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1.
Cureus ; 16(5): e59467, 2024 May.
Article in English | MEDLINE | ID: mdl-38826961

ABSTRACT

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.

2.
Cureus ; 16(5): e59734, 2024 May.
Article in English | MEDLINE | ID: mdl-38841011

ABSTRACT

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.

3.
Best Pract Res Clin Gastroenterol ; 69: 101898, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38749577

ABSTRACT

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.


Subject(s)
Postoperative Complications , Humans , Postoperative Complications/etiology , Postoperative Complications/therapy , Postoperative Complications/surgery , Drainage , Endoscopy, Gastrointestinal/methods , Anastomotic Leak/etiology , Anastomotic Leak/surgery , Anastomotic Leak/therapy , Treatment Outcome
4.
Pancreatology ; 24(4): 643-648, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38584052

ABSTRACT

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.


Subject(s)
Calculi , Lithotripsy , Pancreatic Ducts , Tomography, X-Ray Computed , Humans , Lithotripsy/methods , Male , Female , Adult , Middle Aged , Retrospective Studies , Pancreatic Ducts/diagnostic imaging , Pancreatic Ducts/pathology , Calculi/therapy , Calculi/diagnostic imaging , Treatment Outcome , Pancreatitis, Chronic/therapy , Pancreatitis, Chronic/complications , Pancreatitis, Chronic/diagnostic imaging
5.
Redox Biol ; 72: 103151, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38593631

ABSTRACT

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.


Subject(s)
Bacterial Proteins , Macrophages , Membrane Proteins , NADPH Oxidase 2 , Reactive Oxygen Species , Salmonella typhimurium , Spermidine , Animals , Salmonella typhimurium/metabolism , Salmonella typhimurium/drug effects , Spermidine/metabolism , Mice , Macrophages/microbiology , Macrophages/metabolism , Macrophages/drug effects , Reactive Oxygen Species/metabolism , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Polyamines/metabolism , Phagocytosis/drug effects , Salmonella Infections/microbiology , Salmonella Infections/metabolism , NADPH Oxidases/metabolism , NADPH Oxidases/genetics , Host-Pathogen Interactions , Spermidine Synthase/metabolism , Spermidine Synthase/genetics , Oxidative Stress/drug effects
6.
VideoGIE ; 9(2): 69-71, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38357023

ABSTRACT

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.

7.
Microbiol Res ; 281: 127605, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38232495

ABSTRACT

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.


Subject(s)
Salmonella typhimurium , Spermidine , Animals , Mice , Salmonella typhimurium/metabolism , Spermidine/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Flagellin/genetics , Polyamines/metabolism , Gene Expression Regulation, Bacterial
8.
JCO Oncol Pract ; 20(1): 137-144, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37235818

ABSTRACT

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.


Subject(s)
Burnout, Professional , Oncologists , Psychological Tests , Humans , Burnout, Professional/epidemiology , Emotional Exhaustion , Self Report
9.
SA J Radiol ; 27(1): 2684, 2023.
Article in English | MEDLINE | ID: mdl-38059119

ABSTRACT

Imaging evaluation of the brain and cranium after cranial surgery is a routine and significant part of the workflow of a radiology department. Various normal expected findings and early and late complications are associated with the post-operative cranium. In this pictorial review, the authors describe the typical imaging features of the spectrum of various conditions associated with cranial surgery with illustrative cases. Contribution: A good knowledge and understanding of the spectrum of imaging appearances in the post-operative cranium is vital for the radiologist to accurately diagnose potential complications and distinguish them from normal post-operative findings, improving patient outcomes and guiding further treatment.

10.
Soft Matter ; 19(47): 9239-9253, 2023 Dec 06.
Article in English | MEDLINE | ID: mdl-37999932

ABSTRACT

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.


Subject(s)
Bacteremia , Klebsiella Infections , Animals , Mice , Klebsiella pneumoniae , Klebsiella Infections/drug therapy , Klebsiella Infections/microbiology , Bacteremia/drug therapy , Bacteremia/microbiology , Anti-Bacterial Agents
11.
Pancreatology ; 23(7): 858-867, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37798192

ABSTRACT

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.


Subject(s)
Pancreatic Ducts , Pancreatitis, Chronic , Sphincter of Oddi , Humans , Clinical Relevance , Manometry/methods
12.
BMJ Case Rep ; 16(10)2023 Oct 18.
Article in English | MEDLINE | ID: mdl-37852666

ABSTRACT

We present a report of two adult females who presented to the surgery clinic at different time frames in our hospital with a swelling in the inguinal region. The swelling was painful for one of our patients. The first patient was evaluated with a contrast-enhanced CT and an MRI, while the second patient underwent a ultrasonography and an MRI. Imaging revealed the structure to be cystic in nature and confirmed the diagnosis as a hydrocele of the canal of Nuck in both patients. Our second patient was also found to have concomitant endometriosis, with internal septations seen in the hydrocele. Aspiration revealed altered blood with haemosiderin deposition, which established a diagnosis of endometriosis of the canal of Nuck. The first patient underwent excision, while the second patient refused a surgical approach and opted for medical management for endometriosis.


Subject(s)
Cysts , Endometriosis , Peritoneal Diseases , Male , Female , Adult , Humans , Endometriosis/complications , Endometriosis/diagnostic imaging , Endometriosis/surgery , Peritoneal Diseases/complications , Peritoneal Diseases/diagnostic imaging , Peritoneal Diseases/surgery , Cysts/diagnostic imaging , Cysts/surgery , Inguinal Canal/surgery , Groin
13.
J Clin Imaging Sci ; 13: 28, 2023.
Article in English | MEDLINE | ID: mdl-37810183

ABSTRACT

Objectives: COVID-19 lockdowns resulted in a global shortage of iodinated contrast media. Therefore, alternative imaging protocols were devised to evaluate patients arriving to the emergency department (ED) with suspicion of pulmonary embolism (PE). This quality assurance (QA) aims to compare diagnostic potential between alternative magnetic resonance angiography (MRA) protocol over the gold standard computed tomography angiography (CTA) by evaluating MRA imaging quality, scanner type/imaging sequence, and any risk of misdiagnosis in patients with symptoms of PE. Material and Methods: This retrospective study compromised of 55 patients who arrived to ED and underwent MRA of the chest for suspicion of PE during the months of May to June 2022. Data regarding their chief complaints, imaging sequence, and MRA results were collected. Two fellowship-trained faculty radiologists reviewed the MRA scans of the patients and scored the quality using a Likert scale. Results: Two patients were positive for PE and 53 patients showed negative results. Regarding the scan quality issues, motion was noted in 80% of the 55 studies that we reviewed. Significant associations (P < 0.009) between Likert scale scores and initial complaint category were found. The characteristic symptoms associated with suspicion of PE, namely, shortness of breath, chest pain, and cough were distributed among the 1 and 2 categories, reflecting the most optimal vessel opacification scores. We found no risk of misdiagnosis after reviewing the electronic medical record for follow-up appointments within 6 months of ED visit. Conclusion: Patients were screened for PE with MRA as an alternative imaging tool during times of contrast shortage. Further, evaluation of MRA with CTA, side by side, in a larger patient population is required to increase the validity of our QA study.

14.
Egypt Heart J ; 75(1): 56, 2023 Jul 03.
Article in English | MEDLINE | ID: mdl-37395900

ABSTRACT

BACKGROUND: Ondansetron is a selective 5-hydroxytryptamine type 3 serotonin-receptor antagonist with antiemetic properties used inadvertently in the emergency department for controlling nausea. However, ondansetron is linked with a number of adverse effects, including prolongation of the QT interval. Therefore, the purpose of this meta-analysis was to assess the occurrence of QT prolongation in pediatric, adult, and elderly patients receiving oral or intravenously administered ondansetron. METHODS: A thorough electronic search was conducted on PubMed (Medline) and Cochrane Library from the databases' inception to August 10, 2022. Only those studies were considered in which ondansetron was administered orally or intravenously to participants for the treatment of nausea and vomiting. The prevalence of QT prolongation in multiple predefined age groups was the outcome variable. Analyses were conducted using Review manager 5.4 (Cochrane collaboration, 2020). RESULTS: A total of 10 studies involving 687 ondansetron group participants were statistically analyzed. The administration of ondansetron was associated with a statistically significant prevalence of QT prolongation in all age groups. An age-wise subgroup analysis was conducted which revealed that the prevalence of QT prolongation among participants younger than 18 years was not statistically significant, whereas it was statistically significant among participants aged 18-50 years and among patients older than 50 years. CONCLUSIONS: The present meta-analysis provides further evidence that oral or intravenous administration of Ondansetron may lead to QT prolongation, particularly among patients older than 18 years of age.

15.
Infect Dis (Lond) ; 55(11): 755-766, 2023 11.
Article in English | MEDLINE | ID: mdl-37480325

ABSTRACT

BACKGROUND: Identifying early predictors of severe Covid-19 associated mucormycosis (CAM) can help improve management and treatment outcomes. OBJECTIVES: Primary: To identify clinical and radiological predictors of disease severity in CAM. Secondary: To describe patterns of central nervous system (CNS) involvement in CAM. METHODS: A total of 71 patients with CAM were included in the study. Based on the anatomical extent of involvement on MRI, patients were divided into three groups: Sinus (paranasal sinuses), Orbit (orbital spread), and CNS (CNS spread). Clinical parameters and radiological patterns of involvement of sinuses and extra sinus spaces were studied between the three groups. Patterns of CNS involvement were also described. RESULTS: A shorter time lag between COVID-19 infection and CAM, as well as high HbA1C levels, were found to be associated with severe disease. Involvement of the sphenoid, ethmoid and frontal sinuses, T1 hyperintense signal in the sphenoid, as well as bony involvement of the sphenoid sinus, were significantly associated with severe disease. Extra-sinus spread into pre/retroantral space, pterygopalatine fossa, and masticator spaces were also significantly associated with a severe disease course. The most common pattern of CNS spread was cavernous sinus involvement, followed by pachymeningeal spread and cranial nerve involvement. CONCLUSION: Early identification of the above-described predictors in patients presenting with CAM can help detect those at risk for developing severe disease. A longer duration of amphotericin, combined with a more aggressive surgical approach in selected cases, may lead to better long-term outcomes.


Subject(s)
COVID-19 , Mucormycosis , Paranasal Sinuses , Humans , Mucormycosis/diagnostic imaging , Glycated Hemoglobin , COVID-19/diagnostic imaging , Paranasal Sinuses/diagnostic imaging , Patient Acuity
16.
Microbiol Res ; 273: 127411, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37285689

ABSTRACT

Salmonella is a genus of widely spread Gram negative, facultative anaerobic bacteria, which is known to cause »th of diarrheal morbidity and mortality globally. It causes typhoid fever and gastroenteritis by gaining access to the host gut through contaminated food and water. Salmonella utilizes its biofilm lifestyle to strongly resist antibiotics and persist in the host. Although biofilm removal or dispersal has been studied widely, the inhibition of the initiation of Salmonella Typhimurium (STM WT) biofilm remains elusive. This study demonstrates the anti-biofilm property of the cell-free supernatant obtained from a carbon-starvation induced proline peptide transporter mutant (STM ΔyjiY) strain. The STM ΔyjiY culture supernatant primarily inhibits biofilm initiation by regulating biofilm-associated transcriptional network that is reversed upon complementation (STM ΔyjiY:yjiY). We demonstrate that abundance of FlgM correlates with the absence of flagella in the STM ΔyjiY supernatant treated WT cells. NusG works synergistically with the global transcriptional regulator H-NS. Relatively low abundances of flavoredoxin, glutaredoxin, and thiol peroxidase might lead to accumulation of ROS within the biofilm, and subsequent toxicity in STM ΔyjiY supernatant. This work further suggests that targeting these oxidative stress relieving proteins might be a good choice to reduce Salmonella biofilm.


Subject(s)
Salmonella typhimurium , Typhoid Fever , Humans , Salmonella typhimurium/genetics , Salmonella typhimurium/metabolism , Membrane Transport Proteins/metabolism , Biofilms , Proline/metabolism
17.
Cureus ; 15(5): e38703, 2023 May.
Article in English | MEDLINE | ID: mdl-37292529

ABSTRACT

Chronic mania is a mental health disorder that has been described by various psychiatrists in the past but currently is not a part of nosology. Robust epidemiological data for chronic mania are lacking with regard to its prevalence and clinical features. The present case report is of a 48-year-old male with a six-year history of mood and psychotic symptoms, based on which differential diagnoses of schizoaffective disorder (manic type), schizophrenia, and mania with psychotic symptoms (with chronic course) were made. The diagnosis of chronic mania was confirmed considering the predominance of fluctuating mood symptoms along with psychotic symptoms, lack of remission, and chronic course of illness. Antipsychotics were initially started for six weeks, to which the patient demonstrated a minimal response. A mood stabilizer was added to the regimen, leading to significant improvement, and the patient was discharged. According to existing literature, patients with chronic mania present with severe illness, the presence of psychotic symptoms, and socio-occupational impairment, which was also noticed in this case. The prevalence of chronic mania among patients with bipolar disorder is approximately 13-15%, which constitutes a significant proportion of known mental illnesses. Therefore, chronic mania should be added as a distinct clinical entity in the existing nosological systems.

18.
Traffic ; 24(7): 270-283, 2023 07.
Article in English | MEDLINE | ID: mdl-37114883

ABSTRACT

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.


Subject(s)
Salmonella , Vacuoles , Animals , Mice , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Cell Communication , Qa-SNARE Proteins/genetics , Qa-SNARE Proteins/metabolism , Salmonella/metabolism , SNARE Proteins/metabolism , Vacuoles/microbiology
19.
J Clin Imaging Sci ; 13: 8, 2023.
Article in English | MEDLINE | ID: mdl-36895661

ABSTRACT

Objectives: Iodinated contrast media (ICM) shortage crisis due to COVID-19 lockdowns led to a need for alternate imaging protocols consisting of non-contrast computed tomography (CT) for abdominal complaints and related trauma indications in emergency department (ED) settings. This quality assurance study aims to evaluate clinical outcomes of protocol modifications during ICM shortage and identify potential imaging misdiagnosis of acute abdominal complaints and related trauma. Material and Methods: The study included 424 ED patients with abdominal pain, falls, or motor vehicle collision (MVC)-related trauma who had non-contrast CT of the abdomen and pelvis in May 2022. We accessed the initial complaint, order indication, non-contrast CT results, any acute or incidental findings, and any follow-up imaging of the same body region with their results. We evaluated their association utilizing Chi-squared tests. We assessed sensitivity, specificity, and positive/negative predictive values using follow-up scan confirmation. Results: Across initial complaint categories, 72.9% of cases were abdominal pain, and 37.3% received positive findings. Only 22.6% of patients had follow-up imaging. Most confirmed original reports were for abdominal pain. We also found three reports of missed findings. There were significant associations between complaint categories and initial non-contrast CT report results (P < 0.001), as well as initial complaint categories and whether the patient received follow-up imaging or not (P < 0.004). No significant associations were found between follow-up imaging results and initial report confirmation. Non-contrast CT had 94% sensitivity and 100% specificity, with positive and negative predictive values 100% and 94%, respectively. Conclusion: Rate of missed acute diagnoses using non-contrast CT for patients presenting to the ED with acute abdominal complaints or related trauma has been low during the recent shortage, but further investigation would be needed to verify and quantify the implications of not routinely giving oral or intravenous contrast in the ED.

20.
Bioorg Chem ; 132: 106343, 2023 03.
Article in English | MEDLINE | ID: mdl-36623447

ABSTRACT

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.


Subject(s)
Coordination Complexes , Copper , Molecular Docking Simulation , Copper/chemistry , Nickel , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Density Functional Theory , Antioxidants , Prospective Studies , DNA/chemistry , Cobalt/chemistry , Zinc/chemistry , Biological Assay , Schiff Bases/chemistry , Ligands
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