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Mutations in the Budding uninhibited by benzimidazoles (BUB1) gene were recently associated with neurodevelopmental disorders (Carvalhal et al., 2022). Here, we describe the generation and characterization of two induced pluripotent stem cells (iPSC) clones from a young female with microcephaly. The patient carried two variants in the BUBfibroblast gene (OMIM # 602452), one (c.[2197dupG]; p.[D732fs*11]) paternally inherited and one (c.[2625+1G>A]; p.[V822_L875del] maternally inherited. The generated clones exhibit a normal karyotype (UALGi003-A) and trisomy 8 (UALGi003-B), express pluripotency markers, and differentiate into trilineage cells in vitro. These cell lines can be used to study neurodevelopment and the processes of chromosome segregation.

Objective: Hepatic steatosis is a key initiating event in the pathogenesis of alcohol-associated liver disease (ALD), the most detrimental organ damage resulting from alcohol use disorder. However, the mechanisms by which alcohol induces steatosis remain incompletely understood. We have previously found that alcohol binging impairs brain insulin action, resulting in increased adipose tissue lipolysis by unrestraining sympathetic nervous system (SNS) outflow. Here, we examined whether an impaired brain–SNS–adipose tissue axis drives hepatic steatosis through unrestrained adipose tissue lipolysis and increased lipid flux to the liver. Methods: We examined the role of lipolysis, and the brain–SNS–adipose tissue axis and stress in alcohol induced hepatic triglyceride accumulation in a series of rodent models: pharmacological inhibition of the negative regulator of insulin signaling protein-tyrosine phosphatase 1β (PTP1b) in the rat brain, tyrosine hydroxylase (TH) knockout mice as a pharmacogenetic model of sympathectomy, adipocyte specific adipose triglyceride lipase (ATGL) knockout mice, wildtype (WT) mice treated with β3 adrenergic agonist or undergoing restraint stress. Results: Intracerebral administration of a PTP1b inhibitor, inhibition of adipose tissue lipolysis and reduction of sympathetic outflow ameliorated alcohol induced steatosis. Conversely, induction of adipose tissue lipolysis through β3 adrenergic agonism or by restraint stress worsened alcohol induced steatosis. Conclusions: Brain insulin resistance through upregulation of PTP1b, increased sympathetic activity, and unrestrained adipose tissue lipolysis are key drivers of alcoholic steatosis. Targeting these drivers of steatosis may provide effective therapeutic strategies to ameliorate ALD.

The use of biobased polymers or natural inorganic materials in place of synthetic polymers or liquid crystals derived from petroleum to fabricate optical components establishes the concept of “sustainable optics”, at least for what concerns the environmental dimension of sustainability as these polymers are renewable and often biodegradable or compostable. To identify the main obstacles to be addressed prior to industrial uptake of these polymeric resins in the optics industry, we focus on two promising and widely studied biobased polymeric materials, namely nanocellulose and poly(limonene carbonate). The conclusions have implications also for the emerging bioeconomy and the undergoing reshaping of the chemical industry driven by sustainability megatrend.

Left Ventricular Noncompaction Cardiomyopathy (LVNC) is characterized by abnormal number and prominence of trabeculations of the left ventricle of the heart. Although LVNC has been associated with mutations in several genes encoding for transcriptional regulators, ion channels, sarcomeric and mitochondrial proteins, approximately 60% of LVNC patients do not present these genetic alterations. Here, we describe an induced pluripotent stem cell (hiPSC) line (UALGi002-A) originated from a LVNC female patient (LVNC-hiPSC) who does not present any previously known mutations associated to LVNC. The LVNC-hiPSC exhibited full pluripotency and differentiation potential and retained a normal karyotype after reprogramming. Moreover, the LVNC-hiPSC differentiated into contracting cardiomyocytes. This cellular model will be useful to study the molecular, genetic and functional aspects of LVNC in vitro.

Introduction and Objectives: There is no consensus on the best treatment option for choledocholithiasis. Therefore, the aim of this study was to compare endoscopic retrograde cholangiopancreatography (ERCP) and common bile duct surgery (CBDS) for the treatment of choledocholithiasis. Materials and methods: We performed a systematic review of randomized controlled trials (RCTs) comparing ERCP and CBDS in the treatment of choledocholithiasis. MEDLINE and EMBASE were the used databases. RCTs assessing mortality, bile duct clearance failure, complications, or length of hospital stay were considered eligible. Meta-analysis was performed using random effects model, through the Mantel–Haenszel method for binary outcomes and through the inverse variance method for continuous outcomes. The quality of the evidence was evaluated according to the Grading of Recommendations Assessment, Development and Evaluation Working Group. The study protocol was registered at the PROSPERO platform (CRD42017073196). Results: Nineteen RCTs (2466 patients) were included in the meta-analysis. There was no evidence of significant difference between interventions regarding mortality (risk ratio – RR = 1.31, 95% confidence interval – 95% CI = 0.60–2.85, p = 0.49), bile duct clearance failure (RR = 1.17, 95% CI = 0.86–1.59, p = 0.31), complications (RR = 0.99, 95% CI = 0.82–1.20, p = 0.94) and length of hospital stay (weighted mean difference – MD = 1.06, 95% CI = −0.62–2.73, p = 0.22). Sensitivity analyses failed to demonstrate significant changes in results compared to the main analyses. The quality of the evidence was considered to be low. Conclusion: There was no evidence of significant difference between ERCP and CBDS for the treatment of choledocholithiasis.

Left Ventricular Noncompaction Cardiomyopathy (LVNC) is characterized by excessive trabeculation of the left ventricle. To date, mutations in more than 40 genes have been associated with LVNC, however the exact mechanisms underlying the disease remain unknown. Here, we describe an induced pluripotent stem cell (iPSC) line (UALGi001-A) from a LVNC patient (LVNC-iPSC) that does not present mutations in the genes most commonly associated with the disease (van Waning et al., 2019). The LVNC-iPSC exhibited full pluripotency and differentiation potential, and retained a normal karyotype after reprogramming. This in vitro cellular model will be useful to study the molecular, genetic and functional aspects of LVNC.

Purpose: To present the case of two siblings with a genetic diagnosis of Bardet Biedl syndrome (BBS) type 1, yet different clinical profiles and disease manifestations. Observations: Sequencing analysis revealed a p.Met390Arg pathogenic variant in the BBS1 gene of both patients, as well as several additional variants of uncertain significance Patient 1 was 41 years old, had three primary (cone-rod dystrophy, hypogonadism, and truncal obesity) and three secondary (arterial hypertension, strabismus, and astigmatism) BBS features. He also had insulin resistance, as well as low levels of total testosterone and cortisol. Patient 2 was 43 years old, had two primary (cone-rod dystrophy and truncal obesity), and four secondary (arterial hypertension, diabetes mellitus, strabismus, and astigmatism) BBS features. Both patients had severe maculopathy; however, patient 1 had bone-spicules that extended up to the mid-periphery, in a perivenular pattern, and significant vascular attenuation with “ghost vessel” appearance towards the temporal periphery, a feature that was absent on patient 2. Conclusions and Importance: The intrafamilial phenotypic variability among our patients supports the hypothesis that BBS is a disease with genetic, hormonal, and environmental triggers interacting to produce phenotypic variability. Although our report may not establish a definite relationship between environmental and genetic influences, their role should be explored in future studies.

Retinitis pigmentosa (RP) is an inherited retinal degenerative disease. Mutations in EYS have been associated with autosomal recessive RP. The human iPS cell line, CABi002-A, derived from peripheral blood mononuclear cells from a patient carrying a heterozygous double mutation in EYS gene was generated by non-integrative reprogramming technology, using hOCT3/4, hSOX2, hc-MYC and hKLF4 reprogramming factors. Pluripotency and differentiation capacity were assessed by immunocytochemistry and RT-PCR. This iPSC line can be further differentiated towards the affected cells to understand the pathophysiology of the disease and test new therapeutic strategies.

Purpose: Postoperative recovery is a complex process with physiologic, functional, and psychologic dimensions. Postoperative quality of recovery is considered as a crucial outcome following surgery and anesthesia. The objective of this study was to assess and compare the quality of postoperative recovery and health status before and after surgery, in patients undergoing elective surgery. Methods: This observational, prospective study was conducted on patients proposed for elective surgery. Evaluation of postoperative recovery was performed using the Postoperative Quality of Recovery Scale and health status was assessed by applying the EuroQol assessing problems in five dimensions: mobility, personal care, usual activities, pain/discomfort, and anxiety/depression, and the World Health Organization Disability Assessment Schedule 2.0. Poor quality of recovery was defined as recovery in fewer than two domains at postoperative Day 1 in the Postoperative Quality of Recovery Scale. Results: Before surgery (D0), patients with poor quality of recovery had median Visual Analog Scale scores in EuroQol similar to those of patients without poor quality of recovery, but they had more problems in the mobility, usual activities, pain/discomfort, and anxiety/depression dimensions. At 3 months after surgery, patients with poor quality of recovery had median Visual Analog Scale scores in EuroQol similar to those of patients without poor quality of recovery, but they maintained more problems in the pain/discomfort dimension. Patients with poor quality of recovery scored significantly higher on the World Health Organization Disability Assessment Schedule 2.0 scale at baseline, although the results were similar at 3 months. Conclusions: Patients with poor quality of recovery had the worst health status at D0. Evaluation at 3 months indicated similar rates of problems in EuroQol (except for pain/discomfort) and World Health Organization Disability Assessment Schedule 2.0 scores were similar. Resumo: Objetivo: A recuperação pós-operatória é um processo complexo com dimensões fisiológicas, funcionais e psicológicas. A qualidade da recuperação pós-operatória é considerada um resultado crucial após cirurgia e anestesia. O objetivo deste estudo foi avaliar e comparar a qualidade da recuperação pós-operatória e o estado de saúde antes e depois da cirurgia em pacientes submetidos à cirurgia eletiva. Métodos: Este estudo observacional prospectivo foi feito com pacientes agendados para cirurgia eletiva. A avaliação da recuperação pós-operatória foi feita usando a Escala de Qualidade da Recuperação Pós-operatória (Postoperative Quality of Recovery Scale) e o estado de saúde foi avaliado com a aplicação do EuroQol, que analisa problemas em cinco dimensões (mobilidade, cuidados pessoais, atividades habituais, dor/desconforto e ansiedade/depressão) e a ferramenta para medida de incapacidade desenvolvida pela Organização Mundial da Saúde (World Health Organization Disability Assessment Schedule 2.0). Má qualidade de recuperação foi definida como uma recuperação em menos de dois domínios da Escala de Qualidade da Recuperação Pós-operatória no primeiro dia (D1) de pós-operatório. Resultados: Antes da cirurgia (D0), os pacientes com má qualidade de recuperação apresentaram escores medianos na escala visual analógica semelhantes aos dos pacientes sem má qualidade de recuperação, mas apresentaram mais problemas nas dimensões mobilidade, atividades habituais, dor/desconforto e ansiedade/depressão. No terceiro mês após a cirurgia, os pacientes com má qualidade de recuperação apresentaram escores na escala visual analógica medianos no EuroQol semelhantes aos dos pacientes sem má qualidade de recuperação, mas apresentaram mais problemas na dimensão dor/desconforto. Os escores World Health Organization Disability Assessment Schedule 2.0 dos pacientes com má qualidade de recuperação foram significativamente maiores no início do estudo, embora os resultados tenham sido semelhantes no terceiro mês. Conclusões: Os pacientes com má qualidade de recuperação apresentaram o pior estado de saúde no D0. A avaliação no terceiro mês indicou taxas semelhantes de problemas no EuroQol (exceto dor/desconforto) e escores semelhantes no World Health Organization Disability Assessment Schedule 2.0. Keywords: Postoperative recovery, Poor quality of recovery, Health status, WHODAS, EQ-5D, Palavras-chave: Recuperação pós-operatória, Má qualidade da recuperação, Estado de saúde, WHODAS, EQ-5D

Age-related macular degeneration (AMD) is the leading cause of adult blindness in developed countries and is characterized by progressive degeneration of the macula, the central region of the retina. A human induced pluripotent stem cell (hiPSC) line was derived from peripheral blood mononuclear cells (PBMCs) from a patient with a clinical diagnosis of dry AMD carrying the CFH Y402H polymorphism. Sendai virus was using for reprogramming and the pluripotent and differentiation capacity of the cells were assessed by immunocytochemistry and RT-PCR.

PRPF31 gene codes for a ubiquitously expressed splicing factor but mutations affect exclusively the retina, producing the progressive death of photoreceptor cells. We have identified a novel PRPF31 mutation in a patient with autosomal dominant retinitis pigmentosa. A blood sample was obtained and mononuclear cells were reprogrammed using the non-integrative Sendai virus to generate the cell line CABi001-A. The iPSC line has been characterized for pluripotency and differentiation capacity and will be differentiated toward photoreceptors and retinal pigment epithelium cells to study the molecular mechanism of the disease and test possible therapeutic strategies.

Summary: The host-microbiota relationship has evolved to shape mammalian physiology, including immunity, metabolism, and development. Germ-free models are widely used to study microbial effects on host processes such as immunity. Here, we find that both germ-free and T cell-deficient mice exhibit a robust sebum secretion defect persisting across multiple generations despite microbial colonization and T cell repletion. These phenotypes are inherited by progeny conceived during in vitro fertilization using germ-free sperm and eggs, demonstrating that non-genetic information in the gametes is required for microbial-dependent phenotypic transmission. Accordingly, gene expression in early embryos derived from gametes from germ-free or T cell-deficient mice is strikingly and similarly altered. Our findings demonstrate that microbial- and immune-dependent regulation of non-genetic information in the gametes can transmit inherited phenotypes transgenerationally in mice. This mechanism could rapidly generate phenotypic diversity to enhance host adaptation to environmental perturbations.

Summary: Strain-level variation in Staphylococcus aureus is a factor that contributes to disease burden and clinical outcomes in skin disorders and chronic wounds. However, the microbial mechanisms that drive these variable host responses are poorly understood. To identify mechanisms underlying strain-specific outcomes, we perform high-throughput phenotyping screens on S. aureus isolates cultured from diabetic foot ulcers. Isolates from non-healing wounds produce more staphyloxanthin, a cell membrane pigment. In murine diabetic wounds, staphyloxanthin-producing isolates delay wound closure significantly compared with staphyloxanthin-deficient isolates. Staphyloxanthin promotes resistance to oxidative stress and enhances bacterial survival in neutrophils. Comparative genomic and transcriptomic analysis of genetically similar clinical isolates with disparate staphyloxanthin phenotypes reveals a mutation in the sigma B operon, resulting in marked differences in stress response gene expression. Our work illustrates a framework to identify traits that underlie strain-level variation in disease burden and suggests more precise targets for therapeutic intervention in S. aureus-positive wounds.

Summary: Programmed DNA loss is a gene silencing mechanism that is employed by several vertebrate and nonvertebrate lineages, including all living jawless vertebrates and songbirds. Reconstructing the evolution of somatically eliminated (germline-specific) sequences in these species has proven challenging due to a high content of repeats and gene duplications in eliminated sequences and a corresponding lack of highly accurate and contiguous assemblies for these regions. Here, we present an improved assembly of the sea lamprey (Petromyzon marinus) genome that was generated using recently standardized methods that increase the contiguity and accuracy of vertebrate genome assemblies. This assembly resolves highly contiguous, somatically retained chromosomes and at least one germline-specific chromosome, permitting new analyses that reconstruct the timing, mode, and repercussions of recruitment of genes to the germline-specific fraction. These analyses reveal major roles of interchromosomal segmental duplication, intrachromosomal duplication, and positive selection for germline functions in the long-term evolution of germline-specific chromosomes.

The promising applications of metal-organic frameworks (MOF) can be widened if these materials were additive manufactured to develop three-dimensional (3D) MOF architectures. In this work, iron-based MOF/silicon carbide (SiC) composite aqueous inks with a high solids content (64 ​wt%) are printed into 3D periodic lattices by a direct ink writing technique (Robocasting). MOF appear fully integrated within the cellular architectures, which display total porosities in the range of 74–78% depending on the scaffold design. The 3D MOF-Fe/SiC structures exhibit good mechanical strength (~4.6 ​MPa) and a semiconductor-like behaviour. The structures show a remarkable response in the hydroxylation of phenol with hydrogen peroxide, demonstrating high selectivity and yield to dihydroxybenzene species.

A simple flow chemistry microreactor with an electrospray ionization tip for real time mass spectrometric reaction monitoring is introduced. The microreactor was fabricated by a laser-based additive manufacturing technique from acid-resistant stainless steel 316L. The functionality of the microreactor was investigated by using an inverse electron demand Diels-Alder and subsequent retro Diels-Alder reaction for testing. Challenges and problems encountered are discussed and improvements proposed. Adsorption of reagents to the rough stainless steel channel walls, short length of the reaction channel, and making a proper ESI tip present challenges, but the microreactor is potentially useful as a disposable device.

Neospora caninum is an apicomplexan (family: Sarcocystidae) protozoan parasite with a global distribution. In the N. caninum life cycle, dogs and other related canids are the definitive hosts, while other animals such as water buffaloes (Bubalus bubalis) constitute the intermediate host for this parasite. In many countries, the water buffalo is of high economic importance, providing valuable high-quality products for human needs. Although knowledge concerning the prevalence of this parasite in intermediate animal host populations is crucial, data from water buffalo are scarce. Keeping this in mind, the aim of this study was to examine the presence and assess the prevalence rates of N. caninum infection in water buffaloes in Northern Greece, where this animal husbandry sector started to raise, as well as to determine associated risk factors, with the application of a commercially available Neospora ISCOM ELISA test kit, developed for the detection of antibodies against N. caninum in milk samples The study was conducted during January-June 2023 in a total of 172 individual raw milk samples, collected from dairy buffaloes, reared under a semi extensive system, in three different farms. Information on the status of N. caninum infection in buffaloes from Greece was so far unknown with a lack of epidemiological or risk factors associated. For the detection of N. caninum, the commercially available Neospora ISCOM ELISA test kit (SANOVIR ®, Svanova Biotech AB, Uppsala, Sweden) was utilized. Results demonstrated the presence of N. caninum in water buffaloes from Greece for the first time. All positive N. caninum animal were asymptomatic, with absence of any disease signs. The overall prevalence of infection was 22.10%, whereas the main risk factors include the presence of dogs as well as the low biosecurity measures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this study., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The expansion of the world's merchant fleet poses a great threat to the ocean's biodiversity. Collisions between ships and marine megafauna can have population-level consequences for vulnerable species. The Endangered whale shark (Rhincodon typus) shares a circumglobal distribution with this expanding fleet and tracking of movement pathways has shown that large vessel collisions pose a major threat to the species. However, it is not yet known whether they are also at risk within aggregation sites, where up to 400 individuals can gather to feed on seasonal bursts of planktonic productivity. These "constellation" sites are of significant ecological, socio-economic and cultural value. Here, through expert elicitation, we gathered information from most known constellation sites for this species across the world (>50 constellations and >13,000 individual whale sharks). We defined the spatial boundaries of these sites and their overlap with shipping traffic. Sites were then ranked based on relative levels of potential collision danger posed to whale sharks in the area. Our results showed that researchers and resource managers may underestimate the threat posed by large ship collisions due to a lack of direct evidence, such as injuries or witness accounts, which are available for other, sub-lethal threat categories. We found that constellations in the Arabian Sea and adjacent waters, the Gulf of Mexico, the Gulf of California, and Southeast and East Asia, had the greatest level of collision threat. We also identified 39 sites where peaks in shipping activity coincided with peak seasonal occurrences of whale sharks, sometimes across several months. Simulated collision mitigation options estimated potentially minimal impact to industry, as most whale shark core habitat areas were small. Given the threat posed by vessel collisions, a coordinated, multi-national approach to mitigation is needed within priority whale shark habitats to ensure collision protection for the species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

A study was performed for the development and validation of a method of High Performance Liquid Chromatography (HPLC) for the identification and simultaneous quantification of Gallein and Human Serum Albumin (HSA). In addition, this work presents the development and physicochemical characterization of this new pharmaceutical formulation of HSA nanoparticles loaded with Gallein for potential use in the treatment of Alzheimer's disease. The method was developed with the purpose of determining the performance of the synthesis process of nanoparticles and the efficiency of encapsulation of the drug in the nanosystem. The HPLC mobile phase consisted of ACN:H 2 O:TEA:H 3 PO 4 (50:49.8:0.1:0.1 v/v/v) pumped at a flow rate of 0.8 mL/min, isocratic mode, and the measurement were carried out at 220 nm. Chromatographic runs were performed on a C18 column (150 × 4.60 mm; 5 μm size particles). The HPLC-method was validated following the International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines and was used to simultaneously quantify the two components of the nanoformulation. Thus, the values obtained through the validated method were 43 % for drug encapsulation efficiency (% EE) and the synthesis performance (% yield) was 96 %. Moreover, the nanoformulation was characterized by DLS, the results showed that the average particle size was 217 nm, with a PDI of (0.085 ± 0.005) and a potential Z of -29.7 mV. Therefore, the developed method has proven useful in providing accurate simultaneous measurements of HSA and Gallein from albumin nanoparticles. It is advantageous since it is able to reduce the time and facilitate the determination of Gallein encapsulation efficiency and yield of albumin nanoparticles., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Photoactivated adenylate cyclases (PACs) are light-activated enzymes that combine a BLUF (blue-light using flavin) domain and an adenylate cyclase domain that are able to increase the levels of the important second messenger cAMP (cyclic adenosine monophosphate) upon blue-light excitation. The light-induced changes in the BLUF domain are transduced to the adenylate cyclase domain via a mechanism that has not yet been established. One critical residue in the photoactivation mechanism of BLUF domains, present in the vicinity of the flavin is the glutamine amino acid close to the N5 of the flavin. The role of this residue has been investigated extensively both experimentally and theoretically. However, its role in the activity of the photoactivated adenylate cyclase, OaPAC has never been addressed. In this work, we applied ultrafast transient visible and infrared spectroscopies to study the photochemistry of the Q48E OaPAC mutant. This mutation altered the primary electron transfer process and switched the enzyme into a permanent 'on' state, able to increase the cAMP levels under dark conditions compared to the cAMP levels of the dark-adapted state of the wild-type OaPAC. Differential scanning calorimetry measurements point to a less compact structure for the Q48E OaPAC mutant. The ensemble of these findings provide insight into the important elements in PACs and how their fine tuning may help in the design of optogenetic devices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Premature ventricular contractions (PVC) are a type of ventricular arrhythmias, occurring as a result of formation or reentry of an abnormal impulse in the ventricular myocardium or in the Purkinje system. PVC occurs commonly in healthy individuals and is observed in 1%-4% of the population. Several lifestyle factors like stress levels, caffeine, drugs, alcohol, nicotine, sleep, and physical exercise have been implicated in increasing the risk. Caffeine and drugs precipitate heightened cardiac stimulation, precipitating PVCs. Excessive alcohol and nicotine disturb the electrical pathways resulting in PVCs. Higher rates of PVCs have been associated with obesity. Individuals with insomnia and increased stress levels are also at an increased risk due to an imbalance in the autonomic system. Exercise is known to induce PVCs, including in healthy, asymptomatic individuals. Modification of these factors can decrease PVC risk. This article aims to provide a comprehensive review of the effects of lifestyle factors on PVC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The list of organophosphate esters (OPEs) reported in the environment continues to expand as evidenced by the increasing number of OPE studies in the literature. However, there remains a general dearth of information on more recently produced and used OPEs that are proving to be emerging environmental contaminants. The present review summarizes the available studies in a systematic framework of the current state of knowledge on the analysis, environmental fate, and behavior of emerging OPEs. This review also details future directions to better understand emerging OPEs in the environment. Firstly, we make recommendations that the current structural/practical abbreviations and naming of OPEs be revised and updated. A chemical database (CDB) containing 114 OPEs is presently established based on the suspect list from the current scientific literature. There are 12 established OPEs and a total of 83 emerging OPEs that have been reported in human and/or biota samples. Of the emerging OPEs more than 80% have nearly 100% detection frequencies in samples of certain environmental media including indoor air, wastewater treatment plants, sediment, and fish. In contrast to OPEs considered established contaminants, most emerging OPEs have been identified more recently due to the more pervasive use of high-resolution mass spectrometry (HRMS) based approaches and especially gas or liquid chromatography coupled with HRMS-based non-target analysis (NTA) of environmental sample fractions. Intentional/unintentional industrial use and non-industrial formation are sources of emerging OPEs in the environment. Predicted physical-chemical properties in silico of newer, molecularly larger and more oligomeric OPEs strongly suggest that some compounds such as bisphenol A diphenyl phosphate (BPA-DPP) are highly persistent, bioaccumulative and/or toxic. Limited information on laboratory-based toxicity data has shown that some emerging OPEs elicit harmful effects such as cytotoxicity, development toxicity, hepatotoxicity, and endocrine disruption in exposed humans and mammals. Established, and to a much lesser degree emerging OPEs, have also been shown to transform and degrade in biota and possibly alter their toxicological effects. Research on emerging OPE contaminants is presently limited and more study is warranted on sample analysis methods, source apportionment, transformation processes, environmental behavior, biomarkers of exposure and toxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The U.S. Food and Drug Administration (FDA) developed an oral toxicological reference value (TRV) for characterizing potential health concerns from dietary exposure to cadmium (Cd). The development of the TRV leveraged the FDA's previously published research including (1) a systematic review for adverse health effects associated with oral Cd exposure and (2) a human physiological based pharmacokinetic (PBPK) model adapted from Kjellstrom and Nordberg (1978) for use in reverse dosimetry applied to the U.S. population. Adverse effects of Cd on the bone and kidney are associated with similar points of departure (PODs) of approximately 0.50 μg Cd/g creatinine for females aged 50-60 based on available epidemiologic data. We also used the upper bound estimate of the renal cortical concentration (50 μg/g Cd) occurring in the U.S. population at 50 years of age as a POD. Based on the output from our reverse dosimetry PBPK Model, a range of 0.21-0.36 μg/kg bw/day was developed for the TRV. The animal data used for the animal TRV derivation (0.63-1.8 μg/kg bw/day) confirms biological plausibility for both the bone and kidney endpoints., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

It is widely accepted that different blood collection conditions, including anticoagulants, influence leukocyte phenotype and function. Buffy Coats originated from a donated whole blood bag unit are commonly used in immunological research as a source of leukocytes. They are a residual product of healthy donor whole blood processing. The preservative solution present in the blood bag unit and consequently in the derived Buffy Coat is Citrate-Phosphate-Dextrose (CPD), in which citrate is the anticoagulant. There is a lack of information on the possible difference in the functionality of leukocytes from Buffy Coats originated from a blood bag unit vs leukocytes isolated from blood collection tubes with various anticoagulants. Herein, we aimed at studying monocyte function when the monocytes are isolated from Buffy Coats originated from a blood bag unit vs blood collection tube containing EDTA, CPD with adenine (CPDA), or sodium citrate. The function of monocytes, isolated 20 h after blood collection, to present lipid antigens to invariant Natural Killer T (iNKT) cells was investigated. iNKT cells are activated by lipids bound to CD1d, a non-polymorphic MHC-class I-like molecule, present on the surface of antigen-presenting cells. A striking result showed that monocytes isolated from EDTA blood tubes have a lower capacity to present lipid antigens to iNKT cells than monocytes isolated from Buffy Coats originated from a blood bag unit. No differences were found between monocytes isolated from sodium citrate or CPDA and the ones isolated from Buffy Coats originated from a blood bag unit. This was accompanied by a decrease in viability of the EDTA-isolated monocytes. Expression of the surface markers CD1d and CD86 was higher for monocytes isolated from EDTA than those isolated from Buffy Coats. In conclusion, EDTA-containing blood tubes are not the ideal choice of anticoagulant for monocyte antigen presentation assays. We advise that the blood collection condition and the time between biospecimen collection and analysis should be carefully considered when designing experimental procedures., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Obesity is considered a risk factor for different types of cancer, including colorectal cancer (CRC). Bariatric surgery has been associated with improvements in obesity-related co-morbidities and reductions in overall cancer risk. However, given the contradictory outcomes of several cohort studies, the impact of bariatric surgery on CRC risk appears controversial. Furthermore, measurement of CRC biomarkers following Roux-en-Y gastric bypass (RYGB) has revealed hyperproliferation and increased pro-inflammatory gene expression in the rectal mucosa. The proposed mechanisms leading to increased CRC risk are alterations of the gut microbiota and exposure of the colorectum to high concentrations of bile acids, both of which are caused by RYGB-induced anatomical rearrangements. Studies in animals and humans have highlighted the similarities between RYGB-induced microbial profiles and the gut microbiota documented in CRC. Microbial alterations common to post-RYGB cases and CRC include the enrichment of pro-inflammatory microbes and reduction in butyrate-producing bacteria. Lower concentrations of butyrate following RYGB may also contribute to an increased risk of CRC, given the anti-inflammatory and anticarcinogenic properties of this molecule. Laparoscopic sleeve gastrectomy appears to have a more moderate impact than RYGB; however, relatively few animal and human studies have investigated its effects on CRC risk. Moreover, evidence regarding the impact of anastomosis gastric bypass on one is even more limited. Therefore, further studies are required to establish whether the potential increase in CRC risk is restricted to RYGB or may also be associated with other bariatric procedures., (Copyright © 2023 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate whether physical activity is associated with enhanced immunogenicity of a SARS-CoV-2 inactivated vaccine (Coronavac) in patients with autoimmune rheumatic diseases (ARD) (n = 898) and in non-ARD (n = 197) individuals without pre-existing immunogenicity to SARS-CoV-2., Methods: This was a prospective cohort study within an open-label, single-arm, phase 4 vaccination trial. Immunogenicity was assessed after vaccination by measuring seroconversion rates of total anti-SARS-CoV-2 S1/S2 IgG (SC), geometric mean titers of anti-S1/S2 IgG (GMT), factor-increase in GMT (FI-GMT), frequency of neutralizing antibody (NAb), and median neutralizing activity. Physical activity (active being defined as ≥ 150 min/week) and sedentary behavior (>8h/day) were assessed by questionnaire., Results: Physically active ARD patients (n = 494) were younger and less frequently used prednisone/biologics than inactive patients (n = 404). After controlling for covariates, active patients exhibited greater SC (OR: 1.4 [95%CI: 1.1-2.0]), GMT (32% [95%CI: 8.8-60) and FI-GMT (33% [95%CI: 9.6-63%]) vs. inactive. Cluster analysis (physical activity/sedentary status) revealed greater GMT (43.0% [95% CI: 11.0-84.0%) and FI-GMT (48.0% [95%CI: 14.0-92.0%]) in active/non-sedentary vs. inactive/sedentary ARD patients. A dose-response was observed, with greater benefits for the group of patients performing ≥ 350 min/week of physical activity (OR: 1.6 [95%CI: 1.1-2.4]; 41% [95%CI: 10-80%]; 35% [95%CI: 4.3-74], for SC, GMT, and FI-GMT, respectively) vs. the least active group (≤30 min/week). Greater SC (OR: 9.9 [95%CI: 1.1-89.0]) and GMT (26% [95%CI: 2.2-56.0%]) were observed in active vs. inactive non-ARD., Conclusions: A physically active lifestyle may enhance SARS-CoV-2 vaccine immunogenicity, a finding of particular clinical relevance for immunocompromised patients., Trial Registration: Clinicaltrials.gov #NCT04754698., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19)., Methods: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed., Results: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for >12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11% versus 0%, p=0.030), lymphopenia (42% versus 18%, p=0.020), C-reactive protein level of >30 mg/L (35% versus 0%, p=0.0001), and D-dimer level of >1000 ng/mL (43% versus 6%, p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11% versus 2%, p=0.178) and cardiac alterations on echocardiogram (33% versus 22%, p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100] versus 81 [34-100], p=0.012), and school score (60 [15-100] versus 70 [15-95], p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls., Conclusions: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19.

Objective: To assess the possible factors that influence sleep quality in adolescents with and without chronic immunosuppressive conditions quarantined during the coronavirus disease 2019 (COVID-19) pandemic., Methods: This cross-sectional study included 305 adolescents with chronic immunocompromised conditions and 82 healthy adolescents. Online surveys were completed, which included questions on socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and the following validated questionnaires: the Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0), and Pediatric Outcome Data Collection Instrument (PODCI)., Results: The median current age [14 (10-18) vs. 15 (10-18) years, p=0.847] and frequency of female sex (62% vs. 58%, p=0.571) were similar in adolescents with chronic conditions compared with healthy adolescents. The frequency of poor sleep quality was similar in both groups (38% vs. 48%, p=0.118). Logistic regression analysis, including both healthy adolescents and adolescents with chronic conditions (n=387), demonstrated that self-reported increase in screen time (odds ratio [OR] 3.0; 95% confidence interval [CI] 1.3-6.8; p=0.008) and intrafamilial violence report (OR 2.1; 95% CI 1.2-3.5; p=0.008) were independently associated with poor sleep quality in these adolescents. However, the PODCI global function score was associated with a lower OR for poor sleep quality (OR 0.97; 95% CI 0.94-0.99; p=0.001). Further logistic regression, including only adolescents with chronic conditions (n=305), demonstrated that self-reported increase in screen time (OR 3.1; 95% CI 1.4-6.8; p=0.006) and intrafamilial violence report (OR 2.0; 95% CI 1.2-3.4; p=0.011) remained independently associated with poor quality of sleep, whereas a lower PODCI global function score was associated with a lower OR for sleep quality (OR 0.96; 95% CI 0.94-0.98; p<0.001)., Conclusion: Self-reported increases in screen time and intrafamilial violence report impacted sleep quality in both healthy adolescents and those with chronic conditions. Decreased health-related quality of life was observed in adolescents with poor sleep quality.

Mosaic Variegated Aneuploidy Syndrome 2 (MVA2; MIM 614114) is a rare autosomal recessive disorder, characterized by mosaic aneuploidies involving multiple chromosomes and tissues, caused by biallelic pathogenic variants in the CEP57 gene. Only 10 patients have been reported to date. We report two additional non related cases born to Moroccan consanguineous parents, carrying the previously described c.915&#95;925dup11 CEP57 homozygous variant. Common features of these 12 cases include growth retardation, typically of prenatal onset, distinctive facial features, endocrine, cardiovascular and skeletal, abnormalities while malignancies have not been reported. This report describes the phenotypical spectrum of MVA2., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

This work aimed to evaluate the potential of chitosan/cellulose nanocrystals (CNC) films to be used as active pads for meat packages to prolong its shelf-life and preserve its properties over time. Several CNC concentrations (5, 10, 25, and 50 wt%) were tested and the films were produced by solvent casting. The developed samples were characterized by ATR-FTIR, TGA, FESEM, and XRD. The transparency, antimicrobial, barrier and mechanical properties were also assessed. Finally, the films' ability to prolong food shelf-life was studied in real conditions using chicken meat. CNC incorporation improved the thermal stability and the oxygen barrier while the water vapor permeability was maintained. An enhancement of mechanical properties was also observed by the increase in tensile strength and Young's modulus in chitosan/CNC films. These films demonstrated bactericidal effect against Gram-positive and Gram-negative bacteria and fungicidal activity against Candida albicans. Lastly, chitosan-based films decreased the growth of Pseudomonas and Enterobacteriaceae bacteria in meat during the first days of storage compared to commercial membranes, while chitosan/CNC films reduced the total volatile basic nitrogen (TVB-N), indicating their efficiency in retarding meat's spoilage under refrigeration conditions. This work highlights the great potential of natural-based films to act as green alternatives for food preservation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Cortisol is a steroid hormone that regulates a wide range of vital processes. Its level changes with diurnal rhythm and reacts to stress. Measurement of cortisol levels is still a complex multi-step process. A reversible washing-free registration method is required. Here we describe metal-enhanced fluorescence assay based on a displacement of a dye labeled BSA-cortisol conjugate from the immune complex immobilized on the golden islands by free cortisol. This competitive approach allows time-resolved monitoring of the fluorescent signal, surface-enhanced by the gold film, and provides the possibility of continuous real-time cortisol monitoring based on the implantable surface-enhanced immunosensor, which was not demonstrated so far even in vitro., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Ambient outdoor air pollution has been identified as a key risk factor for adverse health outcomes and mortality, particularly in low- and middle-income countries (LMICs). Small-scale, individual-initiated burning activities are significant contributors to local pollutant emissions but are not well studied. We identified articles that describe small-scale burning interventions in order to characterize current trends, implementation science perspectives, and gaps in the literature., Methods: We conducted a global search of interventions to reduce ambient air pollution, and then conducted a keyword search among these articles to identify literature regarding interventions to reduce individual-initiated burning. We categorized these articles based on whether burning was discussed as an explicit focus or incidental finding and conducted a full-text analysis. We conducted a supplementary review on anthropological aspects of burning behaviors and burning interventions not captured in our review to inform future recommendations., Results: Ten articles describing interventions for small-scale, individual-initiated burning were identified. Four articles examined burning as an explicit focus and six discussed burning as an incidental finding. China was the country most represented in our review. All but one of the articles discussed emissions-related outcomes, while only one article discussed health outcomes. Four articles explored factors affecting implementation of interventions and regulations, but none included implementation as a primary objective. The supplementary review revealed a large amount of literature about burning in the context of spiritual and agricultural practices. However, less is known about everyday burning behaviors, such as trash burning and household burning, as well as reasons why people burn., Conclusion: There is a paucity of research that explicitly discusses interventions for small scale, individual-initiated burning practices. Gaps remain in interventions in LMICs most affected by individual-initiated burning, particularly in sub-Saharan Africa. Most of the current literature does not analyze factors affecting effectiveness of interventions and regulations and does not clearly identify reasons why people choose to burn. More research is needed on how to effectively implement interventions to reduce individual-initiated burning, as well as to target key geographic regions and burning sources that continue to be neglected., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Context: The Cancer Dyspnea Scale (CDS) is a self-reported multidimensional tool used for the assessment of dyspnea, a subjective experience of breathing discomfort, in patients with cancer. The scale describes dyspnea using three distinct factors: physical, psychological, and discomfort at rest., Objectives: To crossculturally validate the Italian version of CDS (CDS-IT) and examine its content validity, feasibility, internal consistency, and construct validity in patients with advanced cancer., Methods: A cross-sectional study was conducted. CDS-IT was forward-backward translated, and its content was validated among a group of experts. Cronbach's α coefficients were used to assess the internal consistency. Construct validity was examined in terms of structural validity through confirmatory factor analysis, and convergent validity was examined with Visual Analogue Scale Dyspnea through the Pearson's correlation coefficient (r). Cancer Quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care) and Italian Palliative Outcome Scale were also tested., Results: The CDS-IT was crossculturally validated and showed satisfactory content validity. A total of 101 patients (mean age = 76 [SD = 12]; 53% females) were recruited in palliative care settings. CDS-IT reported a good internal consistency in the total score and its factors (α = 0.74-0.83). The factor analysis corresponded acceptably but not completely with the original study. CDS-IT strongly correlated with Visual Analogue Scale Dyspnea (r = 0.68) and moderately with Italian Palliative Outcome Scale and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care (r = 0.33-0.36, respectively)., Conclusion: The study findings supported the crosscultural validity of the CDS-IT. Its feasibility, internal consistency, and construct validity are satisfactory for clinical practice. The CDS-IT is available to health care professionals as a useful tool to assess dyspnea in patients with cancer., (Copyright © 2020 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Only a limited number of studies have explored the possible associations between tumour grade and mutated genes in clear cell renal cell carcinoma (ccRCC), and we set out to investigate this further using a multiple sampling and next generation sequencing (NGS) approach in a series of ccRCCs. Multiple regions were sampled from formalin-fixated paraffin-embedded ccRCC tumour blocks from seven patients. In 27 samples from six patients, we performed targeted NGS using a custom 42-gene panel based on the most frequently mutated genes in ccRCC reported in public databases. In four samples from the seventh patient, we performed whole exome sequencing (WES) and array comparative genomic hybridisation for detection of copy number variants (CNVs). Mutated genes and the tumour grades of the samples in which they had been identified were compared both within and between all individual tumours. CNVs were compared across all samples from patient 7. We identified clear genetic heterogeneity within and across tumours, but VHL mutations were seen in all patients. Looking across all samples, we identified eleven genes that were only mutated in samples with one particular tumour grade. However, these genes were never mutated in all samples with that tumour grade. Increasing chromosomal instability corresponded with increasing tumour grade, but we observed minimal association between tumour grade and total mutational load in the WES data. Our study confirms the genetic heterogeneity and tumour grade heterogeneity of ccRCC. Although a relatively small number of samples was analysed, genes were identified that could potentially be specific, though insensitive, markers of higher ccRCC tumour grades., Competing Interests: Declaration of Competing Interest None of the authors have conflicts of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Spinal cord stimulation (SCS) is a well-known treatment in patients with failed back surgery syndrome (FBSS). Burst stimulation is a recently developed stimulation modality that seems to be superior to tonic stimulation., Methods: This observational multicenter study compared tonic and burst stimulation during a trial period in patients with FBSS or radiculopathy. All the patients enrolled underwent two weeks of tonic stimulation followed by another two weeks of BurstDR stimulation, without randomization. The primary outcome was the reduction of pain in the legs and back. Health-related quality of life (EQ-5D) and the pain catastrophizing scale (PCS) were assessed before and after the trial. Patients were reevaluated after 12 months., Results: We recruited 23 patients, 57% of whom had FBSS and 43% had radiculopathies. Five patients failed both the tonic and burst stimulation trials. While tonic stimulation reduced leg pain (p < 0.05), the burst mode added an extra pain reduction (ΔNRS 1.2 ± 1.5) (p < 0.01). No significant reduction in back pain was found (p 0.29). Pain on movement was reduced only by BurstDR (p < 0.01). Both stimulation modalities increased EQ-5D and reduced PCS from the baseline (p < 0.0001). At the end of the SCS trial phase, 26% patients chose tonic SCS, while 74% preferred burst. On 12-month follow-up examination, the benefits recorded at the end of the trial were maintained., Conclusions: Burst stimulation confers a greater reduction in leg pain intensity at rest and on movement. Reducing axial pain is still a challenge. Further studies are needed in order to provide each patient with the most appropriate stimulation paradigm., (© 2018 International Neuromodulation Society.)

We assessed the risk of human salmonellosis from consumption of shelled walnuts in the United States and the impact of 0- to 5-log reduction treatments for Salmonella during processing. We established a baseline model with Salmonella contamination data from 2010 to 2013 surveys of walnuts from California operations to estimate baseline prevalence and levels of Salmonella during preshelling storage and typical walnut processing stages, considered U.S. consumption data, and applied an adapted dose-response model from the Food and Agriculture Organization and the World Health Organization to evaluate risk of illness per serving and per year. Our baseline model predicted 1 case of salmonellosis per 100 million servings (95% confidence interval [CI], 1 case per 3 million to 1 case per 2 billion servings) of walnuts untreated during processing and uncooked by consumers, resulting in an estimated 6 cases of salmonellosis per year (95% CI, <1 to 278 cases) in the United States. A minimum 3-log reduction treatment for Salmonella during processing of walnuts eaten alone or as an uncooked ingredient resulted in a mean risk of <1 case per year. We modeled the impact on risk per serving of three atypical situations in which the Salmonella levels were increased by 0.5 to 1.5 log CFU per unit pretreatment during processing at the float tank or during preshelling storage or posttreatment during partitioning into consumer packages. No change in risk was associated with the small increase in levels of Salmonella at the float tank, whereas an increase in risk was estimated for each of the other two atypical events. In a fourth scenario, we estimated the risk per serving associated with consumption of walnuts with Salmonella prevalence and levels from a 2014 to 2015 U.S. retail survey. Risk per serving estimates were two orders of magnitude larger than those of the baseline model without treatment. Further research is needed to determine whether this finding reflects variability in Salmonella contamination across the supply or a rare event affecting a portion of the supply.