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ObjectiveThe 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.MethodsExpression 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).ResultsAgRP 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.ConclusionsOur 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.

Alcohol-associated liver disease (ALD) is a substantial cause of morbidity and mortality worldwide and represents a spectrum of liver injury beginning with hepatic steatosis (fatty liver) progressing to inflammation and culminating in cirrhosis. Multiple factors contribute to ALD progression and disease severity. Here, we overview several crucial mechanisms related to ALD end-stage outcome development, such as epigenetic changes, cell death, hemolysis, hepatic stellate cells activation, and hepatic fatty acid binding protein 4. Additionally, in this review, we also present two clinically relevant models using human precision-cut liver slices and hepatic organoids to examine ALD pathogenesis and progression.

The ID10 beamline of the SESAME (Synchrotron-light for Experimental Science and Applications in the Middle East) synchrotron light source in Jordan was inaugurated in June 2023 and is now open to scientific users. The beamline, which was designed and installed within the European Horizon 2020 project BEAmline for Tomography at SESAME (BEATS), provides full-field X-ray radiography and microtomography imaging with monochromatic or polychromatic X-rays up to photon energies of 100 keV. The photon source generated by a 2.9 T wavelength shifter with variable gap, and a double-multilayer monochromator system allow versatile application for experiments requiring either an X-ray beam with high intensity and flux, and/or a partially spatial coherent beam for phase-contrast applications. Sample manipulation and X-ray detection systems are designed to allow scanning samples with different size, weight and material, providing image voxel sizes from 13 µm down to 0.33 µm. A state-of-the-art computing infrastructure for data collection, three-dimensional (3D) image reconstruction and data analysis allows the visualization and exploration of results online within a few seconds from the completion of a scan. Insights from 3D X-ray imaging are key to the investigation of specimens from archaeology and cultural heritage, biology and health sciences, materials science and engineering, earth, environmental sciences and more. Microtomography scans and preliminary results obtained at the beamline demonstrate that the new beamline ID10-BEATS expands significantly the range of scientific applications that can be targeted at SESAME.

This paper uses critical discourse analysis and critical literacy to analyze the first in a series of literacy primers developed with US support for children in Afghanistan in the 1980s, called 'Jihad literacy'. The text is analyzed for its ideological content as related to the themes of religion, violence, and martyrdom in the historical perspective of the Cold War and the Soviet Union's invasion of Afghanistan. The paper demonstrates how the notion of 'Jihad' was subverted to promote a holy war against the Soviet invasion. The educational system supported by the US created a radical version of Islam based on violence and martyrdom, shaping the Afghan society to this day. We contend that the same or similar institutions shape current discourses as in the past and that children are the main victims of politico-economic warfare.

Zinner syndrome comprises a triad of unilateral renal agenesis, ipsilateral seminal vesicle cyst, and ejaculatory duct obstruction, which can be accompanied by additional abnormalities of the genitourinary tract in some cases. Patients may be asymptomatic or present with urinary, reproductive, and/or local pain symptoms. Diagnosis is most commonly achieved via MRI. Here, we present the case of an 18-year-old male previously diagnosed with unilateral renal agenesis, who presented with testicular and penile pain, along with urinary urgency and frequency. MRI of the abdomen and pelvis revealed all three components of Zinner syndrome as well as an ectopic ureter emptying into the seminal vesicle. Our case adds to the existing limited literature on this rare syndrome and broadens the understanding of how this syndrome can present both clinically and radiologically.

Summary: Background: Ventilator-associated pneumonia (VAP) is a major cause of morbidity and mortality in patients receiving mechanical ventilation in India. Surveillance of VAP is essential to implement data-based preventive measures. Implementation of ventilator-associated events (VAE) criteria for surveillance has major constraints for low resource settings, which can lead to significant underreporting. Surveillance of VAP using common protocols in a large network of hospitals would give meaningful estimates of the burden of VAP in low resource settings. This study leverages a previously established healthcare-associated infections (HAI) surveillance network to develop and test a modified VAP definition adjusted for Indian settings. Methods: In this observational pilot study, thirteen hospitals from the existing HAI surveillance network were selected for developing and testing a modified VAP definition between February 2021 and April 2023. The criteria used for diagnosing VAP were adapted from the CDC’s Pediatric VAP definition and modified to cater to the needs of Indian hospitals. Designated nurses recorded each VAP event in a case report form (CRF) and also collected denominator data. The data was entered into an indigenously developed database for validation and analysis. At the time of data analysis, a questionnaire was sent to sites to get feedback on the performance of the modified VAP definitions. Findings: Out of 133,445 patient days and 40,533 ventilator days, 261 VAP events were recorded, with an overall VAP rate of 6.4 per 1000 ventilator days and a device utilization ratio (DUR) of 0.3. A total of 344 organisms were reported from the VAP events. Of these, Acinetobacter spp (29.6%, 102) was the most frequent, followed by Klebsiella spp (26.7%, 92). Isolates of Acinetobacter spp (98%) and Enterobacterales (85.5%) showed very high resistance against Carbapenem. Colistin resistance was observed in 6% of Enterobacterales and 3.2% of Acinetobacter spp. Interpretation: Data from this pilot study needs to validated in the larger Indian HAI surveillance network so that it can help in wider implementation of this protocol in order to assess its applicability p VAP across India. Funding: This work was supported by a grant received from the Indian Council of Medical Research (code I-1203).

Abstract Introduction Tafamidis is the first drug approved by the European Commission for the treatment of wild-type or hereditary transthyretin amyloid cardiomyopathy (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. Real-world treatment patterns of tafamidis 61 mg in Germany are not well studied in patients with ATTR-CM. Methods This was a non-interventional, retrospective, observational cohort study of adult patients in Germany based on the IQVIA pharmacy claims database (IQVIA™ LRx). Patients included in the analysis were statutory insured and received at least one prescription of tafamidis 61 mg between March 1, 2020 and August 31, 2022. Treatment adherence was analyzed using the modified medical possession ratio (mMPR) and proportion of days covered (PDC). Results Overall, 1565 adult patients received at least one tafamidis prescription in the study period. Their mean age was 78.3 years, 82.4% were male, and 23.2% were treated by a cardiologist. Persistency rates for patients treated with tafamidis 61 mg were high: 78.0% for 12 months and 65.1% for 24 months after treatment initiation. Patients also had high adherence rate on filling their prescriptions on time: 94.6% and 90.5% of patients had adherence rates of at least 80%, measured by mMPR and PDC, respectively. Conclusions In the IQVIA™ LRx database, patients prescribed tafamidis 61 mg in Germany displayed high adherence and persistency rates, which suggest good drug tolerability and ease of use.

Sediment grains are progressively rounded during their transport down a river. For more than a century, Earth scientists have used the roundness of pebbles within modern sediment, and of clasts within conglomerates, as a key metric to constrain the sediment's transport history and source area(s). However, the current practices of assessment of pebble roundness are mainly qualitative and based on time-consuming manual measurement methods. This qualitative judgement provides the transport history only in a broad sense, such as classifying distance as “near” or “far”. In this study, we propose a new model that quantifies the relationship between roundness and the transport distance. We demonstrate that this model can be applied to the clasts of multiple lithologies including modern sediment, as well as conglomerates, deposited by ancient river systems. We present field data from two Himalayan catchments in Nepal. We use the normalized isoperimetric ratio (IRn), which relates a pebble's area (A) to its perimeter (P), to quantify roundness. The maximum analytical value for IRn is 1, and IRn is expected to increase with transport distance. We propose a non-linear roundness model based on our field data, whereby the difference between a grain's IRn and the maximum value of 1 decays exponentially with transport distance, mirroring Sternberg's model of mass loss or size reduction by abrasion. This roundness model predicts an asymptotic behaviour for IRn, and the distance over which IRn approaches the asymptote is controlled by a rounding coefficient. Our field data suggest that the roundness coefficient for granite pebbles is 9 times that of quartzite pebbles. Using this model, we reconstruct the transport history of a Pliocene paleo-river deposit preserved at the base of the Kathmandu intermontane basin. These results, along with other sedimentary evidence, imply that the paleo-river was much longer than the length of the Kathmandu Basin and that it must have lost its headwaters through drainage capture. We further explore the extreme rounding of clasts from Miocene conglomerate of the Siwalik zone and find evidence of sediment recycling.

AimCompetency frameworks are essential for analyzing capabilities of Schools of Public Health to adequately prepare public health (PH) professionals to address contemporary challenges. This study maps the competency profiles of PH training programs in Israel using a novel curriculum mapping tool.MethodsThis study assessed all five Israeli Health Education Institutions (HEIs) offering MPH or Bachelors in Public Health (BPH) degrees across 57 competencies in six domains to determine the extent to which competencies were addressed in the curriculum. The competencies list was based on the Association of Schools of Public Health in the European Region (ASPHER) List of Core Competences for the Public Health Professional, adapted for Israeli HEIs.ResultsThe core curricula in the four MPH programs addressed 45–84% of all competencies. The BPH program addressed 79% of competencies. In MPH programs, the core curricula addressed most or all competencies in the Methods and the Socioeconomic Determinants of Health domains. Competencies in the domains of Environmental Determinants of Health, Health Policy, Economics & Organization, and Health Promotion and Prevention were less comprehensively addressed in most core curricula. Students’ opportunities to broaden their exposure to competencies outside the core curricula were context dependent.DiscussionThe curriculum competencies mapping tool that was developed served to assess both strengths and shortcomings in PH education in Israel. The findings demonstrate a highly variable array of PH curriculum models in Israeli HEIs, as well as overall shortcomings in the Environmental, Health Policy Economics and Organization, and Health Promotion and Prevention domains. This analysis has already led to reassessment of the curriculum, and will continue to guide the next steps to increase the harmonization of PH training curricula and to better meet PH challenges in Israel.

Key Clinical Message The purpose of this article is to highlight that oral Kaposi's disease can be indicative of a high viral load of HIV, either in the case of primary infection or therapeutic failure. Abstract We report two cases of Kaposi Disease associated with HIV. The first case was a 30‐year‐old patient who unaware of her HIV‐positive status, and who was diagnosed with AIDS stage because of the biopsy revealed a gingival location of Kaposi disease. The second case was a 34‐year‐old patient who was referred to our department with a history of palatal lesion and claimed at first having no previous known medical conditions although his overall health condition seemed deteriorated. Our clinical examination was evocative of Kaposi Disease, which was confirmed by an emergency blood assessment and histological examination. Our diagnosis led us to disclose the HIV‐positive status of the patient and identify a progression to the AIDS stage, which allowed us to reintroduce the patient in the hospital framework. This case emphasizes the role of the oral surgeon as a key actor thanks to their knowledge of the clinical buccal manifestations of sexually transmitted infections (STI), in an era of resurgence of those conditions in vulnerable key populations.

Scorpion envenoming (SE) is a public health problem in developing countries. In Algeria, the population exposed to the risk of SE was estimated at 86.45% in 2019. Thus, the development of a vaccine to protect the exposed population against scorpion toxins would be a major advance in the fight against this disease.This work aimed to evaluate the immunoprotective effect of a Multiple Antigenic Peptide against the Aah II toxin of Androctonus australis hector scorpion, the most dangerous scorpion species in Algeria. The immunogen MAP1Aah2 was designed and tested accordingly. This molecule contains a B epitope, derived from Aah II toxin, linked by a spacer to a universal T epitope, derived from the tetanus toxin.The results showed that MAP1Aah2 was non-toxic despite the fact that its sequence was derived from Aah II toxin. The immunoenzymatic assay revealed that the 3 immunization regimens tested generated specific anti-MAP1Aah2 antibodies and cross-reacted with the toxin. Mice immunized with this immunogen were partially protected against mortality caused by challenge doses of 2 and 3 LD50 of the toxin. The survival rate and developed symptoms varied depending on the adjuvant and the challenge dose used. In the in vitro neutralization test, the immune sera of mice having received the immunogen with incomplete Freund’s adjuvant neutralized a challenge dose of 2 LD50.Hence, the concept of using peptide dendrimers, based on linear epitopes of scorpion toxins, as immunogens against the parent toxin was established. However, the protective properties of the tested immunogen require further optimizations.

Introduction Restrictive anorexia nervosa (AN) is associated with distorted perception of body shape, previously linked to hypoactivity and reduced excitability of the right inferior parietal lobe (rIPL). Here, we investigated the impact of high‐frequency repetitive transcranial magnetic stimulation (HF rTMS) of the rIPL on body shape perception in patients with AN. Methods Seventeen patients with AN (median [Q1_Q3] age, 35 [27_39] years; disease duration, 12 [6_18] years) were randomly assigned to receive real or sham HF (10 Hz) rTMS of the rIPL over a period of 2 weeks, comprising 10 sessions. The primary outcome measure was the Body Shape Questionnaire (BSQ). Secondary outcomes included eating disorder symptoms, body mass index, mood, anxiety, and safety. Data collection were done at baseline, post‐rTMS, and at 2 weeks and 3 months post‐rTMS. Results Following both real and sham rTMS of the rIPL, no significant differences were observed in body shape perception or other parameters. Both real and sham rTMS interventions were deemed safe and well tolerated. Notably, serious adverse events were associated with the underlying eating and mood disorders, resulting in hospitalization for undernutrition (five patients) or suicidal attempts (two patients). Conclusion This pilot study does not support the use of rTMS of the rIPL as an effective method for improving body shape perception in individuals with the restrictive form of AN. Further research is warranted to comprehensively explore both the clinical and neurophysiological effects of HF rTMS in this population.

Abstract Objective To evaluate the shear bond strength (SBS) of a restorative resin-modified glass ionomer cement (RMGIC) for orthodontic bracket bonding. Materials and methods One hundred twenty-one human teeth were randomly divided into 11 groups (n = 11) according to the surface treatment applied (H3PO4 ± Transbond Plus (TSEP) or Scotchbond Universal (SU)), and the adhesive used (Riva LC HV (RIVA), Fuji Ortho (FUJI), and Transbond XT (TXT)). For each sample, a metal button was bonded. SBS tests were performed at 1 week and debonded specimens were observed for failure modes determination. One-way ANOVA followed by Tukey’s post hoc test was used to compare SBS differences and Fisher’s exact test to analyze the failure modes (p

Large earthquakes can contribute to mountain growth by building topography but also contribute to mass removal from mountain ranges through widespread mass wasting. On annual to decadal or centennial timescales, large earthquakes also have the potential to significantly alter fluvial sediment dynamics if a significant volume of the sediment generated reaches the fluvial network. In this contribution, we focus on the Melamchi–Indrawati and Bhote Koshi rivers in central Nepal, which have both experienced widespread landsliding associated with the 2015 Gorkha (Nepal) earthquake. Using a time series of high-resolution satellite imagery, we have mapped exposed sediment along the rivers from 2012–2021 to identify zones of active channel deposition and document changes over time. Counter to expectations, we show negligible increases in coarse-sediment accumulation along both river corridors since the Gorkha earthquake. However, an extremely high-concentration flow event on 15 June 2021 caused an approximately 4-fold increase in exposed sediment along a 30 km reach of the channel with up to 12 m of channel aggradation in the Melamchi–Indrawati rivers; this event was localised and did not impact the neighbouring Bhote Koshi catchment. Based on published reports, new helicopter-based photography, and satellite data, we demonstrate that this event was sourced from a localised rainfall event between 4500 and 4800 m and that a significant fraction of the sediment was supplied from sources that were unrelated to the landslides generated by the Gorkha earthquake.

Abstract Objective Evaluation of the Shear bond strength over zirconia and titanium alloy and degree of conversion of extraoral compared to intraoral self-adhesive resin cements. Materials and methods Nine bonding protocols were carried out on zirconia 4Y-TZP and titanium alloy (Ti-6Al-4V). Seven resin cement (one extraoral and six intraoral) were tested in the shear bond strength test and the degree of conversion measurements. Results The significantly highest value was obtained for Monobond Plus + Multilink Hybrid Abutment, the extraoral resin cement for both titanium alloy (35.1 MPa) and zirconia (32.9 MPa). For each resin, significantly higher DC values were obtained for the dual-cure mode compared with the self-cure mode. Regardless of the cure mode, Nexus Universal reached the highest DC (78.4%). Discussion/Conclusions In this study, the extraoral self-curing resin cement showed the higher bond strength values on zirconia and titanium alloy when associated with a universal primer. Some intraoral dual-cure resin cements showed closed performances when used with universal primers. There is no direct correlation between the degree of conversion of the resin cement and the shear bond strength obtained on the prosthetic materials tested.

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.