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1.
BMJ Case Rep ; 17(7)2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38960427

ABSTRACT

Factor X (FX) is a vitamin K-dependent enzyme, which acts as an important coagulation factor of coagulation cascade. FX deficiency is an autosomal recessive inherited disease and is often demonstrated in families with consanguity. Pregnancy in women with congenital FX deficiency has been associated with adverse fetal outcomes. We report a case of pregnancy in women with FX deficiency. The patient needed an immediate caesarean section at 38 weeks of gestation because of severe oligohydramnios and fetal distress. FX deficiency during pregnancy was effectively managed, leading to a positive outcome through the optimal utilisation of available resources.


Subject(s)
Cesarean Section , Factor X Deficiency , Humans , Female , Pregnancy , Factor X Deficiency/diagnosis , Factor X Deficiency/complications , Adult , Oligohydramnios , Pregnancy Complications, Hematologic/diagnosis , Pregnancy Outcome , Fetal Distress/etiology
2.
Methods Appl Fluoresc ; 12(4)2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39013401

ABSTRACT

Guanine-rich single-stranded DNA folds into G-quadruplex DNA (GqDNA) structures, which play crucial roles in various biological processes. These structures are also promising targets for ligands, potentially inducing antitumor effects. While thermodynamic parameters of ligand/DNA interactions are well-studied, the kinetics of ligand interaction with GqDNA, particularly in cell-like crowded environments, remain less explored. In this study, we investigate the impact of molecular crowding agents (glucose, sucrose, and ficoll 70) at physiologically relevant concentrations (20% w/v) on the association and dissociation rates of the benzophenoxazine-core based ligand, cresyl violet (CV), with human telomeric antiparallel-GqDNA. We utilized fluorescence correlation spectroscopy (FCS) along with other techniques. Our findings reveal that crowding agents decrease the binding affinity of CV to GqDNA, with the most significant effect-a nearly three-fold decrease-observed with ficoll 70. FCS measurements indicate that this decrease is primarily due to a viscosity-induced slowdown of ligand association in the crowded environment. Interestingly, dissociation rates remain largely unaffected by smaller crowders, with only small effect observed in presence of ficoll 70 due to direct but weak interaction between the ligand and ficoll. These results along with previously reported data provide valuable insights into ligand/GqDNA interactions in cellular contexts, suggesting a conserved mechanism of saccharide crowder influence, regardless of variations in GqDNA structure and ligand binding mode. This underscores the importance of considering crowding effects in the design and development of GqDNA-targeted drugs for potential cancer treatment.


Subject(s)
G-Quadruplexes , Spectrometry, Fluorescence , Spectrometry, Fluorescence/methods , Ligands , Kinetics , Humans , DNA/chemistry
3.
Plant Physiol ; 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39046110

ABSTRACT

Plants adapt to changing environmental conditions by adjusting their growth physiology. Nitrate (NO3-) and ammonium (NH4+) are the major inorganic nitrogen forms for plant uptake. However, high NH4+ inhibits plant growth, and roots undergo striking changes, such as inhibition of cell expansion and division, leading to reduced root elongation. In this work, we show that high NH4+ modulates nitrogen metabolism and root developmental physiology by inhibiting iron (Fe)-dependent Jasmonate (JA) signaling and response in Arabidopsis (Arabidopsis thaliana). Transcriptomic data suggested that NH4+ availability regulates Fe and JA-responsive genes. High NH4+ levels led to enhanced root Fe accumulation, which impaired nitrogen balance and growth by suppressing JA biosynthesis and signaling response. Integrating pharmacological, physiological, and genetic experiments revealed the involvement of NH4+ and Fe-derived responses in regulating root growth and nitrogen metabolism through modulation of the JA pathway during NH4+ stress. The JA signaling transcription factor MYC2 directly bound the promoter of the NITRATE TRANSPORTER 1.1 (NRT1.1) and repressed it to optimize the NH4+/Fe-JA balance for plant adaptation during NH4+ stress. Our findings illustrate the intricate balance between nutrient and hormone-derived signaling pathways that appear essential for optimizing plant growth by adjusting physiological and metabolic responses during NH4+/Fe stress.

4.
J Infect Public Health ; 17(8): 102486, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39002466

ABSTRACT

High mortality has been reported in severe cases of COVID-19. Emerging reports suggested that the severity is not only due to SARS-CoV-2 infection, but also due to coinfections by other pathogens exhibiting symptoms like COVID-19. During the COVID-19 pandemic, simultaneous respiratory coinfections with various viral (Retroviridae, Flaviviridae, Orthomyxoviridae, and Picoviridae) and bacterial (Mycobacteriaceae, Mycoplasmataceae, Enterobacteriaceae and Helicobacteraceae) families have been observed. These pathogens intensify disease severity by potentially augmenting SARSCoV-2 replication, inflammation, and modulation of signaling pathways. Coinfection emerges as a critical determinant of COVID-19 severity, principally instigated by heightened pro-inflammatory cytokine levels, as cytokine storm. Thereby, in co-infection scenario, the severity is also driven by the modulation of inflammatory signaling pathways by both pathogens possibly associated with interleukin, interferon, and cell death exacerbating the severity. In the current review, we attempt to understand the role of co- infections by other pathogens and their involvement in the severity of COVID-19.


Subject(s)
COVID-19 , Coinfection , SARS-CoV-2 , Severity of Illness Index , Humans , Coinfection/microbiology , Coinfection/virology , COVID-19/complications , Bacterial Infections/complications , Cytokine Release Syndrome , Cytokines/metabolism
5.
BMC Plant Biol ; 24(1): 702, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39054439

ABSTRACT

BACKGROUND: Climate change exacerbates abiotic stresses, which are expected to intensify their impact on crop plants. Drought, the most prevalent abiotic stress, significantly affects agricultural production worldwide. Improving eggplant varieties to withstand abiotic stress is vital due to rising drought from climate change. Despite the diversity of wild eggplant species that thrive under harsh conditions, the understanding of their drought tolerance mechanisms remains limited. In the present study, we used chlorophyll fluorescence (ChlaF) imaging, which reveals a plant's photosynthetic health, to investigate desiccation tolerance in eggplant and its wild relatives. Conventional fluorescence measurements lack spatial heterogeneity, whereas ChlaF imaging offers comprehensive insights into plant responses to environmental stresses. Hence, employing noninvasive imaging techniques is essential for understanding this heterogeneity. RESULTS: Desiccation significantly reduced the leaf tissue moisture content (TMC) across species. ChlaF and TMC displayed greater photosystem II (PSII) efficiency after 54 h of desiccation in S. macrocarpum, S. torvum, and S. indicum, with S. macrocarpum demonstrating superior efficiency due to sustained fluorescence. PSII functions declined gradually in S. macrocarpum and S. torvum, unlike those in other species, which exhibited abrupt declines after 54 h of desiccation. However, after 54 h, PSII efficiency remained above 50% of its initial quantum yield in S. macrocarpum at 35% leaf RWC (relative water content), while S. torvum and S. indicum displayed 50% decreases at 31% and 33% RWC, respectively. Conversely, the susceptible species S. gilo and S. sisymbriifolium exhibited a 50% reduction in PSII function at an early stage of 50% RWC, whereas in S. melongena, this reduction occurred at 40% RWC. CONCLUSION: Overall, our study revealed notably greater leaf desiccation tolerance, especially in S. macrocarpum, S. torvum, and S. indicum, attributed to sustained PSII efficiency at low TMC levels, indicating that these species are promising sources of drought tolerance.


Subject(s)
Chlorophyll , Solanum melongena , Chlorophyll/metabolism , Fluorescence , Solanum melongena/physiology , Solanum melongena/metabolism , Plant Leaves/physiology , Plant Leaves/metabolism , Desiccation , Photosystem II Protein Complex/metabolism , Photosynthesis/physiology , Stress, Physiological , Droughts , Dehydration , Species Specificity
6.
Sci Rep ; 14(1): 17254, 2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39060290

ABSTRACT

In many Indian regions, paddy wheat is the main crop rotation and facing the problem of straw incorporation for seed bed preparation in short period. The handling of straw in combine harvested paddy fields is a significant issue in the paddy wheat rotation. In order to solve this issue, efforts were carried out to cut paddy straw into small pieces by the newly proposed counter-rotating blades, followed by the simultaneous incorporation of a rotary tiller into the soil. Therefore, a tractor operated chopping cum tilling mixing machine was developed. In the study, three different blades (straw management system (SMS) Serrated, cutter bar and SMS plain) were tested in the terms of torque and required to chop the straw. SMS serrated blade was best suitable for the chopping mechanism as it required minimum cutting torque for the straw bunches. The developed chopping cum tilling mixing machine was tested at three different levels of forward speed (1.77, 2.3, and 3 km h-1), moisture content at three levels (35 ± 3.4, 24 ± 2.2 and 17 ± 2.6%) with fix rotary tiller rotational speed of 810 rev min-1. Optimum operating condition of the machine was obtained at a forward speed of 1.9 km h-1 and a moisture of 24%. At these optimized values, the mixing index (96%), mean weight diameter (7.9 mm), bulk density (1230 g cc-1) and fuel consumption (3 l h-1) were 96%, 7.9 mm, 1230 g cc-1 and 3.0 l h-1 respectively. The developed machine performs three operations i.e., chopping, tilling, and mixing in single pass for effective in-situ straw management.


Subject(s)
Triticum , Agriculture/methods , Equipment Design , Soil/chemistry , Crop Production/methods
7.
Ann Afr Med ; 23(3): 324-327, 2024 Jul 01.
Article in French, English | MEDLINE | ID: mdl-39034554

ABSTRACT

BACKGROUND: Diabetes mellitus (DM) has affected over 387 million patients globally, expected to reach 592 million by the end of 2035. It is a metabolic disorder characterized by chronic hyperglycemia caused by either insulin deficiency, insulin resistance, or both. MATERIALS AND METHODS: The present study was designed to estimate the levels of different bone markers; serum Vitamin D, alkaline phosphatase, phosphorus, and calcium in patients with type 2 DM (T2DM). The study was conducted on patients aged 20-50 years diagnosed with T2DM, who were attending the outpatient/inpatient department of internal medicine. RESULTS: The levels of calcium were decreased in the patients with diabetes and also the study proved a negative correlation between calcium and random plasma glucose (RPG). There was a significant negative correlation between RPG and serum 25(OH)D3. CONCLUSION: We conclude that Vitamin D insufficiency is frequent in Moradabad, Uttar Pradesh. Sunshine exposure daily for 15 min on the face and hands is necessary to elevate the sunlight Vitamin D levels.


Résumé Contexte:Le diabète sucré (DM) a touché plus de 387 millions de patients dans le monde et devrait atteindre 592 millions d'ici la fin de l'année. 2035. Il s'agit d'un trouble métabolique caractérisé par une hyperglycémie chronique provoquée soit par un déficit en insuline, soit par une résistance à l'insuline, ou les deux.Matériels et méthodes:La présente étude a été conçue pour estimer les niveaux de différents marqueurs osseux; sérum Vitamine D, alkaline.Résultats:Les niveaux de calcium ont diminuéles patients diabétiques ainsi que l'étude ont prouvé une corrélation négative entre le calcium et le glucose plasmatique aléatoire (RPG). Il y avaitune corrélation négative significative entre le RPG et le sérum 25(OH)D3 phosphatase, phosphore et calcium chez les patients atteints de diabète de type 2 (DT2). L'étude a été menée sur des patients âgés de 20 à 50 ansdiagnostiqués atteints de DT2, qui fréquentaient le service de médecine interneambulatoire/hospitalisé.Conclusion:Nous concluons que l'insuffisance en vitamine D est fréquente chez Moradabad, Uttar Pradesh. Une exposition quotidienne au soleil pendant 15 minutes sur le visage et les mains est nécessaire pour élever les niveaux de vitamine D du soleil.


Subject(s)
Alkaline Phosphatase , Biomarkers , Blood Glucose , Calcium , Diabetes Mellitus, Type 2 , Phosphorus , Vitamin D Deficiency , Vitamin D , Humans , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Middle Aged , Male , Adult , Biomarkers/blood , Female , Vitamin D Deficiency/blood , Vitamin D Deficiency/complications , Vitamin D Deficiency/epidemiology , Alkaline Phosphatase/blood , Blood Glucose/metabolism , Blood Glucose/analysis , Vitamin D/blood , Vitamin D/analogs & derivatives , Phosphorus/blood , Calcium/blood , India/epidemiology , Young Adult
9.
J Biomater Sci Polym Ed ; : 1-25, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38970296

ABSTRACT

Recent advancements in tissue engineering have witnessed luffa-derived scaffolds, exhibiting their exceptional potential in cellular proliferation, biocompatibility, appropriate interconnectivity, and biomechanical strength. In vivo studies involved implanting fabricated scaffolds subcutaneously in Wistar rats to evaluate their impact on the heart, liver, and kidneys. This approach provided a safe and minimally invasive means to evaluate scaffold compatibility with surrounding tissues. Male Wistar rats were categorized into four distinct groups, Group A, B, C, and D are referred to as 3% LC implanted scaffolds, 5% LC implanted scaffolds, control (without luffa scaffolds), and Sham (without any scaffold implantation), respectively. Histological analysis in all the groups indicated that the animal models did not exhibit any signs of inflammation or toxicity, suggesting favorable tissue response to the implanted scaffolds. Initial observations revealed elevated levels of enzymes and biomarkers in the experimental groups after a 24 h interval, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, creatine kinase-MB (CK-MB), and serum creatinine. However, these parameters normalized 3 weeks post-implantation, with no significant increase compared to the control groups, suggesting that the implanted luffa-based scaffolds did not induce adverse effects on the heart, liver, and kidneys. Furthermore, the scaffold's significant pore size and porosity enable it to release drugs, including antibacterial medications. This study demonstrates promising results, indicating excellent scaffold porosity, sustained drug release, affirming the in vivo biocompatibility, absence of inflammatory responses, and overall tissue compatibility highlighting the immense potential of these luffa-based scaffolds in various tissue engineering and regenerative medicine applications.

10.
World J Virol ; 13(2): 92944, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38984074

ABSTRACT

BACKGROUND: The advent of coronavirus disease 2019 (COVID-19) unveiled the worst national blood crisis that the United States had witnessed in over a decade. With the pandemic influencing the different stages of the acquisition of blood products outside the hospital setting, we aimed to explore the possible barriers contributing to the shortage of blood products within the medical community. AIM: To assess the adherence to restrictive blood transfusion practices for patients in the COVID era and pre-COVID era. METHODS: We conducted a retrospective cross-sectional study on hospitalized patients distinguishing the pattern of blood transfusion during the COVID and pre-COVID era in a community hospital. Data was tabulated to include the number of red blood cell (RBC) transfusions and if transfusions met restrictive blood transfusion criteria as per institutional guidelines. Chi-square was applied to test the statistical association between qualitative variables. Unpaired t test and Mann Whitney U test were applied respectively to test the mean difference of quantitative variables. RESULTS: A total of 208 patients were included in the study, of which 108 were during COVID era and 100 were during pre-COVID era. The leading reason for admission in both the COVID era and pre-COVID era transfused patients was shortness of breath (53.7% and 36% P = 0.001), followed by gastrointestinal bleeding (25.9% and 21% P = 0.001). There was a higher percentage of RBC transfusions in the intensive care unit in the COVID-era group than in the pre-COVID era group (38.9% vs 22%, P = 0.008). The restrictive transfusion criteria were met in 62% vs 79% in the COVID and pre-COVID eras, respectively (P = 0.008). CONCLUSION: The COVID-era group received RBC transfusions with less stringent adherence to restrictive blood transfusion practices in comparison to pre-COVID era group.

11.
Lung India ; 41(4): 251-258, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38953187

ABSTRACT

BACKGROUND AND OBJECTIVE: Tobacco smoking is an established risk factor for chronic obstructive pulmonary disease (COPD). Current evidence suggests that non-tobacco-related risk factors vary geographically and are less understood than smoking. This study aims to compare the risk factors, symptoms, and clinical features of smoking (S-COPD) and non-smoking (NS-COPD) in a COPD population. MATERIALS AND METHODS: In this retrospective cross-sectional study, 489 COPD patients were screened. Data on socio-demographics, smoking and medical history, other risk factors, symptoms, and clinical characteristics including COPD Assessment Test (CAT) score, and Modified Medical Research Council (mMRC) Dyspnea Scale were examined. RESULTS: Of the total selected 416 COPD patients, 35.34% were NS-COPD while 64.66% were S-COPD. S-COPD was predominant in males, whereas NS-COPD was predominant in females (P < 0.0001). In NS-COPD, biomass fuel exposure was a major risk factor (P < 0.0001), and 61% of subjects had a biomass fuel exposure index of >60. In bivariate and multivariate analyses, no risk factors were correlated with forced expiratory volume in 1 second (FEV1)% predicted, while among clinical features, duration of illness (P = 0.001) was correlated with lower values of FEV1 in the multivariate table of S-COPD. In the multivariate analysis, biomass fuel exposure (P = 0.039) and CAT score (P < 0.0001) were correlated with FEV1(%) in NS-COPD. CONCLUSION: Biomass fuel exposure is a substantial risk factor for NS-COPD and was correlated with FEV1(%) predicted. In addition, the CAT score correlated with disease severity in patients with NS-COPD. The development of COPD in non-smokers is being recognized as a separate phenotype and it should be managed according to risk factors.

12.
Asian J Transfus Sci ; 18(1): 73-78, 2024.
Article in English | MEDLINE | ID: mdl-39036689

ABSTRACT

INTRODUCTION: Hepcidin is the key regulator of systemic iron homeostasis. In iron-loading anemias, hepcidin levels are regulated by opposite forces of erythropoiesis and iron overload. In ß-thalassemia major patients, transfusions are the predominant cause of iron overload; in such chronically transfused patients, hepcidin concentrations are significantly higher than nontransfused patients, due to both increased iron load of transfusions and the suppression of ineffective erythropoiesis. AIM: This study aims to evaluate the effect of blood transfusions on serum hepcidin levels in chronically transfused patients of ß-thalassemia major and correlate with hemoglobin and serum ferritin levels of pre- and posttransfusion. MATERIALS AND METHODS: Thirty-three ß-thalassemia major patients requiring monthly transfusions were included in the study. Blood samples, collected pretransfusion and 7 days posttransfusion, were evaluated for hemoglobin, serum ferritin, and serum hepcidin using enzyme immunoassay. STATISTICAL ANALYSIS: Data were statistically analyzed through SPSS software and P < 0.05 is considered statically significant. RESULTS: Posttransfusion levels of hemoglobin, serum ferritin, and serum hepcidin increased. Posttransfusion levels of hepcidin were near normal levels. Pre- and posttransfusion hepcidin concentrations were significantly associated with hemoglobin levels. CONCLUSION: Serum hepcidin concentrations vary depending on the degree of erythropoiesis drive and level of anemia. We found that the serum hepcidin levels decrease over the inter-transfusion interval and transfusions cause suppression of ineffective erythropoiesis by the increase in hemoglobin. Posttransfusion values of hepcidin in our study were closer to normal levels which may be due to lower erythropoietic drive posttransfusion. We suggest that the measurement of serum hepcidin in chronically transfused ß-thalassemia patients can be used as a follow-up investigation for better management of these patients.

13.
Int J Mol Sci ; 25(13)2024 Jun 27.
Article in English | MEDLINE | ID: mdl-39000138

ABSTRACT

The ongoing battle against viral pandemics continues, with the possibility of future outbreaks. The search for effective antiviral compounds that can combat a diverse range of viruses continues to be a focal point of research. This study investigated the efficacy of two natural antimicrobial peptides (AMPs) (lactoferricin and LL-37), two synthetic AMPs (melimine and Mel4), and nine AMP mimics (758, 1091, 1096, 1083, 610, NAPL, 3-BIPL, 4-BIPL, and Sau-22) against influenza A virus strains H1N1 and H3N2, human adenovirus 5 (HAdV-5), and murine norovirus 1 (MNV-1). These compounds were tested using virus pre-treatment, cell pre-treatment, or post-cell entry treatment assays, electron microscopy, and circular dichroism (CD), alongside evaluations of cytotoxicity against the host cells. After virus pre-treatment, the AMP mimics 610 and Sau-22 had relatively low IC50 values for influenza strains H1N1 (2.35 and 6.93 µM, respectively) and H3N2 (3.7 and 5.34 µM, respectively). Conversely, natural and synthetic AMPs were not active against these strains. For the non-enveloped viruses, the AMP Mel4 and mimic 1083 had moderate activity against HAdV-5 (Mel4 IC50 = 47.4 µM; 1083 IC50 = 47.2 µM), whereas all AMPs, but none of the mimics, were active against norovirus (LL-37 IC50 = 4.2 µM; lactoferricin IC50 = 23.18 µM; melimine IC50 = 4.8 µM; Mel4 IC50 = 8.6 µM). Transmission electron microscopy demonstrated that the mimics targeted the outer envelope of influenza viruses, while the AMPs targeted the capsid of non-enveloped viruses. CD showed that Mel4 adopted an α-helical structure in a membrane mimetic environment, but mimic 758 remained unstructured. The diverse activity against different virus groups is probably influenced by charge, hydrophobicity, size, and, in the case of natural and synthetic AMPs, their secondary structure. These findings underscore the potential of peptides and mimics as promising candidates for antiviral therapeutics against both enveloped and non-enveloped viruses.


Subject(s)
Antiviral Agents , Norovirus , Norovirus/drug effects , Animals , Humans , Mice , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Influenza A virus/drug effects , Influenza A virus/physiology , Antimicrobial Peptides/pharmacology , Antimicrobial Peptides/chemistry , Influenza A Virus, H3N2 Subtype/drug effects , Dogs , Adenoviridae/drug effects , Influenza A Virus, H1N1 Subtype/drug effects , Madin Darby Canine Kidney Cells , Antimicrobial Cationic Peptides/pharmacology , Antimicrobial Cationic Peptides/chemistry
14.
BMC Plant Biol ; 24(1): 668, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39004715

ABSTRACT

BACKGROUND: Biofortification represents a promising and sustainable strategy for mitigating global nutrient deficiencies. However, its successful implementation poses significant challenges. Among staple crops, wheat emerges as a prime candidate to address these nutritional gaps. Wheat biofortification offers a robust approach to enhance wheat cultivars by elevating the micronutrient levels in grains, addressing one of the most crucial global concerns in the present era. MAIN TEXT: Biofortification is a promising, but complex avenue, with numerous limitations and challenges to face. Notably, micronutrients such as iron (Fe), zinc (Zn), selenium (Se), and copper (Cu) can significantly impact human health. Improving Fe, Zn, Se, and Cu contents in wheat could be therefore relevant to combat malnutrition. In this review, particular emphasis has been placed on understanding the extent of genetic variability of micronutrients in diverse Triticum species, along with their associated mechanisms of uptake, translocation, accumulation and different classical to advanced approaches for wheat biofortification. CONCLUSIONS: By delving into micronutrient variability in Triticum species and their associated mechanisms, this review underscores the potential for targeted wheat biofortification. By integrating various approaches, from conventional breeding to modern biotechnological interventions, the path is paved towards enhancing the nutritional value of this vital crop, promising a brighter and healthier future for global food security and human well-being.


Subject(s)
Biofortification , Malnutrition , Micronutrients , Triticum , Triticum/metabolism , Triticum/genetics , Micronutrients/metabolism , Malnutrition/metabolism , Crops, Agricultural/genetics , Crops, Agricultural/metabolism , Zinc/metabolism , Nutritive Value
15.
World J Cardiol ; 16(6): 318-328, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38993586

ABSTRACT

BACKGROUND: Infective endocarditis (IE) is a life-threatening infection with an annual mortality of 40%. Embolic events reported in up to 80% of patients. Vegetations of > 10 mm size are associated with increased embolic events and poor prognosis. There is a paucity of literature on the association of multiple vegetations with outcome. AIM: To study the echocardiographic (ECHO) features and outcomes associated with the presence of multiple vegetations. METHODS: In this retrospective, single-center, cohort study patients diagnosed with IE were recruited from June 2017 to June 2019. A total of 84 patients were diagnosed to have IE, of whom 67 with vegetation were identified. Baseline demographic, clinical, laboratory, and ECHO parameters were reviewed. Outcomes that were studied included recurrent admission, embolic phenomenon, and mortality. RESULTS: Twenty-three (34%) patients were noted to have multiple vegetations, 13 (56.5%) were male and 10 (43.5%) were female. The mean age of these patients was 50. Eight (35%) had a prior episode of IE. ECHO features of moderate to severe valvular regurgitation [odds ratio (OR) = 4], presence of pacemaker lead (OR = 4.8), impaired left ventricle (LV) relaxation (OR = 4), and elevated pulmonary artery systolic pressure (PASP) (OR = 2.2) are associated with higher odds of multiple vegetations. Of these moderate to severe valvular regurgitation (P = 0.028), pacemaker lead (P = 0.039) and impaired relaxation (P = 0.028) were statistically significant. These patients were noted to have an increased association of recurrent admissions (OR = 3.6), recurrent bacteremia (OR = 2.4), embolic phenomenon (OR = 2.5), intensive care unit stay (OR = 2.8), hypotension (OR = 2.1), surgical intervention (OR = 2.8) and device removal (OR = 4.8). Of this device removal (P = 0.039) and recurrent admissions (P = 0.017) were statistically significant. CONCLUSION: This study highlights the associations of ECHO predictors and outcomes in patients with IE having multiple vegetations. ECHO features of moderate to severe regurgitation, presence of pacemaker lead, impaired LV relaxation, and elevated PASP and outcomes including recurrent admissions and device removal were found to be associated with multiple vegetations.

16.
Biogerontology ; 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39017749

ABSTRACT

Long noncoding RNAs (lncRNAs) are important regulatory biomolecules responsible for many cellular processes. The aging of mammals is manifested by a slow and gradual decline of physiological functions after adulthood, progressively resulting in age-related diseases. Testis comprises different cell-types with defined functions for producing haploid gametes and androgens in males, contributing gene-pool to the next generation with genetic variations to species for evolutionary advantage. The LINC-RBE (long intergenic noncoding-rat brain expressed) RNA showed highest expression in the Leydig cells, responsible for steroidogenesis and production of testosterone; higher expression in primary spermatocytes (pachytene cells), responsible for generation of haploid gametes and high expression in Sertoli cells, the nursing cells of the testes. Testes of immature (4-weeks), adult (16- and 44-weeks), and nearly-old (70-weeks) rats showed low, high, and again low levels of expression, respectively. This along with the nuclear-cytoplasmic localization of LINC-RBE RNA showed age-related expression and function. Thus, expression of LINC-RBE is involved in the molecular physiology of testes, especially Leydig cells, primary spermatocytes, and Sertoli cells. The decline in its expression correlates with diminishing reproductive function of the testes during aging of the rat.

18.
J Family Med Prim Care ; 13(5): 2037-2043, 2024 May.
Article in English | MEDLINE | ID: mdl-38948635

ABSTRACT

Background: Hypertension is one of the leading causes of death worldwide, affecting over one billion people. It is responsible for roughly half of all heart disease and stroke-related deaths globally. Because hypertension does not cause any symptoms on its own, it is commonly referred to as "the silent killer." Objective: This study aimed to determine (1) the prevalence of hypertension and its associated risk factors and (2) the level of awareness of hypertension status among study participants. Material and Methods: A facility-based cross-sectional analytical study was conducted for 3 months during January-March 2023 at the teaching institution in Etawah District, Uttar Pradesh. It was conducted among 392 study participants who were ≥18 years old. Data were collected through a predesigned, pretested, semi-structured questionnaire, and anthropometric measurement was determined using standard guidelines. Results: The overall prevalence of hypertension screening was 69.4% (male: 33.8% and female: 66.2%), respectively. The majority of hypertensives were found in female participants. Tobacco and alcohol consumption, obesity, physical inactivity, stress and strain, and an unhealthy diet were also associated with hypertension. Among 392 study participants, only 67 (24.6%) were aware of their hypertension status. Conclusion: We conclude that hypertension has been described as an "Iceberg disease" as those who suffer are usually unaware and hence usually seek healthcare services at a very late stage. Preventive measures should be needed to improve hypertension screening, awareness, treatment, and control.

19.
J Cancer Prev ; 29(2): 32-44, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38957589

ABSTRACT

Cancer drug resistance is associated with metabolic adaptation. Cancer cells have been shown to implicate acetylated polyamines in adaptations during cell death. However, exploring the mimetic of acetylated polyamines as a potential anticancer drug is lacking. We performed intracellular metabolite profiling of human breast cancer MCF-7 cells treated with doxorubicin (DOX), a well known anticancer drug. A novel and in-house vertical tube gel electrophoresis assisted procedure followed by LC-HRMS analysis was employed to detect acetylated polyamines such as N1-acetylspermidine. We designed a mimetic N1-acetylspermidine (MINAS) which is a known substrate of histone deacetylase 10 (HDAC10). Molecular docking and molecular dynamics (MDs) simulations were used to evaluate the inhibitory potential of MINAS against HDAC10. The inhibitory potential and the ADMET profile of MINAS were compared to a known HDAC10 inhibitor Tubastatin A. N1-acetylspermidine, an acetylated form of polyamine, was detected intracellularly in MCF-7 cells treated with DOX over DMSO-treated MCF-7 cells. We designed and curated MINAS (PubChem CID 162679241). Molecular docking and MD simulations suggested the strong and comparable inhibitory potential of MINAS (-8.2 kcal/mol) to Tubastatin A (-8.4 kcal/mol). MINAS and Tubastatin A share similar binding sites on HDAC10, including Ser138, Ser140, Tyr183, and Cys184. Additionally, MINAS has a better ADMET profile compared to Tubastatin A, with a high MRTD value and lower toxicity. In conclusion, the data show that N1-acetylspermidine levels rise during DOX-induced breast cancer cell death. Additionally, MINAS, an N1-acetylspermidine mimetic compound, could be investigated as a potential anticancer drug when combined with chemotherapy like DOX.

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