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Background Caring for a child with long-term functional limitations can have a negative impact on the physical and psychological well-being of the caregiver. Family-centered care (FCC) interventions have the potential to empower caregivers and contribute to their well-being. This systematic review aimed to synthesize existing evidence on the effectiveness of FCC interventions in improving the well-being of caregivers of children with cerebral palsy (CP), and identify the key components of such interventions that are most commonly practiced and deemed effective. Methods This review systematically searched seven databases for randomized controlled trials that evaluated the effectiveness of any FCC intervention on the well-being of caregivers of children with or at risk of CP. We used the Cochrane RoB 2.0 tool to assess risk of bias and Critical Appraisal Skills Programme (CASP) checklist for critical appraisal. Due to high heterogeneity of studies, narrative synthesis was used to summarize the data. Results The review consists of 11 studies which were categorized into five sections based on the components of FCC intervention provided in each individual study: 1. Information provision, and Enabling and partnership (n= 5); 2. Information provision, and Respectful and supportive care (n= 1); 3. Enabling and partnership (n= 2); 4. Enabling and partnership, and Respectful and supportive care (n= 2); 5. Information provision, Enabling and partnership and Respectful and supportive care (n= 1). Risk of bias was low in four studies, unclear in two studies, and high in five studies. Conclusion FCC interventions were found to be effective in improving caregivers’ satisfaction with attainment of child and caregiver goals. Evidence from multiple studies does not strongly support the effectiveness of FCC interventions on caregiver’s mental health, parenting and personal outcomes. Limited evidence precludes a conclusion on the effectiveness of the components of FCC on well-being of caregivers of children with CP.

ABSTRACT Bioindustrial manufacturing is undergoing rapid expansion and investment and is seen as integral to nations’ economic progress. Ensuring that bioindustrial manufacturing benefits society as the field expands is of critical, urgent importance. To better understand the industry’s ethical trajectory and to shape policy, we explored the views of biotechnology leaders on four aspects of ethical and social responsibility—safety, security, social responsibility, and sustainability—what we have termed “4S principles.” We identified policy actions governments and other stakeholders may take to maximize societal benefits in industrial biotechnology.IMPORTANCEWe analyzed biotech leaders’ views on safety, security, social responsibility, and sustainability to recommend policies to maximize benefits and economic growth.

IntroductionThe Profamille V3.2 multi-family psycho-educational program directed at caregivers of relatives with schizophrenia or schizophrenia related disorder has been shown to decrease the annual prevalence of suicide attempts. It has been reported that psychoeducation of families can sometimes improve compliance with treatment. This study investigates whether the Profamille program improves compliance and thus reduces the risk of suicide among patients.MethodThis is a retrospective study of 179 groups of family caregivers, encompassing 1946 participants enrolled in Module 1 of the Profamille program and followed up one year after completion of the module. Evaluations were conducted using questionnaires filled out by family caregivers at three distinct times: prior to beginning the program, upon its completion, and again one year following its conclusion. The annual prevalence of suicide attempts was measured both before the program began and one year after its conclusion, while compliance to treatment was evaluated at the start and end of the program.ResultAfter the Profamille program, the annual prevalence of suicide attempts fell by a factor of 2 (p-value = 0.00002) and patient compliance improved (p-value

Cancer cells are very diverse but mostly share a common metabolic property: they are strongly glycolytic even though oxygen is available. Herein, the metabolic abnormalities of cancer cells are interpreted as modifications of the electric currents in redox reactions. A lower current in the electron transport chain, an increase of the concentration of reduced cofactors and a partial reversal of the tricarboxylic acid cycle are physical characteristics of several forms of cancer. The existence of electric short-circuits between oxidative branches and reductive branches of the metabolic network argue in favor of an electronic approach of cancer in the nanoscopic scale. These changes of electron flows induce a pseudo-hypoxia and the Warburg effect through succinate production and divert electrons from oxygen to biosynthetic pathways. This new look at cancer may have potential therapeutic applications.

Key Clinical Message Treatment of patients with amelogenesis imperfecta extends over many years, from childhood to early adulthood. Their management at any age is complex and has to be adapted in relation to therapies validated in the general population.

Background: COVID-19 pneumonia with an unusual outbreak is considered a new, global public health threat. Microbiological characterization of co-infections in patients with COVID-19 is important, and antimicrobial use is high. We aimed to describe microbiologically confirmed co-infections and the antimicrobial resistance of the causative pathogens.Method: From January to December 2020, we tested 1,301 patients who were COVID-19 positive. We received clinical samples (blood, respiratory and sterile body fluids) of COVID-19 patients who were suspected to have bacterial co-infections. Samples were processed and antimicrobial susceptibility testing was performed based on the CLSI recommendation. Demographic, clinical, laboratory and outcome data of those with positive cultures were collected.Result: A total of 1301 COVID-19 patients (568 from the COVID ward and 733 from ICU) were admitted to the Covid care ward of a tertiary care hospital. 363 samples were sent for culturing and testing antibiotic susceptibility, of which 131 (36%) were found to be culture-positive (9rom ICUs, 41 from wards). Out of the 143 total isolates thus obtained from 131 samples, the majority (62.2%) were Gram-negative bacteria, and most of them were (70.8%) multidrug resistant.Discussion: Bacterial co-infection in patients with COVID-19 is more commonly reported in the severely ill hospitalized individuals (58%), particularly in the ICU (73.3%) setting. In terms of mortality, almost half of co-infected patients died (51.1%). In most of them, the cause of death was found to be sepsis with post-COVID ARDS (58%).Conclusion: Co-infection in COVID-19 patients may affect the outcome in terms of increasing the hospital stay.

Using adaptive radiotherapy (ART), to determine objective clinical criteria that identify extremity soft tissue sarcoma (ESTS) patients requiring adaptation of their preoperative radiotherapy (RT) plan.

Introduction: Vitiligo is a skin disease affecting melanocytes, characterised by the development of depigmented skin lesions. Methods: We used bibliometric analysis (BA) to identify high-quality research articles on vitiligo using criteria such as total citations, annual citations (AC) and journal impact factors. We extracted the 100 most-cited articles on vitiligo using the Web of Science database and analysed the results using Microsoft Excel 2019. Our search was limited to manuscript titles or abstracts containing the keyword ‘vitiligo’. The data extracted information such as title, author, year of publication, journal of publication, total citations and research area. We also calculated the AC rate to account for bias. Results: A total of 6,189 studies were retrieved. The 100 most-cited articles were published between 1976 and 2017. Of those, 75 were original articles, with the research foci being mainly pathogenesis (29%) and treatment (26%). The US was the most prolific publisher overall. We separately retrieved the highest cited data from 2018 to 2022 and tabled the top 10. Of those, 50% were original articles. Discussion: Our BA shows that developed countries published most of the vitiligo literature. Additionally, recent research has focused on targeted treatment approaches. We also highlight the increasing paediatric vitiligo research, specifically regarding therapies.

Non-melanoma skin cancers (NMSC) form the majority of skin cancers, with basal cell carcinoma (BCC) being the most common and cutaneous squamous cell carcinoma (cSCC) being second. Prolonged ultraviolet (UV) exposure, aging, male gender, and immunosuppression represent most of the causes of this category of diseases. BCCs and cSCCs both include different types of skin cancers, such as nodular or morpheaform BCC or flat cSCC. Locally advanced and metastatic NMSCs cannot be treated surgically; thus, systemic therapy (TKI and Immunotherapy) is needed. Interestingly, NMSCs are frequently linked to abnormal Hedgehog (HH) signaling which most systemic immunotherapies for these cancers are based upon. Of note, the first line therapies of BCC, sonidegib and vismodegib, are HH inhibitors. Programmed death receptor 1 antibody (PD-1) inhibitors such as cemiplimab, pembrolizumab, and nivolumab have been approved for the treatment of cSCC. Thus, this paper reviews the epidemiology, risk factors, clinical features, and treatment options for both BCC and cSCC.

Abstract The humoral response after the fourth dose of a mRNA vaccine against COVID-19 has not been adequately described in elderly recipients, particularly those not exposed previously to SARS-CoV-2. Serum anti-RBD IgG levels (Abbott SARS-CoV-2 IgG II Quant assay) and neutralizing capacities (spike SARS-CoV-2 pseudovirus Wuhan and Omicron BA.1 variant) were measured after the third and fourth doses of a COVID-19 mRNA vaccine among 46 elderly residents (median age 85 years [IQR 81; 89]) of an assisted living facility. Among participants never infected by SARS-CoV-2, the mean serum IgG levels against RBD (2025 BAU/ml), 99 days after the fourth vaccine, was as high as 76 days after the third vaccine (1987 BAU/ml), and significantly higher (p = 0.030) when the latter were corrected for elapsed time. Neutralizing antibody levels against the historical Wuhan strain were significantly higher (Mean 1046 vs 1573; p = 0.002) and broader (against Omicron) (Mean 170 vs 375; p = 0.018), following the fourth vaccine. The six individuals with an Omicron breakthrough infection mounted strong immune responses for anti-RBD and neutralizing antibodies against the Omicron variant indicating that the fourth vaccine dose did not prevent a specific adaptation of the immune response. These findings point out the value of continued vaccine boosting in the elderly population

Abstract The Gangetic Plains comprise steep gravelly river channels that transition to low gradient sandy channels 10-40 km downstream of the mountain front. This “gravel-sand transition" is characterized by an abrupt greater-than-one-order-of-magnitude drop in both gradient and sediment grain size, suggesting a degree of long-term stability. However, the stratigraphic record of the gravel-sand transition in the Miocene Siwalik Group demonstrates intermittent transport of coarse gravels tens of kilometres downstream of the transition; such events in contemporary channels would drive channel avulsion(s) and increase flood risk, devastating communities across the plains. We combine sedimentological analysis of Siwalik deposits with entrainment calculations which demonstrate that hyperconcentration is required to transport coarse bedload over low-gradient plains. Transport conditions are attainable when intense monsoon precipitation (a 200- to 1000-year event) is combined with increased suspended sediment concentrations in channels. Predicted climate change and ongoing seismicity increase the likelihood of such extreme events within this century.

Abstract Purpose Radiotherapy is, with surgery, one of the main therapeutic treatment strategies for meningiomas. No prospective study has defined a consensus for the delineation of target volumes for meningioma radiotherapy. Therefore, target volume definition is mainly based on information from retrospective studies that include heterogeneous patient populations. The aim is to describe delineation guidelines for meningioma radiotherapy as an adjuvant or definitive treatment with intensity-modulated radiation therapy and stereotactic radiation therapy techniques. This guideline is based on a consensus endorsed by a multidisciplinary group of brain tumor experts, members of the Association of French-speaking Neuro-oncologists (ANOCEF). Materials and methods A 3-step procedure was used. First, the steering group carried out a comprehensive review to identify divergent issues on meningiomas target volume delineation. Second, an 84-item web-questionnaire has been developed to precisely define meningioma target volume delineation in the most common clinical situations. Third, experts members of the ANOCEF were requested to answer. The first two rounds were completed online. A third round was carried out by videoconference to allow experts to debate and discuss the remaining uncertain questions. All questions remained in a consensus. Results Limits of the target volume were defined using visible landmarks on computed tomography and magnetic resonance imaging, considering the pathways of tumor extension. The purpose was to develop clear and precise recommendations on meningiomas target volumes. Conclusion New recommendations for meningiomas delineation based on simple anatomic boundaries are proposed by the ANOCEF. Improvement in uniformity in target volume definition is expected.

BackgroundAntimicrobial stewardship programs attempting to optimize antibiotic therapy and clinical outcomes mainly focus on inpatient and outpatient settings. The lack of antimicrobial stewardship program studies in the emergency department (ED) represents a gap in tackling the problem of antimicrobial resistance as EDs treat a substantial number of upper respiratory tract infection cases throughout the year. ObjectiveWe intend to implement two evidence-based interventions: (1) patient education and (2) providing physician feedback on their prescribing rates. We will incorporate evidence from a literature review and contextualizing the interventions based on findings from a local qualitative study. MethodsOur study uses a quasi-experimental design to evaluate the effects of interventions over time in the EDs of 4 public hospitals in Singapore. We will include an initial control period of 18 months. In the next 6 months, we will randomize 2 EDs to receive 1 intervention (ie, patient education) and the other 2 EDs to receive the alternative intervention (ie, physician feedback). All EDs will receive the second intervention in the subsequent 6 months on top of the ongoing intervention. Data will be collected for another 6 months to assess the persistence of the intervention effects. The information leaflets will be handed to patients at the EDs before they consult with the physician, while feedback to individual physicians by senior doctors is in the form of electronic text messages. The feedback will contain the physicians’ antibiotic prescribing rate compared with the departments’ overall antibiotic prescribing rate and a bite-size message on good antibiotic prescribing practices. ResultsWe will analyze the data using segmented regression with difference-in-difference estimation to account for concurrent cluster comparisons. ConclusionsOur proposed study assesses the effectiveness of evidence-based, context-specific interventions to optimize antibiotic prescribing in EDs. These interventions are aligned with Singapore’s national effort to tackle antimicrobial resistance and can be scaled up if successful. Trial RegistrationClinicalTrials.gov NCT05451863; https://clinicaltrials.gov/study/NCT05451836 International Registered Report Identifier (IRRID)DERR1-10.2196/50417

Objective: The central melanocortin system is essential for the regulation of food intake and body weight. Agouti-related protein (AgRP) is the sole orexigenic component of the central melanocortin system and is conserved across mammalian species. AgRP is currently known to be expressed exclusively in the mediobasal hypothalamus, and hypothalamic AgRP-expressing neurons are essential for feeding. Here we characterized a previously unknown population of AgRP cells in the mouse hindbrain. Methods: Expression of AgRP in the hindbrain was investigated using gene expression analysis, single-cell RNA sequencing, immunofluorescent analysis and multiple transgenic mice with reporter expressions. Activation of AgRP neurons was achieved by Designer Receptors Exclusively Activated by Designer Drugs (DREADD) and by transcranial focal photo-stimulation using a step-function opsin with ultra-high light sensitivity (SOUL). Results: AgRP expressing cells were present in the area postrema (AP) and the adjacent subpostrema area (SubP) and commissural nucleus of the solitary tract (cNTS) of the mouse hindbrain (termed AgRPHind herein). AgRPHind cells consisted of locally projecting neurons as well as tanycyte-like cells. Food deprivation stimulated hindbrain Agrp expression as well as neuronal activity of subsets of AgRPHind cells. In adult mice that lacked hypothalamic AgRP neurons, chemogenetic activation of AgRP neurons resulted in hyperphagia and weight gain. In addition, transcranial focal photo-stimulation of hindbrain AgRP cells increased food intake in adult mice with or without hypothalamic AgRP neurons. Conclusions: Our study indicates that the central melanocortin system in the hindbrain possesses an orexigenic component, and that AgRPHind neurons stimulate feeding independently of hypothalamic AgRP neurons.

Background: In 2018, 66,859 migrant careworkers were in Israel, most of whom originated from Southeast Asian countries and 81 % of whom are women. Stringent regulations combined with social invisibility creates vulnerabilities that may contribute to emotional distress. This study aimed to assess psychosocial status and determine mechanisms of emotional distress and resilience in this population. Methods: Mixed methods were used in this cross-section study. An online survey measured demographic variables, psychosocial wellbeing using the HSCL-25 questionnaire, general health, perceived social support, cultural identity, and perceived othering. Based on the survey's results, interviews were conducted with a subpopulation of respondents (n = 15) to further understand the mechanisms of emotional distress and resilience, and were analyzed using a postcolonial feminist framework and grounded theory. Data collection took place during 2018–2019. Results: In total, 263 careworkers completed the survey and 15 careworkers were interviewed. The overall prevalence of emotional distress according to the HSCL-25 was 36.8 %, 22.6 % on the anxiety subscale, and 41.8 % on the depression subscale. Emotional distress was associated with female sex, not being parents, poorer general health, high perceived othering, and low perceived social support. Interviews revealed that Israeli policy, and relationships with family in their country of origin and with Israeli employers and their families can either contribute to or mitigate emotional stressors. Conclusions: Symptoms of emotional distress among Southeast Asian migrant careworkers in Israel are frequently reported, and may indicate rates of anxiety and depression higher than in careworkers’ countries of origin and host country. Increased monitoring to protect careworkers’ rights and including mental health services as part of their health insurance plan are warranted.

IntroductionEarlier studies exploring the value of executive functioning (EF) indices for assessing treatment effectiveness and predicting treatment response in attention-deficit/hyperactivity disorder (ADHD) mainly focused on pharmacological treatment options and revealed rather heterogeneous results. Envisioning the long-term goal of personalized treatment selection and intervention planning, this study comparing methylphenidate treatment (MPH) and a home-based neurofeedback intervention (NF@Home) aimed to expand previous findings by assessing objective as well as subjectively reported EF indices and by analyzing their value as treatment and predictive markers.MethodsChildren and adolescents (n = 146 in the per protocol sample) aged 7–13 years with a formal diagnosis of an inattentive or combined presentation of ADHD were examined. We explored the EF performance profile using the Conners Continuous Performance Task (CPT) and the BRIEF self-report questionnaire within our prospective, multicenter, randomized, reference drug-controlled NEWROFEED study with sites in five European countries (France, Spain, Switzerland, Germany, and Belgium). As primary outcome for treatment response, the clinician-rated ADHD Rating Scale-IV was used. Patients participating in this non-inferiority trial were randomized to either NF@home (34–40 sessions of TBR or SMR NF depending on the pre-assessed individual alpha peak frequency) or MPH treatment (ratio: 3:2). Within a mixed-effects model framework, analyses of change were calculated to explore the predictive value of neurocognitive indices for ADHD symptom-related treatment response.ResultsFor a variety of neurocognitive indices, we found a significant pre-post change during treatment, mainly in the MPH group. However, the results of the current study reveal a rather limited prognostic value of neurocognitive indices for treatment response to either NF@Home or MPH treatment. Some significant effects emerged for parent-ratings only.DiscussionCurrent findings indicate a potential value of self-report (BRIEF global score) and some objectively measured neurocognitive indices (CPT commission errors and hit reaction time variability) as treatment markers (of change) for MPH. However, we found a rather limited prognostic value with regard to predicting treatment response not (yet) allowing recommendation for clinical use. Baseline symptom severity was revealed as the most relevant predictor, replicating robust findings from previous studies.

Abstract This paper introduces a new challenge and datasets to foster research toward designing systems that can understand medical videos and provide visual answers to natural language questions. We believe medical videos may provide the best possible answers to many first aid, medical emergency, and medical education questions. Toward this, we created the MedVidCL and MedVidQA datasets and introduce the tasks of Medical Video Classification (MVC) and Medical Visual Answer Localization (MVAL), two tasks that focus on cross-modal (medical language and medical video) understanding. The proposed tasks and datasets have the potential to support the development of sophisticated downstream applications that can benefit the public and medical practitioners. Our datasets consist of 6,117 fine-grained annotated videos for the MVC task and 3,010 questions and answers timestamps from 899 videos for the MVAL task. These datasets have been verified and corrected by medical informatics experts. We have also benchmarked each task with the created MedVidCL and MedVidQA datasets and propose the multimodal learning methods that set competitive baselines for future research.