Coverage gaps in empiric antibiotic regimens used to treat serious bacterial infections in neonates and children in Southeast Asia and the Pacific.

Background: High levels of antimicrobial resistance (AMR) are propagating deaths due to neonatal and paediatric infections globally. This is of particular concern in Southeast Asia and the Pacific, where healthcare resources are constrained and access to newer agents to treat multidrug-resistant pathogens is limited. Methods: To assess the coverage provided by commonly prescribed empiric antibiotic regimens for children in low- and middle-income countries in Southeast Asia and the Pacific, we built a weighted incidence syndromic combination antibiogram (WISCA), parameterised using data obtained from a systematic review of published literature incorporating WHO-defined SEARO and WPRO regions in Ovid MEDLINE, EMBASE, Global Health and PubMed. Susceptibility data for bacterial pathogens were extracted to provide coverage estimates for pre-specified antibiotics (aminopenicillins, gentamicin, third-generation cephalosporins and carbapenems), reported at the regional level. Findings: 6648 bacterial isolates from 11 countries across 86 papers were included in the Bayesian WISCA model, which weighted bacterial incidence and antimicrobial susceptibility of relevant isolates. Coverage provided by aminopenicillins in neonatal sepsis/meningitis was 26% (80% credible interval: 16-49) whilst gentamicin coverage was 45% (29-62). Third-generation cephalosporin coverage was only 29% (16-49) in neonatal sepsis/meningitis, 51% (38-64) in paediatric sepsis and 65% (51-77) in paediatric meningitis. Carbapenems were estimated to provide the highest coverage: 81% (65-90) in neonatal sepsis/meningitis, 83% (72-90) in paediatric sepsis and 79% (62-91) in paediatric meningitis. Interpretation: These findings reveal alarmingly high rates of resistance to commonly prescribed empirical therapies for neonatal and paediatric sepsis and meningitis in the Asia-Pacific region. Funding: This research was funded in whole, or in part, by the Wellcome Trust [220211]. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. PCMW is supported by a National Health and Medical Research Council (NHMRC) Investigator Grant. NHMRC had no involvement in the design or conduct of the research.

Antigen stasis and airway nitrosative stress in human primary ciliary dyskinesia.

Nasal nitric oxide (nNO) is low in most patients with primary ciliary dyskinesia (PCD). Decreased ciliary motion could lead to antigen stasis, increasing oxidant production and NO oxidation in the airways. This could both decrease gas phase NO and increase nitrosative stress. We studied primary airway epithelial cells from healthy controls (HCs) and patients with PCD with several different genotypes. We measured antigen clearance in fenestrated membranes exposed apically to the fluorescently labeled antigen Dermatophagoides pteronyssinus (Derp1-f). We immunoblotted for 3-nitrotyrosine (3-NT) and for oxidative response enzymes. We measured headspace NO above primary airway cells without and with a PCD-causing genotype. We measured nNO and exhaled breath condensate (EBC) H2O2 in vivo. Apical Derp1-f was cleared from HC better than from PCD cells. DUOX1 expression was lower in HC than in PCD cells at baseline and after 24-h Derp1-f exposure. HC cells had less 3-NT and NO3- than PCD cells. However, NO consumption by HC cells was less than that by PCD cells; NO loss was prevented by superoxide dismutase (SOD) and by apocynin. nNO was higher in HCs than in patients with PCD. EBC H2O2 was lower in HC than in patients with PCD. The PCD airway epithelium does not optimally clear antigens and is subject to oxidative and nitrosative stress. Oxidation associated with antigen stasis could represent a therapeutic target in PCD, one with convenient monitoring biomarkers.NEW & NOTEWORTHY The PCD airway epithelium does not optimally clear antigens, and antigen exposure can lead to NO oxidation and nitrosative stress. Oxidation caused by antigen stasis could represent a therapeutic target in PCD, and there are convenient monitoring biomarkers.

Changing the global obesity narrative to recognize and reduce weight stigma: A position statement from the World Obesity Federation.

Weight stigma, defined as pervasive misconceptions and stereotypes associated with higher body weight, is both a social determinant of health and a human rights issue. It is imperative to consider how weight stigma may be impeding health promotion efforts on a global scale. The World Obesity Federation (WOF) convened a global working group of practitioners, researchers, policymakers, youth advocates, and individuals with lived experience of obesity to consider the ways that global obesity narratives may contribute to weight stigma. Specifically, the working group focused on how overall obesity narratives, food and physical activity narratives, and scientific and public-facing language may contribute to weight stigma. The impact of weight stigma across the lifespan was also considered. Taking a global perspective, nine recommendations resulted from this work for global health research and health promotion efforts that can help to reduce harmful obesity narratives, both inside and outside health contexts.

Validating the Sociocultural Influences on Fear of Fat Scale (SI-FAT) on a racially and ethnically diverse sample of college women.

The fear of fat, or fear of gaining weight, is conceptually related to both weight stigma and eating disorders. Since sociocultural pressures related to the thin ideal are important to examine within sociocultural models of body image, the Sociocultural Influences on Fear of Fat (SI-FAT) was created and validated on a sample of predominantly White college women. The purpose of this study was to examine the factor structure of the SI-FAT in a sample of racially and ethnically diverse college women, given potential differences in experiences of fear of fat and the need to measure sociocultural pressures related to fear of fat in multiple groups. A sample of college women (72.8% Hispanic/Latina, 14.85% Black, and 12.35% White) completed the SI-FAT as well as measures of weight stigma and body image. Results suggested that the factor structure of the SI-FAT were consistent across racial and ethnic groups. These findings indicate that the SI-FAT is appropriate for use among racially and ethnically diverse samples of young women. Directions for future research, including examining differences between sociocultural pressures related to weight gain and self-reported fear of fat are discussed.

Effects of pH alteration on respiratory syncytial virus in human airway epithelial cells.

Background: Respiratory syncytial virus (RSV) is a leading cause of respiratory distress and hospitalisation in the paediatric population. Low airway surface pH impairs antimicrobial host defence and worsens airway inflammation. Inhaled Optate safely raises airway surface pH in humans and raises intracellular pH in primary human airway epithelial cells (HAECs) in vitro. We aimed to determine whether raising intracellular pH with Optate would decrease infection and replication of RSV in primary HAECs. Methods: We cultured HAECs from healthy subjects in both air-liquid interface and submerged conditions. We infected HAECs with green fluorescent protein-labelled RSV (GFP-RSV; multiplicity of infection=1) and treated them with Optate or PBS control. We collected supernatant after a 4-h incubation and then every 24 h. We used fluorescence intensity, fluorescent particle counts, plaque assays, Western blots and ELISA to quantitate infection. Results: In submerged culture, fluorescence intensity decreased in Optate-treated cells (48 h p=0.0174, 72 h p≤0.001). Similarly, Optate treatment resulted in decreased fluorescent particle count (48 h p=0.0178, 72 h p=0.0019) and plaque-forming units (48 h p=0.0011, 72 h p=0.0148) from cell culture supernatant. In differentiated HAECs cultured at ALI, Optate treatment decreased fluorescence intensity (p≤0.01), GFP via Western blot and ELISA (p<0.0001), and RSV-fusion protein via ELISA (p=0.001). Additionally, RSV infection decreased as Optate concentration increased in a dose-dependent manner (p<0.001). Conclusions: Optate inhibits RSV infection in primary HAECs in a dose-dependent manner. These findings suggest that Optate may have potential as an inhaled therapeutic for patients with RSV.

Validation of a Farsi version of the Eating Disorder Examination Questionnaire (F-EDE-Q) in adolescents and university students from Iran.

BACKGROUND: Although the Farsi version of the Eating Disorder Examination-Questionnaire (F-EDE-Q) is frequently utilized to assess disordered eating in Iran, its factor structure, reliability, and validity have not been investigated in Iranian samples, which is the aim of the current investigation. METHOD: Using convenience sampling, this study recruited 1112 adolescents and 637 university students to complete disordered eating and mental health-focused questionnaires, including the F-EDE-Q. RESULTS: Confirmatory factor analyses of the 22 attitudinal items in the F-EDE-Q indicated that a brief seven-item, three-factor model (i.e., Dietary Restraint, Shape/Weight Overvaluation, Body Dissatisfaction with Shape and Weight) was the only factor structure that fit the data well for either sample. This brief version of the F-EDE-Q was invariant across gender, body weight, and age. Adolescent and university participants with higher weight reported higher average scores on each of the three subscales. Subscale scores showed good internal consistency reliability in the two samples. Further, supporting convergent validity, subscales were significantly associated with measures of body image-related preoccupation and bulimia symptoms, as well as measures of other theoretically related constructs including depressive symptoms and self-esteem. CONCLUSION: Findings suggest that this brief, validated measure will enable researchers and clinical providers to appropriately assess disordered eating symptoms in adolescent and young adult Farsi-speaking populations.

Characterization of Switch/Sucrose Nonfermenting Complex Proteins and Nestin Expression in a Cohort of Pediatric Central Nervous System Tumors.

Tumors of the central nervous system (CNS) in pediatric patients have undergone significant diagnostic refinement through the use of immunohistochemistry (IHC) and molecular techniques. The utility of these novel IHC antibodies has been demonstrated with the inactivation of the switch/sucrose nonfermenting (SWI/SNF) chromatin-remodeling complex in the diagnosis of atypical teratoid/rhabdoid tumors, predominantly through the loss of integrase interactor 1 (INI1; SMARCB1 ). Alternatively, these tumors may have inactivation of brahma-related gene 1 (BRG1; SMARCA4 ) in a subset of cases. The role of other SWI/SNF component proteins and their expression in pediatric brain tumors is not well established. Nestin, an intermediate filament, has been shown to be present in some pediatric CNS tumors, but of uncertain diagnostic and prognostic significance. We sought to explore the immunohistochemical expression profile for common SWI/SNF subunits and nestin in a pediatric CNS tumor cohort. Using a 118-sample tissue microarray, we performed IHC for INI1, BRG1, brahma (BRM), ARID1A, ARID1B, polybromo 1, and nestin. In 19 cases, INI1 was lost and BRG1 was lost in 2 cases. Interestingly, 6 cases originally diagnosed as primitive neuroectodermal tumors showed isolated loss of BRM. Other SWI/SNF proteins did not provide further diagnostic resolution. Nestin was positive in 76.2% of INI1/BRG1-deficient tumors, compared with 29.1% in INI1/BRG1-intact tumors yielding a sensitivity of 76.2%, specificity of 68.0%, and a P value of <0.001, but nestin positivity did not correlate specifically with poor outcomes. In conclusion, we confirm the utility of BRG1 IHC in the workup of pediatric CNS tumors, which may facilitate a difficult diagnosis when conventional markers are inconclusive, or as a first-line marker in cases where intraoperative smears are suggestive of atypical teratoid/rhabdoid tumor. Although nestin expression was associated with SWI/SNF inactivation, it did not yield statistically significant diagnostic or prognostic information in our study. Interestingly, we identified 6 tumors with isolated BRM IHC loss, the significance of which is uncertain but warrants further investigation.

A test for implicit bias in discretionary criminal justice decisions.

OBJECTIVE: Our goal was to develop a framework to test for implicit racial bias in discretionary decisions made by community supervision agents in conditions with increasing information ambiguity. HYPOTHESES: We reasoned that as in-person contact decreases, community supervision officers' specific knowledge of clients would be replaced by heuristics that lead to racially disproportionate outcomes in higher discretion events. Officers' implicit biases would lead to disproportionately higher technical violation rates among Black community corrections' clients when they have less personal contact, but we expected no analogous increase in nondiscretionary decisions. METHOD: Using data from Black and White clients entering probation and postrelease supervision in North Carolina from 2012 through 2016, we estimated the difference in racial disparities in discretionary versus nondiscretionary decisions across five levels of supervision. We evaluated the robustness of our main fixed-effects model using an alternative regression discontinuity design. RESULTS: Racial disparities in discretionary decisions grew as supervision intensity decreased, and the bias was larger for women than men. There was no similar pattern of increased disparity for nondiscretionary decisions. CONCLUSIONS: Criminal justice system actors have a great deal of discretion, particularly in how they deal with less serious criminal behavior. Although decentralized decisions are foundational to the function of the criminal justice system, they provide an opportunity for implicit bias to seep in. Shortcuts and mental heuristics are more influential when the decision-maker's mental resources are already strained-for instance, if someone is tired, distracted, or overworked. Therefore, limiting discretion and increasing oversight and accountability may reduce the impact of implicit bias on criminal justice system outcomes. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

In vitro-in vivocorrelation of aerosol deposition before and after metered-dose inhaler coaching in healthy children.

Although pressurized metered dose inhaler (pMDI) education is a routine part of childhood asthma management and encouraging 'optimal breathing patterns' (i.e. slowly, deeply, completely, and with a mouth seal on the mouthpiece) is an integral part of recommended pMDI education, there is currently no quantifiable way to determine if a child is inhaling their medication correctly or optimally through a valved holding chamber (VHC). The TipsHaler™ (tVHC) is a prototype VHC device that measures inspiratory time, flow, and volume without changing the properties of the medication aerosol. The measurementsin vivorecorded by the tVHC can be downloaded and transferred to a spontaneous breathing lung model to simulate the inhalational patternsin vitroand also determine the deposition of inhaled aerosol mass with each pattern. We hypothesized that pediatric patients' inhalational patterns when using a pMDI would improve after active coaching via tVHC. This would increase the pulmonary deposition of inhaled aerosols in anin vitromodel. To test this hypothesis, we conducted a single-site, prospective, pilot, pre-and-post intervention study paired with a bedside-to-bench experiment. Healthy, inhaler-naïve subjects used a placebo inhaler in conjunction with the tVHC before and after coaching and recorded inspiratory parameters. These recordings were then implemented into a spontaneous breathing lung model during albuterol MDI delivery, and pulmonary deposition of albuterol was quantified. In this pilot study, active coaching resulted in a statistically significant increase in inspiratory time (n= 8,p= 0.0344, 95%CI: 0.082 to ∞). tVHC recorded inspiratory parameters obtained from patients were successfully implemented in thein vitromodel, which demonstrated that both inspiratory time (n= 8,r= 0.78,p <0.001, 95%CI: 0.47-0.92) and volume (n= 8,r= 0.58,p =0.0186, 95%CI: 0.15-0.85) strongly correlate with pulmonary deposition of inhaled drugs.

Validation of a Farsi version of the Eating Pathology Symptoms Inventory (F-EPSI) among Iranian adolescents.

PURPOSE: Limited research has validated eating pathology assessments in Iranian adolescent boys and girls. In particular, the measures that have been validated do not capture both boys' and girls' eating behaviors in adolescence. The purpose of the current study was to validate a Farsi version of the Eating Pathology Symptoms Inventory (F-EPSI) for use in Iranian adolescents. METHODS: Participants (N = 913; 85.3% girls) were adolescents who completed a battery of questionnaires including the F-EPSI. In addition, F-EPSI data for Iranian adolescents were compared with those of previously published data of adult Iranian college students. RESULTS: Confirmatory Factor Analysis (CFA) indicated that the F-EPSI had an acceptable fit to the data and supported the eight-factor model. The scale was invariant by gender, weight status, eating disorder, and age groups. Boys reported higher scores than girls on the Excessive Exercise, Muscle Building, Body Dissatisfaction, and Binge Eating subscales. Adolescents with higher weight and eating disorder symptoms endorsed higher scores on the F-EPSI subscales. Older adolescents and adults reported higher scores than younger adolescents and adolescents, respectively. Adolescents had higher scores than adults on Restricting and Excessive Exercise subscales. The F-EPSI demonstrated good convergent validity through correlations with other eating pathology symptoms. The F-EPSI subscales were associated with depression and body mass index (zBMI) in expected directions that indicate criterion validity of the scale. CONCLUSIONS: Findings suggest that the F-EPSI is a reliable and valid measure in Iranian non-clinical adolescents. The F-EPSI will enable researchers to examine a broad array of eating pathology symptoms in adolescents for whom Farsi is their official language. LEVEL OF EVIDENCE: Level V; Cross-sectional descriptive study.

In Vitro and In Vivo Antischistosomal Activity Profiling and Pharmacokinetics of Ozonide Carboxylic Acids.

Praziquantel, the only drug in clinical use for the treatment and control of schistosomiasis, is inactive against developing infections. Ozonides are synthetic peroxide derivatives inspired by the naturally occurring artemisinin and show particularly promising activity against juvenile schistosomes. We conducted an in-depth characterization of the in vitro and in vivo antischistosomal activity and pharmacokinetics of lead ozonide carboxylic acid OZ418 and four of its active analogs. In vitro, the ozonides featured rapid and consistent activity against schistosomula and adult schistosomes at double-digit micromolar EC50 values. Potency did not vary considerably between Schistosoma spp. The zwitterionic OZ740 and OZ772 were more active in vivo compared to their non-amphoteric carboxylic acids OZ418 and OZ748, despite their much lower systemic plasma exposure (AUC). The most active compound in vivo was ethyl ester OZ780, which was rapidly transformed to its parent zwitterion OZ740 and achieved ED50 values of 35 ± 2.4 and 29 ± 2.4 mg/kg against adult and juvenile Schistosoma mansoni, respectively. Ozonide carboxylic acids represent promising candidates for further optimization and development due to their good efficacy against both life stages together with their broad activity range against all relevant parasite species.

Early childhood growth in Daasanach pastoralists of Northern Kenya: Distinct patterns of faltering in linear growth and weight gain.

OBJECTIVES: Investigations of early childhood growth among small-scale populations are essential for understanding human life history variation and enhancing the ability to serve such communities through global public health initiatives. This study characterizes early childhood growth trajectories and identifies differences in growth patterns relative to international references among Daasanach semi-nomadic pastoralist children living in a hot, arid region of northern Kenya. METHODS: A large sample of height and weight measures were collected from children (N = 1756; total observations = 4508; age = 0-5 years) between 2018 and 2020. Daasanach growth was compared to international reference standards and Daasanach-specific centile growth curves and pseudo-velocity models were generated using generalized additive models for location scale and size. RESULTS: Compared to World Health Organization (WHO) reference, relatively few Daasanach children were stunted (14.3%), while a large proportion were underweight (38.5%) and wasted (53.6%). Additionally, Daasanach children had a distinctive pattern of growth, marked by an increase in linear growth velocity after 24 months of age and relatively high linear growth velocity throughout the rest of early childhood. CONCLUSIONS: These results identify a unique pattern of early childhood growth faltering among children in a small-scale population and may reflect a thermoregulatory adaptation to their hot, arid environment. As linear growth and weight gain remain important indicators of health, the results of this study provide insight into growth velocity variations. This study has important implications for global public health efforts to identify and address sources of early growth faltering and undernutrition in small-scale populations.

The enigma of weight: Figures, flux, and fitting in.

Purpose: In Western society, the measurement of weight is prioritized over a person's bodily experience. Hermeneutic philosopher Gadamer warned against the emphasis on measurement, rather than experience, in the medical sciences. An examination of the complexity of the experience of weight provides the opportunity to shift focus from quantifying the connection between health and weight to the experience of the person being weighed. Methods: This qualitative hermeneutic study aims to understand people's experiences of weight from the interviews of professionals (n = 7) and lay experts (n = 10). Interviews were analyzed using an interpretive hermeneutic method. Results: The interviews revealed that weight was experienced as a number imbued with meaning and bias, as a number that could be manipulated, and as a constant and anticipated bodily change. Weight change was expected and often unwelcomed, despite weight being a quality of the body that is always in flux. External measures of weight meant to monitor wellness and health inadvertently became an unhealthy fixation that prevented some participants from fully participating in life events and appreciating the stages their bodies were in. Conclusion: Weight change is a necessary condition of being human, and bodies are and will be constantly changing. To achieve health and harmony, one must fit together the acceptance of change and their bodily experience of weight. It is often the preoccupation with weight, not weight itself, that gets in the way of living.

The optics of weight: expert perspectives from the panopticon and synopticon.

Objective: That we all weigh something is a fact of life, yet the material reality of weight is refracted through multiple layers of surveillance revealing contradictions in experience and understanding, depending on one's vantage point. We explored the complexities of weight with the specific aim of furthering understanding of this multifaceted surveillance.Methods and Measures: We used hermeneutics, the philosophy and practice of interpretation, as the method of inquiry. Ten experts by experience and seven professional experts participated in interviews, which were audio- recorded, transcribed, and analyzed. Interpretations were developed through group discussions among the eight authors and reiterative writing.Results: Using the metaphor of optics, we demonstrate how the interplay of the panopticon (the few watching the many) and synopticon (the many watching the few) help us gain a deeper understanding of weight through "fitting in," being "captured by numbers," "dieting: the tyrannic tower," and "the male gaze."Conclusion: Monitoring and judging body weight have become so normative in Western society that "weight watching" practices are synonymous with good citizenship and moral character. This study offers insight about how weight is conceptualized in personal and professional contexts, with implications for body image, dieting, eating disorders, public health, and weight bias.

Corrigendum: Examining the Conceptual and Measurement Overlap of Body Dissatisfaction and Internalized Weight Stigma in Predominantly Female Samples: A Meta-Analysis and Measurement Refinement Study.

[This corrects the article DOI: 10.3389/fgwh.2022.877554.].

Examining the Conceptual and Measurement Overlap of Body Dissatisfaction and Internalized Weight Stigma in Predominantly Female Samples: A Meta-Analysis and Measurement Refinement Study.

Both body dissatisfaction and internalized weight stigma have been identified as risk factors for many negative health outcomes for women, including depression and eating disorders. In addition to these contributions, these concepts have been found to overlap to various degrees in existing literature. We conducted a systematic review and meta-analysis on articles published prior to February 2022 to demonstrate the conceptual and measurement overlap between body dissatisfaction and internalized weight stigma as currently quantified. We identified 48 studies examining the interrelation between body dissatisfaction and internalized weight stigma in predominantly female samples. Stronger correlations between these two constructs, some bordering on multicollinearity, were prevalent in community samples compared to clinical samples and with some but not all the commonly used measures in the body image and weight stigma fields. Body mass index (BMI) moderated these relations such that individuals with higher self-reported BMI were more likely to report lower correlations between the constructs. This concept proliferation, stronger for individuals with lower BMIs and community samples, necessitates the need change how we conceptualize and measure body dissatisfaction and internalized weight stigma. To this end, we conducted study two to refine existing measures and lessen the degree of measurement overlap between internalized weight stigma and body dissatisfaction, particularly in community samples of women. We aimed to clarify the boundaries between these two concepts, ensuring measurement error is better accounted for. Female university students completed existing measures of body satisfaction and internalized weight stigma, which were analyzed using an exploratory followed by a confirmatory factor analysis. In our attempts to modify two existing measures of internalized weight stigma and body dissatisfaction, the majority of the internalized weight stigma items were retained. In contrast, most of the body dissatisfaction items either cross-loaded onto both factors or loaded on to the internalized weight stigma factor despite being intended for the body dissatisfaction factor, suggesting that the measurement issues identified in recent prior research may be due not only to the way we conceptualize and quantify weight stigma, but also the ways in which we quantify body dissatisfaction, across the existing corpus of body dissatisfaction scales.

Nasal nitric oxide May not differentiate primary ciliary dyskinesia from certain primary immunodeficiencies.

The diagnosis of primary ciliary dyskinesia (PCD) is made through a combination of clinical features supported by a panel of diagnostic tests. Our cases highlight the similarities in the clinical presentation of patients with the specific immunodeficiency activated phosphatidylinositol 3-kinase delta syndrome 1 (or PIK3CD-related disorder) and PCD. We highlight the importance of repeating nasal nitric oxide testing when PCD has not been confirmed by genetic or ciliary electron micrograph analysis in the setting of an expanded suppurative lung disease differential that includes considerations for immunodeficiency as well as PCD.