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1.
World J Surg ; 48(1): 175-185, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38436211

RESUMO

BACKGROUND: Obesity worsens various gastrointestinal pathologies. While bariatric surgery ameliorates obesity, it substantially modifies the gastrointestinal system depending on surgery type, with limited data on subsequent impact on obesity-related gastrointestinal admissions. METHODS: Using the 2012-2014 Nationwide Readmission Database, we included individuals with obesity who received vertical sleeve gastrectomy (VSG), Roux-en-Y gastric bypass (RYGB), or hernia repair (HR-control surgery). Our main focus was the adjusted odds ratio (aOR) for gastrointestinal inpatient admissions within 6 months following surgery compared to the 6 months preceding it, while controlling for several confounding factors. Gastrointestinal admissions were grouped into postoperative complications or obesity-associated gastrointestinal conditions. RESULTS: Our cohort included 140,103 adults with RYGB, 132,253 with VSG, and 12,436 HR controls. Postoperative gastrointestinal complications were most common after RYGB, prominently obstruction (aOR = 33.17, 95%CI: 18.01, 61.10), and Clostridium difficile infection (aOR: 12.52, 95%CI: 6.22, 25.19). VSG also saw significantly increased but less frequent similar conditions. Notably, for gastrointestinal conditions associated with obesity, acute pancreatitis risk was higher post-VSG (aOR = 6.26, 95%CI: 4.02, 9.73). Post-RYGB patients were most likely to be admitted for cholelithiasis with cholecystitis (aOR: 4.15, 95% CI: 3.24, 5.31), followed by chronic liver disease (aOR: 3.00, 95% CI: 2.33, 3.87). The risk of noninfectious colitis admissions was threefold higher after RYGB and VSG. No gastrointestinal conditions showed an increase after HR. CONCLUSION: Despite weight loss, bariatric surgery was associated with an increased risk of hepato-pancreatobiliary and colitis admissions related to obesity in the first six postoperative months, with considerable variations in rates of gastrointestinal conditions by surgery type.


Assuntos
Cirurgia Bariátrica , Colite , Gastroenteropatias , Pancreatite , Adulto , Humanos , Doença Aguda , Cirurgia Bariátrica/efeitos adversos , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/cirurgia , Gastroenteropatias/epidemiologia , Gastroenteropatias/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
2.
Sci Immunol ; 9(93): eadj7363, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38427721

RESUMO

Peyer's patches (PPs) are lymphoid structures situated adjacent to the intestinal epithelium that support B cell responses that give rise to many intestinal IgA-secreting cells. Induction of isotype switching to IgA in PPs requires interactions between B cells and TGFß-activating conventional dendritic cells type 2 (cDC2s) in the subepithelial dome (SED). However, the mechanisms promoting cDC2 positioning in the SED are unclear. Here, we found that PP cDC2s express GPR35, a receptor that promotes cell migration in response to various metabolites, including 5-hydroxyindoleacetic acid (5-HIAA). In mice lacking GPR35, fewer cDC2s were found in the SED, and frequencies of IgA+ germinal center (GC) B cells were reduced. IgA plasma cells were reduced in both the PPs and lamina propria. These phenotypes were also observed in chimeric mice that lacked GPR35 selectively in cDCs. GPR35 deficiency led to reduced coating of commensal bacteria with IgA and reduced IgA responses to cholera toxin. Mast cells were present in the SED, and mast cell-deficient mice had reduced PP cDC2s and IgA+ cells. Ablation of tryptophan hydroxylase 1 (Tph1) in mast cells to prevent their production of 5-HIAA similarly led to reduced PP cDC2s and IgA responses. Thus, mast cell-guided positioning of GPR35+ cDC2s in the PP SED supports induction of intestinal IgA responses.


Assuntos
Linfócitos B , Mastócitos , Animais , Camundongos , Ácido Hidroxi-Indolacético , Movimento Celular , Imunoglobulina A Secretora , Nódulos Linfáticos Agregados , Receptores Acoplados a Proteínas G/genética
3.
Trop Med Int Health ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481292

RESUMO

AIM: This study aimed to investigate the impact of communicable diseases with epidemic potential in complex emergency (CE) situations, focusing on the epidemiological profile of incidence and mortality and exploring underlying factors contributing to increased epidemic risks. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Review (PRISMA-ScR) guidelines, we conducted a scoping review of articles published between 1990 and 2022. The search included terms related to complex emergencies, communicable diseases, outbreaks, and epidemics. We identified 92 epidemics related to CE occurring in 32 different countries. RESULTS: Communicable diseases like Shigellosis, Cholera, Measles, Meningococcal meningitis, Yellow Fever, and Malaria caused significant morbidity and mortality. Diarrhoeal diseases, particularly Cholera and Shigellosis, had the highest incidence rates. Shigella specifically had an incidence of 241.0 per 1000 (people at risk), with a mortality rate of 11.7 per 1000, while Cholera's incidence was 13.0 per 1000, with a mortality rate of 0.22 per 1000. Measles followed, with an incidence of 25.0 per 1000 and a mortality rate of 0.76 per 1000. Meningococcal Meningitis had an incidence rate of 1.3 per 1000 and a mortality rate of 0.13 per 1000. Despite their lower incidences, yellow fever at 0.8 per 1000 and malaria at 0.4 per 1000, their high case fatality rates of 20.1% and 0.4% remained concerning in CE. The qualitative synthesis reveals that factors such as water, sanitation, and hygiene, shelter and settlements, food and nutrition, and public health and healthcare in complex emergencies affect the risk of epidemics. CONCLUSION: Epidemics during complex emergencies could potentially lead to a public health crisis. Between 1990 and 2022, there have been no statistically significant changes in the trend of incidence, mortality, or fatality rates of epidemic diseases in CE. It is crucial to understand that all epidemics identified in CE are fundamentally preventable.

4.
Heliyon ; 10(5): e27417, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38486755

RESUMO

Klebsiella pneumoniae (K. pneumoniae) is a common bacterium that can cause iatrogenic infection. Recently, the rise of antibiotic resistance among K. pneumoniae strains is one key factor associated with antibiotic treatment failure. Hencefore, there is an urgent need for effective K. pneumoniae vaccines. This study aimed to design a multi-epitope vaccine (MEV) candidate against K. pneumonia by utilizing an immunoinformatics method. In this study, we obtained 15 cytotoxic T lymphocyte epitopes, 10 helper T lymphocyte epitopes, 6 linear B-cell epitopes, and 2 conformational B-cell epitopes for further research. Then, we designed a multi-epitope vaccine composed of a total of 743 amino acids, containing the epitopes linked by GPGPG flexible links and an EAAAK linker to the Cholera Toxin Subunit B coadjuvant. The observed properties of the MEV, including non-allergenicity, high antigenicity, and hydrophilicity, are noteworthy. The improvements in the tertiary structure through structural refinement and disulfide bonding, coupled with promising molecular interactions revealed by molecular dynamics simulations with TLR4, position the MEV as a strong candidate for further investigation against K. pneumoniae.

5.
J Biomol Struct Dyn ; : 1-17, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38486475

RESUMO

Foot and mouth Disease virus (FMDV) belongs to Picornaviridae family and Aphthovirus genus causing Foot and mouth disease (FMD) in cloven-hoofed animals. FMDV, a prevalent virus induces both acute and chronic infections with high mutation rates resulting in seven primary serotypes, making vaccine development indispensable. Due to time and cost effectiveness of the immunoinformatic approach, we designed in-silico polyepitope vaccine (PEV) for the curtailment of FMDV. Structural and immunogenic parts of FMDV (Viral Protein 1 (VP1), Viral Protein 2 (VP2), Viral Protein 3 (VP3), and Viral Protein 4 (VP4)) were used to design the cytotoxic T Lymphocyte (CTL), Helper T Lymphocyte (HTL), and B-cell epitopes, followed by screening for antigenic, non-allergenic, Interferon (IFN) simulator, and non-toxicity, which narrowed down to 7 CTL, 3 HTL, and 12 B-cell epitopes. These selected epitopes were linked using appropriate linkers and Cholera Toxin B (CTB) adjuvant for immunological modulation. The physiochemical analyses followed by the structure prediction demonstrated the stability, hydrophilicity and solubility of the PEV. The interactions and stability between the vaccine, Toll like Receptor 3 (TLR3) and Toll like receptor 7 (TLR7) were revealed by molecular docking and Molecular Mechanics/Poisson Boltzmann Surface Area (MMPBSA) with high stability and compactness verified by MD simulation. In-silico immune simulation demonstrated a strong immunological response. FMDV-PEV (Poly epitope vaccine) will be effectively produced in an E. coli system, as codon optimization and cloning in an expression vector was performed. The effectiveness, safety, and immunogenicity profile of FMDV-PEV may be confirmed by further experimental validations.Communicated by Ramaswamy H. Sarma.


The structural and immunogenic parts of FMDV were targeted for developing VaccineCTB-adjuvant and appropriate linkers, enhancing the immunogenicity of the PEVMinimal deformability and high stability of Vaccine using immunoinformaticsStrong antigen-specific humoral and cellular immune response of potential vaccineResults indicating the effectiveness, safety, and immunogenicity of the PEV.

6.
Mucosal Immunol ; 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38492746

RESUMO

Induction and regulation of specific intestinal IgA responses critically depend on dendritic cell subsets and the T cells they activate in the Peyer's patches (PP). We found that oral immunization with cholera toxin (CT) as an adjuvant resulted in migration-dependent changes in the composition and localization of PP DC subsets with increased numbers of CD103- cDC2s and LysoDCs in the subepithelial dome and of CD103+ cDC2s that expressed CD101 in the T cell zones (TZ), while oral OVA tolerization was instead associated with larger quantities of TZ cDC1s and pTregs. Decreased IgA responses were observed after CT adjuvanted immunization in huCD207DTA mice lacking CD103+ cDC2s, while oral OVA tolerization was inefficient in cDC1-deficient Batf3-/- mice. Using Ovalbumin (OVA) TCR transgenic CD4 T cell adoptive transfer models, we found that co-transferred endogenous WT CD4 T cells can hinder the induction of OVA-specific IgA responses through secretion of IL-10. CT could overcome this blocking effect, apparently through a modulating effect on peripherally induced Tregs (pTreg) while promoting an expansion of follicular helper T cells (Tfh). The data support a model where cDC1-induced pTreg normally supress PP responses for any given antigen and where CT's oral adjuvanticity effect is dependent on promoting Tfh responses through induction of CD103+ cDC2s.

8.
Nat Med ; 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443690

RESUMO

Systematic testing for Vibrio cholerae O1 is rare, which means that the world's limited supply of oral cholera vaccines (OCVs) may not be delivered to areas with the highest true cholera burden. Here we used a phenomenological model with subnational geographic targeting and fine-scale vaccine effects to model how expanding V. cholerae testing affected impact and cost-effectiveness for preventive vaccination campaigns across different bacteriological confirmation and vaccine targeting assumptions in 35 African countries. Systematic testing followed by OCV targeting based on confirmed cholera yielded higher efficiency and cost-effectiveness and slightly fewer averted cases than status quo scenarios targeting suspected cholera. Targeting vaccine to populations with an annual incidence rate greater than 10 per 10,000, the testing scenario averted 10.8 (95% prediction interval (PI) 9.4-12.6) cases per 1,000 fully vaccinated persons while the status quo scenario averted 6.9 (95% PI 6.0-7.8) cases per 1,000 fully vaccinated persons. In the testing scenario, testing costs increased by US$31 (95% PI 25-39) while vaccination costs reduced by US$248 (95% PI 176-326) per averted case compared to the status quo. Introduction of systematic testing into cholera surveillance could improve efficiency and reach of global OCV supply for preventive vaccination.

9.
BMC Public Health ; 24(1): 697, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38439016

RESUMO

BACKGROUND: Understanding the temporal and geographic distribution of disease incidences is crucial for effective public health planning and intervention strategies. This study presents a comprehensive analysis of the spatiotemporal distribution of disease incidences in Ethiopia, focusing on six major diseases: Malaria, Meningitis, Cholera and Dysentery, over the period from 2010 to 2022, whereas Dengue Fever and Leishmaniasis from 2018 to 2023. METHODS: Using data from Ethiopian public health institute: public health emergency management (PHEM), and Ministry of Health, we examined the occurrence and spread of each disease across different regions of Ethiopia. Spatial mapping and time series analysis were employed to identify hotspots, trends, and seasonal variations in disease incidence. RESULTS: The findings reveal distinct patterns for each disease, with varying cases and temporal dynamics. Monthly wise, Malaria exhibits a cyclical pattern with a peak during the rainy and humid season, while Dysentery, Meningitis and Cholera displays intermittent incidences. Dysentery cases show a consistent presence throughout the years, while Meningitis remains relatively low in frequency but poses a potential threat due to its severity. Dengue fever predominantly occurs in the eastern parts of Ethiopia. A significant surge in reported incident cases occurred during the years 2010 to 2013, primarily concentrated in the Amhara, Sidama, Oromia, Dire Dawa, and Benishangul-Gumuz regions. CONCLUSIONS: This study helps to a better understanding of disease epidemiology in Ethiopia and can serve as a foundation for evidence-based decision-making in disease prevention and control. By recognizing the patterns and seasonal changes associated with each disease, health authorities can implement proactive measures to mitigate the impact of outbreaks and safeguard public health in the region.


Assuntos
Cólera , Dengue , Disenteria , Leishmaniose , Malária , Meningite , Estados Unidos , Humanos , Incidência , Etiópia/epidemiologia , Cólera/epidemiologia , Estudos Retrospectivos , Dengue/epidemiologia
10.
J Drugs Dermatol ; 23(3): SF395747s12-SF395747s22, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38443135

RESUMO

Atopic Dermatitis (AD) is a chronic relapsing inflammatory skin disease associated with a significant patient burden on quality-of-life. Given skin barrier including skin microbiome changes are linked to AD pathogenesis, prebiotic emollients are shown to improve disease symptoms and maintain skin barrier integrity, normalizing skin microbiota. In this study, we evaluated the efficacy and safety of a prebiotic skincare routine in improving AD and xerosis, and ultimately quality-of-life in ethnically diverse patients. A total of 140 subjects from different racial/ethnic backgrounds, aged 3-80 years old with skin phototypes I-VI, and presenting with mild-AD or severe xerosis completed study. Expert grading, instrumentation, self-assessment questionnaires, plus clinical imaging demonstrated that a prebiotic cleanser and moisturizer routine significantly reduced skin conditions severity, strengthened skin barrier properties in both lesional and normal skin, and improved patients' quality-of-life while providing itch relief as soon as 4 weeks. The results of this research indicate that a prebiotic cleanser and moisturizer regimen offers benefits for diverse patient’s daily skincare routine by effectively managing AD and xerosis severity and symptoms, normalizing skin microbiota, plus preserving skin barrier integrity to prevent long-term sequelae. J Drugs Dermatol. 2024;23:3(Suppl 2):s12-22.


Assuntos
Dermatite Atópica , Gastroenteropatias , Humanos , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Pele , Protocolos Clínicos , Difenidramina , Progressão da Doença , Prebióticos
11.
Mol Biol Rep ; 51(1): 409, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38461219

RESUMO

BACKGROUND: This is a unique and novel study delineating the genotyping and subsequent prediction of AMR determinants of Vibrio cholerae revealing the potential of contemporary strains to serve as precursors of severe AMR crisis in cholera. METHODS AND RESULTS: Genotyping of representative strains, VC1 and VC2 was undertaken to characterize antimicrobial resistance genes (ARGs) against chloramphenicol, SXT, nalidixic acid and streptomycin against which they were found to be resistant by antibiogram analysis in our previous investigation. strAB, sxt, sul2, qace∆1-sul1 were detected by PCR. Genome annotation and identification of ARGs with WGS helped to detect the presence of almG, varG, strA (APH(3'')-Ib), strB (APH(6)-Id), sul2, catB9, floR, CRP, dfrA1 genes. Signatures of resistance determinants and protein domains involved in antimicrobial resistance, primarily, efflux of antibiotics were identified on the basis of 30-100% homology to reference proteins. These domains were predicted to be involved in other metabolic functions on the basis of 100% identity with 100% coverage with reference protein and nucleotide sequences and were predicted to be of a diverse taxonomic origin accentuating the influence of the microbiota on AMR acquisition. Sequence analysis of QRDR (quinolone resistance-determining region) revealed SNPs. Cytoscape v3.8.2 was employed to analyse protein-protein interaction of MDR proteins, MdtA and EmrD-2, with nodes of vital AMR pathways. Vital nodes involved in efflux of different classes of antibiotics were found to be absent in VC1 and VC2 justifying the sensitivity of these strains to most antibiotics. CONCLUSIONS: The study helped to examine the resistome of VC isolated from recent outbreaks to understand the underlying reason of sensitivity to most antibiotics and also to characterize the ARGs in their genome. It revealed that VC is a reservoir of signatures of resistance determinants and serving as precursors for severe AMR crisis in cholera. This is the first study, to our knowledge, which has scrutinized and presented systematically, information on prospective domains which bear the potential of serving as AMR determinants in VC with the help of bioinformatic tools. This pioneering approach may help in the prediction of AMR landfalls and benefit epidemiological surveillance and early warning systems.


Assuntos
Cólera , Vibrio cholerae , Humanos , Vibrio cholerae/genética , Cólera/tratamento farmacológico , Cólera/epidemiologia , Antibacterianos/farmacologia , Estudos Prospectivos , Farmacorresistência Bacteriana/genética , Testes de Sensibilidade Microbiana
12.
bioRxiv ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38463981

RESUMO

Breast cancer is one of the leading causes of mortality among women. The tumor microenvironment, consisting of host cells and extracellular matrix, has been increasingly studied for its interplay with cancer cells, and the resulting effect on tumor progression. While the breast is one of the most innervated organs in the body, the role of neurons, and specifically sensory neurons, has been understudied, mostly for technical reasons. One of the reasons is the anatomy of sensory neurons: sensory neuron somas are located in the spine, and their axons can extend longer than a meter across the body to provide innervation in the breast. Next, neurons are challenging to culture, and there are no cell lines adequately representing the diversity of sensory neurons. Finally, sensory neurons are responsible for transporting several different types of signals to the brain, and there are many different subtypes of sensory neurons. The subtypes of sensory neurons which innervate and interact with breast tumors are unknown. To establish the tools for labeling and subtyping neurons that interact with breast cancer cells, we utilized two retrograde tracer's standards in neuroscience, wheat-germ agglutinin (WGA) and cholera toxin subunit B (CTB). In vitro , we employed primary sensory neurons isolated from mouse dorsal root ganglia, cultured in a custom-built microfluidic device DACIT, that mimics the anatomical compartmentalization of the sensory neuron's soma and axons. In vivo , we utilized both syngeneic and transgenic mouse models of mammary carcinoma. We show that CTB and WGA trace different but overlapping sensory neuronal subpopulations: while WGA is more efficient in labeling CGRP+ neurons, CTB is superior in labeling the NF200+ neurons. Surprisingly, both tracers are also taken up by a significant population of breast cancer cells, both in vitro and in vivo . In summary, we have established methodologies for retrograde tracing of sensory neurons interacting with breast cancer cells. Our tools will be useful for future studies of breast tumor innervation, and development of therapies targeting breast cancer-associated neuron subpopulations of sensory neurons.

13.
Sci Rep ; 14(1): 5312, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438432

RESUMO

Classical swine fever has been spreading across the country since its re-emergence in Japan in 2018. Gifu Prefecture has been working diligently to control the disease through the oral vaccine dissemination targeting wild boars. Although vaccines were sprayed at 14,000 locations between 2019 and 2020, vaccine ingestion by wild boars was only confirmed at 30% of the locations. Here, we predicted the vaccine ingestion rate at each point by Random Forest modeling based on vaccine dissemination data and created prediction surfaces for the probability of vaccine ingestion by wild boar using spatial interpolation techniques. Consequently, the distance from the vaccination point to the water source was the most important variable, followed by elevation, season, road density, and slope. The area under the curve, model accuracy, sensitivity, and specificity for model evaluation were 0.760, 0.678, 0.661, and 0.685, respectively. Areas with high probability of wild boar vaccination were predicted in northern, eastern, and western part of Gifu. Leave-One-Out Cross Validation results showed that Kriging approach was more accurate than the Inverse distance weighting method. We emphasize that effective vaccination strategies based on epidemiological data are essential for disease control and that our proposed tool is also applicable for other wildlife diseases.


Assuntos
Peste Suína Clássica , Vacinas , Suínos , Animais , Peste Suína Clássica/epidemiologia , Peste Suína Clássica/prevenção & controle , Japão/epidemiologia , Vacinação/veterinária , Aprendizado de Máquina , Sus scrofa
14.
Expert Opin Ther Pat ; : 1-18, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38446009

RESUMO

INTRODUCTION: Vibrio cholerae bacteria cause an infection characterized by acute diarrheal illness in the intestine. Cholera is sustained by people swallowing contaminated food or water. Even though symptoms can be mild, if untreated disease becomes severe and life-threatening, especially in low-income countries. AREAS COVERED: After a description of the most recent literature on the pathophysiology of this infection, we searched for patents and literature articles following the PRISMA guidelines, filtering the results disclosed from 2020 to present. Moreover, some innovative molecular targets (e.g., carbonic anhydrases) and pathways to counteract this rising problem were also discussed in terms of design, structure-activity relationships and structural analyses. EXPERT OPINION: This review aims to cover and analyze the most recent advances on the new druggable targets and bioactive compounds against this fastidious pathogen, overcoming the use of old antibiotics which currently suffer from high resistance rate.

16.
Vet Res ; 55(1): 30, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493107

RESUMO

Epithelial damage due to gastrointestinal disorders frequently causes severe disease in horses. To study the underlying pathophysiological processes, we aimed to establish equine jejunum and colon enteroids (eqJE, eqCE) mimicking the in vivo epithelium. Therefore, enteroids were cultivated in four different media for differentiation and subsequently characterized histomorphologically, on mRNA and on protein level in comparison to the native epithelium of the same donor horses to identify ideal culture conditions for an in vitro model system. With increasing enterocyte differentiation, the enteroids showed a reduced growth rate as well as a predominantly spherical morphology and less budding compared to enteroids in proliferation medium. Combined or individual withdrawal of stem cell niche pathway components resulted in lower mRNA expression levels of stem cell markers and concomitant differentiation of enterocytes, goblet cells and enteroendocrine cells. For eqCE, withdrawal of Wnt alone was sufficient for the generation of differentiated enterocytes with a close resemblance to the in vivo epithelium. Combined removal of Wnt, R-spondin and Noggin and the addition of DAPT stimulated differentiation of eqJE at a similar level as the in vivo epithelium, particularly with regard to enterocytes. In summary, we successfully defined a medium composition that promotes the formation of eqJE and eqCE consisting of multiple cell types and resembling the in vivo epithelium. Our findings emphasize the importance of adapting culture conditions to the respective species and the intestinal segment. This in vitro model will be used to investigate the pathological mechanisms underlying equine gastrointestinal disorders in future studies.


Assuntos
Gastroenteropatias , Doenças dos Cavalos , Animais , Cavalos , Mucosa Intestinal , Intestinos , Diferenciação Celular , Gastroenteropatias/veterinária , RNA Mensageiro
17.
J Pediatr Gastroenterol Nutr ; 78(3): 583-591, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38504414

RESUMO

OBJECTIVES: Small fiber neuropathy (SFN) affects the fibers involved in cutaneous and visceral pain and temperature sensation and are a crucial part of the autonomic nervous system. Autonomic dysfunction secondary to SFN and autoimmune receptor antibodies is being increasingly recognized, and gastrointestinal (GI) manifestations include constipation, early satiety, nausea, vomiting, and diarrhea. Enteric nervous system involvement may be a possible explanation of abnormal GI motility patterns seen in these patients. METHODS: Children suspected to have SFN based on symptoms underwent skin biopsy at the Child Neurology clinic at Arnold Palmer Hospital for Children, which was processed at Therapath™ Neuropathology. SFN was diagnosed using epidermal nerve fiber density values that were below 5th percentile from the left distal leg (calf) as reported per Therapath™ laboratory. RESULTS: Twenty-six patients were diagnosed with SFN. Retrospective chart review was performed, including demographic data, clinical characteristics, and evaluation. A majority of patients were white adolescent females. Autonomic dysfunction, including orthostasis and temperature dysregulation were seen in 61.5% of patients (p = 0.124). Somatosensory symptoms, including pain or numbness were seen in 85% of patients (p < 0.001). GI symptoms were present in 85% of patients (p < 0.001) with constipation being the most common symptom seen in 50% of patients. This correlated with the motility testing results. CONCLUSIONS: Pediatric patients with SFN commonly have GI symptoms, which may be the main presenting symptom. It is important to recognize and look for symptoms of small fiber neuropathy in children with refractory GI symptoms that may explain multisystemic complaints often seen in these patients.


Assuntos
Gastroenteropatias , Neuropatia de Pequenas Fibras , Feminino , Adolescente , Humanos , Criança , Neuropatia de Pequenas Fibras/diagnóstico , Neuropatia de Pequenas Fibras/etiologia , Estudos Retrospectivos , Fibras Nervosas/patologia , Pele/patologia , Gastroenteropatias/diagnóstico , Gastroenteropatias/etiologia , Gastroenteropatias/patologia , Biópsia , Constipação Intestinal/diagnóstico , Constipação Intestinal/etiologia , Constipação Intestinal/patologia
18.
J Int Med Res ; 52(3): 3000605241233972, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38488658

RESUMO

Light chain deposition disease (LCDD) is an under-recognized condition characterized by deposition of abnormal monoclonal light chains in tissues, leading to organ dysfunction. LCDD involving the gastrointestinal tract is very uncommon, and its diagnosis is challenging. We herein report two cases of LCDD that manifested as inflammatory bowel disease-like symptoms and protein-losing gastroenteropathy. Both patients were women in their early 60s. Tissue biopsies from the gastrointestinal mucosa demonstrated extracellular deposits, which were negative by Congo red staining but positive for κ-light chain by immunohistochemistry. The recent literature on LCDD was reviewed. When patients unexpectedly show extracellular deposits in gastrointestinal biopsy specimens, evaluation of immunoglobulin chains is recommended for diagnosis of LCDD after systemic amyloidosis has been excluded.


Assuntos
Amiloidose , Gastroenteropatias , Mieloma Múltiplo , Humanos , Feminino , Masculino , Cadeias Leves de Imunoglobulina , Cadeias kappa de Imunoglobulina , Amiloidose/patologia , Gastroenteropatias/complicações , Gastroenteropatias/diagnóstico
19.
Appl Microbiol Biotechnol ; 108(1): 267, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38498053

RESUMO

ADP-activated ß-D-manno-heptoses (ADP-ß-D-manno-heptoses) are precursors for the biosynthesis of the inner core of lipopolysaccharide in Gram-negative bacteria. Recently, ADP-D-glycero-ß-D-manno-heptose (ADP-D,D-manno-heptose) and its C-6'' epimer, ADP-L-glycero-ß-D-manno-heptose (ADP-L,D-manno-heptose), were identified as potent pathogen-associated molecular patterns (PAMPs) that can trigger robust innate immune responses. Although the production of ADP-D,D-manno-heptose has been studied in several different pathogenic Gram-negative bacteria, current knowledge of ADP-ß-D-manno-heptose biosynthesis in Vibrio strains remains limited. Here, we characterized the biosynthetic enzymes of ADP-D,D-manno-heptose and the epimerase that converts it to ADP-L,D-manno-heptose from Vibrio cholerae (the causative agent of pandemic cholera) and Vibrio parahaemolyticus (non-cholera pathogen causing vibriosis with clinical manifestations of gastroenteritis and wound infections) in comparison with their isozymes from Escherichia coli. Moreover, we discovered that ß-D-mannose 1-phosphate, but not α-D-mannose 1-phosphate, could be activated to its ADP form by the nucleotidyltransferase domains of bifunctional kinase/nucleotidyltransferases HldEVC (from V. cholerae) and HldEVP (from V. parahaemolyticus). Kinetic analyses of the nucleotidyltransferase domains of HldEVC and HldEVP together with the E. coli-derived HldEEC were thus carried out using ß-D-mannose 1-phosphate as a mimic sugar substrate. Overall, our works suggest that V. cholerae and V. parahaemolyticus are capable of synthesizing ADP-ß-D-manno-heptoses and lay a foundation for further physiological function explorations on manno-heptose metabolism in Vibrio strains. KEY POINTS: • Vibrio strains adopt the same biosynthetic pathway as E. coli in synthesizing ADP-ß-D-manno-heptoses. • HldEs from two Vibrio strains and E. coli could activate ß-D-mannose 1-phosphate to ADP-ß-D-mannose. • Comparable nucleotidyltransfer efficiencies were observed in the kinetic studies of HldEs.


Assuntos
Escherichia coli , Vibrio , Escherichia coli/genética , Cinética , Vibrio/genética , Imunidade Inata , Nucleotidiltransferases
20.
Food Funct ; 15(6): 3122-3129, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38426554

RESUMO

Little is known regarding the effects of xylooligosaccharides (XOS) on insulin resistance (IR) in gestational diabetes mellitus (GDM). We aimed to investigate this issue and its mechanism. Sixty female mice were randomly allotted to 4 groups (n = 15): control, high fat diet (HFD), GDM, and GDM + XOS. The control mice were fed an AIN-93 diet, while the mice in the other groups were fed 45% HFD. After pregnancy, mice in GDM and GDM + XOS groups were intraperitoneally injected with 30 mg kg-1 streptozocin for 3 days from the first day of pregnancy. Mice in the GDM + XOS group were then fed an HFD containing 2% XOS. Fasting glucose and insulin levels were monitored. The fecal Akkermansia muciniphila (Akk. muciniphila) and Bifidobacterium were measured by qPCR. The Chiu scores were calculated from hematoxylin-eosin (HE)-stained ileal tissues. Phosphorylated Akt in the liver and occludin and ZO-1 in the intestinal tissues were determined by western blotting. XOS reduced (p < 0.05) fasting blood glucose and insulin and HOMA-IR, and increased (p < 0.05) Akt phosphorylation in the livers of GDM mice. Moreover, XOS decreased (p < 0.05) TNFα, IL-1ß, IL-15 and LPS in the serum, increased (p < 0.05) fecal Akk. muciniphila abundance, lowered (p < 0.05) Chiu's scores, and enhanced (p < 0.05) occludin and ZO-1 expression. XOS ameliorate IR by increasing Akk. muciniphila and improving intestinal barrier dysfunction in GDM mice.


Assuntos
Diabetes Gestacional , Gastroenteropatias , Glucuronatos , Resistência à Insulina , Enteropatias , Oligossacarídeos , Gravidez , Humanos , Feminino , Animais , Camundongos , Diabetes Gestacional/tratamento farmacológico , Diabetes Gestacional/metabolismo , Proteínas Proto-Oncogênicas c-akt , Ocludina , Insulina , Akkermansia
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