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Cephalexin (CEX) is an antibiotic commonly used to treat bacterial infections in humans and animals. However, it is also a micropollutant. Thus, this study evaluated the degradation of CEX using ultraviolet irradiation (UV-C) and analyzed the by-products as well as their residual antimicrobial activity. A reactor with a mercury vapor lamp was used for the degradation. Irradiated CEX solutions were collected over a period of 4 hours and analyzed using high-performance liquid chromatography coupled with mass spectrometry. For the residual antimicrobial activity the susceptibility test was performed using Staphylococcus aureus and Escherichia coli microorganisms by broth microdilution. It was found that CEX, after treatment, generated a metabolite with a mass of 150 m/z in 15 min. A four- and eightfold increase in the minimum inhibitory concentration of the drug against S. aureus and E. coli could be observed, respectively, after 20 min. Therefore, this treatment proved to be effective in the degradation of CEX, being able to degrade 81% of the initial molecule of the drug in 20 min. Furthermore, the antimicrobial activity of the CEX solution decreased as the irradiation time increased, indicating loss of antimicrobial function of the initial CEX molecule and the resulting by-products. HIGHLIGHTS Degradation of micropollutant cephalexin.; Metabolites analyzed and residual antimicrobial activity.; Water treatment with irradiation.; Antimicrobial activity using susceptibility test.;

Abstract While classical cannabinoid receptors are known to crucially impact on myocardial infarction (MI) repair, a function of the cannabinoid-sensitive receptor GPR55 herein is poorly understood. We investigated the role of GPR55 in cardiac physiology and post-MI inflammation and remodelling. Global GPR55−/− and wildtype (WT) mice were basally characterized or assigned to 1, 3 or 28 days permanent MI and subsequently analysed via pro-inflammatory and pro-hypertrophic parameters. GPR55−/− deficiency was basally associated with bradycardia, increased diastolic LV volume and sarcomere length and a subtle inflammatory phenotype. While infarct size and myeloid cell infiltration were unaffected by GPR55 depletion, acute cardiac chemokine production was prolonged post-MI. Concurrently, GPR55−/− hearts exhibited a premature expansion of pro-reparative and phagocytic macrophages paralleled by early up-regulation of extracellular matrix (ECM) factors 3 days post-MI, which could be mimicked by sole haematopoietic GPR55 depletion. Moreover, global GPR55 deficiency mitigated MI-induced foetal gene re-programming and cardiomyocyte hypertrophy, culminating in aggravated LV dilatation and infarct expansion. GPR55 regulates cardiac homeostasis and ischaemia responses by maintaining adequate LV filling and modulating three crucial processes post-MI: wound healing kinetics, cardiomyocyte hypertrophy and maladaptive remodelling.

Background: Posterior urethral valves (PUVs) and ureteropelvic junction obstruction (UPJO) are congenital obstructive uropathies that may impair kidney development. Objective: To identify genetic variants associated with kidney injury in patients with obstructive uropathy. Design, setting, and participants: We included 487 patients born in 1981 or later who underwent pyeloplasty or valve resection before 18 yr of age in the discovery phase, 102 PUV patients in a first replication phase, and 102 in a second replication phase. Outcome measurements and statistical analysis: Signs of kidney injury were defined as dialysis, nephrectomy, kidney transplantation, estimated glomerular filtration rate (eGFR) 600 000 single-nucleotide polymorphisms (SNPs) in the discovery sample comparing patients with and without signs of kidney injury within 5 yr after surgery. We performed stratified analyses for PUV and UPJO and Kaplan-Meier and Cox regression analyses in the discovery and two replication samples for the associated SNPs, and RNA and protein expression analyses for the associated gene in fetal tissues. Results and limitations: Despite the small and nonhomogeneous sample, we observed suggestive associations for six SNPs in three loci, of which rs6874819 in the CDH12 gene was the most clear (p = 7.5 × 10–7). This SNP also seemed to be associated with time to kidney injury in the PUV discovery and replication samples. RNA expression analyses showed clear CDH12 expression in fetal kidneys, which was confirmed by protein immunolocalization. Conclusions: This study identified CDH12 as a candidate gene for kidney injury in PUV. Patient summary: We found that variants of the CDH12 gene increase the risk of kidney injury in patients with extra flaps of tissue in the urethra (posterior urethral valves). This is the first report on this gene in this context. Our study provides interesting new information about the pathways involved and important leads for further research for this condition.

Previous studies have shown that the CD40L-CD40 signaling axis plays a role in atherosclerosis. Here the authors investigate the cell-specific functions of the most relevant CD40L-expressing cell types in atherosclerosis. Deficiency of T cell-derived CD40L reduces and stabilizes plaques through impaired Th1 polarization while platelet-derived CD40L ameliorates atherothrombosis.

Abstract Background Many evidence-based interventions (EBIs) found to be effective in research studies often fail to translate into meaningful patient outcomes in practice. The purpose of this study was to identify facilitators and barriers that affect the implementation of three EBIs to improve colorectal cancer (CRC) screening in an urban federally qualified health center (FQHC) and offer actionable recommendations to improve future implementation efforts. Methods We conducted 16 semi-structured interviews guided by the Consolidation Framework for Implementation Research (CFIR) to describe diverse stakeholders’ implementation experience. The interviews were conducted in the participant’s clinic, audio-taped, and professionally transcribed for analysis. Results We used the five CFIR domains and 39 constructs and subconstructs as a coding template to conduct a template analysis. Based on experiences with the implementation of three EBIs, stakeholders described barriers and facilitators related to the intervention characteristics, outer setting, and inner setting. Implementation barriers included (1) perceived burden and provider fatigue with EHR (Electronic Health Record) provider reminders, (2) unreliable and ineffectual EHR provider reminders, (3) challenges to providing health care services to diverse patient populations, (4) lack of awareness about CRC screening among patients, (5) absence of CRC screening goals, (6) poor communication on goals and performance, and (7) absence of printed materials for frontline implementers to educate patients. Implementation facilitators included (1) quarterly provider assessment and feedback reports provided real-time data to motivate change, (2) integration with workflow processes, (3) pressure from funding requirement to report quality measures, (4) peer pressure to achieve high performance, and (5) a culture of teamwork and patient-centered mentality. Conclusions The CFIR can be used to conduct a post-implementation formative evaluation to identify barriers and facilitators that influenced the implementation. Furthermore, the CFIR can provide a template to organize research data and synthesize findings. With its clear terminology and meta-theoretical framework, the CFIR has the potential to promote knowledge-building for implementation. By identifying the contextual determinants, we can then determine implementation strategies to facilitate adoption and move EBIs to daily practice.

A large fraction of ice sheet discharge enters the ocean subsurface from underneath large floating ice-tongues. Here the authors show that associated nutrient export may be governed by shelf circulation and, especially for Fe, particle-dissolved phase exchanges, which is largely independent from freshwater Fe content.

Neuropsychiatric symptoms (NPSs) are hallmarks of Alzheimer's disease (AD), causing substantial distress for both people with dementia and their caregivers, and contributing to early institutionalization. They are among the earliest signs and symptoms of neurocognitive disorders and incipient cognitive decline, yet are under-recognized and often challenging to treat. With this in mind, the Alzheimer's Association convened a Research Roundtable in May 2016, bringing together experts from academia, industry, and regulatory agencies to discuss the latest understanding of NPSs and review the development of therapeutics and biomarkers of NPSs in AD. This review will explore the neurobiology of NPSs in AD and specific symptoms common in AD such as psychosis, agitation, apathy, depression, and sleep disturbances. In addition, clinical trial designs for NPSs in AD and regulatory considerations will be discussed.

Angioedema is a relatively rare but potentially life-threatening adverse reaction to angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As with hereditary forms of angioedema (HAE), this adverse reaction is mediated by bradykinin. Research suggests that ACEi/ARB-induced angioedema has a multifactorial etiology. In addition, recent case reports suggest that some ACEi/ARB-induced angioedema patients may carry pathogenic HAE variants. The aim of the present study was to investigate the possible association between ACEi/ARB-induced angioedema and HAE genes via systematic molecular genetic screening in a large cohort of ACEi/ARB-induced angioedema cases. Targeted re-sequencing of five HAE-associated genes (SERPING1, F12, PLG, ANGPT1, and KNG1) was performed in 212 ACEi/ARB-induced angioedema patients recruited in Germany/Austria, Sweden, and Denmark, and in 352 controls from a German cohort. Among patients, none of the identified variants represented a known pathogenic variant for HAE. Moreover, no significant association with ACEi/ARB-induced angioedema was found for any of the identified common [minor allele frequency (MAF) >5%] or rare (MAF < 5%) variants. However, several non-significant trends suggestive of possible protective effects were observed. The lowest p-value for an individual variant was found in PLG (rs4252129, p.R523W, p = 0.057, p.adjust > 0.999, Fisher’s exact test). Variant p.R523W was found exclusively in controls and has previously been associated with decreased levels of plasminogen, a precursor of plasmin which is part of a pathway directly involved in bradykinin production. In addition, rare, potentially functional variants (MAF < 5%, Phred-scaled combined annotation dependent depletion score >10) showed a nominally significant enrichment in controls both: 1) across all five genes; and 2) in the F12 gene alone. However, these results did not withstand correction for multiple testing. In conclusion, our results suggest that HAE-associated mutations are, at best, a rare cause of ACEi/ARB-induced angioedema. Furthermore, we were unable to identify a significant association between ACEi/ARB-induced angioedema and other variants in the investigated genes. Further studies with larger sample sizes are warranted to draw more definite conclusions concerning variants with limited effect sizes, including protective variants.

Immunocompromised persons are at an increased risk for a severe SARS-CoV-2 infection and their safety behaviors may influence their social participation. Vaccinated persons have a lower incidence of infection and severe disease when infected compared to non-vaccinated persons. Therefore, their behavior may change and their social participation may increase after a complete vaccination. The aim of this study was to explore social participation of immunocompromised persons before and after complete COVID-19 vaccination. Between March and September 2021, 274 immunocompromised participants were recruited. Survey data were collected at baseline and follow-up from 194 participants including the Index for the Assessment of Health Impairments [IMET], Patient Health Questionnaire-4 [PHQ-4], subjective health status and quality of life. At baseline, participants were not yet completely vaccinated. Complete vaccination was achieved prior to the follow-up questionnaire. IMET scores decreased significantly at follow-up, indicating a higher social participation after complete vaccination. PHQ-4, subjective health status and quality of life did not differ between baseline and follow-up. There were no significant differences across sociodemographic factors. Significant PHQ-4 differences were observed regarding the population size of the participants' home community. Social participation of immunocompromised persons in our study increased after COVID-19 vaccination. Therefore, social participation should be explored further, especially with regards to the impact of vaccination on groups with a high health risk.

Resumo O objetivo deste trabalho foi avaliar o efeito do retardo de resfriamento de morangos ‘San Andreas’ sobre a manutenção da qualidade dos frutos, bem como sobre os compostos fenólicos totais (CFT) e a atividade antioxidante total (AAT), após o armazenamento refrigerado. Os tratamentos consistiram no resfriamento nos tempos de 0 (controle, resfriamento imediato), 3, 6, 9 e 12 horas (em temperatura ambiente), após a colheita. Após a aplicação dos tratamentos, os frutos foram armazenados sob refrigeração (4 ± 0,5 °C e 92 ± 2% de UR), durante 5, 6, 7 e 8 dias, seguidos por mais 2 dias de exposição, em condição ambiente (20 ± 2 °C e 65 ± 5% de UR). Os morangos com o maior retardo de resfriamento apresentaram maior perda de massa fresca, além de menor firmeza, a partir de 7 dias de armazenamento. De maneira geral, os menores valores de incidência e severidade de podridões foram observados nos frutos do tratamento com resfriamento imediato após a colheita, quando armazenados por 7 e 8 dias, seguidos por mais 2 dias em condições ambiente. O retardo do resfriamento por até 6 horas não causa aumento de podridões até 5 dias de armazenamento refrigerado, mais 2 dias em condições ambiente. Os valores de CFT e AAT apresentaram aumento com o retardo de até 6 horas do resfriamento dos frutos, aos 6 dias de armazenamento seguidos por mais 2 dias em condições ambiente, e a AAT aumentou com o aumento do atraso no resfriamento dos frutos em até 12 horas, após 8 dias de armazenamento mais 2 dias em condições ambiente. O atraso no resfriamento causa perdas na qualidade dos frutos de morango, de acordo com o tempo de armazenamento.

– The objective of this work was to evaluate the effects of pre-harvest application on ‘Baigent’ apple trees cultivated under black anti-hail nets with aminoethoxyvinylglycine (AVG), in a single or split dose, combined or not with ethephon, on the quality, the antioxidant activity, and the content of phenolic compounds of the fruits after storage in controlled atmosphere (CA). The pre-harvest applications of AVG alone, both at a dose of 0.125 g L−1, as well as in split dose and at a dose of 0.0625 g L−1, reduced the rate of ethylene production, showed less yellowing fruits and a lower incidence of cracks, maintaining high flesh firmness, texture attributes, and fruit acidity, without causing negative effects on the incidence of mealiness and decay. The pre-harvest applications of AVG at a dose of 0.125 g L−1 and in split dose combined with ethephon also contributed to the reduction of the ethylene production rate and yellowing, showed high flesh firmness and texture, however, it showed a high incidence of decay and cracking when ethephon was combined with AVG at a dose of 0.125 g L−1. In the skin, application of AVG only at a dose of 0.125 g L−1 reduced the total phenolic compounds values, however, total antioxidant activity was reduced with any form of AVG application. In the flesh, there was no effect of pre-harvest application of AVG. Regardless of the dose and form of application, AVG reduced the contents of chlorogenic acid, phloridizin, and epicatechin in the skin of fruits harvested at commercial harvest.

Anthropologists develop long-term engagements with communities, animals, and the ecosystems they all share. This approach can provide important context that is necessary for One Health research, which may otherwise overlook the perspectives and lived experiences of community members. This paper presents two case studies that illustrate the importance of leveraging long-term, holistic, engagements with communities in moving the One Health concept forward. The first illustrates the complexity of understanding the health of people and animals within the context of environmental change in South India. The second provides insights into how the conservation of endangered species requires considering the entanglements of people, domestic animals, and the landscapes they share with wildlife in Madagascar. We demonstrate the value of integrating anthropological perspectives within interdisciplinary One Health research and interventions to better understand the complexity of systems.

Objectives To investigate whether citizens’ adherence to health-protective non-pharmaceutical interventions (NPIs) during the COVID-19 pandemic is predicted by identity leadership, wherein leaders are perceived to create a sense of shared national identity.Design Observational two-wave study. Hypotheses testing was conducted with structural equation modelling.Setting Data collection during the COVID-19 pandemic in China, Germany, Israel and the USA in April/May 2020 and four weeks later.Participants Adults in China (n=548, 66.6% women), Germany (n=182, 78% women), Israel (n=198, 51.0% women) and the USA (n=108, 58.3% women).Measures Identity leadership (assessed by the four-item Identity Leadership Inventory Short-Form) at Time 1, perceived shared national identification (PSNI; assessed with four items) and adherence to health-protective NPIs (assessed with 10 items that describe different health-protective interventions; for example, wearing face masks) at Time 2.Results Identity leadership was positively associated with PSNI (95% CI 0.11 to 0.30, p

Which different feelings and reactions do different family members show if an adult family member who has long been perceived as heterosexual discloses their sexual identity as lesbian, gay, or bisexual (LGB)? Previous studies have investigated reactions of spouses and sometimes children in the United States. This article describes the findings of qualitative interviews and a German-language quantitative survey (N = 188) in which family members were asked about their emotions, experiences during the coming out process, and their use of support options. The samples were recruited via different LGB+ online forums and organizations in Germany, Austria, and Switzerland (age M = 44.08). The results demonstrate that a coming out after years of a heterosexual biography and family life affects adults’ parents and siblings in addition to spouses and children. Siblings were perceived as a supportive group of family members showing calm and mostly positive reactions. Parents mainly reported surprise but also showed on the one hand interest in supporting their children in the coming out process; on the other hand, we find also evidence for negative reactions including rejecting behavior. Children’s coping and well-being depended on the time that had passed since the coming out and their age at the time of the coming out. Spouses felt shocked, angry, and the ground was pulled from under their feet. Comparing the perspectives of these groups of family members, differences between them, and their specific needs are discussed. Practical implications are derived from the support options mentioned, and range from information from books, the internet to professional advice. Spouses report the need of diverse support options, whereas other family members ask friends and other family members for support. Forums, counseling and the possibility to exchange were perceived as a support but were more accessible for women than for men. They provide the chance for a communicative exchange before the stress becomes too strong.

Introduction: Psychoactive substance use among adolescents influences behavioral and cognitive processes and is associated with adolescents' performance in school. We therefore sought to investigate association of PASU with adolescents' school performance. Methods: We employed quantitative methods of data collection and analysis. To test the substance use-school performance association, we specified and estimated fixed effects hierarchical linear models (HLMs). We nested the data in their respective four regions of Uganda. Results: Model estimates show that only alcohol use had significant t-values in association with school performance (b = 1.15, SE = 0.32, t = 3.83, p = 0.029 for beer use; b = 0.82, SE = 0.18, t = 4.49, p < 0.001 for wines; and b = 0.89, SE = 0.19, t = 4.53, p< 0.001 for spirits). Conclusions: Alcohol use significantly contributed to the model estimating association between PASU and adolescents' school performance.

Abstract Introduction The aim of this study was to investigate the effects of clinical information on the accuracy, timeliness, reporting confidence and clinical relevance of the radiology report. Methods A systematic review of studies that investigated a link between primary communication of clinical information to the radiologist and the resultant report was conducted. Relevant studies were identified by a comprehensive search of electronic databases (PubMed, Scopus and EMBASE). Studies were screened using pre‐defined criteria. Methodological quality was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Quasi‐Experimental Studies. Synthesis of findings was narrative. Results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Results There were 21 studies which met the inclusion criteria, of which 20 were included in our review following quality assessment. Sixteen studies investigated the effect of clinical information on reporting accuracy, three studies investigated the effect of clinical information on reporting confidence, three studies explored the impact of clinical information on clinical relevance, and two studies investigated the impact of clinical information on reporting timeliness. Some studies explored multiple outcomes. Studies concluded that clinical information improved interpretation accuracy, clinical relevance and reporting confidence; however, reporting time was not substantially affected by the addition of clinical information. Conclusion The findings of this review suggest clinical information has a positive impact on the radiology report. It is in the best interests of radiologists to communicate the importance of clinical information to reporting via the creation of criteria standards to guide the requesting practices of medical imaging referrers. Further work is recommended to establish these criteria standards.

Abstract Introduction To assess computed tomography kidneys, ureters and bladder (CTKUB) scan extent protocol compliance and associated doses in the Emergency Department (ED) of an Australian tertiary hospital. Methods A retrospective clinical audit of 150 consecutive ED CTKUB cases was completed. For each patient, scan extent compliance at the superior (kidneys) and inferior (pubic symphysis) borders, in reference to the protocol was recorded. Compliance and non‐compliance (over‐/under‐scanning) was identified, described (superior/inferior), quantified (via IMPAX measurements) and recorded via a purpose‐built audit tool. In addition, a PBU40 phantom was scanned to assess the percentage of dose (DLP) increase per centimetre of over‐scanning to contextualise results. Results A notable non‐compliance with department protocol was noted. Eight cases (5.3%) demonstrated overall CT scan extent compliance. The remaining 142 cases (94.7%) demonstrated some form of non‐compliance; superiorly, inferiorly or both. Analysing the 150 superior and 150 inferior data points independently, the most common non‐compliance was over‐scanning at the kidneys by 4 cm to5 cm (19 cases, ~10% extra DLP) beyond tolerance and over‐scanning inferiorly at the pubic symphysis by 1 cm to 2 cm (29 cases, ~6.4% extra DLP). Estimated dose increases of up to 35% to 45% were found when clinical audit results were simulated using a PBU40. Conclusions Over‐scanning is a predominant occurrence in CTKUB scans in this department. Reasons for over‐scanning weren't investigated. It's anticipated this audit will lead to greater awareness of scan extent compliance and dose ramifications of non‐compliance. The usage of more easily identified anatomical landmarks and a follow‐up audit is suggested.

Background and purpose — There is ongoing debate as to whether commercial funding influences reporting of medical studies. We asked: Is there a difference in reported tones between abstracts, introductions, and discussions of orthopedic journal studies that were commercially funded and those that were not commercially funded? Methods — We conducted a systematic PubMed search to identify commercially funded studies published in 20 orthopedic journals between January 1, 2000 and December 1, 2019. We identified commercial funding of studies by including in our search the names of 10 medical device companies with the largest revenue in 2019. Commercial funding was designated when either the study or 1 or more of the authors received funding from a medical device company directly related to the content of the study. We matched 138 commercially funded articles 1 to 1 with 138 non-commercially funded articles with the same study design, published in the same journal, within a time range of 5 years. The IBM Watson Tone Analyzer was used to determine emotional tones (anger, fear, joy, and sadness) and language style (analytical, confident, and tentative). Results — For abstract and introduction sections, we found no differences in reported tones between commercially funded and non-commercially funded studies. Fear tones (non-commercially funded studies 5.1%, commercially funded studies 0.7%, p = 0.04), and analytical tones (non-commercially funded studies 95%, commercially funded studies 88%, p = 0.03) were more common in discussions of studies that were not commercially funded. Interpretation — Commercially funded studies have comparable tones to non-commercially funded studies in the abstract and introduction. In contrast, the discussion of non-commercially funded studies demonstrated more fear and analytical tones, suggesting them to be more tentative, accepting of uncertainty, and dispassionate. As text analysis tools become more sophisticated and mainstream, it might help to discern commercial bias in scientific reports.

Abstract Background A barrier to the uptake of robotic-assisted surgery (RAS) continues to be the perceived high costs. A lack of detailed costing information has made it difficult for public hospitals in particular to determine whether use of the technology is justified. This study aims to provide a detailed description of the patient episode costs and the contribution of RAS specific costs for multiple specialties in the public sector. Methods A retrospective descriptive costing review of all RAS cases undertaken at a large public tertiary referral hospital in Sydney, Australia from August 2016 to December 2018 was completed. This included RAS cases within benign gynaecology, cardiothoracic, colorectal and urology, with the total costs described utilizing various inpatient costing data, and RAS specific implementation, maintenance and consumable costs. Results Of 211 RAS patients, substantial variation was found between specialties with the overall median cost per patient being $19,269 (Interquartile range (IQR): $15,445 to $32,199). The RAS specific costs were $8828 (46%) made up of fixed costs including $4691 (24%) implementation and $2290 (12%) maintenance, both of which are volume dependent; and $1848 (10%) RAS consumable costs. This was in the context of 37% robotic theatre utilisation. Conclusions There is considerable variation across surgical specialties for the cost of RAS. It is important to highlight the different cost components and drivers associated with a RAS program including its dependence on volume and how it fits within funding systems in the public sector.

Here, we report on the development of lipid-based nanostructures containing zidovudine (1 mg/mL) and lamivudine (0.5 mg/mL) for oral administration in the pediatric population, eliminating the use of organic solvents, which is in accordance with green chemistry principles. The formulations were obtained by ultrasonication using monoolein (MN) or phytantriol (PN), which presented narrow size distributions with similar mean particle sizes (~150 nm) determined by laser diffraction. The zeta potential and the pH values of the formulations were around −4.0 mV and 6.0, respectively. MN presented a slightly higher incorporation rate compared to PN. Nanoemulsions were obtained when using monoolein, while cubosomes were obtained when using phytantriol, as confirmed by Small-Angle X-ray Scattering. The formulations enabled drug release control and protection against acid degradation. The drug incorporation was effective and the analyses using an electronic tongue indicated a difference in palatability between the nanotechnological samples in comparison with the drug solutions. In conclusion, PN was considered to have the strongest potential as a novel oral formulation for pediatric HIV treatment.