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Abstract Background Cannabis sativa is seeing a global resurgence as a food, fiber and medicinal crop for industrial hemp and medicinal Cannabis industries respectively. However, a widespread moratorium on the use and research of C. sativa throughout most of the 20th century has seen the development of improved cultivars for specific end uses lag behind that of conventional crops. While C. sativa research and development has seen significant investments in the recent past, resulting in a suite of publicly available genomic resources and tools, a versatile and cost-effective mid-density genotyping platform for applied purposes in breeding and pre-breeding is lacking. Here we report on a first mid-density fixed-target SNP platform for C. sativa. Results The High-throughput Amplicon-based SNP-platform for medicinal Cannabis and industrial Hemp (HASCH) was designed using a combination of filtering and Integer Linear Programming on publicly available whole-genome sequencing and RNA sequencing data, supplemented with in-house generated genotyping-by-sequencing (GBS) data. HASCH contains 1,504 genome-wide targets of high call rate (97% mean) and even distribution across the genome, designed to be highly informative (> 0.3 minor allele frequency) across both medicinal cannabis and industrial hemp gene pools. Average numbers of mismatch SNP between any two accessions were 251 for medicinal cannabis (N = 116) and 272 for industrial hemp (N = 87). Comparing HASCH data with corresponding GBS data on a collection of diverse C. sativa accessions demonstrated high concordance and resulted in comparable phylogenies and genetic distance matrices. Using HASCH on a segregating F2 population derived from a cross between a tetrahydrocannabinol (THC)-dominant and a cannabidiol (CBD)-dominant accession resulted in a genetic map consisting of 310 markers, comprising 10 linkage groups and a total size of 582.7 cM. Quantitative Trait Locus (QTL) mapping identified a major QTL for CBD content on chromosome 7, consistent with previous findings. Conclusion HASCH constitutes a versatile, easy to use and cost-effective genotyping solution for the rapidly growing Cannabis research community. It provides consistent genetic fingerprints of 1504 SNPs with wide applicability genetic resource management, quantitative genetics and breeding.

Global changes in cannabis legislation after decades of stringent regulation and heightened demand for its industrial and medicinal applications have spurred recent genetic and genomics research. An international research community emerged and identified the need for a web portal to host cannabis-specific datasets that seamlessly integrates multiple data sources and serves omics-type analyses, fostering information sharing. The Tripal platform was used to host public genome assemblies, gene annotations, quantitative trait loci and genetic maps, gene and protein expression data, metabolic profiles and their sample attributes. Single nucleotide polymorphisms were called using public resequencing datasets on three genomes. Additional applications, such as SNP-Seek and MapManJS, were embedded into Tripal. A multi-omics data integration web-service Application Programming Interface (API), developed on top of existing Tripal modules, returns generic tables of samples, properties and values. Use cases demonstrate the API’s utility for various omics analyses, enabling researchers to perform multi-omics analyses efficiently. Availability and implementation The web portal can be accessed at www.icgrc.info.

A growing interest in Cannabis sativa uses for food, fiber, and medicine, and recent changes in regulations have spurred numerous genomic studies of this once-prohibited plant. Cannabis research uses Next Generation Sequencing technologies for genomics and transcriptomics. While other crops have genome portals enabling access and analysis of numerous genotyping data from diverse accessions, leading to the discovery of alleles for important traits, this is absent for cannabis. The CannSeek web portal aims to address this gap. Single nucleotide polymorphism datasets were generated by identifying genome variants from public resequencing data and genome assemblies. Results and accompanying trait data are hosted in the CannSeek web application, built using the Rice SNP-Seek infrastructure with improvements to allow multiple reference genomes and provide a web-service Application Programming Interface. The tools built into the portal allow phylogenetic analyses, varietal grouping and identifications, and favorable haplotype discovery for cannabis accessions using public sequencing data. Availability and implementation The CannSeek portal is available at https://icgrc.info/cannseek, https://icgrc.info/genotype_viewer.

Abstract Remdesivir (RDV) was the first Food and Drug Administration (FDA)-approved medication for COVID-19, with discordant data on efficacy in reducing mortality risk and disease progression. In the context of a dynamic and rapidly changing pandemic landscape, the utilization of real-world evidence is of utmost importance. The objective of this study is to evaluate the impact of RDV on patients who have been admitted to two university referral hospitals in Italy due to COVID-19. All patients older than 18 years and hospitalized at two different universities (Bari and Palermo) were enrolled in this study. To minimize the effect of potential confounders, we used propensity score matching with one case (Remdesivir) and one control that never experienced this kind of intervention during hospitalization. Mortality was the primary outcome of our investigation, and it was recorded using death certificates and/or medical records. Severe COVID-19 was defined as admission to the intensive care unit or a qSOFAscore ≥ 2 or CURB65scores ≥ 3. After using propensity score matching, 365 patients taking Remdesivir and 365 controls were included. No significant differences emerged between the two groups in terms of mean age and percentage of females, while patients taking Remdesivir were less frequently active smokers (p

Background: Males and females present different sleep alterations, so the aim of the study was to investigate gender differences in residual excessive sleepiness (RES) post continuous positive airway pressure (CPAP) treatment in a population with obstructive sleep apnea (OSA). Methods: The study was conducted on consecutive subjects with moderate-severe OSA treated by CPAP for one year. Clinical and sleep data were collected from the sample, including RES calculated according to an Epworth sleepiness scale (ESS) threshold score >10 points at yearly follow-up. Of this sample, gender differences were investigated. Results: 157 patients (125 males and 32 females) with a mean age of 62,84±11,81 years were included in the study. Overall, females were more obese (p = 0,001) with no differences in OSA severity compared to males.At yearly follow-up, sleepiness was significantly reduced in both sexes but 25 % of males reported RES compared to 13 % of females (p = 0,03). In addition, females were more adherent to CPAP (p = 0,008) than males.However, by observing the residual sleepiness data, it was noticed that sleepy females were more elderly and obese than sleepy males. Females also presented a higher nocturnal time with oxygen saturation

RESUMO Objetivo Verificar a eficácia do uso da bandagem elástica funcional associada à terapia miofuncional no tratamento fonoaudiológico da paralisia facial pós-acidente vascular cerebral na fase aguda. Método Estudo clínico controlado randomizado com 88 pacientes com paralisia facial na fase aguda do acidente vascular cerebral. A amostra foi alocada em: Grupo 1: reabilitação com terapia miofuncional orofacial e utilização da bandagem elástica funcional nos músculos zigomáticos maior e menor paralisados; Grupo 2: reabilitação apenas com terapia miofuncional orofacial na face paralisada; Grupo 3: sem qualquer intervenção fonoaudiológica para paralisia facial. Na avaliação foram solicitados os movimentos de mímica facial e o grau do comprometimento foi determinado de acordo com a escala de House e Brackmann. A incompetência do movimento foi obtida a partir de medições da face com paquímetro digital. Após a avaliação, a intervenção foi realizada de acordo como determinado para os grupos 1 e 2. Os participantes dos três grupos foram reavaliados após 15 dias. A análise estatística utilizada foi das equações generalizadas. Resultados Os grupos foram homogêneos quanto à idade, medida de incapacidade e funcionalidade, gravidade do comprometimento neurológico e da paralisia facial pré-intervenção. O grupo 1 teve melhora significativa na medida canto externo do olho à comissura labial, com melhores resultados quando comparado aos grupos 2 e 3. Conclusão A bandagem elástica funcional associada a terapia miofuncional orofacial apresentou melhor resultado no tratamento da paralisia facial após acidente vascular cerebral no local onde foi aplicado.

RESUMO Objetivo validar o conteúdo do Teste de Concordância de Scripts em Fonoaudiologia, denominado FonoTCS. Método Trata-se de estudo de validação de conteúdo de instrumento. Participaram da construção do FonoTCS cinco fonoaudiólogas, doutoras e docentes, com média de 24,8 anos de atuação profissional, que chegaram a um consenso durante o processo de construção do teste. Elaborou-se 30 questões e 120 itens contemplando as áreas de atuação fonoaudiológica. Em seguida, 15 fonoaudiólogas com titulação mínima de mestre, e com, no mínimo, 10 anos de atuação clínica generalista receberam eletronicamente o FonoTCS para validação de conteúdo por meio de questionário sobre critérios de clareza, ética e pertinência do conteúdo das questões. Para a análise das respostas calculou-se o Coeficiente de Validade de Conteúdo Corrigido de todas as afirmativas. Foram revisadas as questões com porcentagem de concordância igual ou inferior a 80%. Resultados 13 avaliadores responderam a análise, todos do sexo feminino, com média de idade de 39,07 anos, sendo oito mestres e cinco doutoras, com atuação clínica generalista média de 15,38 anos. Os valores médios do Coeficiente de Validade de Conteúdo Corrigido foram 0,93 e 0,95 para o critério de clareza; 0,98 e 0,92 para o critério de pertinência; e 0,99 para o critério de ética. Duas questões apresentaram notas de 0,78 e 0,80, sendo ambas da área de audiologia no domínio de avaliação/diagnóstico, para a questão relacionada ao critério de pertinência, sendo revisadas e reestruturadas pelos juízes. Conclusão O FonoTCS é um instrumento válido do ponto de vista do conteúdo.

Abstract Objective: To create a protocol for performing minimally invasive autopsies (MIA) in detecting deaths from arboviruses and report preliminary data from its application in Ceará state, Brazil. Methods: Training was provided to medical pathologists on MIA. Results: A protocol was established for performing MIA, defining criteria for sample collection, storage methods, and diagnoses to be carried out according to the type of biological sample; 43 MIAs were performed in three months. Of these, 21 (48.8%) arrived at the Death Verification Service (SVO) with arboviruses as a diagnostic hypothesis, and seven (16.3%) were confirmed (six chikungunya cases and one dengue case); cases of COVID-19 (n = 9), tuberculosis (n = 5), meningitis (n = 4), cryptococcosis (n = 1), Creutzfeldt-Jakob disease (n = 1), breast cancer (n = 1), and human rabies (n = 1) were also confirmed. Conclusion: The protocol implemented enabled identification of a larger number of suspected arbovirus-related deaths, as well as confirmation of other diseases of interest for surveillance.

RESUMO Objetivo Verificar os efeitos imediatos da fotobiomodulação na produção do fluxo salivar e a correlação dos dados demográficos, antropométricos e de uso de medicamentos. Método Participaram do estudo 100 indivíduos saudáveis, com idade entre 18 e 76 anos (média 27,2 anos), divididos de forma randomizada em grupo experimental e grupo placebo. Foram realizadas as avaliações das medidas antropométricas, autopercepção da produção de saliva e a sialometria. Na sequência, realizou-se a irradiação do LASER no comprimento de onda infravermelho (808 nanômetros) com 100 miliwatts (mw) de potência em cinco pontos intraorais: nas glândulas sublingual e bilateralmente nas submandibulares e parótidas, nas doses 9, 18 e 24 joules (J). A sialometria foi repetida após cada aplicação. O grupo controle recebeu os mesmos procedimentos com equipamento placebo. Resultados Houve associação estatística na autopercepção de redução da saliva no grupo experimental para a dose de 24J e na sialometria e na redução do fluxo salivar para as doses 18J e 24J e aumento para 9J, em ambos os grupos. Não houve associação quando comparado entre os grupos experimental e placebo. A análise de regressão multinomial múltipla revelou que a redução ou o aumento do fluxo salivar independe das variáveis demográficas, antropométricas e uso de medicamentos. Conclusão A ação bioinibitória da fotobiomodulação sobre as glândulas salivares saudáveis ocorreu em dose de 18J e 24J, já ação bioestimulante na dose 9J, independe das variáveis demográficas, antropométricas e uso de medicamentos. A autopercepção da redução do fluxo salivar ocorreu em 24J.

Sarcopenia has been described as a muscle disease, with multiple adverse consequences on human health. Recommendations aimed at supporting awareness, prevention, early detection and treatment of this disease are needed. This review focuses on the epidemiology, pathophysiology and early detection of elderly sarcopenia. As far as treatment is concerned, physical activity and nutritional support are specifically evaluated. An individually tailored resistance exercise training program appears to be crucial for a positive outcome of the sarcopenia prevention and treatment. The nutritional intervention is mostly based on the supplementation with high-quality proteins (i.e., whey protein) in order to increase the intake of essential amino acids and in particular of leucine. In addition, of relevant importance appears to be the supplementation with vitamin D, with omega-3 fatty acids and probiotics. This review evaluates the results of the most qualified studies on the nutritional supplementation of sarcopenic elderly subjects and shows that promising results have been achieved in community elderly subjects, or subjects followed in rehabilitation centers and in nursing homes, with additional resistance exercise programs.

This study aimed to introduce specific image feature analysis, focusing on pancreatic margins, and to provide a quantitative measure of edge irregularity, evidencing correlations with the presence/absence of pancreatic adenocarcinoma. We selected 50 patients (36 men, 14 women; mean age 63.7 years) who underwent Multi-detector computed tomography (MDCT) for the staging of pancreatic adenocarcinoma of the tail of the pancreas. Computer-assisted quantitative edge analysis was performed on the border fragments in MDCT images of neoplastic and healthy glandular parenchyma, from which we obtained the root mean square deviation SD of the actual border from the average boundary line. The SD values relative to healthy and neoplastic borders were compared using a paired t-test. A significant SD difference was observed between healthy and neoplastic borders. A threshold SD value was also found, enabling the differentiation of adenocarcinoma with 96% specificity and sensitivity. We introduced a quantitative measure of boundary irregularity, which correlates with the presence/absence of pancreatic adenocarcinoma. Quantitative edge analysis can be promptly performed on select border fragments in MDCT images, providing a useful supporting tool for diagnostics and a possible starting point for machine learning recognition based on lower-dimensional feature space.

Background/objectiveDepression is a growing concern in university students and resilience has shown to play a protective role. The impact of stigma is still under-explored, with reference to its moderating role between depression and resilience. The present study investigate such a relationship among Italian university students.MethodsA cross-sectional design was applied in a simple of 1,912 students to examine the interrelationships between depression (Patient Health Questionnaire-9), resilience (Nicholson McBride Resilience questionnaire), and stigma (Stigma-9). Correlation, predictor, and moderation analyses were applied in RStudio.ResultsA negative correlation was found between depressive symptoms and resilience (r = −0.455, p

Summary:. Giant cell tumor of bone (GCTB) typically presents in the epiphysis of long bones and occurs in the skull in less than 1% of cases. When GCTB is diagnosed in the skull, it is primarily seen in the temporal and sphenoid bones. GCTB is an osteoclastic stromal tumor that is locally aggressive and tends to recur. We present a case of a 43-year-old woman with slowly progressive, left-sided proptosis, eyelid swelling, photophobia, epiphora, and pressure sensation. Computed tomography and magnetic resonance imaging revealed an enhancing tumor in the left inferior orbit with infiltration into the maxillary sinus roof. Histological examination was conclusive for a giant cell tumor of the maxillary bone presenting as an inferior orbital mass. Gross total surgical resection was performed via an inferior anterior orbitotomy, and the patient had resolution of symptoms without recurrence in her postoperative course to date. This report contributes to the scarce literature available on this type of tumor of skull bones, specifically presenting the first case in the maxillary bone of the floor of the orbit.

RESUMO Objetivo Analisar a associação da independência funcional com aspectos clínicos de comprometimento neurológico, a localização e extensão do dano neuronal e os fatores sociodemográficos em pacientes na fase aguda do AVC. Método Estudo analítico de recorte transversal, realizado com 90 pacientes adultos e idosos acometidos por AVC isquêmico, que tiveram admissão no ambiente hospitalar nas primeiras 24 horas após o evento vascular. A coleta dos dados referentes aos aspectos clínicos e fatores sociodemográficos foi realizada pelo prontuário eletrônico e/ou entrevista para descrever o perfil dos pacientes, Oxfordshire Community Stroke Project, Alberta Stroke Programme Early CT Score, National Institute of Health Stroke Scale e a Medida de Independência Funcional. Resultados O comprometimento neurológico, de acordo com a National Institute of Health Stroke Scale, foi associado à funcionalidade nas primeiras 24 horas após o AVC. Além disso, a presença de hipertensão arterial, idade, trabalho inativo, tabagismo e extensão do dano neuronal estiveram associados à dependência funcional, mas não permaneceram no modelo final deste estudo. Conclusão A dependência funcional está associada à hipertensão arterial, idade, trabalho inativo, tabagismo, extensão do dano neuronal e grau de comprometimento neurológico nas primeiras 24 horas após o evento vascular. Além disso, um nível mais elevado de comprometimento neurológico foi independentemente associado a níveis aumentados de dependência funcional.

Over 8% of couples worldwide are affected by infertility and nearly half of these cases are due to male-specific issues where the underlying cause is often unknown. Therefore, discovery of new genetic factors contributing to male-specific infertility in model organisms can enhance our understanding of the etiology of this disorder. Here we show that murine ATP10A, a phospholipid flippase, is highly expressed in male reproductive organs, specifically the testes and vas deferens. Therefore, we tested the influence of ATP10A on reproduction by examining fertility of Atp10A knockout mice. Our findings reveal that Atp10A deficiency leads to male-specific infertility, but does not perturb fertility in the females. The Atp10A deficient male mice exhibit smaller testes, reduced sperm count (oligozoospermia) and lower sperm motility (asthenozoospermia). Additionally, Atp10A deficient mice display testes and vas deferens histopathological abnormalities, as well as altered total and relative amounts of hormones associated with the hypothalamic-pituitary-gonadal axis. Surprisingly, circulating testosterone is elevated 2-fold in the Atp10A knockout mice while luteinizing hormone, follicle stimulating hormone, and inhibin B levels were not significantly different from WT littermates. The knockout mice also exhibit elevated levels of gonadotropin receptors and alterations to ERK, p38 MAPK, Akt, and cPLA2-dependent signaling in the testes. Atp10A was knocked out in the C57BL/6J background, which also carries an inactivating nonsense mutation in the closely related lipid flippase, Atp10D. We have corrected the Atp10D nonsense mutation using CRISPR/Cas9 and determined that loss of Atp10A alone is sufficient to cause infertility in male mice. Collectively, these findings highlight the critical role of ATP10A in male fertility in mice and provide valuable insights into the underlying molecular mechanisms.

Urinary tract infections (UTIs) are the most common bacterial infections in postmenopausal women, and women with diabetes are possibly at a higher risk. The aim of this study is to evaluate the potential benefit on the prevention of UTI episodes, assessed by urinalysis and urine culture (primary outcome) after two, four and six months, of daily oral dietary supplement (120 mg highly standardized cranberry extract phytosome), compared to placebo, in diabetic postmenopausal women taking SGLT-2 inhibitors. Forty-six subjects (mean age 72.45 ± 1.76) completed the study (23 placebo/23 supplement). Considering UTI episodes, during the six-month supplementation period, an increase of 1.321 (95% CI: −0.322; 2.9650) was observed in the placebo group, while it remained at a steady value of 0.393 (95% CI: −4.230; 5.016) in the supplemented group. Regarding UTI episodes, in both groups, interaction between times for supplementation was statistically significant (p = 0.001). In particular, at follow-up 4, 9% of the placebo group showed infection versus only 3% with cranberry supplementation. Glycaemia and glycated hemoglobin values (secondary outcomes) were not modified at the end of six months with respect to the basal values in both groups, as expected. While in terms of quality of life per the SF-12 health questionnaire, there were no differences between the two groups, an improvement in SF-12 quality of life was observed in both groups (six months vs. basal). In conclusion, highly standardized cranberry extract phytosome supplementation reduced UTI recurrence.

Approximately 15–50% of patients with Crohn’s disease (CD) will require surgery within ten years following the diagnosis. The management of modifiable risk factors before surgery is essential to reduce postoperative complications and to promote a better postoperative recovery. Preoperative malnutrition reduced functional capacity, sarcopenia, immunosuppressive medications, anemia, and psychological distress are frequently present in CD patients. Multimodal prehabilitation consists of nutritional, functional, medical, and psychological interventions implemented before surgery, aiming at optimizing preoperative status and improve postoperative recovery. Currently, studies evaluating the effect of multimodal prehabilitation on postoperative outcomes specifically in CD are lacking. Some studies have investigated the effect of a single prehabilitation intervention, of which nutritional optimization is the most investigated. The aim of this narrative review is to present the physiologic rationale supporting multimodal surgical prehabilitation in CD patients waiting for surgery, and to describe its main components to facilitate their adoption in the preoperative standard of care.

The tumor microenvironment modulates cancer growth. Extracellular vesicles (EVs) have been identified as key mediators of intercellular communication, but their role in tumor growth is largely unexplored. Here, we demonstrate that EVs from sarcoma patients promote neoangiogenesis via a purinergic X receptor 4 (P2XR4) -dependent mechanism in vitro and in vivo. Using a proteomic approach, we analyzed the protein content of plasma EVs and identified critical activated pathways in human umbilical vein endothelial cells (HUVECs) and human progenitor hematopoietic cells (CD34+). We then showed that vessel formation was due to rapid mitochondrial activation, intracellular Ca2+ mobilization, increased extracellular ATP, and trafficking of the lysosomal P2XR4 to the cell membrane, which is required for cell motility and formation of stable branching vascular networks. Cell membrane translocation of P2XR4 was induced by proteins and chemokines contained in EVs (e.g. Del-1 and SDF-1). Del-1 was found expressed in many EVs from sarcoma tumors and several tumor types. P2XR4 blockade reduced EVs-induced vessels in angioreactors, as well as intratumor vascularization in mouse xenografts. Together, these findings identify P2XR4 as a key mediator of EVs-induced tumor angiogenesis via a signaling mediated by mitochondria-lysosome-sensing response in endothelial cells, and indicate a novel target for therapeutic interventions.