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1.
Open Forum Infect Dis ; 11(5): ofae197, 2024 May.
Article in English | MEDLINE | ID: mdl-38698896

ABSTRACT

Background: We compared long-term mortality and readmission rates after COVID-19 hospitalization based on rural-urban status and assessed the impact of COVID-19 vaccination introduction on clinical outcomes by rurality. Methods: The study comprised adults hospitalized for COVID-19 at 17 hospitals in 4 US states between March 2020 and July 2022, followed until May 2023. The main analysis included all patients, whereas a sensitivity analysis focused on residents from 4 states containing 17 hospitals. Additional analyses compared the pre- and postvaccination periods. Results: The main analysis involved 9325 COVID-19 hospitalized patients: 31% were from 187 rural counties in 31 states; 69% from 234 urban counties in 44 states; the mean age was 65 years (rural, 66 years; urban, 64 years); 3894 women (rural, 41%; urban, 42%); 8007 Whites (rural, 87%; urban, 83%); 1738 deaths (rural, 21%; urban, 17%); and 2729 readmissions (rural, 30%; urban, 29%). During a median follow-up of 602 days, rural residence was associated with a 22% higher all-cause mortality (log-rank, P < .001; hazard ratio, 1.22; 95% confidence interval, 1.10-1.34, P < .001), and a trend toward a higher readmission rate (log-rank, P = .038; hazard ratio, 1.06; 95% confidence interval, .98-1.15; P = .130). The results remained consistent in the sensitivity analysis and in both pre- and postvaccination time periods. Conclusions and Relevance: Patients from rural counties experienced higher mortality and tended to be readmitted more frequently following COVID-19 hospitalization over the long term compared with those from urban counties, a difference that remained even after the introduction of COVID-19 vaccines.

2.
PLoS One ; 19(5): e0302968, 2024.
Article in English | MEDLINE | ID: mdl-38709803

ABSTRACT

INTRODUCTION: Micronutrient deficiencies are prevalent in West Africa, particularly among women of reproductive age (WRA) and young children. Bouillon is a promising food fortification vehicle due to its widespread consumption. This study aims to evaluate the impact of multiple micronutrient-fortified bouillon cubes, compared to control bouillon cubes (fortified with iodine only), on micronutrient status and hemoglobin concentrations among lactating and non-lactating WRA and young children in northern Ghana. METHODS: This randomized, controlled doubly-masked trial will be conducted in the Kumbungu and Tolon districts in the Northern Region of Ghana, where prior data indicate multiple micronutrient deficiencies are common. Participants will be: 1) non-pregnant non-lactating WRA (15-49 y), 2) children 2-5 y, and 3) non-pregnant lactating women 4-18 months postpartum. Eligible participants will be randomly assigned to receive household rations of one of two types of bouillon cubes: 1) a multiple micronutrient-fortified bouillon cube containing vitamin A, folic acid, vitamin B12, iron, zinc, and iodine, or 2) a control cube containing iodine only. Each participant's household will receive a ration of bouillon cubes every 2 weeks, and households will be advised to prepare meals as usual, using the study-provided cubes. The trial duration will be 9 months for non-pregnant non-lactating WRA and children, and 3 months for lactating women. The primary outcomes will be changes in biomarkers of micronutrient status and hemoglobin among WRA and children and milk micronutrient concentrations among lactating women. Secondary outcomes will include change in prevalence of micronutrient deficiency and anemia; dietary intake of bouillon and micronutrients; inflammation, malaria, and morbidity symptoms; and child growth and development. DISCUSSION: Evidence from this study will inform discussions about bouillon fortification in Ghana and West Africa. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov (NCT05178407) and the Pan-African Clinical Trial Registry (PACTR202206868437931). This manuscript reflects protocol version 4 (August 29, 2022).


Subject(s)
Food, Fortified , Micronutrients , Nutritional Status , Humans , Female , Ghana/epidemiology , Micronutrients/deficiency , Micronutrients/administration & dosage , Micronutrients/analysis , Adult , Adolescent , Child, Preschool , Middle Aged , Young Adult , Lactation , Male , Hemoglobins/analysis , Iodine/deficiency , Iodine/administration & dosage , Iodine/analysis
3.
Mymensingh Med J ; 33(2): 426-432, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38557521

ABSTRACT

Functional dyspepsia (FD) is a common gastrointestinal problem in the world. The Rome III consensus subdivided functional dyspepsia into two groups: meal-related postprandial distress syndrome (PDS) and meal-unrelated epigastric pain syndrome (EPS). Limited data are available regarding FD in Bangladesh. The aim of this study was to investigate the demographic and clinical characteristics of FD and its sub-types. This cross-sectional study was conducted in which we recruited patients who attended the outpatient department of Gastroenterology of Bangabandhu Sheikh Mujib Medical University, Bangladesh from March 2017 to February 2018. Patients fulfilling Rome III FD criteria and a negative upper GIT endoscopy were included for this study. The patients were then subdivided into 'pure' PDS (i.e. meeting criteria for PDS without EPS symptoms), 'pure' EPS (i.e., meeting criteria for EPS without PDS symptoms), and overlapping PDS-EPS (i.e., symptoms of both PDS and EPS) groups. Total of 368 FD patients (56.0% females, mean age 32.8±8.6 years, BMI: 22.0±2.7), were included in this study. Out of them, 112(30.4%) patients (57.2% females, mean age 33.9±9.3 years, BMI: 22.0±2.7) fulfilled criteria of pure EPS and 64(17.4%) patients (68.8% females, mean age 33.2±7.8 years, BMI: 22.1±2.4) fulfilled criteria of pure PDS. However, the majority of patients [192(52.2%), 52.1% females, mean age 32.0±8.4 years, BMI: 21.9±2.8] had symptoms of overlapping EPS-PDS. More than 40% of patients in our study presented with 3 or more of the four key symptoms of FD. A longer duration of presenting symptoms was seen among patients with overlapping EPS-PDS in comparison to pure EPS and pure PDS (p<0.001). A significant overlap of symptoms of both EPS and PDS was noticed among patients with FD. The value of dividing functional dyspepsia into the subgroups of PDS and EPS is thus questionable. Further research and modification of the diagnostic criteria for FD subtypes are necessary.


Subject(s)
Dyspepsia , Adult , Female , Humans , Young Adult , Male , Dyspepsia/diagnosis , Dyspepsia/epidemiology , Abdominal Pain/epidemiology , Abdominal Pain/etiology , Bangladesh/epidemiology , Tertiary Care Centers , Cross-Sectional Studies , Demography
4.
Am J Physiol Gastrointest Liver Physiol ; 326(5): G591-G606, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38469632

ABSTRACT

Ulcerative colitis (UC) is an idiopathic inflammatory disease of the large intestine, which impacts millions worldwide. Current interventions aimed at treating UC symptoms can have off-target effects, invoking the need for alternatives that may provide similar benefits with less unintended consequences. This study builds on our initial data, which showed that panaxynol-a novel, potent, bioavailable compound found in American ginseng-can suppress disease severity in murine colitis. Here we explore the underlying mechanisms by which panaxynol improves both chronic and acute murine colitis. Fourteen-week-old C57BL/6 female mice were either given three rounds of dextran sulfate sodium (DSS) in drinking water to induce chronic colitis or one round to induce acute colitis. Vehicle or panaxynol (2.5 mg/kg) was administered via oral gavage three times per week for the study duration. Consistent with our previous findings, panaxynol significantly (P < 0.05) improved the disease activity index and endoscopic scores in both models. Using the acute model to examine potential mechanisms, we show that panaxynol significantly (P < 0.05) reduced DSS-induced crypt distortion, goblet cell loss, and mucus loss in the colon. 16S Sequencing revealed panaxynol altered microbial composition to suppress colitis-enriched genera (i.e., Enterococcus, Eubacterium, and Ruminococcus). In addition, panaxynol significantly (P < 0.05) suppressed macrophages and induced regulatory T-cells in the colonic lamina propria. The beneficial effects of panaxynol on mucosal and crypt architecture, combined with its microbial and immune-mediated effects, provide insight into the mechanisms by which panaxynol suppresses murine colitis. Overall, this data is promising for the use of panaxynol to improve colitis in the clinic.NEW & NOTEWORTHY In the current study, we report that panaxynol ameliorates chemically induced murine colitis by improving colonic crypt and mucosal architecture, suppressing colitis-enriched microbes, reducing macrophages, and promoting the differentiation of regulatory T-cells in the colonic lamina propria. This study suggests that this novel natural compound may serve as a safe and effective treatment option for colitis patients.


Subject(s)
Colitis , Dextran Sulfate , Gastrointestinal Microbiome , Intestinal Mucosa , Mice, Inbred C57BL , Animals , Female , Mice , Intestinal Mucosa/drug effects , Intestinal Mucosa/pathology , Intestinal Mucosa/microbiology , Intestinal Mucosa/immunology , Gastrointestinal Microbiome/drug effects , Colitis/drug therapy , Colitis/chemically induced , Colitis/pathology , Colitis/immunology , Colitis/microbiology , Fatty Alcohols/pharmacology , Diynes/pharmacology , Disease Models, Animal , Colon/drug effects , Colon/pathology , Colon/immunology , Colon/microbiology , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunology , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/immunology , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/pathology , Colitis, Ulcerative/microbiology
5.
ERJ Open Res ; 10(2)2024 Mar.
Article in English | MEDLINE | ID: mdl-38444659

ABSTRACT

Introduction: Nearly all patients with primary ciliary dyskinesia (PCD) report ear-nose-throat (ENT) symptoms. However, scarce evidence exists about how ENT symptoms relate to pulmonary disease in PCD. We explored possible associations between upper and lower respiratory disease among patients with PCD in a multicentre study. Methods: We included patients from the ENT Prospective International Cohort (EPIC-PCD). We studied associations of several reported ENT symptoms and chronic rhinosinusitis (defined using patient-reported information and examination findings) with reported sputum production and shortness of breath, using ordinal logistic regression. In a subgroup with available lung function results, we used linear regression to study associations of chronic rhinosinusitis and forced expiratory volume in 1 s (FEV1) accounting for relevant factors. Results: We included 457 patients (median age 15 years, interquartile range 10-24 years; 54% males). Shortness of breath associated with reported nasal symptoms and ear pain of any frequency, often or daily hearing problems, headache when bending down (OR 2.1, 95% CI 1.29-3.54) and chronic rhinosinusitis (OR 2.3, 95% CI 1.57-3.38) regardless of polyp presence. Sputum production associated with daily reported nasal (OR 2.2, 95% CI 1.20-4.09) and hearing (OR 2.0, 95% CI 1.10-3.64) problems and chronic rhinosinusitis (OR 2.1, 95% CI 1.48-3.07). We did not find any association between chronic rhinosinusitis and FEV1. Conclusion: Reported upper airway symptoms and signs of chronic rhinosinusitis associated with reported pulmonary symptoms, but not with lung function. Our results emphasise the assessment and management of upper and lower respiratory disease as a common, interdependent entity among patients with PCD.

6.
bioRxiv ; 2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38352330

ABSTRACT

Background: Primary immunodeficiencies are heritable defects in immune system function. Antibody deficiency is the most common form of primary immunodeficiency in humans, can be caused by abnormalities in both the development and activation of B cells, and may result from B-cell-intrinsic defects or defective responses by other cells relevant to humoral immunity. Inflammatory gastrointestinal complications are commonly observed in antibody-deficient patients, but the underlying immune mechanisms driving this are largely undefined. Methods: In this study, several mouse strains reflecting a spectrum of primary antibody deficiency (IgA -/- , Aicda -/- , CD19 -/- and J H -/- ) were used to generate a functional small-bowel-specific cellular atlas using a novel high-parameter flow cytometry approach that allows for the enumeration of 59 unique cell subsets. Using this cellular atlas, we generated a direct and quantifiable estimate of immune dysregulation. This estimate was then used to identify specific immune factors most predictive of the severity of inflammatory disease of the small bowel (small bowel enteropathy). Results: Results from our experiments indicate that the severity of primary antibody deficiency positively correlates with the degree of immune dysregulation that can be expected to develop in an individual. In the SI of mice, immune dysregulation is primarily explained by defective homeostatic responses in T cell and invariant natural killer-like T (iNKT) cell subsets. These defects are strongly correlated with abnormalities in the balance between protein (MHCII-mediated) versus lipid (CD1d-mediated) antigen presentation by intestinal epithelial cells (IECs) and intestinal stem cells (ISCs), respectively. Conclusions: Multivariate statistical approaches can be used to obtain quantifiable estimates of immune dysregulation based on high-parameter flow cytometry readouts of immune function. Using one such estimate, we reveal a previously unrecognized tradeoff between iNKT cell activation and type 1 immunity that underlies disease in the small bowel. The balance between protein/lipid antigen presentation by ISCs may play a crucial role in regulating this balance and thereby suppressing inflammatory disease in the small bowel.

7.
Cureus ; 16(1): e52970, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38406149

ABSTRACT

Primary Ewing sarcoma of the kidney (ESK) is a rare and aggressive entity, with a poor prognosis. It often presents as metastatic disease with the lungs being the most common site. In adults, the occurrence of these tumors is uncommon, with patients exhibiting non-specific symptoms such as weight loss, flank pain, hematuria, and an abdominal mass. The combination of these vague clinical symptoms and the rarity of these tumors often results in a delayed diagnosis, leading to poorer outcomes for these patients. We present a case of a 38-year-old female with metastatic ESK. The patient initially presented with abdominal pain, vomiting, and a four-day history of constipation. The diagnosis was confirmed through computed tomography scans, ultrasound-guided biopsy of the lesion, and fluorescence in situ hybridization that revealed translocation of the EWS gene on chromosome 22q12. She was managed with chemotherapy regimens and palliative care; however, the disease progressed and she passed away six months after her initial diagnosis.

9.
Polymers (Basel) ; 16(4)2024 Feb 18.
Article in English | MEDLINE | ID: mdl-38399925

ABSTRACT

BISCO plaster (BRP) is an environmentally friendly material with high mechanical properties and is considered a great elective to conventional materials such as gypsum and cement. Our investigation seeks to examine BISCO plaster (BRP) and a mixture of resin and hardener in three proportions (30%, 45%, and 60%) to achieve our ultimate goal, which is to preserve the environment and achieve the vision of the Kingdom of Saudi Arabia 2030 to reach zero carbon emissions by 2060? Emissions tests were performed, and although the CO2 level was zero, they emitted SO2 sulfur dioxide and NO2 nitrogen dioxide, and 60% was the lowest emission rate. We also used ANSYS 2023 R1 software to compare them with their mechanical properties resulting from tensile and compression testing. In this study, we looked closely at the mechanical characteristics of different materials designed for wall coverings, with particular emphasis on their environmental sustainability. We carried out experiments to gauge the tensile and compressive stress on samples with varying mixing ratios. Our main objective was on crucial mechanical properties such as the modulus of elasticity, ultimate tensile strength, yield strength, yield strain, modulus of resilience, and ductility. Through meticulous scrutiny, we determined that the amalgamation of these mechanical attributes at the 30% mixing ratio provides an optimal combination for attaining structural integrity, adaptability, and resilience in wall coverings. Significantly, this ratio also underscores a commitment to environmentally conscious material selection. Our study offers important new insights into the selection of wall covering materials by providing a detailed understanding of their mechanical behavior under various stress conditions. It aligns with the increasing significance of environmental responsibility in contemporary design and construction. By emphasizing the 30% mixing ratio, our findings establish a foundation for informed decision making, promoting the utilization of sustainable materials that achieve a balance between strength, flexibility, and longevity. This ensures optimal performance in practical applications while simultaneously minimizing the environmental impact.

10.
J Org Chem ; 89(6): 3781-3799, 2024 03 15.
Article in English | MEDLINE | ID: mdl-38408196

ABSTRACT

An efficient synthesis of 3-amino-2-formyl-functionalized benzothiophenes by a domino reaction protocol and their use to synthesize a library of novel scaffolds have been reported. Reactions of ketones and 1,3-diones with these amino aldehyde derivatives formed a series of benzothieno[3,2-b]pyridine and 3,4-dihydro-2H-benzothiopheno[3,2-b]quinolin-1-one, respectively. A plausible mechanism for the formation of fused pyridine derivatives by the Friedlander reaction has been elucidated by density functional theory (DFT) calculations. Furthermore, hydrazones were obtained by reacting the aldehyde functional group of benzothiophenes with different hydrazine derivatives. Preliminary screening of these compounds against several bacterial strains and cancer cell lines led to the discovery of several hit molecules. Hydrazone and benzothieno[3,2-b]pyridine derivatives are potent cytotoxic and antibacterial agents, respectively. One of the potent compounds effected ∼97% growth inhibition of the LOX IMVI cell line at 10 µM concentration.


Subject(s)
Anti-Bacterial Agents , Antineoplastic Agents , Anti-Bacterial Agents/chemistry , Thiophenes/pharmacology , Thiophenes/chemistry , Cell Line , Antineoplastic Agents/chemistry , Pyridines/chemistry , Structure-Activity Relationship
11.
Am J Physiol Cell Physiol ; 326(2): C606-C621, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38189130

ABSTRACT

Immune cell-driven pathways are linked to cancer cachexia. Tumor presence is associated with immune cell infiltration whereas cytotoxic chemotherapies reduce immune cell counts. Despite these paradoxical effects, both cancer and chemotherapy can cause cachexia; however, our understanding of immune responses in the cachexia condition with cancer and chemotherapy is largely unknown. We sought to advance our understanding of the immunology underlying cancer and cancer with chemotherapy-induced cachexia. CD2F1 mice were given 106 C26 cells, followed by five doses of 5-fluorouracil (5FU; 30 mg/kg LM, ip) or PBS. Indices of cachexia and tumor (TUM), skeletal muscle (SKM), and adipose tissue (AT) immune cell populations were examined using high-parameter flow cytometry. Although 5FU was able to stunt tumor growth, % body weight loss and muscle mass were not different between C26 and C26 + 5FU. C26 increased CD11b+Ly6g+ and CD11b+Ly6cInt inflammatory myeloid cells in SKM and AT; however, both populations were reduced with C26 + 5FU. tSNE analysis revealed 24 SKM macrophage subsets wherein 8 were changed with C26 or C26 + 5FU. C26 + 5FU increased SKM CD11b-CD11c+ dendritic cells, CD11b-NK1.1+ NK-cells, and CD11b-B220+ B-cells, and reduced Ly6cHiCX3CR1+CD206+CD163IntCD11c-MHCII- infiltrated macrophages and other CD11b+Ly6cHi myeloid cells compared with C26. Both C26 and C26 + 5FU had elevated CD11b+F480+CD206+MHCII- or more specifically Ly6cLoCX3CR1+CD206+CD163IntCD11c-MHCII- profibrotic macrophages. 5FU suppressed tumor growth and decreased SKM and AT inflammatory immune cells without protecting against cachexia suggesting that these cells are not required for wasting. However, profibrotic cells and muscle inflammatory/atrophic signaling appear consistent with cancer- and cancer with chemotherapy-induced wasting and remain potential therapeutic targets.NEW & NOTEWORTHY Despite being an immune-driven condition, our understanding of skeletal muscle and adipose tissue immune cells with cachexia is limited. Here, we identified immune cell populations in tumors, skeletal muscle, and adipose tissue in C26 tumor-bearing mice with/without 5-fluorouracil (5FU). C26 and C26 + 5FU had increased skeletal muscle profibrotic macrophages, but 5FU reduced inflammatory myeloid cells without sparing mass. Tumor presence and chemotherapy have contrasting effects on certain immune cells, which appeared not necessary for wasting.


Subject(s)
Antineoplastic Agents , Fluorouracil , Mice , Animals , Fluorouracil/adverse effects , Cachexia/metabolism , Muscle, Skeletal/metabolism , Muscular Atrophy/pathology , Antineoplastic Agents/pharmacology
13.
Cureus ; 15(10): e47645, 2023 Oct.
Article in English | MEDLINE | ID: mdl-38022329

ABSTRACT

Spontaneous coronary artery dissection (SCAD) is a non-atherosclerotic separation of the coronary artery wall with subsequent intramural hematoma (IMH) formation in the false lumen. It can be associated with or without an intimal tear. It is clinically divided into three types based on its angiographic appearance. Most SCAD cases are seen in young or middle-aged women, especially in a peripartum state. Additionally, SCAD patients usually have fewer cardiovascular risk factors and more commonly have predisposing conditions like fibromuscular dysplasia (FMD). Patients present with features of chest pain that radiates to the left arm or neck, shortness of breath (SOB), as well as nausea and vomiting. Coronary angiography is the most widely used first-line modality to diagnose this condition. Management is usually conservative; however, invasive procedures can be utilized for high-risk patients. We present a case of a 54-year-old woman with SCAD diagnosed using coronary angiography and treated conservatively with dual-antiplatelet therapy, culminating with resolution.

14.
Medicine (Baltimore) ; 102(45): e35925, 2023 Nov 10.
Article in English | MEDLINE | ID: mdl-37960760

ABSTRACT

With coronavirus disease-2019 (COVID-19) pandemic restrictions and lockdown, children and adolescents have experienced emotional and physical isolation from family and community members. This isolation has a negative impact on children's and adolescents' mental health, physical health, and behavior. An online cross-sectional study of children and adolescents aged 5 to 11 years was conducted to assess the effect of the COVID-19 pandemic on their behavior, emotions, and sleep routines. A total of 413 participants, with a mean age of seven (217 boys and 195 girls), were included in the study. Most of the children were in primary school and lived with both parents. Boys and older children were found to have been fatigued during the pandemic. A significant association was found between the participants' age and regression, opposition, and adaptation behaviors. A significant increase in screen usage and decrease in children's physical activity after the outbreak were noted. The COVID-19 pandemic has negatively affected children's and adolescents' psychosocial, behavioral, and physical habits. Government programs to support the mental and psychological well-being of children and adolescents should be encouraged. Social communication, physical activity, and collaborative games are also important factors.


Subject(s)
COVID-19 , Pandemics , Male , Female , Humans , Adolescent , Child , Bahrain , Cross-Sectional Studies , COVID-19/epidemiology , Communicable Disease Control , Disease Outbreaks
15.
Cureus ; 15(9): e45557, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37868583

ABSTRACT

Calciphylaxis, or calcific uremic arteriolopathy, is a rare and deadly disease that affects patients with end-stage renal disease (ESRD). It typically manifests in the abdomen and lower extremities. We present a case of a 59-year-old female patient on dialysis due to ESRD who complained of a three-week history of hemorrhagic and painful bilateral lower limb lesions. The predominant clinical suspicion was warfarin-induced skin necrosis (WISN); however, the persistence of unresolved skin lesions post-warfarin cessation generated the impression of calciphylaxis. A skin biopsy confirmed the classical histological findings associated with calciphylaxis. This paper highlights the possible importance of warfarin being an inciting event, as well as the early differentiation between the presentations of WISN and calciphylaxis.

16.
J R Soc Interface ; 20(206): 20230281, 2023 09.
Article in English | MEDLINE | ID: mdl-37727072

ABSTRACT

Type-B aortic dissection is a cardiovascular disease in which a tear develops in the intimal layer of the descending aorta, allowing pressurized blood to delaminate the layers of the vessel wall. In medically managed patients, long-term aneurysmal dilatation of the false lumen (FL) is considered virtually inevitable and is associated with poorer disease outcomes. While the pathophysiological mechanisms driving FL dilatation are not yet understood, haemodynamic factors are believed to play a key role. Computational fluid dynamics (CFD) and 4D-flow MRI (4DMR) analyses have revealed correlations between flow helicity, oscillatory wall shear stress and aneurysmal dilatation of the FL. In this study, we compare CFD simulations using a patient-specific, three-dimensional, three-component inlet velocity profile (4D IVP) extracted from 4DMR data against simulations with flow rate-matched uniform and axial velocity profiles that remain widely used in the absence of 4DMR. We also evaluate the influence of measurement errors in 4DMR data by scaling the 4D IVP to the degree of imaging error detected in prior studies. We observe that oscillatory shear and helicity are highly sensitive to inlet velocity distribution and flow volume throughout the FL and conclude that the choice of IVP may greatly affect the future clinical value of simulations.


Subject(s)
Aortic Dissection , Cardiovascular Diseases , Humans , Bays , Aortic Dissection/diagnostic imaging , Hemodynamics , Hydrodynamics
17.
Cureus ; 15(7): e41720, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37575761

ABSTRACT

Bile acid synthesis disorders (BASD) are a group of rare autosomal recessive disorders. Of the nine different versions, BASD type 4 is characterized by a gene mutation in alpha-methylacyl-CoA racemase (AMACR), which is located on chromosome 5p13. These disorders generally present with a normal gamma-glutamyl transferase with cholestasis, absence of pruritis, and malabsorption of fat, which can lead to fat-soluble vitamin deficiencies. In adulthood, patients usually develop neurological sequelae. Initial testing can be done through the measurement of urine metabolites; however, confirmation of the diagnosis is achieved through whole exome sequencing. Treatment involves supplementation of oral cholic acid and modification of diet. Only 23 patients with this disease have been described. Here, we report two cases of siblings from a family in Bahrain with a novel AMACR mutation and a unique association with autoimmune antibodies alongside a literature review.

18.
Inflammopharmacology ; 31(6): 3115-3125, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37543980

ABSTRACT

Because of evident role of renin-angiotensin system in the etiology of rheumatoid arthritis, the current study's objective was to assess the anti-arthritic efficacy of ramipril through CFA-instigated arthritic model. The drug has been shown to have anti-inflammatory potential. CFA-instigated arthritic model assessed the anti-arthritic efficacy of ramipril by estimating different parameters, including paw volume, arthritic index scoring, haematological and biochemical attributes, histological and radiographic analyses, and various cytokines level. Ramipril significantly (p < 0.001) reduced paw volume and the arthritic index especially at the dose of 4mg/kg. The biochemical and haematological changes were likewise restored to normal by ramipril administration with an increase in anti-inflammatory cytokines while reducing pro-inflammatory cytokines level. Ramipril's ability to prevent arthritis by preserving the normal architecture of arthritis-induced joints is further supported by radiographic and histological investigation. The study's findings demonstrated ramipril's considerable anti-arthritic activity. To identify the precise mechanism of action, however, thorough mechanistic studies are still needed.


Subject(s)
Arthritis, Experimental , Ramipril , Rats , Animals , Freund's Adjuvant , Ramipril/adverse effects , Plant Extracts/pharmacology , Arthritis, Experimental/chemically induced , Arthritis, Experimental/drug therapy , Arthritis, Experimental/pathology , Anti-Inflammatory Agents/therapeutic use , Cytokines
19.
Life Sci ; 324: 121742, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37146938

ABSTRACT

Enalapril with documented anti-inflammatory potential was evaluated in current investigation to explore its anti-arthritic efficacy. For anti-arthritic evaluation of enalapril, CFA-instigated arthritic model was employed after which various parameters comprising paw volume, body weight, arthritic index, hematological and biochemical parameters, radiographic analysis and level of various cytokines were estimated. Enalapril demonstrated significant (p˂0.001) anti-arthritic activity by suppressing paw volume, arthritic index while preserved CFA instigated weight loss. Likewise, enalapril also normalized the hematological and biochemical alterations, suppressed the level of proinflammatory cytokines with elevation of anti-inflammatory cytokines. Radiographic and histopathological analysis also further validates the anti-arthritic attribute of enalapril where enalapril preserved the normal architecture of arthritis induced joints. Outcomes of the study pointed out a notable anti-arthritic activity of enalapril. However detailed mechanistic studies are still required to point out the exact mechanism of action.


Subject(s)
Arthritis, Experimental , Cytokines , Animals , Humans , Cytokines/therapeutic use , Plant Extracts/pharmacology , Enalapril/pharmacology , Enalapril/therapeutic use , Arthritis, Experimental/pathology , Anti-Inflammatory Agents/adverse effects
20.
JAMA Otolaryngol Head Neck Surg ; 149(7): 587-596, 2023 07 01.
Article in English | MEDLINE | ID: mdl-37166807

ABSTRACT

Importance: Otologic disease is common among people with primary ciliary dyskinesia (PCD), yet little is known about its spectrum and severity. Objective: To characterize otologic disease among participants with PCD using data from the Ear-Nose-Throat Prospective International Cohort. Design, Setting, and Participants: This cross-sectional analysis of baseline cohort data from February 2020 through July 2022 included participants from 12 specialized centers in 10 countries. Children and adults with PCD diagnoses; routine ear, nose, and throat examinations; and completed symptom questionnaires at the same visit or within 2 weeks were prospectively included. Exposures: Potential risk factors associated with increased risk of ear disease. Main Outcomes and Measures: The prevalence and characteristics of patient-reported otologic symptoms and findings from otologic examinations, including potential factors associated with increased risk of ear inflammation and hearing impairment. Results: A total of 397 individuals were eligible to participate in this study (median [range] age, 15.2 [0.2-72.4] years; 186 (47%) female). Of the included participants, 204 (51%) reported ear pain, 110 (28%) reported ear discharge, and 183 (46%) reported hearing problems. Adults reported ear pain and hearing problems more frequently when compared with children. Otitis media with effusion-usually bilateral-was the most common otoscopic finding among 121 of 384 (32%) participants. Retracted tympanic membrane and tympanic sclerosis were more commonly seen among adults. Tympanometry was performed for 216 participants and showed pathologic type B results for 114 (53%). Audiometry was performed for 273 participants and showed hearing impairment in at least 1 ear, most commonly mild. Season of visit was the strongest risk factor for problems associated with ear inflammation (autumn vs spring: odds ratio, 2.40; 95% CI, 1.51-3.81) and age 30 years and older for hearing impairment (41-50 years vs ≤10 years: odds ratio, 3.33; 95% CI, 1.12-9.91). Conclusion and Relevance: In this cross-sectional study, many people with PCD experienced ear problems, yet frequency varied, highlighting disease expression differences and possible clinical phenotypes. Understanding differences in otologic disease expression and progression during lifetime may inform clinical decisions about follow-up and medical care. Multidisciplinary PCD management should be recommended, including regular otologic assessments for all ages, even without specific complaints.


Subject(s)
Ciliary Motility Disorders , Hearing Loss , Humans , Female , Male , Cross-Sectional Studies , Prospective Studies , Hearing Loss/etiology , Ciliary Motility Disorders/complications , Pain
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