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1.
Traffic ; 24(7): 270-283, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37114883

RESUMO

Intracellular membrane fusion is mediated by membrane-bridging complexes of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). SNARE proteins are one of the key players in vesicular transport. Several reports shed light on intracellular bacteria modulating host SNARE machinery to establish infection successfully. The critical SNAREs in macrophages responsible for phagosome maturation are Syntaxin 3 (STX3) and Syntaxin 4 (STX4). Reports also suggest that Salmonella actively modulates its vacuole membrane composition to escape lysosomal fusion. Salmonella containing vacuole (SCV) harbours recycling endosomal SNARE Syntaxin 12 (STX12). However, the role of host SNAREs in SCV biogenesis and pathogenesis remains unclear. Upon knockdown of STX3, we observed a reduction in bacterial proliferation, which is concomitantly restored upon the overexpression of STX3. Live-cell imaging of Salmonella-infected cells showed that STX3 localises to the SCV membranes and thus might help in the fusion of SCV with intracellular vesicles to acquire membrane for its division. We also found the interaction STX3-SCV was abrogated when we infected with SPI-2 encoded Type 3 secretion system (T3SS) apparatus mutant (STM ∆ssaV) but not with SPI-1 encoded T3SS apparatus mutant (STM ∆invC). These observations were also consistent in the mice model of Salmonella infection. Together, these results shed light on the effector molecules secreted through T3SS encoded by SPI-2, possibly involved in interaction with host SNARE STX3, which is essential to maintain the division of Salmonella in SCV and help to maintain a single bacterium per vacuole.


Assuntos
Salmonella , Vacúolos , Animais , Camundongos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Comunicação Celular , Proteínas Qa-SNARE/genética , Proteínas Qa-SNARE/metabolismo , Salmonella/metabolismo , Proteínas SNARE/metabolismo , Vacúolos/microbiologia
2.
Pancreatology ; 24(4): 643-648, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38584052

RESUMO

BACKGROUND & AIM: Extracorporeal shock wave lithotripsy (ESWL) is used for the treatment of pancreatic duct stones (PDS) in patients with chronic pancreatitis (CP). We aimed to develop a CT based index to predict the required number of ESWL sessions for technical success. METHODS: We retrospectively evaluated patients with PDS secondary to CP who underwent ESWL. Technical success was defined as the complete fragmentation of stones to <3 mm. CT features including PDS size, number, location, and density in Hounsfield units (HU) were noted. We analyzed the relationship between PDS characteristics and the number of ESWL sessions required for technical success. A multiple linear regression model was used to combine size and density into the pancreatic duct stone (PDS) index that was translated into a web-based calculator. RESULTS: There were 206 subjects (mean age 38.6 ± 13.7 years, 59.2% male) who underwent ESWL. PDS size showed a moderate correlation with the number of ESWL sessions (r = 0.42, p < 0.01). PDS in the head required a fewer number of sessions in comparison to those in the body (1.4 ± 0.6 vs. 1.6 ± 0.7, p = 0.01). There was a strong correlation between PDS density and the number of ESWL sessions (r = 0.617, p-value <0.01). The PDS index {0.3793 + [0.0009755 x PDS density (HU)] + [0.02549 x PDS size (mm)]} could accurately predict the required number of ESWL sessions with an AUC of 0.872 (p < 0.01). CONCLUSION: The PDS index is a useful predictor of the number of ESWL sessions needed for technical success that can help in planning and patient counseling.


Assuntos
Cálculos , Litotripsia , Ductos Pancreáticos , Tomografia Computadorizada por Raios X , Humanos , Litotripsia/métodos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Ductos Pancreáticos/diagnóstico por imagem , Ductos Pancreáticos/patologia , Cálculos/terapia , Cálculos/diagnóstico por imagem , Resultado do Tratamento , Pancreatite Crônica/terapia , Pancreatite Crônica/complicações , Pancreatite Crônica/diagnóstico por imagem
3.
Pancreatology ; 23(7): 858-867, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37798192

RESUMO

Pancreatic duct pressure (PDP) dynamics comprise an intricately modulated system that helps maintain homeostasis of pancreatic function. It is affected by various factors, including the rate of pancreatic fluid secretion, patency of the ductal system, sphincter of Oddi function, and pancreatic fluid characteristics. Disease states such as acute and chronic pancreatitis can alter the normal PDP dynamics. Ductal hypertension or increased PDP is suspected to be involved in the pathogenesis of pancreatic pain, endocrine and exocrine pancreatic insufficiency, and recurrent pancreatitis. This review provides a comprehensive appraisal of the available literature on PDP, including the methods used in the measurement and clinical implications of elevated PDP.


Assuntos
Ductos Pancreáticos , Pancreatite Crônica , Esfíncter da Ampola Hepatopancreática , Humanos , Relevância Clínica , Manometria/métodos
4.
Soft Matter ; 19(47): 9239-9253, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-37999932

RESUMO

In the present work, experiments are conducted to understand the consequence of stresses generated by flowing fluid on the bacterial morphology and virulence in microfluidic channels. We consider Klebsiella pneumoniae (KP, a clinical isolate), an ESKAPE pathogen, to be the model bacteria responsible for blood stream infections, bacteremia, including pneumonia, urinary tract infections and more. Four different stress conditions are generated by changing the flow rate and channel geometry subsequently altering the shear rate and stressing time (τ). We observe significant changes in the structural aspects of the stressed bacteria. With an increase in stressing parameters, the viability of the bacterial sample deteriorated. Most importantly, these stressed samples proliferate much more than unstressed samples inside the RAW264.7 murine macrophages. The results shed light on the complex relationship between flow stresses and bacterial virulence. Furthermore, the bacterial samples are challenged with ciprofloxacin to see how they behave under different stress conditions. The observations presented in the present study can be extended to model deadly diseases including bacteremia using organ-on-a-chip technology and to understand bacterial pathogenicity under realistic environments.


Assuntos
Bacteriemia , Infecções por Klebsiella , Animais , Camundongos , Klebsiella pneumoniae , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Antibacterianos
5.
Bioorg Chem ; 132: 106343, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36623447

RESUMO

A novel Schiff base ligand 2-(((2-(benzylthio)phenyl)imino)methyl)-4-chlorophenol and its cobalt, nickel, copper, and zinc metal complexes were prepared. Using B3LYP/6-31++G(d,p) method with LanL2DZ as basis set, the molecular structure of metal complexes has been optimized, and their parameters have been explored. The distorted octahedral geometries have been observed in cobalt, nickel, and copper complexes. In contrast, zinc complex exhibited distorted tetrahedral geometry indicating the coordination of metal ions with ligands through ONS binding sites, which are confirmed by various spectroscopic techniques, magnetic measurements, molar conductivity, elemental analysis, and DFT studies. The intercalative binding mode between CT-DNA and synthesized metal complexes has been determined by absorption and fluorescence spectroscopy. The binding constant values of metal complexes found to be varied from 5.28 × 103 M-1 to 9.18 × 104 M-1. Furthermore, several methods have been used to scrutinize the bioactivities, such as in vitro anti-diabetic, anti-inflammatory, and antioxidant. From the obtained results, it can be concluded that zinc metal complex exhibited excellent anti-inflammatory and anti-diabetic activity compared to others. However, the copper complex has good antioxidant property. Besides deducing the prospective binding energies of inhibitors, molecular docking simulations have also been conducted utilizing the enzyme structures of B-DNA, 6-COX, α-amylase, and α-glucosidase.


Assuntos
Complexos de Coordenação , Cobre , Simulação de Acoplamento Molecular , Cobre/química , Níquel , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Teoria da Densidade Funcional , Antioxidantes , Estudos Prospectivos , DNA/química , Cobalto/química , Zinco/química , Bioensaio , Bases de Schiff/química , Ligantes
6.
Environ Res ; 217: 114733, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36402185

RESUMO

Biochar has been evaluated globally to improve soil fertility and mitigate climate change. However, the long-term effects of successive biochar application on carbon (C) accumulation in soil irrigated with saline versus non-saline water (canal water) has not been investigated. A field experiment was conducted to study the effects of rice straw biochar addition rates (0, 2, 4, 8 Mg ha-1) on C storage in soil irrigated with water of different electrical conductivity [EC, dS m-1]; 0.3 (non-saline canal irrigation water; CIW), 5 (saline irrigation water; SIW5), 10 (SIW10), and 15 (SIW15) in a cotton-wheat system. Long-term irrigation with saline water of variable EC levels adversely affected soil functions, reducing above-ground biomass in cotton (12-48%) and wheat (5-27%). In contrast, plots irrigated with saline water but amended with rice straw biochar showed significant improvement in aboveground biomass (both in cotton and wheat), possibly due to its beneficial effects on soil properties such as soil EC, organic carbon, microbial population, water and nutrient availability, bulk density, soil aggregation, and proliferation of roots. Interestingly, the change in total organic C (TOC) stocks (8.5, 17, and 27.5 Mg C ha-1) after 5 years were found to be almost double the amount of biochar C added (4.3, 8.6, 17.2 Mg ha-1), indicating stabilization of belowground C inputs from the root biomass by the applied biochar and also possibly through its physical interaction with aggregates and minerals. Even though biochar application to saline water irrigated plots increased the contribution of plant-derived C to overall soil TOC stocks, it was still lower compared with canal water irrigated plots. The study conclusively established that the long-term stabilization of biogenic C through biochar has essential implications for mitigating climate change by accumulating additional C beyond the recalcitrant C contained in biochar.


Assuntos
Carbono , Oryza , Solo , Carvão Vegetal
7.
Curr Opin Gastroenterol ; 38(5): 472-480, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35881970

RESUMO

PURPOSE OF REVIEW: Bulking agents are inert materials injected into an organ to affect the physical properties of the organ for a therapeutic purpose. Various agents have been developed to aid in the treatment of diseases like gastroesophageal reflux disease (GERD), fecal incontinence, obesity, malignancy, hemostasis, and tissue dissection. Here, we review the state of the art in bulking agents in gastrointestinal endoscopy, past failures, current limitations, and where we see the field heading in the future. RECENT FINDINGS: Though bulking agents have been trialed for various different gastrointestinal diseases, there are currently limited uses in gastrointestinal endoscopy. Though various agents have been trialed for GERD, numerous complications and adverse events have limited its current use. However, for the treatment of fecal incontinence endoscopic bulking agent therapy is a reasonable option. Though in early stages of exploration, bulking agent therapy for enteric protection from radiotherapy may be a promising tool to improve treatment of pancreatic cancer. Bulking agents for tissue dissection have substantially improved lifting agents and complex polyp removal. Bulking agent therapy has not really been explored for endoscopic bariatric therapy or hemostasis but may be a fruitful area for exploration in the future. SUMMARY: Bulking agent therapy has been trialed for various gastrointestinal diseases with mixed success. There is currently a therapeutic roll in the endoscopic management of fecal incontinence and tissue dissection. A future role in the treatment of GERD, obesity, malignancy, and hemostasis seem feasible.


Assuntos
Incontinência Fecal , Refluxo Gastroesofágico , Endoscopia Gastrointestinal , Humanos , Obesidade
8.
Pancreatology ; 22(7): 887-893, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35872074

RESUMO

BACKGROUND: Acute pancreatitis remains the most common and morbid complication of endoscopic retrograde cholangiopancreatography (ERCP). The use of rectal indomethacin and pancreatic duct stenting has been shown to reduce the incidence and severity of post-ERCP pancreatitis (PEP), but these interventions have limitations. Recent clinical and translational evidence suggests a role for calcineurin inhibitors in the prevention of pancreatitis, with multiple retrospective case series showing a reduction in PEP rates in tacrolimus users. METHODS: The INTRO trial is a multicenter, international, randomized, double-blinded, controlled trial. A total of 4,874 patients undergoing ERCP will be randomized to receive either oral tacrolimus (5 mg) or oral placebo 1-2 h before ERCP, and followed for 30 days post-procedure. Blood and pancreatic aspirate samples will also be collected in a subset of patients to quantify tacrolimus levels. The primary outcome of the study is the incidence of PEP. Secondary endpoints include the severity of PEP, ERCP-related complications, adverse drug events, length of hospital stay, cost-effectiveness, and the pharmacokinetics, pharmacodynamics, and pharmacogenomics of tacrolimus immune modulation in the pancreas. CONCLUSIONS: The INTRO trial will assess the role of calcineurin inhibitors in PEP prophylaxis and develop a foundation for the clinical optimization of this therapeutic strategy from a pharmacologic and economic standpoint. With this clinical trial, we hope to demonstrate a novel approach to PEP prophylaxis using a widely available and well-characterized class of drugs. TRIAL REGISTRATION: NCT05252754, registered on February 14, 2022.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Pancreatite , Humanos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Indometacina/uso terapêutico , Pancreatite/prevenção & controle , Pancreatite/induzido quimicamente , Tacrolimo/uso terapêutico , Inibidores de Calcineurina , Estudos Retrospectivos , Doença Aguda , Anti-Inflamatórios não Esteroides , Administração Retal , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
9.
Support Care Cancer ; 30(1): 897-906, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34401981

RESUMO

PURPOSE: Adults with acute myeloid leukemia (AML) face considerable distress and often have a poor prognosis. However, little is known about these patients' perceptions of prognosis and how this relates to emotional well-being (EWB). METHODS: We conducted a prospective, observational study of 50 adult patients with AML initiating chemotherapy, and surveyed them longitudinally for 6 months about their prognosis, treatment goals, quality of life, and EWB (by FACT-G). We derived a prognostic estimate for each patient based on data from published trials summarized in National Comprehensive Care Network Guidelines. We used descriptive statistics and longitudinal modeling to test the hypothesis that more accurate prognostic awareness is associated with worse EWB. RESULTS: Most patients (n = 43; 86%) had an objectively poor prognosis attributable to relapsed disease, complex karyotype, or FLT3 mutation. Yet, 74% of patients reported expecting a 50% or greater chance of cure. Patients with a poor prognosis more often had discordant prognostic estimates, compared to those with favorable risk AML (OR = 7.25, 95% CI 1.21, 43.37). Patient-reported prognostic estimates did not vary significantly over time. At baseline, patients who better understood their prognosis had worse EWB and overall quality-of-life scores (EWB 12 vs. 19.5; p = 0.01; FACT-G 65 vs. 75.5; p = 0.01). CONCLUSION: Patients with AML overestimate their prognosis, and awareness of a poor prognosis is associated with worse emotional well-being. Efforts are needed to improve patients' understanding of their prognosis, and to provide more psychosocial support and attention to well-being as part of high-quality leukemia care.


Assuntos
Leucemia Mieloide Aguda , Qualidade de Vida , Adulto , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Mutação , Prognóstico , Estudos Prospectivos
10.
Environ Monit Assess ; 195(1): 26, 2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36278964

RESUMO

Hazardous dyes used in textile industries are considered high-risk pollutants to the environment. The raw as well as acid-treated Plumeria alba (white frangipani) leaf powder (WFLP and SWFLP) were used for the adsorption of methylene blue (MB) that is available in industrial wastewaters following the batch adsorption technique. The characterizations of adsorbents were done by FTIR, SEM, EDX, TGA, and zeta potential parameters. The adsorption was considered for the effects of temperature, initial dye concentration, solution pH, adsorbent dosage, and contact time. The experimental results obtained in the adsorption of MB were examined by nonlinear error functions like chi-square (χ2), ARE, and MPSD for three isotherm models: Langmuir, Freundlich, and Temkin. The maximum monolayer adsorption capacity, qmax (mg/g), was 45.45 mg/g for raw WFLP and 250 mg/g for SWFLP. The adsorbents fitted to the pseudo-second-order kinetic model (R2 = 0.99) using the experimental data of batch adsorption. The thermodynamic studies explained the spontaneity and nature of adsorption for raw and acid-treated adsorbents. The batch experimental results and characterizations of the adsorbents revealed that the selected adsorbents would be the best adsorbents for the removal of MB from the wastewater solution.


Assuntos
Apocynaceae , Poluentes Químicos da Água , Purificação da Água , Azul de Metileno/química , Cinética , Águas Residuárias , Biomassa , Pós , Poluentes Químicos da Água/química , Monitoramento Ambiental , Adsorção , Termodinâmica , Corantes/química , Ácidos , Concentração de Íons de Hidrogênio , Purificação da Água/métodos
11.
Pol J Radiol ; 87: e584-e591, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36420126

RESUMO

Purpose: Hirayama disease (HD) is a rare disease that was commonly mis-diagnosed in the past. The importance of neutral and flexion magnetic resonance imaging (MRI) in its accurate diagnosis has been emphasized along with utility of the inter-segmental angle of flexion. Aim of the study was to observe MRI findings of HD in neutral and flexion position and measure the inter-segmental angle of flexion. Material and methods: Cervical MR images of 17 patients of suspected HD were evaluated retrospectively for loss of attachment (LOA) of posterior dura, lower cervical cord atrophy, T2 hyperintensity, loss of cervical lordosis, enhancement of posterior epidural venous plexus, and inter-segmental angle of flexion on neutral and flexion MRIs. Results: Flexion MRI showed LOA of posterior dura (most commonly and maximum at C6 vertebral level) and intense enhancement in posterior epidural space in almost all patients. The mean inter-segmental angle of flexion at C5-C6 was 9.2°, and at C6-C7 it was 6°. Neutral MRI revealed LOA in 64.7%, lower cervical cord atrophy in all patients, T2 hyperintensity in the lower cervical cord in 35.2% of patients, and loss of cervical lordosis in 58.8% of patients. Conclusions: Flexion MRI is the gold standard for diagnosis of HD; however, certain imaging attributes, i.e. loss of attachment of posterior dura, asymmetrical lower cervical cord atrophy, T2 hyperintensity, and loss of cervical lordosis, can be seen on neutral MRI as well, which subsequently prompts the radiologist to include flexion MRI for confirmation. The inter-segmental angle of flexion is increased in patients with HD, which plays a role in planning timely surgical intervention.

12.
J Exp Bot ; 72(6): 2212-2230, 2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33197257

RESUMO

Rice, a staple food worldwide, contains varying amounts of nutrients in different grain tissues. The underlying molecular mechanism of such distinct nutrient partitioning remains poorly investigated. Here, an optimized rapid laser capture microdissection (LCM) approach was used to individually collect pericarp, aleurone, embryo and endosperm from grains 10 days after fertilization. Subsequent RNA-Seq analysis in these tissues identified 7760 differentially expressed genes. Analysis of promoter sequences of tissue-specific genes identified many known and novel cis-elements important for grain filling and seed development. Using the identified differentially expressed genes, comprehensive spatial gene expression pathways were built for accumulation of starch, proteins, lipids, and iron. The extensive transcriptomic analysis provided novel insights about nutrient partitioning mechanisms; for example, it revealed a gradient in seed storage protein accumulation across the four tissue types analysed. The analysis also revealed that the partitioning of various minerals, such as iron, is most likely regulated through transcriptional control of their transporters. We present the extensive analysis from this study as an interactive online tool that provides a much-needed resource for future functional genomics studies aimed to improve grain quality and seed development.


Assuntos
Oryza , Grão Comestível/genética , Grão Comestível/metabolismo , Endosperma/genética , Endosperma/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Nutrientes , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sementes/genética , Sementes/metabolismo
13.
Crit Rev Biotechnol ; 40(4): 490-507, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32204608

RESUMO

Rice has been a staple food for more than half of the global population. Different parts of rice grains contain different amounts of macro- and micro-nutrients. Polished white rice, which is the main form of rice consumption, mainly contains starch, however, the bran and germ, which are removed during polishing, contain large amounts of micronutrients and bioactive compounds. To engineer nutritionally superior rice varieties, it is imperative to understand the spatial and temporal distribution of different nutrients in different parts of the rice grain. Keeping this in mind, in this review, we have performed a comprehensive literature review to put together all the recent findings regarding the spatio-temporal distribution of all the important micronutrients in different cell-layers/tissues of developing seeds and mature seed grains. Furthermore, we have overviewed the underlying cell-layer specific possible regulatory mechanism responsible for the loading/partitioning for each of the micronutrients into specific tissue types. Most of the nutrient filling occurs between 7 and 18 days after fertilization (DAF) through the dorsal vascular bundle and the aleurone layer. During the last few years, spatio-temporal distribution of various minerals and the role of their transporters has been studied in great detail. However, with regard to vitamins and other bioactive compounds, such studies are still very limited. Distribution of minerals in the grain is mainly regulated by the distribution of their ligands and transporters, whereas the accumulation of various vitamins is mainly metabolic enzyme activity. Collective knowledge discussed here in this niche area would help to design new studies to improve the micronutrient content located in the inner part of the seed.


Assuntos
Micronutrientes/metabolismo , Oryza/metabolismo , Antocianinas/metabolismo , Grão Comestível/genética , Grão Comestível/metabolismo , Minerais/metabolismo , Oryza/genética
14.
Cureus ; 16(5): e59467, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38826961

RESUMO

Wrist pain is a common presentation in primary care clinics. Chronic pain after trauma with non-acute radiographs requires careful physical examination and a case-specific workup. We present a case of a 32-year-old female evaluated at the primary care clinic with two months of left wrist pain after a hypersupination injury that was found to be secondary to avascular necrosis of the lunate on the left wrist with no radiographic signs of fracture or focal sclerosis on plain films. This case demonstrates the importance of identifying less common chronic wrist pain etiologies.

15.
Redox Biol ; 72: 103151, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38593631

RESUMO

Salmonella infection entails a cascade of attacks and defence measures. After breaching the intestinal epithelial barrier, Salmonella is phagocytosed by macrophages, where the bacteria encounter multiple stresses, to which it employs relevant countermeasures. Our study shows that, in Salmonella, the polyamine spermidine activates a stress response mechanism by regulating critical antioxidant genes. Salmonella Typhimurium mutants for spermidine transport and synthesis cannot mount an antioxidative response, resulting in high intracellular ROS levels. These mutants are also compromised in their ability to be phagocytosed by macrophages. Furthermore, it regulates a novel enzyme in Salmonella, Glutathionyl-spermidine synthetase (GspSA), which prevents the oxidation of proteins in E. coli. Moreover, the spermidine mutants and the GspSA mutant show significantly reduced survival in the presence of hydrogen peroxide in vitro and reduced organ burden in the mouse model of Salmonella infection. Conversely, in macrophages isolated from gp91phox-/- mice, we observed a rescue in the attenuated fold proliferation previously observed upon infection. We found that Salmonella upregulates polyamine biosynthesis in the host through its effectors from SPI-1 and SPI-2, which addresses the attenuated proliferation observed in spermidine transport mutants. Thus, inhibition of this pathway in the host abrogates the proliferation of Salmonella Typhimurium in macrophages. From a therapeutic perspective, inhibiting host polyamine biosynthesis using an FDA-approved chemopreventive drug, D, L-α-difluoromethylornithine (DFMO), reduces Salmonella colonisation and tissue damage in the mouse model of infection while enhancing the survival of infected mice. Therefore, our work provides a mechanistic insight into the critical role of spermidine in stress resistance of Salmonella. It also reveals a bacterial strategy in modulating host metabolism to promote their intracellular survival and shows the potential of DFMO to curb Salmonella infection.


Assuntos
Proteínas de Bactérias , Macrófagos , Proteínas de Membrana , NADPH Oxidase 2 , Espécies Reativas de Oxigênio , Salmonella typhimurium , Espermidina , Animais , Salmonella typhimurium/metabolismo , Salmonella typhimurium/efeitos dos fármacos , Espermidina/metabolismo , Camundongos , Macrófagos/microbiologia , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Poliaminas/metabolismo , Fagocitose/efeitos dos fármacos , Infecções por Salmonella/microbiologia , Infecções por Salmonella/metabolismo , NADPH Oxidases/metabolismo , NADPH Oxidases/genética , Interações Hospedeiro-Patógeno , Espermidina Sintase/metabolismo , Espermidina Sintase/genética , Estresse Oxidativo/efeitos dos fármacos
16.
VideoGIE ; 9(2): 69-71, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38357023

RESUMO

Video 1Successful management of a postsurgical bronchoesophageal fistula with a combination of a self-expanding vascular plug, glue containing cyanoacrylate, and a fully covered metal stent.

17.
Best Pract Res Clin Gastroenterol ; 69: 101898, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38749577

RESUMO

While the endoscopic management of surgical complications like leaks, fistulas, and perforations is rapidly evolving, its core principles revolve around closure, drainage, and containment. Effectively managing these conditions relies on several factors, such as the underlying cause, chronicity of the lesion, tissue viability, co-morbidities, availability of devices, and expertise required to perform the endoscopy. In contrast to acute perforation, fistulas and leaks often demand a multimodal approach requiring more than one session to achieve the required results. Although the ultimate goal is complete resolution, these endoscopic interventions can provide clinical stability, enabling enteral feeding to lead to early hospital discharge or elective surgery. In this discussion, we emphasize the current state of knowledge and the prospective role of endoscopic interventions in managing surgical complications.


Assuntos
Complicações Pós-Operatórias , Humanos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Complicações Pós-Operatórias/cirurgia , Drenagem , Endoscopia Gastrointestinal/métodos , Fístula Anastomótica/etiologia , Fístula Anastomótica/cirurgia , Fístula Anastomótica/terapia , Resultado do Tratamento
18.
Microbiol Res ; 281: 127605, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38232495

RESUMO

Spermidine is a poly-cationic molecule belonging to the family of polyamines and is ubiquitously present in all organisms. Salmonella synthesizes, and harbours specialized transporters to import spermidine. A group of polyamines have been shown to assist in Salmonella Typhimurium's virulence and regulation of Salmonella pathogenicity Inslad 1 (SPI-1) genes and stress resistance; however, the mechanism remains elusive. The virulence trait of Salmonella depends on its ability to employ multiple surface structures to attach and adhere to the surface of the target cells before invasion and colonization of the host niche. Our study discovers the mechanism by which spermidine assists in the early stages of Salmonella pathogenesis. For the first time, we report that Salmonella Typhimurium regulates spermidine transport and biosynthesis processes in a mutually inclusive manner. Using a mouse model, we show that spermidine is critical for invasion into the murine Peyer's patches, which further validated our in vitro cell line observation. We show that spermidine controls the mRNA expression of fimbrial (fimA) and non-fimbrial adhesins (siiE, pagN) in Salmonella and thereby assists in attachment to host cell surfaces. Spermidine also regulated the motility through the expression of flagellin genes by enhancing the translation of sigma-28, which features an unusual start codon and a poor Shine-Dalgarno sequence. Besides regulating the formation of the adhesive structures, spermidine tunes the expression of the two-component system BarA/SirA to regulate SPI-1 encoded genes. Thus, our study unravels a novel regulatory mechanism by which spermidine exerts critical functions during Salmonella Typhimurium pathogenesis.


Assuntos
Salmonella typhimurium , Espermidina , Animais , Camundongos , Salmonella typhimurium/metabolismo , Espermidina/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Flagelina/genética , Poliaminas/metabolismo , Regulação Bacteriana da Expressão Gênica
19.
JCO Oncol Pract ; 20(1): 137-144, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37235818

RESUMO

PURPOSE: Burnout is a psychological occupational syndrome defined by the Maslach Burnout Inventory (MBI) as emotional exhaustion, depersonalization, and a low sense of personal accomplishment. We sought to characterize the prevalence of burnout among early-career medical oncologists at The University of Texas MD Anderson Cancer Center (MDACC). METHODS: For this institutional review board-approved study, an electronic survey was developed for Assistant Professors in the MDACC Division of Cancer Medicine. All participants were involved directly in patient care. Our survey included questions assessing self-reported burnout, nine questions validated in the abbreviated MBI, and 31 questions to assess potential contributors to burnout. Each question was scaled 1-5, with higher scores associated with higher burnout. Descriptive statistics were used to estimate the prevalence of burnout, and logistic regression analyses were performed to identify contributing factors. RESULTS: Among 86 Assistant Professors, 56 (65%) responded to the survey. The mean duration on faculty was 3.1 years. The mean clinical effort was 67% (range, 19-95). Fifty-four percent of respondents self-reported symptoms of burnout including 21% indicating severe burnout. Using the MBI, sentiments of being emotionally drained (54%), fatigued facing another day on the job (45%), and becoming more callous (30%) were especially notable. Twenty-five percent of respondents exhibited severe emotional exhaustion, which was more prevalent (P < .0001) than depersonalization (6%) or lack of personal accomplishment (17%). CONCLUSION: Burnout exists with high prevalence among early-career medical oncologists, with emotional exhaustion being the most common manifestation of burnout. Interventions focusing on reducing emotional exhaustion are needed to reduce burnout among early-career medical oncologists.


Assuntos
Esgotamento Profissional , Oncologistas , Testes Psicológicos , Humanos , Esgotamento Profissional/epidemiologia , Exaustão Emocional , Autorrelato
20.
Cureus ; 16(5): e59734, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38841011

RESUMO

BACKGROUND: Obstructive sleep apnea (OSA) has been a significant contributor to mortality all across the globe. The most attributing factors to pathogenesis are metabolic syndrome, obesity, diabetes, and so on, but the indicators of its early detection are still elusive. OBJECTIVE: The study aimed to compare the clinical, biochemical, and polysomnographic characteristics of type 2 diabetes patients with and without OSA. DESIGN AND METHODS: This cross-sectional study was conducted at the Department of Medicine and Endocrinology Unit of Dayanand Medical College and Hospital, Ludhiana. A total of 584 patients with type 2 diabetes were assessed using the Berlin questionnaire, with 302 fulfilling the criteria for a high risk of OSA. Out of 302 patients who met the criteria for the high-risk category, 110 patients underwent a sleep study. RESULTS:  Three hundred and two patients satisfying the inclusion and exclusion criteria were enrolled in the study. A total of 110 patients underwent a sleep study, of which 68 (61.8%) had evidence of OSA. The waist-to-hip ratio was considerably higher in the OSA patients than in the non-OSA group (1.09 vs 0.930, p = 0.001). HbA1c >7% was found in 58.8% of OSA patients contrary to 38.1% of non-OSA patients. Fasting plasma glucose levels (>126 mg/dl) were identified in a substantially larger proportion of OSA patients than the non-OSA patients (64.7% vs 45.2%, p = 0.04). Similarly, peripheral neuropathy was found more commonly in the OSA patients than in the non-OSA patients (47% vs. 26.1%, p = 0.02). Prevalence of retinopathy, nephropathy, coronary artery disease, stroke, heart failure, and peripheral vascular disease did not differ significantly between the two groups. CONCLUSIONS: OSA frequently occurs among individuals diagnosed with type 2 diabetes mellitus. The prompt identification of OSA within this demographic is imperative to pinpoint those at an elevated risk of succumbing to conditions such as peripheral neuropathy, the exacerbation of glycemic control, and the onset of unmanaged hypertension. Moreover, there exists a positive correlation between the waist-to-hip ratio and the prevalence of OSA in persons with type 2 diabetes mellitus, highlighting the critical role of waist-to-hip ratio assessments in this patient population.

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