were 38 cases with H5N6 clade 2.3.4.4h viruses (n = 35) and H5N8 clade 2.3.4.4b viruses (n = 3). Compared to the 112 controls, raising poultry in uncovered or partially covered ponds (odds ratio [OR], 7.52; 95% confidence interval [CI], 1.44-39.27), poultry traders visiting the farm (OR, 8.66; 95% CI, 2.7-27.69), farms with 50-2,000 birds (OR, 3.00; 95% CI, 1.06-8-51), and farms with ≥ 2,000 birds (OR, 11.35; 95% CI, 3.07-41.94) were significantly associated with HPAI outbreaks. CONCLUSIONS: Combining biosecurity measures, such as restricting visitor entry and vaccination in farms with more than 50 birds, can enhance the control and prevention of HPAI in Quang Ninh and its spread across borders.

"Multiplexed screen identifies a Pseudomonas aeruginosa -specific small molecule targeting the outer membrane protein OprH and its interaction with LPS".

The surge of antimicrobial resistance threatens efficacy of current antibiotics, particularly against Pseudomonas aeruginosa , a highly resistant gram-negative pathogen. The asymmetric outer membrane (OM) of P. aeruginosa combined with its array of efflux pumps provide a barrier to xenobiotic accumulation, thus making antibiotic discovery challenging. We adapted PROSPECT 1 , a target-based, whole-cell screening strategy, to discover small molecule probes that kill P. aeruginosa mutants depleted for essential proteins localized at the OM. We identified BRD1401, a small molecule that has specific activity against a P. aeruginosa mutant depleted for the essential lipoprotein, OprL. Genetic and chemical biological studies identified that BRD1401 acts by targeting the OM ß-barrel protein OprH to disrupt its interaction with LPS and increase membrane fluidity. Studies with BRD1401 also revealed an interaction between OprL and OprH, directly linking the OM with peptidoglycan. Thus, a whole-cell, multiplexed screen can identify species-specific chemical probes to reveal novel pathogen biology.

How much is invested in obesity prevention in Australia? An analysis of major research and Federal Government funding, 2013-2022.

Objective and importance of study: Overweight and obesity are the second leading risk factors for death and non-communicable disease in Australia. This study aimed to examine the Australian Federal Government funding landscape for population-level obesity prevention from 2013 to 2022. STUDY TYPE: A retrospective analysis and narrative synthesis of publicly available data on obesity prevention funding from the Federal Government and major federally funded Australian research organisations. METHODS: Searches were conducted of Australian Federal Government Budget documents and funding announcements from the National Health and Medical Research Council (NHMRC), Australian Research Council (ARC) and Medical Research Future Fund (MRFF). Funding allocations targeting obesity prevention, or the prevention of risk factors associated with obesity, were included. These were determined by the presence of keywords related to obesity, unhealthy diet, physical activity and sedentary behaviour. Data were extracted verbatim, coded and narratively synthesised by funding source. RESULTS: From 2013 to 2022, 186 funding allocations for obesity prevention in Australia were identified, totalling approximately A$778 million. The proportion of funding allocated to obesity prevention compared to the total annual budget of each funding source was relatively low: NHMRC = 1.1%; ARC = 0.2%; MRFF = 0.8%; Federal Government = 0.1% (of health budget). Funding for obesity prevention initiatives fluctuated over time. CONCLUSIONS: Findings underscore the need for strategic and ongoing funding allocation to support obesity prevention research, implementation and sustainment of evidence-based obesity prevention initiatives in Australia.