Desafios e mudanças no processo de trabalho das equipes de saúde da família no cenário pandêmico: relato de experiência / Challenges and changes in the work process of family health teams in the pandemic scenario: experience report

O presente estudo tem por objetivo realizar um relato de experiência demonstrando a percepção de discentes do curso de odontologia na sua participação na prática da atenção primária à saúde (APS), vivenciadas em um cenário pandêmico e com base no combate a enfrentamentos e desafios impostos no processo de trabalho das equipes de saúde da família. Este estudo trata - se de relato de experiência, de caráter descritivo e retrospectivo, associado à uma pesquisa bibliográfica para que trousse o embasamento teórico necessário para a descrição do relato de experiência vivenciado. No decorrer da pandemia, a Equipe de saúde da família exerceu importante papel e atuou na linha de prevenção e controle desta, sendo uma das maiores ferramentas de apoio. Na odontologia, a atuação da equipe de saúde bucal devido a fatores de risco inerentes à esta modalidade de ocupação, ficou limitada em seu exercício. O conhecimento de muitos dos profissionais da rede pública foi colocado em questão, assim como sua vivência, limitações e o medo de contrair a doença. Os profissionais da equipe de saúde, mostraram que o trabalho interprofissional e um bom relacionamento aumentou o incentivo e a responsabilidade de equipe.

This study aims to carry out an experience report demonstrating the perception of students of the dentistry course in their participation in the practice of primary health care (PHC), experienced in a pandemic scenario and based on the fight against confrontations and challenges imposed on the work process of family health teams. This study is an experience report, descriptive and retrospective, associated with bibliographical research to bring the necessary theoretical basis for the description of the lived experience report. During the pandemic, the Family Health Team played an important role and acted in the line of prevention and control of this, being one of the greatest support tools. In dentistry, the performance of the oral health team, due to risk factors inherent to this type of occupation, was limited in its exercise. The knowledge of many public health professionals was questioned, as well as their experience, limitations and fear of contracting the disease. Health team professionals showed that interprofessional work and a good relationship increased team incentive and responsibility.

Etiopatogenia e tratamento da osteonecrose dos maxilares induzida por medicamentos: aspectos essenciais ao dentista / Etiopathogenesis and treatment of medication-related osteonecrosis of the jaw: essential aspects for the dentist

A osteonecrose dos maxilares induzida por medicamentos (MRONJ) caracteriza-se por exposição óssea ou osso que pode ser sondado através de fístula intra ou extraoral, em região maxilofacial, e que não cicatriza dentro de oito semanas. A MRONJ é uma condição rara e debilitante que pode causar dor, disfagia e odor desagradável na cavidade oral, afetando pacientes com histórico ou sob uso contínuo de terapia antirreabsortiva, isolada ou associada a imunomoduladores ou drogas antiangiogênicas, mas sem histórico de radioterapia nos maxilares. O objetivo desta revisão narrativa de literatura é compilar os principais aspectos sobre a etiopatogenia da MRONJ e as opções terapêuticas disponíveis. A etiologia da MRONJ é multifatorial, complexa, e não está totalmente compreendida, não havendo um tratamento definitivo, mas diversas modalidades terapêuticas que visam o controle da dor e da progressão da osteonecrose. Conclui-se com essa revisão que o entendimento da etiopatogenia da MRONJ pelo cirurgião-dentista lhe permite adotar medidas preventivas, bem como o conhecimento das modalidades terapêuticas disponíveis lhe possibilita oferecer o manejo adequado para seu paciente, conforme o estágio da doença.

Medication-related osteonecrosis of the jaw (MRONJ) is characterized by exposed bone or bone that can be probed through an intra or extraoral fistula, in the maxillofacial region, which does not heal within eight weeks. MRONJ is a rare and debilitating condition that can cause pain, dysphagia and unpleasant odor in the oral cavity, affecting patients with a history or continuous use of antiresorptive therapy, alone or associated with immunomodulators or antiangiogenic drugs, but without a history of radiotherapy to the jaws. The aim of this narrative literature review is to compile the main aspects about the etiopathogenesis of MRONJ and the available therapeutic options. The etiology of MRONJ is multifactorial, complex, and is not fully understood, with no definitive treatment, but several therapeutic modalities that aim to control pain and the progression of osteonecrosis. It is concluded from this review that the understanding of the etiopathogenesis of MRONJ by the dental surgeon allows him to adopt preventive measures, as well as the knowledge of the therapeutic modalities available allows him to offer the appropriate management for his patient, depending on the stage of the disease.

Uso do laser de baixa potência para o tratamento de parestesia: uma revisão de literatura / Use of low-level laser to treat paresthesia: a literature review

Introdução: A parestesia é uma neuropatia que afeta a função sensorial. O Laser de Baixa Potência (LBP), por sua vez, apresenta propriedades analgésicas, bioestimuladoras e reparadoras. Objetivo: Realizar um levantamento na literatura científica sobre os aspectos gerais e benefícios do LBP no manejo terapêutico da parestesia, além de identificar a classificação e métodos de obtenção do diagnóstico desta condição. Materiais e Métodos: Tratou-se de uma revisão narrativa da literatura através da busca nas plataformas PubMed, SciELO, LILACS e Google Schoolar. Após o cruzamento dos descritores com os operadores booleanos e aplicação dos critérios de inclusão/exclusão, 26 estudos foram incluídos. Resultados: A parestesia pode ser classificada em neuropraxia, axonotmese e neurotmese, subdivididas em Grau I ao V. Seu diagnóstico pode ser executado através de testes subjetivos e objetivos. O LBP compreende em um dispositivo tecnológico com efeitos analgésico, anti-inflamatório e fotobiomodulador, que estimula o reparo neural. Os estudos mostram que a dosimetria nos comprimentos de onda vermelho e infravermelho, aplicação intra e extra oral, e com mais de uma sessão semanal exerce efeito modulatório positivo do reparo neural, com retorno progressivo da atividade sensitiva. Além disso, os estudos trazem uma ampla variação no número de pontos de aplicação, bem como no tempo de irradiação e quantidade de sessões, em virtude da extensão e tempo de diagnóstico da parestesia. Considerações finais: Apesar da alta complexidade da parestesia, o LBP exerce efeitos benéficos através do retorno da sensibilidade parcial ou total, além de ser um dispositivo bem tolerado pelo organismo e minimamente invasivo.

Introduction: Paresthesia is a neuropathy that affects sensory function. The Low-Level Laser (LLL), in turn, has analgesic, biostimulating and reparative properties. Purpose: Carry out a survey at the scientific literature on the general aspects and benefits of LLL in the therapeutic management of paresthesia in addition to identifying the classification and methods for obtaining a diagnosis of this condition. Materials and Methods: It was a narrative literature review through search in platforms PubMed, SciELO, LILACS and Google Schoolar. After crossing the descriptors with boolean operators and applying the inclusion/exclusion criteria, 26 articles were included in this study. Results: Paresthesia can be classified into neuropraxia, axonotmesis and neurotmesis, subdivided into Grades I to V. Its diagnostic can be carried out through subjective and objective tests. The LLL consists in a technological device with analgesic, anti-inflammatory and photobiomodulatory effects, which stimulates neural repair. Studies show that LLL in dosimetry at red and infrared wavelengths with intra and extra oral application and with more than one-week use exerts a positive modulatory effect on neural repair, with a progressive return of sensory activity. Furthermore, the studies show a wide variation in the number of application points, as well as the irradiation time and number of sessions, due to the extent and time of diagnosis of paresthesia. Final Considerations: Despite the high complexity of paresthesia, the LLL has beneficial effects through the return of partial or total sensitivity in addition being a device well tolerated by the body and minimally invasive.

SERS aptasensor for simultaneous detection of ochratoxin A and zearalenone utilizing a rigid enhanced substrate (ITO/AuNPs/GO) combined with Au@AgNPs.

The contamination of mycotoxins poses a serious threat to global food security, hence the urgent need for simultaneous detection of multiple mycotoxins. Herein, two SERS nanoprobes were synthesized by embedded SERS tags (4-mercaptopyridine, 4MPy; 4-mercaptobenzonitrile, TBN) into the Au and Ag core-shell structure, and each was coupled with the aptamers specific to ochratoxin A (OTA) and zearalenone (ZEN). Meanwhile, a rigid enhanced substrate Indium tin oxide glass/AuNPs/Graphene oxide (ITO/AuNPs/GO) was combined with aptamer functionalized Au@AgNPs via π-π stacking interactions between the aptamer and GO to construct a surface-enhanced Raman spectroscopy (SERS) aptasensor, thereby inducing a SERS enhancement effect for the effective and swift simultaneous detection of both OTA and ZEN. The presence of OTA and ZEN caused signal probes dissociation, resulting in an inverse correlation between Raman signal intensity (1005 cm-1 and 2227 cm-1) and the concentrations of OTA and ZEN, respectively. The SERS aptasensor exhibited wide linear detection ranges of 0.001-20 ng/mL for OTA and 0.1-100 ng/mL for ZEN, with low detection limits (LOD) of 0.94 pg/mL for OTA and 59 pg/mL for ZEN. Furthermore, the developed SERS aptasensor demonstrated feasible applicability in the detection of OTA and ZEN in maize, showcasing its substantial potential for practical implementation.

Perilla frutescens leaf extracts alleviate acute lung injury in mice by inhibiting KAT2A.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute lung injury (ALI) can lead to respiratory failure and even death. KAT2A is a key target to suppress the development of inflammation. A herb, perilla frutescens, is an effective treatment for pulmonary inflammatory diseases with anti-inflammatory effects; however, its mechanism of action remains unclear. AIM OF THE STUDY: The purpose of this study was to investigate the therapeutic effect and underlying mechanism of perilla frutescens leaf extracts (PLE), in the treatment of ALI by focusing on its ability to treat inflammation. MATERIALS AND METHODS: In vivo and in vitro models of ALI induced by LPS. Respiratory function, histopathological changes of lung, and BEAS-2B cells damage were assessed upon PLE. This effect is also tested under conditions of KAT2A over expression and KAT2A silencing. RESULTS: PLE significantly attenuated LPS-induced histopathological changes in the lungs, improved respiratory function, and increased survival rate from LPS stimuation background in mice. PLE remarkably suppressed the phosphorylation of STAT3, AKT, ERK (1/2) and the release of cytokines (IL-6, TNF-α, and IL-1ß) induced by LPS via inhibiting the expression of KAT2A. CONCLUSIONS: PLE has a dose-dependent anti-inflammatory effect by inhibiting KAT2A expression to suppress LPS-induced ALI n mice. Our study expands the clinical indications of the traditional medicine PLE and provide a theoretical basis for clinical use of acute lung injury.

Exploring antiviral effect and mechanism of Jinye Baidu granules（JYBD）against influenza A virus through network pharmacology and in vitro and invivo experiments.

ETHNOPHARMACOLOGICAL RELEVANCE: Jinye Baidu granules (JYBD) have been used to treat acute respiratory tract infections and demonstrated clinical efficacy for the treatment of emerging or epidemic respiratory viruses such as SARS-CoV-2 and influenza virus. AIM OF THE STUDY: This study is to investigate the antiviral effect of JYBD against influenza A viruses (IAV) in vitro and in vivo and elucidate its underlying mechanism. MATERIALS AND METHODS: Ultra-high-performance liquid chromatography connected with Orbitrap mass spectrometer (UHPLC-Orbitrap MS) was employed to describe the chemical profile of JYBD. The potential pathways and targets involved in JYBD against IAV infection were predicted by network pharmacology. The efficacy and mechanism of JYBD were validated through both in vivo and in vitro experiments. Moreover, combination therapy with JYBD and the classic anti-influenza drugs was also investigated. RESULTS: A total of 126 compounds were identified by UHPLC-Orbitrap MS, of which 9 compounds were unambiguously confirmed with reference standards. JYBD could significantly inhibit the replication of multiple strains of IAV, especially oseltamivir-resistant strains. The results of qRT-PCR and WB demonstrated that JYBD could inhibit the excessive induction of pro-inflammatory cytokines induced by IAV infection and regulate inflammatory response through inhibiting JAK/STAT, NF-κB and MAPK pathways. Moreover, both JYBD monotherapy or in combination with oseltamivir could alleviate IAV-induced severe lung injury in mice. CONCLUSIONS: JYBD could inhibit IAV replication and mitigate virus-induced excessive inflammatory response. Combinations of JYBD and neuraminidase inhibitors conferred synergistic suppression of IAV both in vitro and in vivo. It might provide a scientific basis for clinical applications of JYBD against influenza virus infected diseases.

SCN1A intronic variants impact on Nav1.1 protein expression and sodium channel function, and associated with epilepsy phenotypic severity.

High-throughput sequencing has identified numerous intronic variants in the SCN1A gene in epilepsy patients. Abnormal mRNA splicing caused by these variants can lead to significant phenotypic differences, but the mechanisms of epileptogenicity and phenotypic differences remain unknown. Two variants, c.4853-1 G>C and c.4853-25 T>A, were identified in intron 25 of SCN1A, which were associated with severe Dravet syndrome (DS) and mild focal epilepsy with febrile seizures plus (FEFS+), respectively. The impact of these variants on protein expression, electrophysiological properties of sodium channels and their correlation with epilepsy severity was investigated through plasmid construction and transfection based on the aberrant spliced mRNA. We found that the expression of truncated mutant proteins was significantly reduced on the cell membrane, and retained in the cytoplasmic endoplasmic reticulum. The mutants caused a decrease in current density, voltage sensitivity, and an increased vulnerability of channel, leading to a partial impairment of sodium channel function. Notably, the expression of DS-related mutant protein on the cell membrane was higher compared to that of FEFS+-related mutant, whereas the sodium channel function impairment caused by DS-related mutant was comparatively milder than that caused by FEFS+-related mutant. Our study suggests that differences in protein expression levels and altered electrophysiological properties of sodium channels play important roles in the manifestation of diverse epileptic phenotypes. The presence of intronic splice site variants may result in severe phenotypes due to the dominant-negative effects, whereas non-canonical splice site variants leading to haploinsufficiency could potentially cause milder phenotypes.

Prediction Modelling for Gastroesophageal Variceal Bleeding in Patients With Chronic Hepatitis B Using Four-dimensional Flow MRI.

Background/Aims: In this study, we aim to develop a model for predicting gastroesophageal varices (GEV) bleeding in patients with chronic hepatitis B (CHB) by utilizing hemodynamic parameters obtained through four-dimensional flow MRI (4D flow MRI). Methods: This study conducted a prospective enrollment of CHB patients suspected of GEV from October 2021 to May 2022. The severity of varices and bleeding risk were evaluated using clinical findings and upper gastrointestinal endoscopy, and patients were classified into high-risk and non-high-risk groups. The study utilized serological examination, ultrasonographic examination, and 4D flow MRI. Relevant parameters were selected through univariate and multivariate analyses, and a prediction model was established using binary logistic regression analysis. The model was combined with the Baveno Ⅵ/Ⅶ and Expanded Baveno Ⅵ/Ⅶ criteria to evaluate diagnostic efficacy and the risk of avoiding endoscopic examination. Results: A total of 40 CHB patients were enrolled and categorized into the high-risk group (n = 15) and the non-high-risk group (n = 25). The spleen diameter and regurgitant fraction (R%) were independent predictors of variceal bleeding and a predictive model was established. The combination of this prediction model and the Baveno Ⅵ/Ⅶ criteria achieved high diagnostic efficiency, enabling 45.00% (18/40) of patients to be exempted from the unnecessary endoscopic procedure and the high-risk misclassification rate (0%) was less than 5%. Conclusion: The prediction model generated by 4D flow MRI has the potential to assess the likelihood of varices and can be supplemented by the Baveno VI/VII criteria to improve diagnostic accuracy in CHB patients.

Technical review of endoscopic ultrasound-guided drainage/anastomosis and trans-endosonographically created route procedures for the treatment of pancreatic diseases.

Endoscopic ultrasound (EUS)-guided pancreatic duct drainage includes two procedures: EUS-guided drainage/anastomosis (EUS-D/A) and trans-papillary drainage with EUS-assisted pancreatic rendezvous. EUS-guided pancreatogastrostomy is the most common EUS-D/A procedure and is recommended as a salvage procedure in cases in which endoscopic retrograde cholangiopancreatography fails or is difficult. However, initial EUS-D/A is performed in patients with surgically altered anatomy at our institution. It is one of the most difficult interventional EUS procedures and has a high incidence of adverse events. The technical difficulties differ according to etiology, and the incidence of adverse events varies between initial EUS-D/A and subsequent trans-endosonographically/EUS-guided created route procedures. Hence, it is important to meticulously prepare a procedure based on the patient's condition and the available devices. The technical difficulties in EUS-D/A include: (1) determination of the puncture point, (2) selection of a puncture needle and guidewire, (3) guidewire manipulation, and (4) dilation of the puncture route and stenting. Proper technical procedures are important to increase the success rate and reduce the incidence and severity of adverse events. The complexity of EUS-D/A is also contingent on the severity of pancreatic fibrosis and stricture. In post-pancreatectomy cases, determination of the puncture site is important for success because of the remnant pancreas. Trans-endosonographically/EUS-guided created route procedures following initial EUS-D/A are also important for achieving the treatment goal. This article focuses on effective strategies for initial EUS-D/A, based on the etiology and condition of the pancreas. We mainly discuss EUS-D/A, including its indications, techniques, and success-enhancing strategies.

Immobilization of laccase on magnetic PEGDA-CS inverse opal hydrogel for enhancement of bisphenol A degradation in aqueous solution.

Endocrine disruptors such as bisphenol A (BPA) adversely affect the environment and human health. Laccases are used for the efficient biodegradation of various persistent organic pollutants in an environmentally safe manner. However, the direct application of free laccases is generally hindered by short enzyme lifetimes, non-reusability, and the high cost of a single use. In this study, laccases were immobilized on a novel magnetic three-dimensional poly(ethylene glycol) diacrylate (PEGDA)-chitosan (CS) inverse opal hydrogel (LAC@MPEGDA@CS@IOH). The immobilized laccase showed significant improvement in the BPA degradation performance and superior storage stability compared with the free laccase. 91.1% of 100 mg/L BPA was removed by the LAC@MPEGDA@CS@IOH in 3 hr, whereas only 50.6% of BPA was removed by the same amount of the free laccase. Compared with the laccase, the outstanding BPA degradation efficiency of the LAC@MPEGDA@CS@IOH was maintained over a wider range of pH values and temperatures. Moreover, its relative activity of was maintained at 70.4% after 10 cycles, and the system performed well in actual water matrices. This efficient method for preparing immobilized laccases is simple and green, and it can be used to further develop ecofriendly biocatalysts to remove organic pollutants from wastewater.

Selenium deficiency exacerbates ROS/ER stress mediated pyroptosis and ferroptosis induced by bisphenol A in chickens thymus.

Bisphenol A (BPA) is an industrial pollutant that can cause immune impairment. Selenium acts as an antioxidant, as selenium deficiency often accompanies oxidative stress, resulting in organ damage. This study is the first to demonstrate that BPA and/or selenium deficiency induce pyroptosis and ferroptosis-mediated thymic injury in chicken and chicken lymphoma cell (MDCC-MSB-1) via oxidative stress-induced endoplasmic reticulum (ER) stress. We established a broiler chicken model of BPA and/or selenium deficiency exposure and collected thymus samples as research subjects after 42 days. The results demonstrated that BPA or selenium deficiency led to a decrease in antioxidant enzyme activities (T-AOC, CAT, and GSH-Px), accumulation of peroxides (H2O2 and MDA), significant upregulation of ER stress-related markers (GRP78, IER 1, PERK, EIF-2α, ATF4, and CHOP), a significant increase in iron ion levels, significant upregulation of pyroptosis-related gene (NLRP3, ASC, Caspase1, GSDMD, IL-18 and IL-1ß), significantly increase ferroptosis-related genes (TFRC, COX2) and downregulate GPX4, HO-1, FTH, NADPH. In vitro experiments conducted in MDCC-MSB-1 cells confirmed the results, demonstrating that the addition of antioxidant (NAC), ER stress inhibitor (TUDCA) and pyroptosis inhibitor (Vx765) alleviated oxidative stress, endoplasmic reticulum stress, pyroptosis, and ferroptosis. Overall, this study concludes that the combined effects of oxidative stress and ER stress mediate pyroptosis and ferroptosis in chicken thymus induced by BPA exposure and selenium deficiency.

Identifying a Ubiquitinated Adaptor Protein by a Viral E3 Ligase Through Co-immunoprecipitation.

Co-immunoprecipitation is a technique widely utilized to isolate protein complexes and study protein-protein interactions. Ubiquitinated proteins could be identified by combining co-immunoprecipitation with SDS-PAGE followed by immunoblotting. In this chapter, we use Herpes Simplex Virus 1 immediate-early protein ICP0-mediated polyubiquitination of p50 as an example to describe the method to identify a ubiquitinated adaptor protein by a viral E3 ligase by co-immunoprecipitation.

Identifying an Abnormal Phosphorylated Adaptor by Viral Kinase Using Mass Spectrometry.

Mass spectrometers are widely used to identify protein phosphorylation sites. The process usually involves selective isolation of phosphoproteins and subsequent fragmentation to identify both the peptide sequence and phosphorylation site. Immunoprecipitation could capture and purify the protein of interest, greatly reducing sample complexity before submitting it for mass spectrometry analysis. This chapter describes a method to identify an abnormal phosphorylated site of the adaptor protein by a viral kinase through immunoprecipitation followed by LC-MS/MS.

Systematic metabolic engineering enables highly efficient production of vitamin A in Saccharomyces cerevisiae.

Vitamin A is a micronutrient critical for versatile biological functions and has been widely used in the food, cosmetics, pharmaceutical, and nutraceutical industries. Synthetic biology and metabolic engineering enable microbes, especially the model organism Saccharomyces cerevisiae (generally recognised as safe) to possess great potential for the production of vitamin A. Herein, we first generated a vitamin A-producing strain by mining ß-carotene 15,15'-mono(di)oxygenase from different sources and identified two isoenzymes Mbblh and Ssbco with comparable catalytic properties but different catalytic mechanisms. Combinational expression of isoenzymes increased the flux from ß-carotene to vitamin A metabolism. To modulate the vitamin A components, retinol dehydrogenase 12 from Homo sapiens was introduced to achieve more than 90 % retinol purity using shake flask fermentation. Overexpressing POS5Δ17 enhanced the reduced nicotinamide adenine dinucleotide phosphate pool, and the titer of vitamin A was elevated by almost 46 %. Multi-copy integration of the key rate-limiting step gene Mbblh further improved the synthesis of vitamin A. Consequently, the titer of vitamin A in the strain harbouring the Ura3 marker was increased to 588 mg/L at the shake-flask level. Eventually, the highest reported titer of 5.21 g/L vitamin A in S. cerevisiae was achieved in a 1-L bioreactor. This study unlocked the potential of S. cerevisiae for synthesising vitamin A in a sustainable and economical way, laying the foundation for the commercial-scale production of bio-based vitamin A.

Preventive and therapeutic effects of a super-multivalent sialylated filamentous bacteriophage against the influenza virus.

The resurgence of influenza viruses as a significant global threat emphasizes the urgent need for innovative antiviral strategies beyond existing treatments. Here, we present the development and evaluation of a novel super-multivalent sialyllactosylated filamentous phage, termed t-6SLPhage, as a potent entry blocker for influenza A viruses. Structural variations in sialyllactosyl ligands, including linkage type, valency, net charge, and spacer length, were systematically explored to identify optimal binding characteristics against target hemagglutinins and influenza viruses. The selected SLPhage equipped with optimal ligands, exhibited exceptional inhibitory potency in in vitro infection inhibition assays. Furthermore, in vivo studies demonstrated its efficacy as both a preventive and therapeutic intervention, even when administered post-exposure at 2 days post-infection, under 4 lethal dose 50% conditions. Remarkably, co-administration with oseltamivir revealed a synergistic effect, suggesting potential combination therapies to enhance efficacy and mitigate resistance. Our findings highlight the efficacy and safety of sialylated filamentous bacteriophages as promising influenza inhibitors. Moreover, the versatility of M13 phages for surface modifications offers avenues for further engineering to enhance therapeutic and preventive performance.

The Impact of Gender and Race on Outcomes for Hospitalized Hepatitis A Patients Stratified by Liver Disease Severity.

Background: The incidence of hepatitis A virus (HAV) infection is on the rise, with a minority of patients at risk for poor outcomes. This study investigates the prognostic impacts of race and gender on hospital outcomes among admitted HAV-infected patients. Methods: Using the National Inpatient Sample from 2012 to 2017, patients admitted with HAV were selected and stratified by gender (male and female) and race (White, Black, Hispanic, Asian-Pacific Islander, Other). Propensity score-matching and statistical analysis were implemented with comparison to the controls ("Female" and "White"). Primary endpoints included mortality, length of stay (LOS), and hospitalization costs, while secondary endpoints consisted of hepatic-related medical complications such as ascites, hepatic encephalopathy, varices, and acute liver failure. Results: Females with compensated cirrhosis had increased odds of mortality (aOR 2.59, 95% CI: 1.14-5.91, P = 0.02). Otherwise, no other differences in mortality were detected between genders and races. Females had a shorter hospital LOS (aOR 0.97, 95% CI: 0.96-0.98, P < 0.001), lower adjusted cost ($12,241 vs. $13,510, aOR 0.92, 95% CI: 0.92-0.92, P < 0.001), lower odds of esophageal varices (aOR 0.74, 95% CI: 0.57-0.97, P = 0.03) and hepatic encephalopathy (aOR 0.67, 95% CI: 0.53-0.84, P < 0.001) compared to males. Black patients exhibited higher LOS (aOR 1.06, 95% CI: 1.04-1.08, P < 0.001) and adjusted costs ($13,392 vs $12,592, aOR 1.02, 95% CI: 1.02-1.03, P < 0.001). Hispanic patients exhibited higher rates of esophageal varices (aOR 2.19, 95% CI: 1.28-3.76, P = 0.005) and adjusted costs ($14,202 vs. $12,381, aOR 1.07, 95% CI: 1.07-1.07, P < 0.001), and Asian patients experienced higher adjusted costs ($18,426 vs. $13,137, aOR 1.10, 95% CI: 1.10-1.10, P < 0.001) compared to White patients. Conclusion: Various nuanced impacts of gender and race on hospitalization outcomes in HAV infection were observed, with only one subgroup analysis demonstrating a higher rate of mortality. Further research is warranted to better understand these findings and their implications.

Establishment of a rapid detection method for Mycoplasma pneumoniae based on RPA-CRISPR-Cas12a technology.

Mycoplasma pneumoniae can cause respiratory infections and pneumonia, posing a serious threat to the health of children and adolescents. Early diagnosis of Mycoplasma pneumoniae infection is crucial for clinical treatment. Currently, diagnostic methods for Mycoplasma pneumoniae infection include pathogen detection, molecular biology techniques, and bacterial culture, all of which have certain limitations. Here, we developed a rapid, simple, and accurate detection method for Mycoplasma pneumoniae that does not rely on large equipment or complex operations. This technology combines the CRISPR-Cas12a system with recombinase polymerase amplification (RPA), allowing the detection results to be observed through fluorescence curves and immunochromatographic lateral flow strips.It has been validated that RPA-CRISPR/Cas12a fluorescence analysis and RPA-CRISPR/Cas12-immunochromatographic exhibit no cross-reactivity with other common pathogens, and The established detection limit was ascertained to be as low as 102 copies/µL.Additionally, 49 clinical samples were tested and compared with fluorescence quantitative polymerase chain reaction, demonstrating a sensitivity and specificity of 100%. This platform exhibits promising clinical performance and holds significant potential for clinical application, particularly in settings with limited resources, such as clinical care points or resource-constrained areas.

Dietary sn-2 palmitate influences cognitive behavior by increasing the transport of liver-produced lysophosphatidylcholine VLCPUFAs to the brain.

Investigations indicated that sn-2 palmitate have positive effects on brain development, although its mechanism remains largely unexamined. This research delved into how a diet abundant in sn-2 palmitate influenced the cognitive behavior of mice and elucidated the associated mechanisms using metabolomics and lipidomics. The study demonstrated that dietary sn-2 palmitate led to improved working memory and cognition in mice, as well as an increase in brain BDNF concentration when compared to those fed blend vegetable oil (BVO). This was because sn-2 palmitate feeding promoted the synthesis of very long-chain fatty acids (VLCPUFAs) for the lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) in the liver. This led to more efficient delivery of VLCPUFAs to the brain, as indicated by elevated concentration of LPC/LPE-VLCPUFAs in the liver and heightened expression of the major facilitator superfamily domain containing 2a (MFSD2A). In essence, this paper offered a potential mechanism by which sn-2 palmitate enhanced mouse neurodevelopment.

A missense variant in SLC12A3 gene enhances aberrant splicing causing Gitelman syndrome.

Gitelman syndrome (GS) is the most prevalent genetic tubulopathy characterized by several electrolyte abnormalities, including hypokalemia, hypomagnesemia, hypocalciuria, metabolic alkalosis, and hyperreninemic hyperaldosteronism. These features are caused by a bi-allelic mutation in the SLC12A3 gene. In this report, we present a case of GS in an asymptomatic woman who incidentally exhibited hypokalemia during an antenatal check-up. Her biochemical profile was consistent with GS. Genetic analysis revealed two heterozygous variants in trans, namely, NM_001126108.2:c.625C>T; p.(Arg209Trp) and c.965C>T; p.(Ala322Val). The c.625C>T; p.(Arg209Trp) variant has previously been experimentally confirmed as a loss-of-function (LOF) variant. However, the functional impact of the c.965C>T variant, located at the 5 prime end of exon 8, has not been fully elucidated. Through the utilization of both complementary DNA (cDNA) and minigene analysis, we confirmed that the c.965C>T variant can generate two distinct cDNA transcripts. The first transcript carries a missense mutation, p.(Ala322Val) in the full SLC12A3 transcript, while the second transcript consists of an in-frame deletion of both exons 7 and 8 in the SLC12A3 transcript, in which may result in the loss of transmembrane regions 5 - 6 involved in chloride transport. Our findings provide insights into the intricate mechanisms of splicing, highlighting how a variant in one exon can remotely influence the transcription of an upstream exon, as observed with the variant in exon 8 impacting the transcription of exon 7.

A single-chain fab derived drug conjugate for HER2 specific delivery.

Despite the development of antibody-drug conjugates, the fragment Fab-based drug conjugates offer some unique capabilities in terms of safety, clearance, penetration and others. Current methods for preparing Fab drug conjugates are limited by the availability and stability of Fab proteins, leaving reports on this rare. Here, we found that a single-chain scaffold of Fab enables stabilization of the paired structure and supports high-yield expression in bacteria cytoplasm. Furthermore, we conjugated anti-neoplastic agent SN38 to the C-terminus by sortase A ligation and generated a homogenous Fab conjugate with the drug-to-Fab ratio of 1. The resulting anti-HER2 Fab-SN38 conjugate demonstrated potent and antigen-dependent cell-killing ability with the aid of its special cathepsin-triggered cyclization-promoted release mechanism. In vivo, Fab-SN38 can prevent growths of HER2-positive tumors in athymic mice and be well tolerated to the treatment at 7 mg/kg per dose. Anti-tumor activity, high dose tolerance and penetration advantage observed in this study would merit Fab conjugate investigation in target chemotherapy.