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The safety and efficacy of sofosbuvir–velpatasvir in children aged 3–17 years with chronic hepatitis C virus (HCV) infection of any genotype were evaluated. In this Phase 2, multicenter, open‐label study, patients received once daily for 12 weeks either sofosbuvir–velpatasvir 400/100 mg tablet (12–17 years), 200/50 mg low dose tablet or oral granules (3–11 years and ≥17 kg), or 150/37.5 mg oral granules (3–5 years and <17 kg). The efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Dose appropriateness was confirmed by intensive pharmacokinetics in each age group. Among 216 patients treated, 76% had HCV genotype 1% and 12% had genotype 3. Rates of SVR12 were 83% (34/41) among 3–5‐year‐olds, 93% (68/73) among 6–11‐year‐olds, and 95% (97/102) among 12–17‐year‐olds. Only two patients experienced virologic failure. The most common adverse events were headache, fatigue, and nausea in 12–17‐year‐olds; vomiting, cough, and headache in 6–11‐year‐olds; and vomiting in 3–5‐year‐olds. Three patients discontinued treatment because of adverse events. Four patients had serious adverse events; all except auditory hallucination (n= 1) were considered unrelated to study drug. Exposures of sofosbuvir, its metabolite GS‐331007, and velpatasvir were comparable to those in adults in prior Phase 2/3 studies. Population pharmacokinetic simulations supported weight‐based dosing for children in this age range. The pangenotypic regimen of sofosbuvir–velpatasvir is highly effective and safe in treating children 3–17 years with chronic HCV infection. For treating chronic hepatitis C virus (HCV) infection, the combination antiviral regimen sofosbuvir–velpatasvir is highly effective in treating adults with any HCV genotype.In children, the safety, efficacy, and pharmacokinetics of sofosbuvir–velpatasvir had not been evaluated. For treating chronic hepatitis C virus (HCV) infection, the combination antiviral regimen sofosbuvir–velpatasvir is highly effective in treating adults with any HCV genotype. In children, the safety, efficacy, and pharmacokinetics of sofosbuvir–velpatasvir had not been evaluated. In 216 children aged 3–17 years with chronic HCV infection, sofosbuvir–velpatasvir given once daily for 12 weeks had a cure rate of 92%.Rates of cure were 95% among 12–17‐year‐olds (97/102), 93% in 6–11‐year‐olds (68/73), and 83% in 3–5‐year‐olds (34/41).Overall, sofosbuvir–velpatasvir was well tolerated in both tablet and granule formulations; 1.4% (3/216) of participants discontinued because of an adverse event. Pharmacokinetic simulations supported weight‐based dosing for children. In 216 children aged 3–17 years with chronic HCV infection, sofosbuvir–velpatasvir given once daily for 12 weeks had a cure rate of 92%. Rates of cure were 95% among 12–17‐year‐olds (97/102), 93% in 6–11‐year‐olds (68/73), and 83% in 3–5‐year‐olds (34/41). Overall, sofosbuvir–velpatasvir was well tolerated in both tablet and granule formulations; 1.4% (3/216) of participants discontinued because of an adverse event. Pharmacokinetic simulations supported weight‐based dosing for children.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide, with more than three million viraemic adolescents and children. Treatment of adults with HCV infection and HCV‐related liver disease has advanced considerably thanks to development and improvements in therapy. Direct‐acting antiviral regimens are safe and effective. Three regimens with pangenotypic activity (glecaprevir/pibrentasvir, sofosbuvir/velpatasvir and sofosbuvir/velpatasvir/voxilaprevir) and three regimens with genotype‐specific activity (sofosbuvir/ribavirin, sofosbuvir/ledipasvir and elbasvir/grazoprevir) have been approved with age‐specific limitation for treatment of children with chronic hepatitis C by the European Medicines Agency and the United States Food and Drug Administration. The World Health Organization has set the ambitious target to eliminate hepatitis C as a major public health threat by 2030 and based its actions against HCV on the large use of direct acting antivirals. These updated European Society for Pediatric Gastroenterology, Hepatology and Nutrition recommendations on treatment of hepatitis C describe the optimal therapeutic management of adolescents and children with HCV infection including specific indications for those living in resource‐limited settings. Direct‐acting antiviral drug regimens are highly effective and safe for treatment of adults, adolescents and children with chronic hepatitis C.Two combination regimens with pangenotypic activity (sofosbuvir/velpatasvir and glecaprevir/pibrentasvir) and two with genotype‐specific activity (sofosbuvir/ledipasvir and sofosbuvir plus ribavirin) have been approved by both the European Medicines Agency and the United States Food and Drug Administration for use in adolescents and children aged 3 years and older with chronic hepatitis C. Direct‐acting antiviral drug regimens are highly effective and safe for treatment of adults, adolescents and children with chronic hepatitis C. Two combination regimens with pangenotypic activity (sofosbuvir/velpatasvir and glecaprevir/pibrentasvir) and two with genotype‐specific activity (sofosbuvir/ledipasvir and sofosbuvir plus ribavirin) have been approved by both the European Medicines Agency and the United States Food and Drug Administration for use in adolescents and children aged 3 years and older with chronic hepatitis C. We recommend treatment using direct‐acting antiviral regimens for all adolescents and children 3 years of age and above with chronic hepatitis C, regardless of stage of disease.Pangenotypic and genotype‐specific direct‐acting antiviral regimens are equally recommended for treatment.Pangenotypic, ribavirin‐free and regimens with the shortest treatment duration are preferrable when available.Sofosbuvir plus daclatasvir may be considered for adolescents and children with chronic hepatitis C in resource‐limited settings, as it is highly effective and widely available as low‐cost generic formulations. We recommend treatment using direct‐acting antiviral regimens for all adolescents and children 3 years of age and above with chronic hepatitis C, regardless of stage of disease. Pangenotypic and genotype‐specific direct‐acting antiviral regimens are equally recommended for treatment. Pangenotypic, ribavirin‐free and regimens with the shortest treatment duration are preferrable when available. Sofosbuvir plus daclatasvir may be considered for adolescents and children with chronic hepatitis C in resource‐limited settings, as it is highly effective and widely available as low‐cost generic formulations.

This letter proposes a framework for parameter estimation and data detection in the uplink of IRS-assisted MIMO systems in the presence of channel aging. First, we model the received pilot signal as a tensor to estimate the channel parameters and to design the IRS phase shifts. Then, our proposed tensor approach tracks the aging process to jointly estimate the aged components and the transmitted data. Compared to state-of-the-art schemes, the numerical results show that our proposed solution improves the performance of IRS-assisted MIMO systems in terms of normalized mean squared error and bit error ratio.

Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies.

The promising gains of reconfigurable intelligent surface (RIS)-assisted multiple-input multiple-output (MIMO) systems, in terms of extended coverage and enhanced capacity, are critically dependent on the accuracy of the channel state information. However, traditional channel estimation (CE) schemes are not applicable in RIS-assisted MIMO networks, since passive RISs typically lack the signal processing capabilities that are assumed by CE algorithms. This becomes problematic when physical imperfections or electronic impairments affect the RIS due to its exposition to different environmental effects or caused by hardware limitations from the circuitry. While these real-world effects are typically ignored in the literature, in this article we propose efficient CE schemes for RIS-assisted MIMO systems taking different imperfections into account. Specifically, we propose two sets of tensor-based algorithms, based on the parallel factor analysis decomposition schemes. First, assuming a long-term model – where the RIS imperfections, modeled as unknown phase shifts, are static within the channel coherence time – we formulate an iterative alternating least squares (ALS)-based algorithm for the joint estimation of the unknown phase deviations and the communication channels. Then, we develop the short-term imperfection model, which allows both amplitude and phase RIS imperfections to be non-static with respect to the channel coherence time. We propose two iterative ALS-based and closed-form higher-order singular value decomposition-based algorithms for jointly estimating the channels and the unknown impairments. We also investigate the computational complexity and the identifiability of the proposed algorithms and study the effect of various imperfections on the CE quality. Simulation results show the effectiveness of our proposed tensor-based algorithms in terms of estimation accuracy and computational complexity.

Intelligent reconfigurable surface IRS are becoming an attractive component of cellular networks due to their ability to shape the propagation environment and thereby improve coverage. While IRS nodes incorporate a great number of phase-shifting elements and a controller entity, the phase shifts are typically determined by the cellular base station (BS) due to its computational capability. Since controlling a large number of phase shifts may become prohibitive in practice, it is important to reduce the control overhead between the BS and the IRS controller. To this end, in this paper, we propose a low-rank modeling approach for the IRS phase shifts. The key idea is to represent the IRS phase shift vector using a low-rank tensor approximation model, where each rank-one component is modeled as the Kronecker product of a predefined number of factors of smaller sizes, obtained via tensor decomposition algorithms. We show that the proposed low-rank models drastically reduce the required feedback requirements associated with the BS-IRS control links. Our simulation results indicate that the proposed method is especially attractive in scenarios with a strong line of sight component, in which case nearly the same spectral efficiency is reached as in the cases with near-optimal phase shifts, but with significantly lower feedback overhead.

This paper aims to assess the level of credit risk (from the perspective of default risk) among Polish households associated with the physical risks of climate change. In order to determine the potential impact of the physical risk of climate change on household credit risk, we conducted CAWI interviews with 1,006 borrowers residing in different Polish voivodeships (to account for heterogeneity of credit exposures to extreme weather events). According to these respondents, wildfires and storms in Poland are the greatest source of physical risk of climate change. In the event of a wildfire or storm, approximately 13% of borrowers would not be able to repay their loans while not being insured, which potentially increases banks’ credit risk and exposes banks to losses. However, we find that households underestimate the credit risk that could arise from a drought.

I present and discuss an extremely simple algorithm for expanding a formal power series as a continued fraction. This algorithm, which goes back to Euler (1746) and Viscovatov (1805), deserves to be better known. I also discuss the connection of this algorithm with the work of Gauss (1812), Stieltjes (1889), Rogers (1907) and Ramanujan, and a combinatorial interpretation based on the work of Flajolet (1980). [ABSTRACT FROM AUTHOR]

A series of novel CoFe2O4– xBaTiO3(x = 0.6–0.9) phosphate-bonded multifunctional ceramic composites were synthesized and studied both in ‘Salisbury screen’ geometry and as free-standing films in the frequency range of 25–54 GHz and temperature interval of 120–500 K. Experiments prove that the studied system is prospective for shielding applications in both modes providing total transmission losses of the free-standing sample layer of 40 dB for x = 0.9 dominated by absorption and more than 40 dB of reflection losses at resonant conditions in the Salisbury screen geometry. It was demonstrated that the electromagnetic response of multiferroic composite ceramics in microwaves is very sensitive to the temperature changes in the application's significant temperature range, i.e. 150 – 400 K. Notably, a small, i.e. 5 – 10 K, temperature variation drastically changes the shielding efficiency of the Salisbury screen (SER). In particular, SER≥40 dB is achieved in the range of 302–309 K for the sample with x = 0.9, outside of the range SE rapidly decreases to 10–15 dB. The impact of temperature has to be considered for the efficient use of shielding materials in Ka and V bands for different applications.

There are limited data on ethical issues related to the daily practice of members of the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN). The role of the ESPGHAN Ethics Committee (EC) is to provide advice on such matters to its members. The present survey aimed to evaluate the current function, and reasons that ESPGHAN members consulted the ECs. One hundred and five participants from 24 different countries answered the questionnaire. Thirty-five point seven percent of the participants used the ESGHAN EC to ask about clinical practice problems and patient-related issues whereas 21.4% ask about human research questions. An important additional finding was that 66.3% of respondents consulted their hospital’s EC when they had ethical concerns and 17.4% consulted with other colleagues with expertise. This is the first survey in the ESPGHAN and Europe that analyses ethical issues that are important to members of the National Societies for Pediatric Gastroenterology Hepatology and Nutrition.

There are limited data on ethical issues related to the daily practice of members of the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN). The role of the ESPGHAN Ethics Committee (EC) is to provide advice on such matters to its members. The present survey aimed to evaluate the current function, and reasons that ESPGHAN members consulted the ECs. One hundred and five participants from 24 different countries answered the questionnaire. Thirty-five point seven percent of the participants used the ESGHAN EC to ask about clinical practice problems and patient-related issues whereas 21.4% ask about human research questions. An important additional finding was that 66.3% of respondents consulted their hospital’s EC when they had ethical concerns and 17.4% consulted with other colleagues with expertise. This is the first survey in the ESPGHAN and Europe that analyses ethical issues that are important to members of the National Societies for Pediatric Gastroenterology Hepatology and Nutrition.

The development of the human immune system lasts for several years after birth. The impact of this maturation phase on the quality of adaptive immunity and the acquisition of immunological memory after infection at a young age remains incompletely defined. Here, using an antigen-reactive T cell (ARTE) assay and multidimensional flow cytometry, we profiled circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–reactive CD3+CD4+CD154+T cells in children and adults before infection, during infection, and 11 months after infection, stratifying children into separate age groups and adults according to disease severity. During SARS-CoV-2 infection, children younger than 5 years old displayed a lower antiviral CD4+T cell response, whereas children older than 5 years and adults with mild disease had, quantitatively and phenotypically, comparable virus-reactive CD4+T cell responses. Adults with severe disease mounted a response characterized by higher frequencies of virus-reactive proinflammatory and cytotoxic T cells. After SARS-CoV-2 infection, preschool-age children not only maintained neutralizing SARS-CoV-2–reactive antibodies postinfection comparable to adults but also had phenotypically distinct memory T cells displaying high inflammatory features and properties associated with migration toward inflamed sites. Moreover, preschool-age children had markedly fewer circulating virus-reactive memory B cells compared with the other cohorts. Collectively, our results reveal unique facets of antiviral immunity in humans at a young age and indicate that the maturation of adaptive responses against SARS-CoV-2 toward an adult-like profile occurs in a progressive manner.

Neuromuscular blocking agents (NMBAs) relax skeletal muscles to facilitate surgeries and ease intubation but can lead to adverse reactions, including complications because of postoperative residual neuromuscular blockade (rNMB) and, in rare cases, anaphylaxis. Both adverse reactions vary between types of NMBAs, with rocuronium, a widely used nondepolarizing NMBA, inducing one of the longest rNMB durations and highest anaphylaxis incidences. rNMB induced by rocuronium can be reversed by the synthetic γ-cyclodextrin sugammadex. However, in rare cases, sugammadex can provoke anaphylaxis. Thus, additional therapeutic options are needed. Rocuronium-induced anaphylaxis is proposed to rely on preexisting rocuronium-binding antibodies. To understand the pathogenesis of rocuronium-induced anaphylaxis and to identify potential therapeutics, we investigated the memory B cell antibody repertoire of patients with suspected hypersensitivity to rocuronium. We identified polyclonal antibody repertoires with a high diversity among V(D)J genes without evidence of clonal groups. When recombinantly expressed, these antibodies demonstrated specificity and low affinity for rocuronium without cross-reactivity for other NMBAs. Moreover, when these antibodies were expressed as human immunoglobulin E (IgE), they triggered human mast cell activation and passive systemic anaphylaxis in transgenic mice, although their affinities were insufficient to serve as reversal agents. Rocuronium-specific, high-affinity antibodies were thus isolated from rocuronium-immunized mice. The highest-affinity antibody was able to reverse rocuronium-induced neuromuscular blockade in nonhuman primates with kinetics comparable to that of sugammadex. Together, these data support the hypothesis that antibodies cause anaphylactic reactions to rocuronium and pave the way for improved diagnostics and neuromuscular blockade reversal agents.

ABSTRACTBackground:Formative assessment of the rollout process of the California Oral Health Literacy (OHL) toolkit uses a mixed-methods approach. The OHL toolkit is an educational resource for dental professionals to improve communication with patients. This study was intended to obtain user feedback and suggestions for improvement.Methods:This mixed-methods assessment of the OHL toolkit rollout included anonymous post-training surveys distributed at regional dental societies in California and 1:1 interviews with dental champions who would work with the research team on toolkit rollout. Anonymous and deidentified data were analyzed using R and Dedoose.Results:From surveys (n = 37), the OHL toolkit components of highest interest to respondents were teach-back, increasing health literacy awareness among staff and learning to use plain language communication. Perceived implementation barriers were time constraints, insufficient staffing and a need for more training on communication techniques. Impressions, implementation prospects and recommendations for the OHL toolkit were obtained from qualitative interviews (n = 6). Overall, participants had positive impressions of the training presentation, OHL toolkit and implementation prospects.Conclusion:This study identified interest areas and implementation barriers, data that can be used to further improve the OHL toolkit and reduce barriers faced by practitioners. Further assessments at clinician and patient levels will be helpful for outcomes evaluation.Practical implications:The OHL toolkit is perceived positively by dental practitioners in California. Facilitators and barriers identified by dental providers and champions can be addressed through changes to the OHL toolkit and training. Rollout at the national level is being considered.

Healthcare-associated infections (HAI) and antimicrobial use (AMU) are drivers for antimicrobial resistance, and robust data are required to inform interventions and track changes. We aimed to estimate the prevalence of HAI and AMU at Port Moresby General Hospital (PMGH), the largest hospital in Papua New Guinea.

AbstractI give a short and completely elementary proof of Takagi’s 1921 theorem on the zeros of a composite polynomial .

Objective: Orotracheal intubation is a life-saving procedure commonly performed in the Intensive Care unit and Emergency Department as a part of emergency airway management. Prior to the COVID-19 pandemic, our center undertook a prospective observational study to characterize emergency intubation performed in the emergency department and critical care settings at Manitoba’s largest tertiary hospital. During this study, a natural experiment emerged when a standardized “COVID-Protected Rapid Sequence Intubation Protocol” was implemented in response to the pandemic. The resultant study aimed to answer the question; in adult ED patients undergoing emergent intubation by EM and CCM teams, does the use of a “COVID-Protected Rapid Sequence Intubation Protocol” impact first-pass success or other intubation-related outcomes? Methods: A single-center prospective quasi-experimental before and after study was conducted. Data were prospectively collected on consecutive emergent intubations. The primary outcome was the difference in first-pass success rates. Secondary outcomes included best Modified Cormack–Lehane view, hypoxemia, hypotension, esophageal intubation, cannot intubate cannot oxygenate scenarios, CPR post intubation, vasopressors required post intubation, Intensive Care Unit (ICU) mortality, ICU length of stay (LOS), and mechanical ventilation days. Results: Data were collected on 630 patients, 416 in the pre-protocol period and 214 in the post-protocol period. First-pass success rates in the pre-protocol period were found to be 73.1% (n= 304). Following the introduction of the protocol, first-pass success rates increased to 82.2% (n= 176, p= 0.0105). There was a statistically significant difference in Modified Cormack–Lehane view favoring the protocol (p= 0.0191). Esophageal intubation rates were found to be 5.1% pre-protocol introduction versus 0.5% following the introduction of the protocol (p= 0.0172). Conclusion: A “COVID-Protected Protocol” implemented by Emergency Medicine and Critical Care teams in response to the COVID-19 pandemic was associated with increased first-pass success rates and decreases in adverse events.

Alagille syndrome is a rare genetic disease that often presents with severe cholestasis and pruritus. There are no approved drugs for management. Maralixibat, an apical, sodium-dependent, bile acid transport inhibitor, prevents enterohepatic bile acid recirculation. We evaluated the safety and efficacy of maralixibat for children with cholestasis in Alagille syndrome.

Introduction: Oral disease is a widespread problem in Nepal. However, up-to-date information on oral health is limited and oral health initiatives may be shaped by assumptions about insufficient oral health knowledge. Furthermore, the influence of socio-demographic factors on oral health in Nepal remains unclear. This study aims to explore the relationship between demographic background and oral health knowledge, attitudes and behaviors in rural Nepal. Methods: Secondary analysis of data from a community-based survey on oral health knowledge, beliefs, practices, and access to care among residents ages 12 and above across 4 rural villages in Nepal's Kaski District (Total number = 3,243). Chi-square tests were performed to examine associations among oral health knowledge, attitudes and behaviors and demographic characteristics. Results: Participants reported a baseline knowledge of oral health; 92.4% knew about the recommended tooth-brushing regimen. Participants with higher education and younger age demonstrated better oral health knowledge. Misconceptions about dental treatment causing blindness (23.1%), deafness (11.6%), and mental health problems (14.9%) were reported across all groups. Conclusion: Numerous factors besides knowledge likely determine individual oral health behavior. Future interventions should consider community-based outreach programs and dental care delivery through community Health Posts to build trust in dental care, build on existing knowledge and community experiences, and improve access to preventative care. Up-to-date understanding of oral health knowledge and practices and sociocultural influences on oral health behavior will better focus interventions and policy decisions. [ABSTRACT FROM AUTHOR]

En métropole, près de 20 nouveaux cas de lèpre sont diagnostiqués chaque année. L’incidence de la tuberculose en France est de 8/100 000 habitants et l’association des 2 mycobactéries a été exceptionnellement rapportée. Nous rapportons un cas de co-infection lèpre Borderline Tuberculoïde (BT) et tuberculose disséminée, diagnostiqué en métropole.

Ophthalmic abnormalities are amongst the 5 major criteria required for a diagnosis of Alagille syndrome (ALGS), of which embryotoxon, pseudopapilledema, and hypopigmented retinopathy are the most common. Papilledema with or without intracranial hypertension (ICHT) is rarely described. We report 9 pediatric cases of ALGS with bilateral papilledema, 5 of which were diagnosed with ICHT. The ophthalmic data from 85 patients with clinically and/or genetically (n?=?37) proven ALGS were reviewed. The study inclusion criteria were a positive diagnosis of ALGS and availability of ophthalmic follow-up data. Ophthalmic data from 40 patients after liver transplantation (LT) for other indications were also analyzed. Nine (13.0%) of the 69 patients meeting the inclusion criteria had papilledema. The neurological and neuroimaging results in all 9 patients were normal. These 9 patients were categorized into 4 groups: a nontransplant group (n?=?1), a group with pretransplant papilledema persistent after LT (n?=?2), a group with papilledema occurring after LT with spontaneous resolution (n?=?1), and a group with papilledema and signs of ICHT after LT (n?=?5). The patients with ICHT were treated with steroids alone (n?=?1) or with acetazolamide (n?=?4). A ventriculoperitoneal shunt was placed in 2 of the 5 cases because of progressive visual loss. Pseudopapilledema was present in 10 additional patients (14.5%, 10/69). One (2.5%) of the 40 patients without ALGS developed papilledema after LT. True ICHT may be underdiagnosed in patients with ALGS. Our findings underscore the need for close ophthalmic follow-up before and after LT in these patients.

Reactivation of hepatitis B virus (HBV) is a known complication of immune-suppressive, cytotoxic, and biological modifier therapies in patients currently infected with HBV or who have had past exposure to HBV. Nowadays, newer and emerging forms of targeted biologic therapies are available for the management of rheumatologic conditions, malignancies, inflammatory bowel disease, dermatologic conditions and solid-organ, bone marrow, or haematologic stem cell transplant but there is currently a lack of a systematic approach to the care of patients with or at risk of HBV reactivation. The Hepatology Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) together with a working group of ESPGHAN members with clinical and research expertise in viral hepatitis developed an evidence-based position paper on reactivation of HBV infection in children identifying pertinent issues addressing the diagnosis, prevention, and treatment of this condition. Relevant clinical questions were formulated and agreed upon by all the members of the working group. Questions were answered and positions were based on evidence resulting from a systematic literature search on PubMed and Embase from their inception to July 1, 2019. A document was produced and the working group and ESPGHAN Hepatology Committee members voted on each recommendation, using a formal voting technique. A recommendation was accepted provided upon agreement by at least 75% of the working group members. This position paper provides a comprehensive update on the diagnosis, prevention and treatment of HBV reactivation in children.

Senescence-associated beta-galactosidase (SA-β-gal) activity assay is commonly used to evaluate the increased beta-galactosidase (β-gal) activity in senescent cells related to enhanced lysosomal activity. Although the optimal pH for β-gal is 4.0, this enzymatic activity has been most commonly investigated at a suboptimal pH by using histochemical reaction on fresh tissue material. In the current study, we optimized a SA-β-gal activity histochemistry protocol that can also be applied on cryopreserved hepatic tissue. This protocol was developed on livers obtained from control rats and after bile duct resection (BDR). A significant increase in β-gal liver activity was observed in BDR rats vs controls after 2 hr of staining at physiological pH 4.0 (6.98 ± 1.19% of stained/total area vs 0.38 ± 0.22; p<0.01) and after overnight staining at pH 5.8 (24.09 ± 6.88 vs 0.12 ± 0.08; p<0.01). Although we noticed that β-gal activity staining decreased with cryopreservation time (from 4 to 12 months of storage at −80C; p<0.05), the enhanced staining observed in BDR compared with controls remained detectable up to 12 months after cryopreservation (p<0.01). In conclusion, we provide an optimized protocol for SA-β-gal activity histochemical detection at physiological pH 4.0 on long-term cryopreserved liver tissue:

I study the sequences of Euler and Springer numbers from the point of view of the classical moment problem. [ABSTRACT FROM AUTHOR]

AbstractWe consider two different interpretations of the celebrated Chu–Vandermonde identity: as an identity for polynomials, and as an identity for infinite matrices. Each interpretation leads to a class of possible generalizations, and in both cases we obtain a complete characterization of the solutions.

L’angiocholite est une infection de la bile et des voies biliaires, secondaire dans la majorité des cas à une obstruction des voies biliaires. Les étiologies en sont multiples, dominées par la maladie lithiasique et les néoplasies. Le diagnostic clinique repose sur la triade de Charcot (douleur, fièvre, ictère) mais sa sensibilité insuffisante a mené à son remplacement par un score plus complexe, ajoutant des données biologiques et radiologiques, validé par les Tokyo Guidelines depuis 2007. En cas de suspicion diagnostique, l’échographie abdominale permet une exploration rapide des voies biliaires mais ses performances diagnostiques sont médiocres, surtout en cas d’obstacle non lithiasique, contrairement à l’IRM pancréato-biliaire et l’écho-endoscopie dont les performances diagnostiques sont excellentes. Le scanner abdomino-pelvien reste néanmoins le plus disponible, avec des performances diagnostiques intermédiaires. La réalisation de prélèvements microbiologiques tels que les hémocultures (positives dans 40 % des cas) et les cultures biliaires est indispensable. En cas d’angiocholite « communautaire », les 2 pathogènes les plus fréquents sont Escherichia coliet Klebsiellaspp., justifiant une antibiothérapie probabiliste par céphalosporine de 3egénération. L’intérêt d’une couverture systématique des entérocoques et des anaérobies est encore débattu, habituellement recommandée en cas d’angiocholite associée aux soins, en présence de critères de gravité pour l’entérocoque, et en présence d’une anastomose bilio-digestive pour les anaérobies. L’existence d’une prothèse biliaire est le seul facteur de risque identifié d’infection à bactérie multirésistante. À l’antibiothérapie doit s’ajouter un drainage des voies biliaires endoscopique ou radiologique. Malgré les progrès dans la prise en charge, la mortalité des angiocholites reste d’environ 5 %.

Progressive familial intrahepatic cholestasis (PFIC) is a group of autosomal recessive disorders, the most prevalent being BSEP deficiency, resulting in disrupted bile formation, cholestasis, and pruritus. Building on a previous phase 2 study, we aimed to evaluate the efficacy and safety of maralixibat—an ileal bile acid transporter inhibitor—in participants with all types of PFIC.

Stimulation of diuresis is an essential component of heart failure treatment to reduce fluid overload. Over time, increasing doses of loop diuretics are required to achieve adequate urine output, and approximately 30% to 45% of patients develop diuretic resistance. We investigated the feasibility of affecting renal afferent sensory nerves by dorsal root ganglion neurostimulation as an alternative to medication to increase diuresis.

Background: The global nutrition transition is associated with increased consumption of ultra-processed snack foods and sugar-sweetened beverages (UPF/SSB), contributing to the double burden of child obesity and undernutrition. Methods: This cross-sectional study describes the prevalence of maternal and child UPF/SSB consumption and the factors associated with frequent consumption in a convenience sample of 749 children ages 6 months through 6 years and their mothers participating in a community-based child oral health program in five informal settlement communities in Mumbai, India. Mothers were interviewed regarding maternal and child oral health and nutrition characteristics, including consumption of beverages and foods associated with tooth decay—milk, soda, tea with sugar, sweets, and chips/biscuits—using standardized questionnaires. Spearman correlations were used to assess for associations between various social factors and the frequency of maternal and child consumption of the five food categories. Chi-square tests were used to assess differences in child consumption patterns by age groups. Results: Though reported soda consumption was low among both mothers and children, nearly 60% of children consumed sweets and chips/biscuits daily, four to five times the rate of mothers. Factors associated with children’s frequent consumption of UPF/SSB included lower maternal education level, frequent maternal consumption of UPF/SSB, greater number of household members, greater amount of money given to the child, and closer proximity to a store. Conclusion: Our findings demonstrate social factors that may promote UPF/SSB consumption. The nutritional dangers of sugary drinks and non-nutritious snacks for mothers and young children should be addressed across maternal–child health, education, and social service programs. Early childhood nutrition interventions should involve the entire family and community and emphasize the need to limit children’s consumption of unhealthy foods and beverages from an early age.

Most tumours have an aberrantly activated lipid metabolism1,2that enables them to synthesize, elongate and desaturate fatty acids to support proliferation. However, only particular subsets of cancer cells are sensitive to approaches that target fatty acid metabolism and, in particular, fatty acid desaturation3. This suggests that many cancer cells contain an unexplored plasticity in their fatty acid metabolism. Here we show that some cancer cells can exploit an alternative fatty acid desaturation pathway. We identify various cancer cell lines, mouse hepatocellular carcinomas, and primary human liver and lung carcinomas that desaturate palmitate to the unusual fatty acid sapienate to support membrane biosynthesis during proliferation. Accordingly, we found that sapienate biosynthesis enables cancer cells to bypass the known fatty acid desaturation pathway that is dependent on stearoyl-CoA desaturase. Thus, only by targeting both desaturation pathways is the in vitro and in vivo proliferation of cancer cells that synthesize sapienate impaired. Our discovery explains metabolic plasticity in fatty acid desaturation and constitutes an unexplored metabolic rewiring in cancers.