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1.
J Chromatogr Sci ; 2024 May 05.
Article in English | MEDLINE | ID: mdl-38706312

ABSTRACT

Glycyrrhiza glabra is commonly known as licorice. Licorice is the major source of glycyrrhizin. There is no reported stability indicating method for glycyrrhizin in the literature so far. Therefore, it was proposed to develop a stability indicating method and validate the method for glycyrrhizin and its application in G. glabra root extract. Method validation parameters were performed as per the International Council for Harmonization guidelines. The chromatographic separation was achieved on a Zorbax Extended C-18 (250 × 4.6 mm, 5 µm) column. The separation achieved using the mobile phase consisted of 0.1% formic acid in water and acetonitrile in gradient elution. The flow rate was kept at 1 mL/min, and ultraviolet-visible spectroscopy detection was at 250 nm. The average retention time of glycyrrhizin was found to be 7.30 min. Stress degradation studies were performed and confirmed that only acidic degradation has shown a degradation profile of glycyrrhizin up to 40%. The percentage of glycyrrhizin was found to be 0.40% in the G. glabra extract. This may be further explored for commercial applications.

2.
J Neurosci Rural Pract ; 15(2): 217-226, 2024.
Article in English | MEDLINE | ID: mdl-38746514

ABSTRACT

Objectives: In developing nations such as India, a disparity exists between the available resources for stroke rehabilitation and the substantial burden of stroke cases. Consequently, the provision of cost-effective and multidisciplinary post-stroke rehabilitation care to stroke survivors becomes of paramount importance. The utilization of mobile applications (apps) for stroke care has been on the rise, offering a personalized and pragmatic solution with the potential for wider reach in settings constrained by limited resources. To address the unmet needs in the prevention and management of post-stroke complications, we conceptualized a strategy known as a mobile application-based post-stroke care strategy for both survivors and their caregivers. Materials and Methods: The scope of the app's focus was determined based on the incidence of post-stroke complications within a prospective cohort of stroke patients, in conjunction with existing literature. An initial "web-based mobile app" prototype was crafted to align with the identified focus area. Before the development of the final app version, a feasibility study was conducted involving 30 participant dyads (comprising a patient and a caregiver). Content validity was evaluated by a panel of 20 stroke experts encompassing neurologists, nurses, physiotherapists, and psychologists. Results: The "Stroke Home Care" (SHC) mobile app was conceived as a web-based educational tool aimed at preventing and managing post-stroke complications. It seeks to train caregivers of immobile stroke patients in the administration of preventive and therapeutic care procedures, thereby potentially enhancing survivors' quality of life and alleviating caregivers' burden. The feasibility and validity studies indicated "high satisfaction" levels among most caregivers and experts (>75%), with the remainder expressing "satisfaction" and no "dissatisfaction" regarding app utilities. Stroke experts unanimously deemed the app "appropriate", with consensus on contents, video quality, video length, and voice clarity. Caregivers reported "satisfactory" user experiences, encountering no issues during app installation or operation. Suggestions from both caregivers and experts were integrated into the final app version. Conclusion: The "SHC" app represents a feasible and well-received innovation tailored for the use by caregivers of stroke survivors. Consequently, the initial feasibility of the developed app serves as a precursor to a randomized controlled clinical trial aimed at substantiating its effectiveness within the post-stroke survivor and caregiver population. Notably, within resource-constrained contexts, this app has the potential to be a pivotal tool for post-stroke care.

3.
Aging Med (Milton) ; 7(1): 67-73, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38571668

ABSTRACT

Introduction: SuperAgers (SA) are older adults who exhibit cognitive capacities comparable to individuals who are three or more decades younger than them. The current study aimed to identify the characteristics of Indian SA by categorizing 55 older adults into SA and Typical Older Adults (TOA) and comparing their performance with a group of 50 younger participants (YP) (aged 25-50). Methods: A total of 105 participants were recruited after obtaining informed written consent. The cognitive abilities of the participants were assessed using Wechsler Adult Intelligence Scale (WAIS)-IVINDIA, Color Trails Test, Boston Naming Test (BNT), and Rey Auditory Verbal Learning Test. Results: SA outperformed TOA in all cognitive assessments (P < 0.001) and surpassed YP in BNT and WAIS-IV. SA's delayed recall scores were notably higher (12.29 ± 1.51) than TOA (6.32 ± 1.44). Conclusion: SA excelled in all cognitive domains demonstrating resilience to age-related cognitive decline. This study highlights Indian SuperAgers' exceptional cognitive prowess.

4.
Indian J Otolaryngol Head Neck Surg ; 76(2): 2166-2170, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38566724

ABSTRACT

Perioperative high dose rate brachytherapy involves insertion of brachytherapy catheter over the tumor bed during surgical removal of disease followed by radiation in the postoperative period. It has applications in radiotherapy dose escalation or reirradiation and for extending the surgical margins. We report here initial results of treatment in five cases of locally advanced head and neck cancers.

5.
Chemistry ; : e202401105, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38655822

ABSTRACT

This report detailed the synthesis of multi-substituted pyrazoles through the acceptorless dehydrogenative coupling (ADC) reaction catalyzed by a well-defined manganese(I)-pincer complex. Symmetrically substituted pyrazoles were synthesized by reacting 1,3-diols with hydrazines. Unsymmetrically substituted pyrazoles were selectively made via the ADC of primary alcohols with methyl hydrazones. Water and hydrogen are liberated as the green byproducts. The endurance of these methodologies has been presented by producing 30 substrates with varied functionalities. Model reactions were scaled up to demonstrate practicability. The reaction rate and order were measured to transparent the involvement of the reagents during catalysis. Control experiments elucidated the plausible reaction mechanisms.

6.
Cureus ; 16(3): e57235, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38686267

ABSTRACT

Background Plate osteosynthesis is the gold standard treatment for the management of humeral shaft fractures. In the present study, we performed plate osteosynthesis on the anteromedial and anterolateral surfaces using the anterolateral approach to compare the functional outcomes. Aims and objectives To study and compare the functional outcome, time to achieve union and associated complications of anteromedial and anterolateral plating in humerus shaft fracture by anterolateral approach. Methods This prospective, randomised control study was performed at Dr Baba Saheb Ambedkar Medical College and Hospital, New Delhi, India. This study had 46 patients in total, who were divided into two equal groups at random. All of the fractures in group A were treated using a limited contact dynamic compression plate (LCDCP) on the anterolateral surface using an anterolateral approach, while all of the fractures in group B were corrected using an anteromedial surface using an anterolateral approach using LCDCP. All the patients were followed for six months at regular intervals. At each follow-up, patients were assessed radiologically with X-rays and clinically by Rodriguez-Merchan criteria (RM criteria). Results and conclusions The union was achieved in the majority of the cases of the anteromedial plating group within 12 weeks (78.3%) with a mean union time of 11.7±1.5 weeks than the anterolateral group (56.5%) with a mean union time of 12.3±1.8 weeks. Based on functional assessment according to RM criteria, the excellent outcome was achieved in 69.6% and 65.2% of the anterolateral and anteromedial plating groups, respectively. There was no case of non-union and radial nerve palsy in anteromedial plating cases whereas in anterolateral cases one patient did not achieve union and two (8.7%) had radial nerve injury, which recovered completely by the end of the study. An anterolateral approach with anteromedial surface plating on the flat medial aspect of the humerus is a good technique for fixing humeral fractures.

7.
Mol Cell Endocrinol ; 587: 112212, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38521400

ABSTRACT

RESEARCH QUESTION: Premature ovarian insufficiency (POI) is characterised by amenorrhea associated with elevated follicle stimulating hormone (FSH) under the age of 40 years and affects 1-3.7% women. Genetic factors explain 20-30% of POI cases, but most causes remain unknown despite genomic advancements. DESIGN: We used whole exome sequencing (WES) in four Iranian families, validated variants via Sanger sequencing, and conducted the Acyl-cLIP assay to measure HHAT enzyme activity. RESULTS: Despite ethnic homogeneity, WES revealed diverse genetic causes, including a novel homozygous nonsense variant in SYCP2L, impacting synaptonemal complex (SC) assembly, in the first family. Interestingly, the second family had two independent causes for amenorrhea - the mother had POI due to a novel homozygous loss-of-function variant in FANCM (required for chromosomal stability) and her daughter had primary amenorrhea due to a novel homozygous GNRHR (required for gonadotropic signalling) frameshift variant. WES analysis also provided cytogenetic insights. WES revealed one individual was in fact 46, XY and had a novel homozygous missense variant of uncertain significance in HHAT, potentially responsible for complete sex reversal although functional assays did not support impaired HHAT activity. In the remaining individual, WES indicated likely mosaic Turners with the majority of X chromosome variants having an allelic balance of ∼85% or ∼15%. Microarray validated the individual had 90% 45,XO. CONCLUSIONS: This study demonstrates the diverse causes of amenorrhea in a small, isolated ethnic cohort highlighting how a genetic cause in one individual may not clarify familial cases. We propose that, in time, genomic sequencing may become a single universal test required for the diagnosis of infertility conditions such as POI.


Subject(s)
Amenorrhea , Primary Ovarian Insufficiency , Humans , Female , Adult , Male , Amenorrhea/diagnosis , Amenorrhea/genetics , Iran , Primary Ovarian Insufficiency/genetics , Mutation, Missense , Genomics , DNA Helicases/genetics
8.
Exp Gerontol ; 189: 112409, 2024 May.
Article in English | MEDLINE | ID: mdl-38522483

ABSTRACT

Among all non-communicable diseases, Cardiovascular Diseases (CVDs) stand as the leading global cause of mortality. Within this spectrum, Myocardial Infarction (MI) strikingly accounts for over 15 % of all deaths. The intricate web of risk factors for MI, comprising family history, tobacco use, oral health, hypertension, nutritional pattern, and microbial infections, is firmly influenced by the human gut and oral microbiota, their diversity, richness, and dysbiosis, along with their respective metabolites. Host genetic factors, especially allelic variations in signaling and inflammatory markers, greatly affect the progression or severity of the disease. Despite the established significance of the human microbiome-nutrient-metabolite interplay in associations with CVDs, the unexplored terrain of the gut-heart-oral axis has risen as a critical knowledge gap. Moreover, the pivotal role of the microbiome and the complex interplay with host genetics, compounded by age-related changes, emerges as an area of vital importance in the development of MI. In addition, a distinctive disease susceptibility and severity influenced by gender-based or ancestral differences, adds a crucial insights to the association with increased mortality. Here, we aimed to provide an overview on interactions of microbiome (oral and gut) with major risk factors (tobacco use, alcohol consumption, diet, hypertension host genetics, gender, and aging) in the development of MI and therapeutic regulation.


Subject(s)
Gastrointestinal Microbiome , Hypertension , Microbiota , Myocardial Infarction , Humans , Risk Factors
9.
Mol Cell ; 84(6): 1149-1157.e7, 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38309274

ABSTRACT

OCA-B, OCA-T1, and OCA-T2 belong to a family of coactivators that bind to POU transcription factors (TFs) to regulate gene expression in immune cells. Here, we identify IκBζ (encoded by the NFKBIZ gene) as an additional coactivator of POU TFs. Although originally discovered as an inducible regulator of NF-κB, we show here that IκBζ shares a microhomology with OCA proteins and uses this segment to bind to POU TFs and octamer-motif-containing DNA. Our functional experiments suggest that IκBζ requires its interaction with POU TFs to coactivate immune-related genes. This finding is reinforced by epigenomic analysis of MYD88L265P-mutant lymphoma cells, which revealed colocalization of IκBζ with the POU TF OCT2 and NF-κB:p50 at hundreds of DNA elements harboring octamer and κB motifs. These results suggest that IκBζ is a transcriptional coactivator that can amplify and integrate the output of NF-κB and POU TFs at inducible genes in immune cells.


Subject(s)
DNA , NF-kappa B , NF-kappa B/genetics , NF-kappa B/metabolism , Promoter Regions, Genetic , DNA/genetics , DNA/metabolism
10.
Int J Gynaecol Obstet ; 165(2): 462-473, 2024 May.
Article in English | MEDLINE | ID: mdl-38234106

ABSTRACT

OBJECTIVE: This study aimed to investigate the incidence of and risk factors for stillbirth in an Indian population. METHODS: We conducted a secondary data analysis of a hospital-based cohort from the Maternal and Perinatal Health Research collaboration, India (MaatHRI), including pregnant women who gave birth between October 2018-September 2023. Data from 9823 singleton pregnancies recruited from 13 hospitals across six Indian states were included. Univariable and multivariable Poisson regression analysis were performed to examine the relationship between stillbirth and potential risk factors. Model prediction was assessed using the area under the receiver-operating characteristic (AUROC) curve. RESULTS: There were 216 stillbirths (48 antepartum and 168 intrapartum) in the study population, representing an overall stillbirth rate of 22.0 per 1000 total births (95% confidence interval [CI]: 19.2-25.1). Modifiable risk factors for stillbirth were: receiving less than four antenatal check-ups (adjusted relative risk [aRR]: 1.75, 95% CI: 1.25-2.47), not taking any iron and folic acid supplementation during pregnancy (aRR: 7.23, 95% CI: 2.12-45.33) and having severe anemia in the third trimester (aRR: 3.37, 95% CI: 1.97-6.11). Having pregnancy/fetal complications such as hypertensive disorders of pregnancy (aRR: 1.59, 95% CI: 1.03-2.36), preterm birth (aRR: 4.41, 95% CI: 3.21-6.08) and birth weight below the 10th percentile for gestational age (aRR: 1.35, 95% CI: 1.02-1.79) were also associated with an increased risk of stillbirth. Identified risk factors explained 78.2% (95% CI: 75.0%-81.4%) of the risk of stillbirth in the population. CONCLUSION: Addressing potentially modifiable antenatal factors could reduce the risk of stillbirths in India.


Subject(s)
Pregnancy Complications , Premature Birth , Pregnancy , Female , Infant, Newborn , Humans , Stillbirth/epidemiology , Prospective Studies , Premature Birth/epidemiology , Risk Factors , Pregnancy Complications/epidemiology , Hospitals
11.
J Mol Med (Berl) ; 102(3): 287-311, 2024 03.
Article in English | MEDLINE | ID: mdl-38183492

ABSTRACT

Lysosomes function as critical signaling hubs that govern essential enzyme complexes. LGALS proteins (LGALS3, LGALS8, and LGALS9) are integral to the endomembrane damage response. If ESCRT fails to rectify damage, LGALS-mediated ubiquitination occurs, recruiting autophagy receptors (CALCOCO2, TRIM16, and SQSTM1) and VCP/p97 complex containing UBXN6, PLAA, and YOD1, initiating selective autophagy. Lysosome replenishment through biogenesis is regulated by TFEB. LGALS3 interacts with TFRC and TRIM16, aiding ESCRT-mediated repair and autophagy-mediated removal of damaged lysosomes. LGALS8 inhibits MTOR and activates TFEB for ATG and lysosomal gene transcription. LGALS9 inhibits USP9X, activates PRKAA2, MAP3K7, ubiquitination, and autophagy. Conjugation of ATG8 to single membranes (CASM) initiates damage repair mediated by ATP6V1A, ATG16L1, ATG12, ATG5, ATG3, and TECPR1. ATG8ylation or CASM activates the MERIT system (ESCRT-mediated repair, autophagy-mediated clearance, MCOLN1 activation, Ca2+ release, RRAG-GTPase regulation, MTOR modulation, TFEB activation, and activation of GTPase IRGM). Annexins ANAX1 and ANAX2 aid damage repair. Stress granules stabilize damaged membranes, recruiting FLCN-FNIP1/2, G3BP1, and NUFIP1 to inhibit MTOR and activate TFEB. Lysosomes coordinate the synergistic response to endomembrane damage and are vital for innate and adaptive immunity. Future research should unveil the collaborative actions of ATG proteins, LGALSs, TRIMs, autophagy receptors, and lysosomal proteins in lysosomal damage response.


Subject(s)
DNA Helicases , Galectin 3 , Galectin 3/metabolism , Poly-ADP-Ribose Binding Proteins/metabolism , RNA Helicases/metabolism , RNA Recognition Motif Proteins/metabolism , Autophagy/genetics , TOR Serine-Threonine Kinases/metabolism , Lysosomes/metabolism , GTP Phosphohydrolases/metabolism , Endosomal Sorting Complexes Required for Transport/metabolism , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism
12.
Cell Mol Biol Lett ; 29(1): 13, 2024 Jan 16.
Article in English | MEDLINE | ID: mdl-38225560

ABSTRACT

TRIM proteins are characterized by their conserved N-terminal RING, B-box, and coiled-coil domains. These proteins are efficient regulators of autophagy, apoptosis, and innate immune responses and confer immunity against viruses and bacteria. TRIMs function as receptors or scaffold proteins that target substrates for autophagy-mediated degradation. Most TRIMs interact with the BECN1-ULK1 complex to form TRIMosomes, thereby efficiently targeting substrates to autophagosomes. They regulate the functions of ATG proteins through physical interactions or ubiquitination. TRIMs affect the lipidation of MAP1LC3B1 to form MAP1LC3B2, which is a prerequisite for phagophore and autophagosome formation. In addition, they regulate MTOR kinase and TFEB, thereby regulating the expression of ATG genes. TRIM proteins are efficient regulators of apoptosis and are crucial for regulating cell proliferation and tumor formation. Many TRIM proteins regulate intrinsic and extrinsic apoptosis via the cell surface receptors TGFBR2, TNFRSF1A, and FAS. Mitochondria modulate the anti- and proapoptotic functions of BCL2, BAX, BAK1, and CYCS. These proteins use a multipronged approach to regulate the intrinsic and extrinsic apoptotic pathways, culminating in coordinated activation or inhibition of the initiator and executor CASPs. Furthermore, TRIMs can have a dual effect in determining cell fate and are therefore crucial for cellular homeostasis. In this review, we discuss mechanistic insights into the role of TRIM proteins in regulating autophagy and apoptosis, which can be used to better understand cellular physiology. These findings can be used to develop therapeutic interventions to prevent or treat multiple genetic and infectious diseases.


Subject(s)
Apoptosis Regulatory Proteins , Apoptosis , Tripartite Motif Proteins/chemistry , Tripartite Motif Proteins/metabolism , Ubiquitination , Autophagy
13.
Article in English | MEDLINE | ID: mdl-38275062

ABSTRACT

BACKGROUND: Recognizing the potential of the immune system, immunotherapies have brought about a revolution in the treatment of cancer. Low tumour mutational burden and strong immunosuppression in the peritoneal tumor microenvironment (TME) lead to poor outcomes of immune checkpoint inhibition (ICI) and CART cell therapy in ovarian cancer. Alternative immunotherapeutic strategies are of utmost importance to achieve sound clinical success. INTRODUCTION: The development of peptide vaccines based on tumor-associated antigens (TAAs) for ovarian cancer cells can be a potential target to provoke an anti-tumor immune response and subsequent clearance of tumour cells. The purpose of this in-silico study was to find potential epitopes for a multi-epitope vaccine construct using the immunopeptidomics landscape of ovarian carcinoma. METHODS: The four TAAs (MUC16, IDO1, FOLR1, and DDX5) were selected as potential epitopes for B-cells, helper T-lymphocytes (HTLs), and cytotoxic T-lymphocytes (CTLs) predicted on the basis of antigenic, allergenic, and toxic properties. These epitopes were combined with suitable linkers and an adjuvant to form a multi-epitope construct. RESULTS: Four HTLs, 13 CTLs, and 6 potential B-cell epitopes were predicted from the TAAs. The designed multi-epitope construct was potentially immunogenic, non-toxic, and nonallergenic. Physicochemical properties and higher-order structural analyses of the final construct revealed a potential vaccine candidate. CONCLUSION: The designed vaccine construct has the potential to trigger both humoral and cellular immune responses and may be employed as a therapeutic immunization candidate for ovarian malignancies. However, further in vitro and animal experimentation is required to establish the efficacy of the vaccine candidate.

14.
Am J Transplant ; 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38219868

ABSTRACT

Atezolizumab plus bevacizumab is the preferred first-line treatment regimen for patients with advanced hepatocellular carcinoma. Limited data have shown promising results with the use of immune checkpoint inhibitors like nivolumab to downstage these patients for liver transplantation (LT). Here, we describe the first case of successful downstaging with atezolizumab plus bevacizumab in a patient with multifocal hepatocellular carcinoma and main portal vein tumoral thrombosis, followed by ABO-incompatible live donor LT. This illustrated case highlights that atezolizumab plus bevacizumab therapy may be a potential bridging tool for curative LT.

15.
Vet Res Commun ; 48(2): 849-863, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37957451

ABSTRACT

The effect of the insulin-sensitizing drug metformin on preovulatory follicle (POF) number, ovulation rate, fetal rate and prolificacy was studied in forty-six cyclic Malpura ewes. After estrus synchronization, the ewes were equally divided into two groups (n = 23). The treatment group (MET) received a daily oral dose of metformin at a rate of 500 mg/animal for approximately 12 weeks, spanning five estrous cycles, as against untreated control (CON). All the ewes were bred to proven rams at the end of treatment. Ovarian ultrasound scans were performed at each estrus and day 9 of each cycle to assess the number and diameter of POFs and corpora lutea (CL), respectively. A comprehensive assessment of circulating hormones including, estradiol, progesterone, androstenedione, and insulin as well as metabolic indicators such as glucose, and lipid profile parameters was performed. At the end of treatment on the day of estrus (E5D0), the treatment showed a stimulatory effect on follicular development with a 53.2% (P < 0.001) increase in the number of POFs. It also increased the ovulation rate by 67.4% (P < 0.01), with a higher proportion (χ2df1 = 10.7, P < 0.001) of ewes in the MET group having multiple ovulations compared to the CON group (82.6 vs. 30.4%). With 1.48 ± 0.12 prolificacy rate in MET ewes, the proportion of ewes giving birth to multiple lambs was 2.9-fold higher than in the CON group. Plasma estradiol, insulin, glucose, total cholesterol, and LDL-cholesterol concentrations were lower (P < 0.05) in the MET ewes than in the CON. The results of the present study indicate that metformin can increase the number of POF, ovulation rate, fetal rate and prolificacy in ewes, while reducing the plasma estradiol, insulin, glucose and cholesterol in MET ewes.


Subject(s)
Insulin , Metformin , Sheep , Animals , Pregnancy , Female , Male , Insulin/pharmacology , Ovulation , Progesterone/pharmacology , Estradiol/pharmacology , Sheep, Domestic , Cholesterol/pharmacology , Glucose/pharmacology , Metformin/pharmacology
16.
Nanoscale ; 16(2): 604-613, 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38050855

ABSTRACT

A topological insulator has a unique graphene-like Dirac cone conducting surface state, which is excellent for broadband absorption and photodetector applications. Experimental investigations on the Bi2Te3/n-GaN heterojunction exhibited an aberrant photoelectric effect under the influence of unpolarized light. Transport measurements of the Bi2Te3/n-GaN heterojunction revealed a negative photoconductance, with a sudden increase in resistance. This was consistent with the applied range of wavelength and power used for incident light while it was contrary to the usual gap-state transition model, which states that a negative conductance is due to the trapping of charge carriers. The observed aberrant photoelectric effect seen in Bi2Te3/n-GaN heterojunction devices was due to the polycrystalline nature of the Bi2Te3 topological insulator film, where the incident photon-induced bandgap in the Dirac cone surface state resulted in a negative photoelectric effect. This phenomenon opens the possibility for applications in highly sensitive photodetectors and non-volatile memories, along with employing the bandgap-opening concept in retinomorphic devices.

17.
J Agromedicine ; 29(2): 179-188, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37953596

ABSTRACT

OBJECTIVES: This study collected data related to agricultural injuries, analyzed their causes, and suggested possible remedial actions. Few studies from developing countries have investigated this important topic. Such investigations are extremely important and are required to frame national policies. METHODS: A well-designed structured form was developed to collect and evaluate data on agricultural incidents, their causes, the severity of injuries, and possible prevention methods. The authors followed a door-to-door survey methodology to collect data with the help of local village leaders. RESULTS: Less educated and older adults in the age group 31 to 45 years were more prone to agricultural incidents (p < .05). The mean age of the victims was 35.02 years (95% CI 32.7 to 37.3); 124 (91.18%) of the victims were men; and 21 (15.4%) of the cases were fatal. Tractor rollovers caused most of the deaths. Chaff cutters were responsible for most of the incidents that required amputation. Eighteen (45%) of the chaff-cutter incidents occurred in the evening between 3:00 PM and 6:00 PM, and 12 (30%) of these incidents occurred due to fatigue. CONCLUSIONS: The authors strongly recommend that rollover protective structures (ROPS) for tractors and seat belts should be made mandatory in India. Public guidelines emphasizing mandatory higher education for farmers and a model curriculum for both schools and colleges that focuses on the safety of rural populations should be developed. Special training should be provided on the safe operation of machinery and a definitive work - rest schedule should be followed to prevent fatigue and protect agricultural workers from incidents.


Subject(s)
Accidents, Occupational , Wounds and Injuries , Male , Humans , Aged , Adult , Middle Aged , Female , Seat Belts , Farmers , Agriculture , India/epidemiology , Wounds and Injuries/epidemiology
18.
Aliment Pharmacol Ther ; 59(3): 306-321, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38108646

ABSTRACT

BACKGROUND & AIMS: Non-selective ß-blockers (NSBBs) and endoscopic variceal-ligation (EVL) have similar efficacy preventing first variceal bleeding. Compensated and decompensated cirrhosis are markedly different stages, which may impact treatment outcomes. We aimed to assess the efficacy of NSBBs vs EVL on survival in patients with high-risk varices without previous bleeding, stratifying risk according to compensated/decompensated stage of cirrhosis. METHODS: By systematic review, we identified RCTs comparing NSBBs vs EVL, in monotherapy or combined, for primary bleeding prevention. We performed a competing-risk, time-to-event meta-analysis, using individual patient data (IPD) obtained from principal investigators of RCTs. Analyses were stratified according to previous decompensation of cirrhosis. RESULTS: Of 25 RCTs eligible, 14 failed to provide IPD and 11 were included, comprising 1400 patients (656 compensated, 744 decompensated), treated with NSBBs (N = 625), EVL (N = 546) or NSBB+EVL (N = 229). Baseline characteristics were similar between groups. Overall, mortality risk was similar with EVL vs. NSBBs (subdistribution hazard-ratio (sHR) = 1.05, 95% CI = 0.75-1.49) and with EVL + NSBBs vs either monotherapy, with low heterogeneity (I2 = 28.7%). In compensated patients, mortality risk was higher with EVL vs NSBBs (sHR = 1.76, 95% CI = 1.11-2.77) and not significantly lower with NSBBs+EVL vs NSBBs, without heterogeneity (I2 = 0%). In decompensated patients, mortality risk was similar with EVL vs. NSBBs and with NSBBs+EVL vs. either monotherapy. CONCLUSIONS: In patients with compensated cirrhosis and high-risk varices on primary prophylaxis, NSBBs significantly improved survival vs EVL, with no additional benefit noted adding EVL to NSBBs. In decompensated patients, survival was similar with both therapies. The study suggests that NSBBs are preferable when advising preventive therapy in compensated patients.


Subject(s)
Esophageal and Gastric Varices , Varicose Veins , Humans , Esophageal and Gastric Varices/drug therapy , Esophageal and Gastric Varices/prevention & control , Gastrointestinal Hemorrhage , Ligation , Adrenergic beta-Antagonists/therapeutic use , Liver Cirrhosis/complications , Liver Cirrhosis/drug therapy , Varicose Veins/drug therapy
19.
Nano Lett ; 24(1): 362-369, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38157323

ABSTRACT

This work used a highly flexible, sustainable polyimide tape as a substrate to deposit ductile-natured carbonaceous Ni3N (C/Ni3N@polyimide) material for supercapacitor application. C/Ni3N was prepared using a co-sputtering technique, and this method also provided better adhesion of the electrode material over the substrate, which is helpful in improving bending performance. The ductile behavior of the sputter-grown electrode and the high flexibility of the polyimide tape provide ultimate flexibility to the C/Ni3N@polyimide-based supercapacitor. To achieve optimum electrochemical performance, a series of electrochemical tests were done in the presence of various electrolytes. Further, a flexible asymmetric supercapacitor (NC-FSC) (C/Ni3N//carbon@polyimide) was assembled by using C/Ni3N as a cathode and a carbon thin film as an anode, separated by a GF/C-glass microfiber soaked in optimized 1 M Li2SO4 aqueous electrolyte. The NC-FSC offers a capacitance of 324 mF cm-2 with a high areal energy density of 115.26 µWh cm-2 and a power density of 811 µW cm-2, with ideal bending performance.

20.
ACS Pharmacol Transl Sci ; 6(12): 1801-1816, 2023 Dec 08.
Article in English | MEDLINE | ID: mdl-38093838

ABSTRACT

Hepatocellular carcinoma (HCC) remains one of the predominant causes of cancer-related mortality across the globe. It is attributed to obesity, excessive alcohol consumption, smoking, and infection by the hepatitis virus. Early diagnosis of HCC is essential, and local treatments such as surgical excision and percutaneous ablation are effective. Palliative systemic therapy, primarily with the tyrosine kinase inhibitor Sorafenib, is used in advanced cases. However, the prognosis for advanced HCC remains poor. This Review additionally describes the pathophysiological mechanisms of HCC, which include aberrant molecular signaling, genomic instability, persistent inflammation, and the paradoxical position of the immune system in promoting and suppressing HCC. The paper concludes by discussing the growing body of research on the relationship between mitochondria and HCC, suggesting that mitochondrial dysfunction may contribute to the progression of HCC. This Review focuses on immunological interactions between different mechanisms of HCC progression, including obesity, viral infection, and alcohol consumption.

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