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1.
Cureus ; 16(8): e67507, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39310491

RESUMEN

Ovarian torsion is a critical gynecological emergency that presents with sudden-onset abdominal pain and requires immediate intervention to prevent irreversible ovarian damage. This case report describes a 25-year-old female who presented with acute right lower quadrant pain, which had escalated to excruciating levels over the past 45 minutes, accompanied by persistent nausea and vomiting. She had no fever, vaginal bleeding, or dysuria, and her urine pregnancy test was negative. A physical examination revealed significant tenderness and guarding in the right lower abdomen, with no evidence of organomegaly or abnormal pelvic findings. Imaging studies, including ultrasound, confirmed the diagnosis of a complete ovarian torsion with associated necrosis. The patient underwent successful laparoscopic surgery, which involved the removal of the necrotic ovary and affected fallopian tube. Postoperative recovery was uneventful, and the patient fully recovered within a week. This case underscores the importance of early diagnosis and surgical intervention in managing ovarian torsion to preserve ovarian function and prevent complications.

2.
Cureus ; 16(8): e67420, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39310577

RESUMEN

Craniovertebral junction (CVJ) deformities, including basilar invagination and atlanto-occipital assimilation, present significant challenges in diagnosis and management due to their complex nature and impact on neurological function. We report a case of a 28-year-old female who experienced neck pain, weakness, tingling in the upper limbs, restricted neck movements, occipital headaches, and intermittent dizziness. These symptoms progressively worsened over six months, markedly affecting her quality of life. Neurological examination revealed reduced motor power in the upper limbs and a diminished bicipital tendon reflex, while other assessments remained normal. Cervical spine CT imaging was done which revealed basilar invagination and atlanto-occipital assimilation. This case underscores the importance of recognizing and managing CVJ deformities, highlighting the need for a multidisciplinary approach to address anatomical and associated neurological symptoms. Early and accurate diagnosis and a tailored treatment strategy are crucial for improving patient outcomes.

3.
Cureus ; 16(8): e67553, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39310617

RESUMEN

Magnetic resonance imaging (MRI) is a critical diagnostic tool in assessing supratentorial neoplasms, offering unparalleled detail and specificity in brain imaging. Supratentorial neoplasms in the cerebral hemispheres, basal ganglia, thalamus, and other structures above the tentorium cerebelli present significant diagnostic and therapeutic challenges. These challenges vary notably between adult and pediatric populations due to differences in tumor types, biological behavior, and patient management strategies. This comprehensive review explores the role of MRI in diagnosing, planning treatment, monitoring response, and detecting recurrence in supratentorial neoplasms, providing comparative insights into adult and pediatric cases. The review begins with an overview of the epidemiology and pathophysiology of these tumors in different age groups, followed by a detailed examination of standard and advanced MRI techniques, including diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), and magnetic resonance spectroscopy (MRS). We discuss the specific imaging characteristics of various neoplasms and the importance of tailored approaches to optimize diagnostic accuracy and therapeutic efficacy. The review also addresses the technical and interpretative challenges unique to pediatric imaging and the implications for long-term patient outcomes. By highlighting the comparative utility of MRI in adult and pediatric cases, this review aims to enhance the understanding of its pivotal role in managing supratentorial neoplasms. It underscores the necessity of age-specific diagnostic and therapeutic strategies. Emerging MRI technologies and future research directions are also discussed, emphasizing the potential for advancements in personalized imaging approaches and improved patient care across all age groups.

4.
F1000Res ; 13: 614, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39233782

RESUMEN

Cerebral vasculitis is a rare but severe complication of Systemic Lupus Erythematosus (SLE), presenting significant challenges in management due to its potential for devastating neurological consequences and poor prognosis. We present a case of an 18-year-old female with known SLE who presented with seizures, declining cognitive function, and unresponsiveness. Neurological examination, laboratory investigations, and radiological imaging supported the diagnosis of cerebral vasculitis secondary to SLE. Despite aggressive immunosuppressive therapy, the patient's neurological status continued to deteriorate, leading to respiratory failure and multiorgan dysfunction. Ultimately, the patient succumbed to multiorgan failure attributed to severe CNS vasculitis and its complications. This case underscores the importance of early recognition and aggressive management of cerebral vasculitis in SLE while highlighting the need for further research into more effective therapeutic strategies to improve patient outcomes.


Asunto(s)
Lupus Eritematoso Sistémico , Vasculitis del Sistema Nervioso Central , Humanos , Femenino , Adolescente , Lupus Eritematoso Sistémico/complicaciones , Vasculitis del Sistema Nervioso Central/etiología , Vasculitis del Sistema Nervioso Central/complicaciones , Resultado Fatal
5.
Cureus ; 16(8): e66205, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39233932

RESUMEN

Gallbladder carcinoma (GBC) presents a significant clinical challenge due to its aggressive nature and often asymptomatic progression, resulting in late-stage diagnoses and a poor prognosis. Early detection and accurate staging are pivotal for improving patient outcomes, highlighting the critical role of advanced imaging techniques in oncological practice. Magnetic resonance spectroscopy (MRS) has emerged as a valuable non-invasive tool capable of assessing biochemical changes within tissues, including alterations in choline metabolism-a biomarker indicative of cell membrane turnover and proliferation. This review explores the application of MRS in evaluating choline levels in gallbladder carcinoma, synthesizing current literature to elucidate its potential in clinical settings. By analyzing studies investigating the correlation between choline levels detected via MRS and tumor characteristics, this review underscores MRS's role in enhancing diagnostic precision and guiding therapeutic decision-making. Moreover, it discusses the challenges and limitations associated with MRS in clinical practice alongside future research and technological advancement directions. Ultimately, integrating MRS into the diagnostic armamentarium for gallbladder carcinoma promises to improve early detection and treatment outcomes. This review provides insights into the evolving landscape of MRS in oncology, emphasizing its contribution to personalized medicine approaches aimed at optimizing patient care and management strategies for GBC.

6.
Cureus ; 16(8): e66055, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39224717

RESUMEN

Background Type 2 diabetes mellitus is a complex metabolic disorder associated with several complications that determine the quality of life of the patients. Health-related quality of life (HRQoL) is a measurable outcome of the self-perception of a patient's health which is affected due to age, lifestyle changes, medication, and treatment modalities. This study was undertaken to understand the impact of individual parameters of age, medication type and duration, diabetes-associated complications, and levels of glycated hemoglobin (HbA1c) on the quality of life (QoL) of the patient.  Methodology This single-center prospective, cross-sectional study was conducted at the Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, Bihar, India. Participants were recruited from the Outpatient Department of General Medicine, IGIMS. HRQoL was measured using a validated and reliable EuroQol 5-dimensions 5-levels (EQ-5D-5L) questionnaire developed by the EuroQol Research Foundation, along with the EuroQol-Visual Analogue Scale (EQ-VAS). The eligibility criteria included adult diabetic patients above 18 years of age with complete medical records, who had been treated at the outpatient department for a minimum of three months and could be interviewed. Results The results from this study show that 46% of the patients belonged to the age group of 45-65 years. The quality of health index scores and EQ-VAS scores significantly correlated with age (p-values: 1.11 e-4 and 3.09 e-5; <0.05). Of the subjects, 66.4%, 6.7%, and 26.8% were under oral hypoglycaemic agents (OHA), insulin, and both insulin with OHA medications respectively. HbA1C levels were statistically significantly correlated with mobility, self-care, usual activities, pain or discomfort, and anxiety or depression (p-value 0.032; <0.05), along with self-perception of the patient's health (p-value 0.00026; <0.05). Also, the perception of having slight problems in mobility, self-care, usual activities, pain or discomfort, and anxiety or depression was similar irrespective of gender (EQ-5D-5L score for males: 9.47 and females: 9.3). Despite suffering from diabetes-associated chronic complications, 60.5% of the subjects perceived their overall health to be good as indicated by the scores. Conclusion The self-perception of HRQoL concerning mobility, self-care, usual activities, pain or discomfort, and anxiety or depression was correlated with age, duration of anti-diabetic medication, and HbA1C level. Good mobility, self-care, and performing usual activities reduce anxiety or depression as opposed to age, pain, and discomfort. However, the subjects in this study cohort perceived overall good health in themselves in terms of EQ-VAS and 5D-5L scores, indicating effective diabetic care and management options available to them.

7.
Cureus ; 16(7): e65182, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39176350

RESUMEN

Leiomyosarcoma (LMS) is an extremely rare malignant pathology affecting smooth muscle cells, with the uterus being the predominant location of LMS. Its occurrence in the duodenum is rare, making it a diagnostic challenge for radiologists. Patients with duodenal LMS can present with very vague symptoms such as abdominal discomfort, loss of weight, or manifestations associated with internal gastrointestinal bleeding. In this case report, we have an 82-year-old female presenting with duodenal LMS, which is a very atypical location. An esophagogastroduodenoscopy and further workup revealed a duodenal mass, which was biopsied. The lump was identified as an LMS using immunohistochemistry and histopathology. Despite its rarity, it presents diagnostic and therapeutic challenges due to its nonspecific clinical manifestations and radiological findings. By exploring the existing literature and clinical insights, we aim to provide a comprehensive understanding of this rare condition, highlighting the need for interdisciplinary collaboration and tailored therapeutic strategies to diagnose and manage this disease entity effectively.

8.
Cureus ; 16(7): e64622, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39149630

RESUMEN

Traumatic foreign body aspiration (FBA) in adults is a rare yet potentially life-threatening event that requires prompt recognition and management to prevent adverse outcomes. While less common in adults compared to paediatric populations, traumatic FBA incidents often occur in occupational settings, post-trauma, or during high-risk activities, presenting with acute respiratory symptoms and varying degrees of airway obstruction. Diagnosis can be challenging due to the lack of classic symptoms and the potential for delayed presentation, necessitating a thorough history, a focused physical examination, and appropriate imaging techniques such as computed tomography (CT) and bronchoscopy. Prompt intervention is crucial to mitigating complications such as airway obstruction, pneumothorax, and respiratory compromise. Here, we describe an interesting case of a patient with a road traffic accident who aspirated two teeth and thought he lost them in this process. Surprisingly, two lost teeth were found after undergoing diagnostic procedures for mild shortness of breath, further causing aspiration pneumonitis.

9.
Cureus ; 16(5): e60846, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38910606

RESUMEN

Radiation dose optimization in radiology is a critical aspect of modern healthcare, aimed at balancing the necessity of diagnostic imaging with the imperative of patient safety. This comprehensive review explores the fundamental principles, techniques, and considerations in optimizing radiation dose to safeguard patients while preserving image fidelity. Beginning with acknowledging the inherent risks associated with medical radiation exposure, the review highlights strategies such as the As Low as Reasonably Achievable (ALARA) principle, technological advancements, and quality assurance measures to minimize radiation dose without compromising diagnostic accuracy. Regulatory guidelines and the importance of patient education and informed consent are also discussed. Through a synthesis of current knowledge and emerging trends, the review underscores the pivotal role of radiation dose optimization in radiology practice. Furthermore, it emphasizes the need for ongoing research and collaboration to advance dose reduction strategies, establish standards for radiation safety, and explore personalized dose optimization approaches. By prioritizing radiation dose optimization, healthcare providers can ensure the highest standards of patient care while minimizing potential risks associated with medical radiation exposure.

10.
Biochim Biophys Acta Mol Basis Dis ; 1870(6): 167235, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38744343

RESUMEN

Follicular ovarian cysts (FOCs) are characterized by follicles in the ovaries that are >20 mm in diameter and persist for >10 days without the corpus luteum, leading to anovulation, dysregulation of folliculogenesis and subfertility in humans and livestock species. Despite their clinical significance, the precise impact of FOCs on oocyte reserve, maturation, and quality still needs to be explored. While FOCs are observed in both human and livestock populations, they are notably prevalent in livestock species. Consequently, livestock species serve as valuable models for investigating the molecular intricacies of FOCs. Thus, in this study, using goat FOCs, we performed integrated proteomic, metabolomic and functional analyses to demonstrate that oocyte maturation is hampered due to increased reactive oxygen species (ROS) in FOCs follicular fluid (FF) via downregulation of glutathione peroxidase (GPX1), a critical antioxidant seleno enzyme required to negate oxidative stress. Notably, GPX1 reduction was positively correlated with the FF's decline of free selenium and selenocysteine metabolic enzymes, O-phosphoryl-tRNA (Sec) selenium transferase (SEPSECS) and selenocysteine lyase (SCLY) levels. Adding GPX1, selenocysteine, or selenium to the culture media rescued the oocyte maturation abnormalities caused by FOCs FF by down-regulating the ROS. Additionally, we demonstrate that substituting GPX1 regulator, Insulin-like growth factor-I (IGF-1) in the in vitro maturation media improved the oocyte maturation in the cystic FF by down-regulating the ROS activity via suppressing Non-sense-mediated decay (NMD) of GPX1. In contrast, inhibition of IGF-1R and the target of rapamycin complex 1 (mTORC1) hampered the oocyte maturation via NMD up-regulation. These findings imply that the GPX1 regulation via selenocysteine metabolism and the IGF-1-mediated NMD may be critical for the redox homeostasis of FF. We propose that GPX1 enhancers hold promise as therapeutics for enhancing the competence of FOCs oocytes. However, further in vivo studies are necessary to validate these findings observed in vitro.


Asunto(s)
Líquido Folicular , Glutatión Peroxidasa GPX1 , Homeostasis , Factor I del Crecimiento Similar a la Insulina , Quistes Ováricos , Oxidación-Reducción , Selenocisteína , Femenino , Líquido Folicular/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Animales , Quistes Ováricos/metabolismo , Quistes Ováricos/patología , Selenocisteína/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Cabras , Estrés Oxidativo , Glutatión Peroxidasa/metabolismo , Glutatión Peroxidasa/genética , Oocitos/metabolismo , Humanos , Folículo Ovárico/metabolismo , Folículo Ovárico/patología , Proteómica/métodos
11.
Cell Death Discov ; 10(1): 104, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38418811

RESUMEN

Death is the fate of postovulatory aged or unfertilized oocytes (POAO) in many animals. However, precise molecular mechanisms are yet to be discovered. Here, we demonstrate that increased amounts of reactive oxygen species (ROS), calcium ion (Ca+2) channels, and retrotransposon activity induce apoptosis, which in turn causes POAO death. Notably, suppression of ROS, Ca+2 channels, and retrotransposons delayed POAO death. Further, we found that the histone H4K12 and K16 acetylation increased via downregulation of NAD+ and NAD+ -dependent histone deacetylase SIRT3. Furthermore, adding NMN, sodium pyruvate, or CD38 inhibition delayed the death of postovulatory aged oocytes. Finally, we demonstrate the conservation of retrotransposon-induced DNA damage-dependent POAO death in higher-order vertebrates. Our findings suggest that POAO mortality is caused by cyclic cascade metabolic interactions in which low NAD+ levels increase histone acetylation by inhibiting histone deacetylases, resulting in an increase in retrotransposons, ROS, and Ca+2 channel activity and thus contributing to DNA damage-induced apoptosis.

12.
RSC Adv ; 14(10): 6762-6775, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38405071

RESUMEN

In this study, we employed density functional theory coupled with the full-potential linearized augmented plane-wave method (FP-LAPW) to investigate the structural, electronic, and magnetic properties of the Ti2FeAs alloy adopting the Hg2CuTi-type structure. Our findings demonstrate that all the examined structures exhibit ferromagnetic (FM) behaviour. By conducting electronic band structure calculations, we observed an energy gap of 0.739 eV for Ti2FeAs in the spin-down state and metallic intersections at the Fermi level in the spin-up state. These results suggest the half-metallic (HM) nature of Ti2FeAs, where the Ti-d and Fe-d electronic states play a significant role near the Fermi level. Additionally, the obtained total magnetic moments are consistent with the Slater-Pauling rule (Mtot = Ztot - 18), indicating 100% spin polarization for these compounds. To explore their optical properties, we employed the dielectric function to compute various optical parameters, including absorption spectra, energy-loss spectra, refractive index, reflectivity, and conductivity. Furthermore, various thermodynamic parameters were evaluated at different temperatures and pressures. The results obtained from the elastic parameters reveal the anisotropic and ductile nature of the Ti2FeAs compound. These findings suggest that Ti2FeAs has potential applications in temperature-tolerant devices and optoelectronic devices as a UV absorber.

13.
J Cell Physiol ; 239(4): e31201, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38284481

RESUMEN

Dynamic nuclear architecture and chromatin organizations are the key features of the mid-prophase I in mammalian meiosis. The chromatin undergoes major changes, including meiosis-specific spatiotemporal arrangements and remodeling, the establishment of chromatin loop-axis structure, pairing, and crossing over between homologous chromosomes, any deficiencies in these events may induce genome instability, subsequently leading to failure to produce gametes and infertility. Despite the significance of chromatin structure, little is known about the location of chromatin marks and the necessity of their balance during meiosis prophase I. Here, we show a thorough cytological study of the surface-spread meiotic chromosomes of mouse spermatocytes for H3K9,14,18,23,27,36, H4K12,16 acetylation, and H3K4,9,27,36 methylation. Active acetylation and methylation marks on H3 and H4, such as H3K9ac, H3K14ac, H3K18ac, H3K36ac, H3K56ac, H4K12ac, H4K16ac, and H3K36me3 exhibited pan-nuclear localization away from heterochromatin. In comparison, repressive marks like H3K9me3 and H3K27me3 are localized to heterochromatin. Further, taking advantage of the delivery of small-molecule chemical inhibitors methotrexate (heterochromatin enhancer), heterochromatin inhibitor, anacardic acid (histone acetyltransferase inhibitor), trichostatin A (histone deacetylase inhibitor), IOX1 (JmjC demethylases inhibitor), and AZ505 (methyltransferase inhibitor) in seminiferous tubules through the rete testis route, revealed that alteration in histone modifications enhanced the centromere mislocalization, chromosome breakage, altered meiotic recombination and reduced sperm count. Specifically, IOX1 and AZ505 treatment shows severe meiotic phenotypes, including altering chromosome axis length and chromatin loop size via transcriptional regulation of meiosis-specific genes. Our findings highlight the importance of balanced chromatin modifications in meiotic prophase I chromosome organization and instability.


Asunto(s)
Histonas , Profase Meiótica I , Procesamiento Proteico-Postraduccional , Espermatocitos , Animales , Masculino , Ratones , Cromatina/genética , Heterocromatina , Histonas/metabolismo , Meiosis , Espermatocitos/citología , Espermatocitos/metabolismo
14.
Eur J Obstet Gynecol Reprod Biol ; 292: 163-174, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38016417

RESUMEN

OBJECTIVE: To report the utilisation of maternal healthcare services and factors associated with adequate antenatal care and institutional childbirths among mothers in the tribal communities from nine districts in India. METHODS: Cross-sectional data were collected from 2636 tribal women who had a childbirth experience in the past 12 months. Socio-demographic, maternal healthcare services and health system-related details were collected. Multiple logistic regression analyses were done to identify factors associated with adequate antenatal care (receiving at least four antenatal care visits, the first visit being in the first trimester and receiving a minimum of 100 iron-folic acid tablets) and institutional childbirth (mother giving birth in a health facility). RESULTS: Only 23% of the mothers received adequate antenatal care. 82% were institutional childbirths. The logistic regression revealed that particularly vulnerable tribal groups (PVTGs), those lacking all-weather roads, and women of advanced age were at risk of inadequate antenatal care. Mother's education, health worker's home visits during pregnancy and reception of advice on antenatal care were significantly associated with the reception of adequate antenatal care. Having all-weather roads, and education of the mother and head of the household were positively associated with institutional childbirths, whereas PVTGs, children of birth order three or above, and working mothers were more likely to give childbirth at home. CONCLUSION: PVTGs are at risk of foregoing adequate antenatal care and are more likely to give childbirth at home. Having all-weather roads is a strong correlate of adequate maternal care. Outreach activities by the health workers are to be strengthened as they are positively and significantly associated with the reception of adequate antenatal care. Investing in education and other social determinants and addressing certain socio-cultural practices is important to improve maternal health.


Asunto(s)
Parto Domiciliario , Atención Prenatal , Niño , Femenino , Embarazo , Humanos , Estudios Transversales , Accesibilidad a los Servicios de Salud , Aceptación de la Atención de Salud , Instituciones de Salud
15.
J Obstet Gynaecol India ; 73(5): 406-413, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37916044

RESUMEN

Introduction: As the pregnancy advances beyond term, the risk of perinatal morbidity and mortality increases. Hence to prevent these complications associated with postterm pregnancy, induction of labor is done, as per our institution protocol between 40 and 41 weeks of gestation. Induction has its own drawback, so it is essential to identify the women with high chances of failure of induction of labor, to prevent the morbidities associated with induction failure. Aim: To study the role of ultrasonographic fetal adrenal gland enlargement for the prediction of success of labor induction among primigravida beyond 40 weeks gestation. Material and Methods: Low-risk primigravidas beyond 40 weeks gestation, scheduled for induction of labor, were enrolled for the study. Fetal adrenal gland dimensions were measured by using abdominal probe Philips HD 7XE and general electronics logiq P6 pro or any ultrasound machine equipped with 7.5-10 MHz linear array probe and 3.5-5 MHz curved array probe. Results: The fetal adrenal gland length, width and ratio were statistically significant between the successful versus failed induction groups. The cutoff fetal zone ratio > 0.36 for the prediction of successful induction of labor had 90% sensitivity, 89% specificity, 93% PPV and 75% NPV. Conclusion: Fetal zone enlargement (fetal zone ratio > 0.36) is a strong predictor of successful induction of labor as compared to TVL and Bishop's score. It can be used for screening the women, who are destined for induction failure, so that adverse effects of induction of labor can be avoided.

16.
Asian J Pharm Sci ; 18(5): 100845, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37881798

RESUMEN

RNA interference (RNAi) using small interfering RNA (siRNA) has shown potential as a therapeutic option for the treatment of arthritis by silencing specific genes. However, siRNA delivery faces several challenges, including stability, targeting, off-target effects, endosomal escape, immune response activation, intravascular degradation, and renal clearance. A variety of nanotherapeutics like lipidic nanoparticles, liposomes, polymeric nanoparticles, and solid lipid nanoparticles have been developed to improve siRNA cellular uptake, protect it from degradation, and enhance its therapeutic efficacy. Researchers are also investigating chemical modifications and bioconjugation to reduce its immunogenicity. This review discusses the potential of siRNA nanotherapeutics as a therapeutic option for various immune-mediated diseases, including rheumatoid arthritis, osteoarthritis, etc. siRNA nanotherapeutics have shown an upsurge of interest and the future looks promising for such interdisciplinary approach-based modalities that combine the principles of molecular biology, nanotechnology, and formulation sciences.

17.
Int Immunopharmacol ; 124(Pt A): 110894, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37678027

RESUMEN

BACKGROUND: Programmed cell death ligand-1 (PD-L1)is an antitumor immunity molecule and a great target to cure oral cancer; nonetheless, the limited success can be attributed to many complex pathways and tumor-related interferences. METHODS: In the present study, 150 human oral squamous cell carcinoma (OSCC) tissue samples, including 17 adjacent normals, 56 primary tumors, 47 invasive tumors, and 30 therapy-resistant (RT) samples, were included. The parental/cisplatin-resistant (CisR-SCC4/9) cells were utilized for overexpression (Jak1-3 wild type and catalytically inactive), knockdown (PD-L1 siRNA), targeting MAPK/PI3K/Jak-Stat pathways (SMIs) and checking microsomes. The expression of PD-L1, transcription factors (TFs), signaling pathways, survival/apoptosis, therapy resistance, and invasiveness-related molecules/their activity were determined by RT-PCR, Immunohistochemistry, Western blot, Gelatin Zymography, and MTT assay. RESULTS: Advanced OSCC tumors (invasive and drug-resistance), CisR-SCC4/9 cells, and secretory exosomes (CisR-SCC4/9) were found with increased PD-L1 expression. PD-L1 mRNA/protein showed a positive correlation with different TFs (AP1 > Stat3 > c-myc > NFκB) in tumor samples. The PD-L1 expression was more influenced by Jak-Stat/ MAPK-AP1 pathways over PI3K. The ectopic expression of Jak1-3 suggests Jak2 inducted PD-L1 level over Jak1/Jak3. Finally, PD-L1 directly supports survival (Bcl-xL, Bax, cleaved caspase-3), invasion (MMP2/9), and drug-resistance (ALDH-1A1/-3A1) program in OSCC through its link with several molecules. CONCLUSIONS: PD-L1 was regulated mainly by the Jak2-Stat3/ MAPK-AP1 pathway, and besides the routine immunological functions, it supports OSCC survival, invasion, and therapy resistance. PD-L1 can be used as an indicator of severity and can be targeted along with Jak2-Stat3/ MAPK-AP1 for a better outcome OSCC.

18.
iScience ; 26(10): 107817, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37744034

RESUMEN

Extracellular signal-regulated kinases 1 and 2 (ERK1/2) are dysregulated in many pervasive diseases. Recently, we discovered that ERK1/2 is oxidized by signal-generated hydrogen peroxide in various cell types. Since the putative sites of oxidation lie within or near ERK1/2's ligand-binding surfaces, we investigated how oxidation of ERK2 regulates interactions with the model substrates Sub-D and Sub-F. These studies revealed that ERK2 undergoes sulfenylation at C159 on its D-recruitment site surface and that this modification modulates ERK2 activity differentially between substrates. Integrated biochemical, computational, and mutational analyses suggest a plausible mechanism for peroxide-dependent changes in ERK2-substrate interactions. Interestingly, oxidation decreased ERK2's affinity for some D-site ligands while increasing its affinity for others. Finally, oxidation by signal-generated peroxide enhanced ERK1/2's ability to phosphorylate ribosomal S6 kinase A1 (RSK1) in HeLa cells. Together, these studies lay the foundation for examining crosstalk between redox- and phosphorylation-dependent signaling at the level of kinase-substrate selection.

19.
Am J Blood Res ; 13(2): 71-76, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37214645

RESUMEN

BACKGROUND: Limited literature was available on the pattern and determinants of mortality among inborn neonates in comparison to the out born ones. The study's goal was to investigate the patterns and risk factors for mortality among hospitalised, on-ventilator inborn and out born neonates. MATERIALS AND METHODS: It was an unmatched, case-control, pilot study conducted between January and December 2020 using information retrieved from the medical records of patients attending the neonatal intensive care unit (NICU) of a tertiary healthcare facility, namely Narayan Medical College & Hospital, situated in eastern India. RESULTS: Congenital pneumonia was the leading cause of death in inborn neonates, with an overall mortality rate of 33.4%. Meanwhile, the overall fatality rate for out born neonates was found to be 43.3%, with birth hypoxia being the most common cause. The only significant attribute affecting mortality in inborn neonates was low arterial blood gas (ABG) pH, whereas in out born neonates they were prematurity, thrombocytopenia, low ABG pO2, and high pCO2. Overall, new-borns with thrombocytopenia, low ABG pO2, and high pCO2 were observed to be at higher risk for mortality compared to others. CONCLUSION: The mortality rate of out born neonates was higher than inborn ones. The attributes affecting mortality were observed to be prematurity, thrombocytopenia, low ABG pH, pO2, and high pCO2.

20.
Trop Med Int Health ; 28(7): 530-540, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37246307

RESUMEN

OBJECTIVE: To report on vaccination status by 12 months of age among tribal children from nine districts of India. METHODS: Cross-sectional study of 2631 tribal women having a child aged 12 months or below from nine Indian districts with a considerable proportion of the tribal population. Socio-demographic details, reception of various vaccines by 12 months of age, mother's antenatal care utilisation and health system-related details were collected through a pre-tested, interviewer-administered questionnaire from mothers. Multiple logistic regression analysis was used to identify the factors associated with complete vaccination by 12 months of age. RESULTS: Only 52% of children were fully vaccinated by the age of 12 months among the tribal populations; 11% did not receive any vaccine, and 37% of the tribal children received some vaccines. The age-appropriate vaccination was unsatisfactory as only 75% of the infants received all birth dose vaccines, and only 60.5% received all doses by 14 weeks. Only 73% were vaccinated against measles. Illness of the child, home births and communication gaps concerning vaccination were the main reasons for an infant not being vaccinated appropriately. Frequency of health worker's visits to the village, hospital birth, reception of advice on vaccination and educational status of the head of the households were significantly associated with full vaccination status. CONCLUSION: A relatively low proportion of children were fully vaccinated among the tribal populations. Health systems factors, mainly the outreach services and advice by the health workers, were positively and significantly associated with a child being fully vaccinated by 12 months of age. Improving outreach services is crucial to improve vaccination coverage in tribal areas, and there is a need to address the social determinants in the long run.


Asunto(s)
Vacunación , Vacunas , Lactante , Femenino , Niño , Humanos , Embarazo , Estudios Transversales , Cobertura de Vacunación , Madres , Programas de Inmunización
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