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BackgroundAntibiotic self-medication is one of the common causes of antibiotic resistance of bacterial organisms. The COVID-19 pandemic introduced a new paradigm shift and significantly influenced healthcare behaviors, including an increase in antibiotic self-medication, which contributes to antibiotic resistance. This study was aimed at determining the prevalence of antibiotic self-medication and the possible associated factors during the peak of the COVID-19 pandemic among adult residents of Tema in Ghana from April to July 2021.MethodsUsing a cross-sectional design, 400 adults were randomly selected and surveyed using a researcher-assisted questionnaire. Data were analyzed with IBM® SPSS® Statistics Version 22.0, considering associations significant at a 95% confidence interval (p < 0.05).ResultsOf the 400 respondents, (76%) 304 had practiced antibiotic self-medication within the previous 12 months during the COVID-19 pandemic. Significant factors associated with antibiotic self-medication included gender, age, marital status, education, occupation, and National Health Insurance Scheme subscription. Convenience and avoiding long hospital queues were primary non-medical reasons for antibiotic self-medication, while previous successful experience, easy access to antibiotics, treating symptoms, prophylaxis, and fear of hospital infection were the medical reasons for antibiotic self-medication. Commonly self-administered antibiotics were azithromycin (34%), amoxicillin/clavulanic acid (22%), and metronidazole (16%) for perceived respiratory tract and gastrointestinal tract infections.ConclusionsThe high prevalence of antibiotic self-medication observed during the COVID-19 pandemic underscores the need for enhanced public education and stricter enforcement of regulations governing antibiotic sales. The non-medical and medical factors of convenience, avoiding long hospital queues, previous successful experience, easy access to antibiotics, treating symptoms, prophylaxis, and fear of hospital infection which motivated antibiotic self-medication practices require the implementation of antimicrobial stewardship interventions.

Background and aimsFirst-time mothers often need help with breastfeeding and may feel isolated and uncertain about whom they can turn to for help with breastfeeding challenges. Exploration of whether access to breastfeeding advice helps new mothers initiate and continue breastfeeding is necessary. This study investigated the associations between ease of access to breastfeeding advice for first-time mothers and breastfeeding initiation and duration.MethodsThis was a prospective, longitudinal cohort study of 3,006 women who delivered their first child in Pennsylvania, USA; with prenatal and postpartum interviews. At 1-month postpartum participants reported the extent to which they had access to "Someone to give you advice about breastfeeding if you needed it", via a 5-point scale ranging from "none of the time" to "all of the time".ResultsThere were 132 women (4.4%) who reported that they had access to someone to give them advice about breastfeeding "none of the time"; 697 (23.3%) reported access "a little of the time" or "some of the time"; and 2,167 (72.3%) reported access "most of the time" or "all of the time". While the majority of the new mothers were breastfeeding at 1-month postpartum (72.5%), less than half were still breastfeeding at 6-months postpartum (44.5%). The higher the level of access to advice about breastfeeding the more likely women were to establish breastfeeding by 1-month postpartum and to still be breastfeeding at 6-months.ConclusionsFor first-time mothers, ease of access to someone who can give them advice about breastfeeding facilitates breastfeeding establishment and continuation.

Chronic hepatitis negatively affects persons living with HIV. While varying in their transmission efficiency, HIV, HBV, and HCV have shared routes of transmission. Available data suggest widely variable rates of HBV and HCV infections in HIV-infected populations across sub-Saharan Africa. With prolonged survival rates due to increased accessibility to antiretroviral drugs, HBV and HCV have the potential to complicate the prognosis of HIV co-infected patients by contributing significantly to continued morbidity and mortality. The study sought to determine the seroprevalence of HIV/HBV and HIV/HCV co-infections among HIV patients on antiretroviral therapy and to evaluate the effect of HIV/HBV and HIV/HCV co-infections on the immunologic and virologic responses of patients. A cross-sectional study in which samples were taken from 500 people living with HIV and attending ART clinic at the Fevers unit of the Korle Bu Teaching Hospital and tested for Hepatitis B Surface Antigen (HBsAg) and Hepatitis C virus antibody (HCV). CD4 cell counts and HIV-1 RNA levels were estimated as well. Data generated were analysed using IBM SPSS version 22. The seroprevalence of HIV/HBV and HIV/HCV co-infections among people living with HIV was 8.4% and 0.2% respectively. HIV/HBV coinfection included 15/42 (35.7%) males and 27/42 (64.3%) females out of which the majority (97.6%) were in the 21-60 years old bracket. HIV/HBV and HIV/HCV co-infections have varied effects on the immunological and virological response of HIV patients on ART. The mean CD cell count was 361.0 ± 284.0 in HIV/HBV co-infected patients and 473.8 ± 326.7 in HIV mono-infected patients. The mean HIV-1 RNA level was not significantly different (X2 [df] = .057 [1]; P = .811) among HIV/HBV co-infected patients (Log102.9±2.0 copies/mL), compared to that of HIV mono-infected patients (Log102.8±2.1 copies/mL) although HIV mono-infected patients had lower viral load levels. One-third (14/42) of HIV/HBV co-infected patients had virologic failure and the only HIV/HCV co-infected patient showed viral suppression. 336/500 (67.2%) patients had HIV-1 viral suppression (females [66.1%]; males [33.9%]) while 164/500 (32.8%) had virologic failure (females [67.7%]; males [32.3%]). The mean CD4 count of patients with viral suppression and patients with virologic failure was 541.2 cells/μL (95% CI 508.5-573.8) and 309.9 cell/μL (95% CI 261.9-357.9) respectively.The study concludes that, HIV/HBV and HIV/HCV coinfections do not significantly affect the immunologic and virologic responses of patients who have initiated highly active antiretroviral therapy, and treatment outcomes were better in females than in males. There was no HBV/HCV co-infection among patients.

Mixed economies provide a unique context for testing theories of fertility change. Because they have a stake in two traditions, mixed-economy households balance the demands of both a labor-based subsistence economy, which benefits from a large family, and a wage-labor economy, which benefits from reduced fertility. Additionally, household size changes over the course of its life-cycle and shapes available economic opportunities. Here we argue that in mixed economies, fertility may reflect opportunities for livelihood diversity rather than simply responding to the restricted socioeconomic benefits of small families. While low fertility may in some cases have an economic benefit, low fertility can also limit the livelihood diversity of a household which is a key strategy for long-term economic success. We test this prediction with longitudinal data from a Maya community undergoing both a sustained decline in fertility and rapid integration into the market economy. Using household-level fertility, number of adults, and livelihood diversity at two time points, we find that household size is positively related to livelihood diversity, which in turn is positively related to household income per-capita. However, household size also has a negative association with income per capita. The results reflect a balancing act whereby households attempt to maximize the economic diversity with as few members as possible. Broadly, these results suggest that theories of fertility decline must account for how households pool resources and diversify economic activities in the face of increasing market integration, treating fertility as both an outcome and an input into economic and reproductive decision-making.

[This corrects the article DOI: 10.1371/journal.pone.0056823.].

BACKGROUND:Falls are a serious and common problem among older adults. Low-tech, inexpensive, community-based fall prevention programs have been shown to be both effective and cost effective, however, these programs are not well-integrated into clinical practice. RESEARCH DESIGN:We surveyed primary care providers at a convenience sample of two accountable care organizations in Massachusetts to assess their beliefs, attitudes, knowledge, and practices relative to fall risk assessment and intervention for their older patients. RESULTS:Response rate was 71%. Providers' beliefs about the efficacy of fall risk assessment and intervention were mixed. Eighty-seven percent believed that they could be effective in reducing fall risk among their older adult patients. Ninety-six percent believed that all older adults should be assessed for fall risk; and, 85% believed that this assessment would identify fall risk factors that could be modified. Nonetheless, only 52% believed that they had the expertise to conduct fall risk assessment and only 68% believed that assessing older adult patients for fall risk was the prevailing standard of practice among their peer providers. Although most providers believed it likely that an evidence-based program could reduce fall risk among their patients, only 14% were aware of the Centers for Disease Control and Prevention's fall risk assessment algorithm (STEADI Toolkit), and only 15% were familiar with Matter of Balance, the most widely disseminated community fall risk prevention program in Massachusetts. DISCUSSION:New strategies that more directly target providers are needed to accelerate integration of fall risk assessment and intervention into primary care practice.

A novel FLNC c.5161delG (p.Gly1722ValfsTer61) mutation was identified in two members of a French family affected by distal myopathy and in one healthy relative. This FLNC c.5161delG mutation is one nucleotide away from a previously reported FLNC mutation (c.5160delC) that was identified in patients and in asymptomatic carriers of three Bulgarian families with distal muscular dystrophy, indicating a low penetrance of the FLNC frameshift mutations. Given these similarities, we believe that the two FLNC mutations alone can be causative of distal myopathy without full penetrance. Moreover, comparative analysis of the clinical manifestations indicates that patients of the French family show an earlier onset and a complete segregation of the disease. As a possible explanation of this, the two French patients also carry a OBSCN c.13330C>T (p.Arg4444Trp) mutation. The p.Arg4444Trp variant is localized within the OBSCN Ig59 domain that, together with Ig58, binds to the ZIg9/ZIg10 domains of titin at Z-disks. Structural and functional studies indicate that this OBSCN p.Arg4444Trp mutation decreases titin binding by ~15-fold. On this line, we suggest that the combination of the OBSCN p.Arg4444Trp variant and of the FLNC c.5161delG mutation, can cooperatively affect myofibril stability and increase the penetrance of muscular dystrophy in the French family.

Material wealth is a key factor shaping human development and well-being. Every year, hundreds of studies in social science and policy fields assess material wealth in low- and middle-income countries assuming that there is a single dimension by which households can move from poverty to prosperity. However, a one-dimensional model may miss important kinds of prosperity, particularly in countries where traditional subsistence-based livelihoods coexist with modern cash economies. Using multiple correspondence analysis to analyze representative household data from six countries-Nepal, Bangladesh, Ethiopia, Kenya, Tanzania and Guatemala-across three world regions, we identify a number of independent dimension of wealth, each with a clear link to locally relevant pathways to success in cash and agricultural economies. In all cases, the first dimension identified by this approach replicates standard one-dimensional estimates and captures success in cash economies. The novel dimensions we identify reflect success in different agricultural sectors and are independently associated with key benchmarks of food security and human growth, such as adult body mass index and child height. The multidimensional models of wealth we describe here provide new opportunities for examining the causes and consequences of wealth inequality that go beyond success in cash economies, for tracing the emergence of hybrid pathways to prosperity, and for assessing how these different pathways to economic success carry different health risks and social opportunities.

What are the long-term effects of childhood experience on brain development? Research with animals shows that the quality of environmental stimulation and parental nurturance both play important roles in shaping lifelong brain structure and function. Human research has so far been limited to the effects of abnormal experience and pathological development. Using a unique longitudinal dataset of in-home measures of childhood experience at ages 4 and 8 and MRI acquired in late adolescence, we were able to relate normal variation in childhood experience to later life cortical thickness. Environmental stimulation at age 4 predicted cortical thickness in a set of automatically derived regions in temporal and prefrontal cortex. In contrast, age 8 experience was not predictive. Parental nurturance was not predictive at either age. This work reveals an association between childhood experience and later brain structure that is specific relative to aspects of experience, regions of brain, and timing.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder with no effective treatment and commonly diagnosed only on late stages. Amyloid-β (Aβ) accumulation and exacerbated tau phosphorylation are molecular hallmarks of AD implicated in cognitive deficits and synaptic and neuronal loss. The Aβ and tau connection is beginning to be elucidated and attributed to interaction with different components of common signaling pathways. Recent evidences suggest that non-fibrillary Aβ forms bind to membrane receptors and modulate GSK-3β activity, which in turn phosphorylates the microtubule-associated tau protein leading to axonal disruption and toxic accumulation. Available AD animal models, ranging from rodent to invertebrates, significantly contributed to our current knowledge, but complementary platforms for mechanistic and candidate drug screenings remain critical for the identification of early stage biomarkers and potential disease-modifying therapies. Here we show that Aβ1-42 injection in the hindbrain ventricle of 24 hpf zebrafish embryos results in specific cognitive deficits and increased tau phosphorylation in GSK-3β target residues at 5dpf larvae. These effects are reversed by lithium incubation and not accompanied by apoptotic markers. We believe this may represent a straightforward platform useful to identification of cellular and molecular mechanisms of early stage AD-like symptoms and the effects of neuroactive molecules in pharmacological screenings.

Tibial muscular dystrophy (TMD) is a late onset, autosomal dominant distal myopathy that results from mutations in the two last domains of titin. The cascade of molecular events leading from the causative Titin mutations to the preterm death of muscle cells in TMD is largely unknown. In this study we examined the mRNA and protein changes associated with the myopathology of TMD. To identify these components we performed gene expression profiling using muscle biopsies from TMD patients and healthy controls. The profiling results were confirmed through quantitative real-time PCR and protein level analysis. One of the pathways identified was activation of endoplasmic reticulum (ER) stress response. ER stress activates the unfolded protein response (UPR) pathway. UPR activation was supported by elevation of the marker genes HSPA5, ERN1 and the UPR specific XBP1 splice form. However, UPR activation appears to be insufficient to correct the protein abnormalities causing its activation because degenerative TMD muscle fibres show an increase in ubiquitinated protein inclusions. Abnormalities of VCP-associated degradation pathways are also suggested by the presence of proteolytic VCP fragments in western blotting, and VCP's accumulation within rimmed vacuoles in TMD muscle fibres together with p62 and LC3B positive autophagosomes. Thus, pathways controlling turnover and degradation, including autophagy, are distorted and lead to degeneration and loss of muscle fibres.

Research in animals has shown that early life experience, particularly parenting behaviors, influences later-life stress reactivity. Despite the tremendous relevance of this finding to human development and brain function, it has not been tested prospectively in humans. In this study two aspects of parenting were measured at age 4 in a sample of healthy, low socioeconomic status, African American children, and stress reactivity was measured in the same children 11-14 years later using a modified version of the Trier Social Stress Test (n = 55). Salivary cortisol was measured before, during and after the stressor and data were analyzed using piecewise hierarchical linear modeling. Parental responsivity, independent of the use of physical discipline, was positively related to cortisol reactivity. Effects were independent of subjective appraisals of the stressor and were also independent of other environmental risk factors and current psychosocial functioning. Therefore this study demonstrates in a novel and precise fashion that early childhood parental responsivity prospectively and independently predicts stress reactivity in adolescence.

Head and neck squamous cell carcinoma (HNSCC) is a frequently fatal heterogeneous disease. Beyond the role of human papilloma virus (HPV), no validated molecular characterization of the disease has been established. Using an integrated genomic analysis and validation methodology we confirm four molecular classes of HNSCC (basal, mesenchymal, atypical, and classical) consistent with signatures established for squamous carcinoma of the lung, including deregulation of the KEAP1/NFE2L2 oxidative stress pathway, differential utilization of the lineage markers SOX2 and TP63, and preference for the oncogenes PIK3CA and EGFR. For potential clinical use the signatures are complimentary to classification by HPV infection status as well as the putative high risk marker CCND1 copy number gain. A molecular etiology for the subtypes is suggested by statistically significant chromosomal gains and losses and differential cell of origin expression patterns. Model systems representative of each of the four subtypes are also presented.

A novel FLNC c.5161delG (p.Gly1722ValfsTer61) mutation was identified in two members of a French family affected by distal myopathy and in one healthy relative. This FLNC c.5161delG mutation is one nucleotide away from a previously reported FLNC mutation (c.5160delC) that was identified in patients and in asymptomatic carriers of three Bulgarian families with distal muscular dystrophy, indicating a low penetrance of the FLNC frameshift mutations. Given these similarities, we believe that the two FLNC mutations alone can be causative of distal myopathy without full penetrance. Moreover, comparative analysis of the clinical manifestations indicates that patients of the French family show an earlier onset and a complete segregation of the disease. As a possible explanation of this, the two French patients also carry a OBSCN c.13330C>T (p.Arg4444Trp) mutation. The p.Arg4444Trp variant is localized within the OBSCN Ig59 domain that, together with Ig58, binds to the ZIg9/ZIg10 domains of titin at Z-disks. Structural and functional studies indicate that this OBSCN p.Arg4444Trp mutation decreases titin binding by ~15-fold. On this line, we suggest that the combination of the OBSCN p.Arg4444Trp variant and of the FLNC c.5161delG mutation, can cooperatively affect myofibril stability and increase the penetrance of muscular dystrophy in the French family.

Tibial muscular dystrophy (TMD) is a late onset, autosomal dominant distal myopathy that results from mutations in the two last domains of titin. The cascade of molecular events leading from the causative Titin mutations to the preterm death of muscle cells in TMD is largely unknown. In this study we examined the mRNA and protein changes associated with the myopathology of TMD. To identify these components we performed gene expression profiling using muscle biopsies from TMD patients and healthy controls. The profiling results were confirmed through quantitative real-time PCR and protein level analysis. One of the pathways identified was activation of endoplasmic reticulum (ER) stress response. ER stress activates the unfolded protein response (UPR) pathway. UPR activation was supported by elevation of the marker genes HSPA5, ERN1 and the UPR specific XBP1 splice form. However, UPR activation appears to be insufficient to correct the protein abnormalities causing its activation because degenerative TMD muscle fibres show an increase in ubiquitinated protein inclusions. Abnormalities of VCP-associated degradation pathways are also suggested by the presence of proteolytic VCP fragments in western blotting, and VCP's accumulation within rimmed vacuoles in TMD muscle fibres together with p62 and LC3B positive autophagosomes. Thus, pathways controlling turnover and degradation, including autophagy, are distorted and lead to degeneration and loss of muscle fibres.