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High-weight-percentage silicon (Si) in graphite (Gr) anodes face commercialization hurdles due to fundamental and interrelated challenges. Nevertheless, using the existing manufacturing line, the optimized Si/Gr ratio is the most efficient and valuable way to fabricate high-energy-density lithium-ion batteries (LIBs). Still, literature has not thoroughly examined the Si/Gr ratio. This study addresses this critical gap by systematically evaluating Si content (5-20 wt %) in commercial graphite. The goal is to optimize the Si/Gr ratio for exceptional specific capacity while mitigating inherent Si limitations like cyclic stability and first-cycle irreversible capacity loss. This work employs a multidirectional approach, including in situ electrochemical impedance spectroscopy for interface analysis, rate capability assessment (up to 3 C-rate), Li diffusion coefficient measurement, and thorough cyclic stability evaluation. Increasing the silicon (Si) weight percent from 10% to 15% in the Si15Gr75 composite anode resulted in significant improvements in the first lithiation and delithiation capacities by approximately 16.8% and 16.0%, respectively. The Si15Gr75 cell delivered a high initial Coulombic efficiency of roughly 82.9%, nearly equivalent to a pure graphite anode. Furthermore, the Si15Gr75 Li cell exhibited excellent cyclic stability at a current rate of 0.5 C, retaining about 60% of its capacity after 215 cycles. Additionally, full-cell testing against a commercial NMC622 cathode showcases excellent performance across various current rates (0.1-0.5 C). This study paves the way for the development of high-energy-density LIBs by providing valuable insights into the optimization of Si/Gr composite anodes for commercial viability.
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Ir-catalyzed arene C-H borylations (CHB) of anilines can be highly ortho selective by using a small B2eg2 (eg = ethane-1,2-diol) as the borylating reagent. Unfortunately, the products are prone to decomposition, and transesterification with pinacol is required prior to isolation. This work offers a solution by adjusting the size of the diboron reagent. Based on our evaluation, we conclude that B2bg2 (bg = butane-1,2-diol) achieves an optimal balance between CHB regioselectivity and stability for the borylated products.
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Purpose: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and impaired glucose homeostasis. In recent years, there has been growing interest in the role of hunger and satiety hormones such as ghrelin and leptin in the development and progression of T2DM. In this context, the present literature review aims to provide a comprehensive overview of the current understanding of how ghrelin and leptin influences food intake and maintain energy balance and its implications in the pathophysiology of T2DM. Methods: A thorough literature search was performed using PubMed and Google Scholar to choose the studies that associated leptin and ghrelin with T2DM. Original articles and reviews were included, letters to editors and case reports were excluded. Results: This narrative review article provides a comprehensive summary on mechanism of action of leptin and ghrelin, its association with obesity and T2DM, how they regulate energy and glucose homeostasis and potential therapeutic implications of leptin and ghrelin in managing T2DM. Conclusion: Ghrelin, known for its appetite-stimulating effects, and leptin, a hormone involved in the regulation of energy balance, have been implicated in insulin resistance and glucose metabolism. Understanding the complexities of ghrelin and leptin interactions in the context of T2DM may offer insights into novel therapeutic strategies for this prevalent metabolic disorder. Further research is warranted to elucidate the molecular mechanisms underlying these hormone actions and to explore their clinical implications for T2DM prevention and management.
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Context: Asthma is a chronic disease and its chronicity demands therapy with minimal harm and a good impact on the quality of life of asthmatics. Objective: This study evaluates the efficacy of structured yoga intervention integrated with routine care on asthma patients in improving their pulmonary function and quality of life. Design: The study was a single-blind (outcome assessor) hospital-based randomized controlled trial. Participants: Adults between 18 to 60 years, diagnosed with mild to moderate asthma as per Global Initiative for Asthma guidelines, with no exacerbation in the past month before screening, were included in the study. Intervention: A thirty-minute structured yoga intervention was delivered daily by a qualified yoga instructor through a virtual platform. Outcome measures: Questionnaires were utilized to assess the quality of life, and Breath-o-meter equipment was used to measure peak expiratory flow rate (PEFR). It was tested at baseline and then at 15 days, 45 days, and 90 days, whereas the quality of life was evaluated once a month. Statistical analysis: Intention to treat analysis was performed to compare the mean outcome between the yoga and control groups using an independent sample t test and repeated measures analysis of variance. Results: The yoga group significantly improved their PEFR and asthma-related quality of life scores compared to the control group (P < .001). A significant difference (F = 539.72, degree of freedom = 1.1618; P < .001) was detected between PEFR values at several time intervals (baseline, day 15, day 45, day 90) in the intervention group on repeated measures analysis of variance. The difference in quality-of-life scores between yoga and control was also statistically significant (P < .001), with an improvement in the quality-of-life domain of external stimuli. Conclusion: When combined with normal asthma treatment, the findings of this study show that structured yoga intervention integrated with routine care is more beneficial than traditional breathing exercises in increasing PEFR and quality of life.
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Asma , Calidad de Vida , Yoga , Humanos , Asma/terapia , Adulto , Femenino , Masculino , Persona de Mediana Edad , Método Simple Ciego , Adulto Joven , Adolescente , Terapia por Ejercicio/métodos , Ejercicio Físico/fisiología , Pruebas de Función Respiratoria , Resultado del TratamientoRESUMEN
Tetraalkoxydiborons can be easily prepared by acid-catalyzed reactions of tetrahydroxydiboron or its anhydride with trialkyl orthoformates. Addition of diols to these reaction mixtures afforded diboron diolates in high yield. In both cases, removal of volatile byproducts is all that is required for the isolation of the diboron. These methods constitute a convenient alternative to previous preparations from tetrakis (dimethylamino) diboron and tetrahydroxydiboron.
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BACKGROUND: Asthma is a chronic respiratory disease with symptoms of attacks of wheezing, shortness of breath, & tightness in the chest. Even with pre-existing treatment exacerbations go uncontrolled. OBJECTIVE: This study compared asthma control in yoga intervention versus non-yoga intervention group using Asthma Control Test. METHODS: In this randomized controlled trial, participants were allocated into two groups in 1:1 ratio - yoga intervention versus non-yoga intervention. Only outcome assessor was blinded. Sample size of 200 was calculated. Individuals between 18 and 60 years of age, diagnosed with mild to moderate asthma with no exacerbation in past one month were screened and enrolled. Per-protocol analysis was done to assess the outcomes of Asthma Control Test and expenditure.(CTRI/2020/02/023534) RESULTS: A total of 192 participants enrolled, 165 completed this study who were considered for final analysis. A significant difference (p < 0.001) was found between yoga and non-yoga exercise group at 13 weeks. Expenses were more in non-yoga exercise group. CONCLUSION: Our findings confirm that yoga exercise with routine medical care reduces exacerbations and improves asthma control.
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Alzheimer disease (AD) is the most common cause of dementia worldwide. Its clinical manifestations include a progressive loss of memory and other cognitive domains, as well as brain atrophy. An elevated homocysteine level (>15 µmol/L), known as hyperhomocysteinemia, is also an attributing risk factor for AD, vascular pathologies, and brain atrophy. Neuroimaging studies including T2-weighted magnetic resonance imaging scans revealed white matter hyperintensities in the periventricular and deep white matter, enlarged ventricles, widened sulci, and decreased white matter mass, which are features of aging, as well as cerebrovascular changes. This case series investigated changes in biochemical marker levels including serum homocysteine, folate, and vitamin B12, and the degree of atrophic variations in cortical-subcortical white matter in AD. The present study hypothesized that serum homocysteine levels might be used as a surrogate marker to screen for AD at an earlier stage.
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Enfermedad de Alzheimer , Atrofia , Biomarcadores , Encéfalo , Homocisteína , Imagen por Resonancia Magnética , Humanos , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/diagnóstico , Atrofia/patología , Homocisteína/sangre , Anciano , Masculino , Femenino , Biomarcadores/sangre , Encéfalo/patología , Encéfalo/diagnóstico por imagen , Anciano de 80 o más Años , Hiperhomocisteinemia/sangre , Hiperhomocisteinemia/diagnóstico , Ácido Fólico/sangre , Persona de Mediana Edad , Sustancia Blanca/patología , Sustancia Blanca/diagnóstico por imagen , Vitamina B 12/sangreRESUMEN
Purpose: This study focused on the genetic screening of Myocilin (MYOC), Cytochrome P450 family 1 subfamily B member 1 (CYP1B1), Optineurin (OPTN), and SIX homeobox 6 (SIX6) genes in a family with coexistence of primary congenital glaucoma (PCG) and juvenile open-angle glaucoma (JOAG). Methods: Sanger sequencing was used to examine the coding region of all four genes. Six different online available algorithms were used for the pathogenicity prediction of missense variant. Structural analysis was done using Garnier-Osguthorpe-Robson (GOR), PyMol, ChimeraX, and Molecular Dynamic (MD) Simulations (using Graphics Processing Unit (GPU)-enabled Desmond module of Schrödinger). Results: There were a total of three sequence variants within the family. All seven algorithms determined that a single mutation, G538E, in the OPTN gene is pathogenic. The loops connecting the strands became more flexible, as predicted structurally and functionally by pathogenic mutations. Mutations create perturbations and conformational rearrangements in proteins, hence impairing their functioning. Conclusion: In this study, we describe a North Indian family in which members were having JOAG and PCG due to a rare homozygous/heterozygous mutation in OPTN. The coexistence of two types of glaucoma within a single pedigree suggests that certain OPTN mutations may be responsible for the onset of different glaucoma phenotypes.
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Glaucoma de Ángulo Abierto , Glaucoma , Humanos , Mutación , Pruebas Genéticas , Linaje , Proteínas del Ojo/genética , Proteínas del Ojo/metabolismo , Análisis Mutacional de ADNRESUMEN
Glaucoma is a series of linked optic diseases resulting in progressive vision loss and total blindness due to the acquired loss of retinal ganglion cells. This harm to the optic nerve results in visual impairment and, ultimately, total blindness if left untreated. Primary open-angle glaucoma (POAG) is the most frequent variety within the large family of glaucoma. It is a multifaceted and heterogeneous condition with several environmental and genetic variables aiding in its etiology. By 2040, there will be 111.8 million glaucoma patients globally, with Asia and Africa accounting for the vast majority. The goal of this review is to elaborate on the role of genes (nuclear and mitochondrial) as well as their variants in the pathogenesis of POAG. PubMed and Google Scholar databases were searched online for papers until September 2022. Prevalence and inheritance patterns vary significantly across different ethnic and geographic populations. Numerous causative genetic loci may exist; however, only a few have been recognized and characterized. Further investigation into the genetic etiology of POAG is expected to uncover novel and intriguing causal genes, allowing for a more precise pathogenesis pattern of the disease.
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Glaucoma de Ángulo Abierto , Humanos , Glaucoma de Ángulo Abierto/genética , Trastornos de la Visión , Ojo , Ceguera , Biología MolecularRESUMEN
BACKGROUND: It is essential to investigate the prevalence of CYP2C19 alleles that affect drug metabolism. This study measures the allelic and genotypic frequencies of CYP2C19 loss-of-function (LoF) alleles CYP2C19∗2, CYP2C19∗3, and gain-of-function (GoF) alleles CYP2C19∗17 in the general population. METHODOLOGY: The study involved 300 healthy subjects between the ages of 18 and 85 recruited by simple random sampling. Allele-specific touchdown PCR was employed to identify the various alleles. The genotype and allele frequencies were calculated and checked for Hardy-Weinberg equilibrium. The phenotypic prediction of ultra-rapid metabolizer (UM = ∗17/∗17), extensive metabolizer (EM = ∗1/∗17, ∗1/∗1), intermediate metabolizer (IM = ∗1/∗2, ∗1/∗3, ∗2/∗17) and poor metabolizer (PM = ∗2/∗2, ∗2/∗3, ∗3/∗3) was made based on their genotype. RESULTS: The allele frequency of CYP2C19∗2, CYP2C19∗3, and CYP2C19∗17 was 0.365, 0.0033, and 0.18, respectively. The IM phenotype predominated with an overall frequency of 46.67%, including 101 subjects with ∗1/∗2, two subjects with ∗1/∗3, and 37 subjects with ∗2/∗17 genotype. This was followed by EM phenotype with an overall frequency of 35%, including 35 subjects with ∗1/∗17 and 70 subjects with ∗1/∗1 genotype. PM phenotype had an overall frequency of 12.67%, including 38 subjects with ∗2/∗2 genotype, and UM phenotype had an overall frequency of 5.67%, including 17 subjects with ∗17/∗17 genotype. CONCLUSION: Given the high allelic frequency of PM in the study population, a pre-treatment test to identify the individual's genotype may be recommended to decide the dosage, monitor the drug response, and avoid adverse drug reactions.
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Hidrocarburo de Aril Hidroxilasas , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Clopidogrel , Hidrocarburo de Aril Hidroxilasas/genética , Citocromo P-450 CYP2C19/genética , Frecuencia de los Genes , Genotipo , Alelos , Inhibidores de Agregación Plaquetaria/uso terapéuticoRESUMEN
OBJECTIVE: To investigate the relationship between progesterone (P4) levels on the day of hCG trigger and IVF outcomes. METHODS: This is a retrospective analysis of IVF cycles from January-2013 to December-2019 from a single center. Women (21-39 years) submitted to IVF treatment for various infertility factors were included, while donor oocyte cycles and cancelled cycles were excluded from the study. The primary outcome measure was live birth rate. RESULTS: A total of 2149 cycles were analyzed. Of these, 223 (10.38%) were in the low P4 group (<0.5 ng/ml), 1163 (54.12%) in the normal P4 group (0.5-1.5 ng/ml), and 763 (35.50%) in the high P4 group (>1.5ng/ml). The groups were comparable with respect to age, factor of infertility and baseline AMH. The antagonist protocol was significantly more prescribed to the high P4 group (p<0.001). Live birth rates were 14.4%, 21.6%, and 21% (p<0.001), respectively, in three groups. Univariate analysis found that total cetrotide dose, total number of retrieved and fertilized oocytes, total number of embryos formed, transferred, and vitrified, and P4 on the day of hCG (p<0.001) were statistically significant after adjusting for age and BMI. In multivariate logistic regression after adjusting for age and BMI, only high P4 (aOR:0.60; p<0.001), total cetrotide dose (aOR: 0.82; p<0.001), and total utilizable embryos (aOR:1.11; p=0.029) were statistically significant. CONCLUSIONS: Having an elevated serum progesterone level on the day of hCG trigger was associated with lower pregnancy rates, but this is still not a robust marker to predict live births. More good quality evidence is needed.
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Gonadotropina Coriónica , Fertilización In Vitro , Progesterona , Femenino , Humanos , Embarazo , Gonadotropina Coriónica/uso terapéutico , Infertilidad/terapia , Progesterona/sangre , Estudios Retrospectivos , Adulto Joven , Adulto , Resultado del TratamientoRESUMEN
Retinitis pigmentosa (RP) belongs to a group of pigmentary retinopathies. It is the most common form of inherited retinal dystrophy, characterized by progressive degradation of photoreceptors that leads to nyctalopia, and ultimately, complete vision loss. RP is distinguished by the continuous retinal degeneration that progresses from the mid-periphery to the central and peripheral retina. RP was first described and named by Franciscus Cornelius Donders in the year 1857. It is one of the leading causes of bilateral blindness in adults, with an incidence of 1 in 3000 people worldwide. In this review, we are going to focus on the genetic heterogeneity of this disease, which is provided by various inheritance patterns, numerosity of variations and inter-/intra-familial variations based upon penetrance and expressivity. Although over 90 genes have been identified in RP patients, the genetic cause of approximately 50% of RP cases remains unknown. Heterogeneity of RP makes it an extremely complicated ocular impairment. It is so complicated that it is known as "fever of unknown origin". For prognosis and proper management of the disease, it is necessary to understand its genetic heterogeneity so that each phenotype related to the various genetic variations could be treated.
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Retinitis Pigmentosa , Ceguera , Humanos , Fenotipo , Retina , Retinitis Pigmentosa/diagnóstico , Retinitis Pigmentosa/genéticaRESUMEN
A bidentate monoanionic ligand system was developed to enable iridium catalyzed C(sp3)-H activation borylation of N-methyl amides. Borylated amides were obtained in moderate to good isolated yields, and exclusive mono-borylation allowed the amide to be the limiting reagent. Selectivity for C(sp3)-H activation was demonstrated in the presence of sterically available C(sp3)-H bonds. Competitive kinetic isotope studies revealed a large primary isotope effect, implicating C-H activation as the rate limiting step.
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Ovarian hyperstimulation syndrome (OHSS) is an entity associated with controlled ovarian stimulation (COS) in assisted reproduction. It presents a great challenge for clinicians concerning a timely diagnosis and intervention, because it is a life-threatening condition. We came across a rare case of late onset severe OHSS, which lasted till 19 weeks of gestation (POG) with diagnostic challenge in which the patient had hemorrhagic ascites post embryo transfer, and transaminitis. The case was managed effectively with repeated paracentesis along with replacement therapy, and the transaminitis was also gradually resolved. Severe OHSS may follow an unusually prolonged course associated with transaminitis. Our case suggests that it is crucial to distinguish between the nature and etiology of transaminitis along with OHSS, and other pathologies like drug induced transaminitis should also be kept in mind.
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Síndrome de Hiperestimulación Ovárica , Femenino , Humanos , Síndrome de Hiperestimulación Ovárica/diagnóstico , ParacentesisRESUMEN
OBJECTIVE: To study the knowledge, attitude, and intentions towards fertility preservation (FP) in cancer patients among healthcare workers (HCWs) in Northern India. METHODS: The survey discussed in this study was a 23-item structured questionnaire on oncofertility designed based on previous studies on the topic. A link to the questionnaire was sent through WhatsApp to healthcare workers involved in the care of cancer patients. Their responses were analyzed subsequently. RESULTS: More than a third (37.7%) of the 750 HCWs contacted answered the questionnaire. The group included gynecologists, surgeons, and oncologists. Although 90% of the respondents were aware of the harmful effects of cancer therapy on ovarian function, 76% claimed they had only partial knowledge about fertility preservation (FP). Only a fourth of the respondents were aware of the time needed for oocyte cryopreservation and a third had knowledge of the number of semen samples required for FP. Among HCWs involved in the care of young cancer patients, only 50% reported that they had referred patients for FP. The most common reason for not referring patients for FP was lack of knowledge about FP (43%). More than 90% claimed they wanted to improve their knowledge about oncofertility through continued medical education programs and seminars. CONCLUSIONS: The study emphasizes the need for establishing well-structured networks to improve knowledge about FP among HCWs, so that cancer patients are offered the chance of using their gametes to have children after they have been cured from cancer.
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Preservación de la Fertilidad , Neoplasias , Conocimientos, Actitudes y Práctica en Salud , Personal de Salud , Humanos , India , Intención , Neoplasias/complicaciones , Neoplasias/terapiaRESUMEN
Objective Pregnancy with an autoimmune disorder is faced with several risks for mother and fetus. The aim of the present study is to analyze the course and outcome of pregnancy in women with autoimmune disorders (AIDs). Methods A retrospective cohort study was conducted at a tertiary care teaching hospital. The hospital records of 153 pregnancies with autoimmune disorders and 1095 low-risk pregnant women who served as controls were reviewed. An adverse perinatal outcome was defined as the presence of any obstetric complications, including preeclampsia, eclampsia, abruption, antepartum hemorrhage (APH), prematurity, fetal growth restriction (FGR), intrauterine death (IUD), intrapartum event, mode of delivery, birth weight, neonatal intensive care unit (NICU) stay, or disease-specific neonatal complications. For all statistical tests with two-tailed probability, p<0.05 was considered statistically significant. Results A high incidence of adverse perinatal outcomes was observed in all women with AIDs when compared with age-matched controls. The highest incidence of adverse perinatal outcomes was observed in women with Takayasu's arteritis. The incidence of abortions was more in women with antiphospholipid antibody syndrome (APS) and Grave's disease (22.2% and 33.3%, respectively). The incidence of prematurity, fetal growth restriction (FGR), and low birth weight were highest in women with systemic lupus erythematosus (SLE). Pregnancy with myasthenia gravis and rheumatoid arthritis did not have any significant adverse impact on pregnancy outcomes. Conclusion We found a strong association between autoimmune disorders and obstetric complications. The multidisciplinary team approach and pre-pregnancy optimization of the disease improve maternal and fetal outcomes.
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In the present study, sewage sludge (SS) was used to synthesize activated carbon (AC) which was further utilized as adsorbent for the removal of ciprofloxacin (CPX) from synthetic wastewater. The adsorbent was prepared by chemical activation method using ZnCl2 as activating agent. Design of experiments (DOE) approach was explored to determine the optimum operating conditions for the synthesis of AC and CPX removal from the wastewater. The optimum conditions for AC synthesis (i.e., carbonization temperature = ~500°C, activation time = 30 min, and impregnation ratio = 2.26) were decided based on results for three response parameters, that is, adsorbent yield, methylene blue removal, and iodine number. The synthesized adsorbent showed ~93% CPX removal (initial CPX concentration = 100 mg/L) at the following optimum conditions: adsorbent dose = 1.31 g/L, pH = 7 and reaction time = 12 h. Langmuir isotherm model was best fit to the equilibrium adsorption data (maximum adsorption capacity of SS derived AC = 102 mg/g) whereas pseudo-second order model showed the best fit to adsorption kinetic data (adsorption capacity = 77.5 mg/g). An effort was also made to reduce fresh water requirement for adsorbent synthesis by recycling the wastewater produced during chemical activation of SS. PRACTITIONER POINTS: Experiment design approach was used for optimization of adsorbent preparation conditions and CPX removal conditions by waste derived adsorbent. Sewage sludge derived adsorbent had BET surface area of 564 m2 /g which is comparable to commercial activated carbon. 93% CPX adsorption with the sewage sludge derived adsorbent at optimum conditions. Langmuir model better suited the CPX adsorption data. Wastewater recycling and ZnO recovery from wastewater produced during adsorbent synthesis were performed.
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Aguas del Alcantarillado , Contaminantes Químicos del Agua , Adsorción , Ciprofloxacina , Concentración de Iones de Hidrógeno , Cinética , Aguas Residuales , Contaminantes Químicos del Agua/análisisRESUMEN
OBJECTIVE: To study donor and recipient factors affecting cumulative live birth rate (CLBR) in oocyte donor IVF (OD- IVF) cycles. METHODS: The present retrospective study was conducted at the ART center of a tertiary care referral hospital after ethical approval, and included all OD-IVF cycles done between January 2014 - October 2019. Donor parameters included age, body mass index (BMI), ovarian reserve markers, serum estradiol (E2) on trigger day, and number of total/grade 1 oocytes; recipient parameters included age and BMI. The primary outcome was CLBR resulting from one complete donor-recipient (D-R) cycle through fresh/frozen embryo transfer. Secondary outcomes included number of total and grade 1 oocytes, fertilization rate, cleavage rate and clinical pregnancy rate (CPR). RESULTS: We analyzed 262 D-R cycles for donor characteristics and 260 cycles for CLBR. The mean age of the recipients was 35.20±4.05, and for donors it was 25.29±2.03 years. The CPR and CLBR per started cycle was 60% and 55.7%, respectively. Recipient BMI and grade 1 oocytes were found to be independent predictors of CLBR in multivariate analysis. As the number of grade 1 oocytes increased, the likelihood of live births increased by 10% (95% CI, 1.04 - 1.32, p=0.008). Recipient BMI ≥25kg/m2 reduced the chances of CLBR by 50% (95% CI, 0.27 - 0.81, p=0.007). CONCLUSIONS: Number of grade 1 oocytes and recipient BMI significantly affect CLBR in OD-IVF cycles. Recipients with BMI ≥25kg/m² may be advised to lose weight and improve CLBR likelihood.
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Tasa de Natalidad , Recuperación del Oocito , Femenino , Fertilización In Vitro , Humanos , Nacimiento Vivo/epidemiología , Análisis Multivariante , Oocitos , Embarazo , Estudios RetrospectivosRESUMEN
CONTEXT: Vulvar carcinoma accounts for 3%-5% of gynecologic malignancies. The past three decades has observed changes in the trends of clinical characteristics and treatment modalities used in managing this disease. AIMS: The aim of the present study is to analyze the clinic-pathological characteristics and survival of women with squamous cell carcinoma vulva who underwent primary surgical management. SETTINGS AND DESIGN: This was a retrospective observational study. SUBJECTS AND METHODS: Case records of 30 consecutive patients with squamous cell carcinoma of vulva during the period of 2010-2016 were retrospectively reviewed and their clinical profile, treatment details, complications, and survival were analyzed. STATISTICAL ANALYSIS USED: Kaplan-Meier survival analysis, followed by logrank test, was used for survival outcome, and Cox proportional hazard model was used to assess significant risk factors. RESULTS: The mean age of patients was 58 ± 12.9 years. The most common symptom was growth over vulva (73.3%), itching (63.3%), and nonhealing vulval ulcer (26.6%). The most common site for disease was labia majora. The surgical treatments ranged from wide local excision to radical vulvectomy. Postoperative adjuvant therapy was required for 16 patients. The median (95% confidence interval [CI]) overall survival was 27 (21.7-32.2) months. Five-year survival probability for early-stage disease (I + II) was 49% (95% CI: 12.9, 78.4) and for advanced disease (III + IV) was 24.8% (95% CI: 4.8, 42.6). Lymph node-positive status was found to have a significant impact on survival (hazard ratio of 4.9 [95% CI: 1.15-21.02, P = 0.02]). CONCLUSIONS: Despite advances in detection and management modalities, the survival for vulval malignancies has not improved.
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Carcinoma de Células Escamosas/patología , Recurrencia Local de Neoplasia/patología , Neoplasias de la Vulva/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/cirugía , Femenino , Humanos , Metástasis Linfática , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Neoplasias de la Vulva/cirugíaRESUMEN
The levels of different molecules in the cell are rhythmically cycled by the molecular clock present at the cellular level. The circadian rhythm is closely linked to the metabolic processes in the cells by an underlying mechanism whose intricacies need to be thoroughly investigated. Nevertheless, Nrf2 has been identified as an essential bridge between the circadian clock and cellular metabolism and is activated by the by-product of cellular metabolism like hydrogen peroxide. Once activated it binds to the specific DNA segments and increases the transcription of several genes that play a crucial role in the normal functioning of the cell. The central clock located in the suprachiasmatic nucleus of the anterior hypothalamus synchronizes the timekeeping in the peripheral tissues by integrating the light-dark input from the environment. Several studies have demonstrated the role of circadian rhythm as an effective tumor suppressor. Tumor development is triggered by the stimulation or disruption of signaling pathways at the cellular level as a result of the interaction between cells and environmental stimuli. Oxidative stress is one such external stimulus that disturbs the prooxidant/antioxidant equilibrium due to the loss of control over signaling pathways which destroy the bio-molecules. Altered Nrf2 expression and impaired redox balance are associated with various cancers suggesting that Nrf2 targeting may be used as a novel therapeutic approach for treating cancers. On the other hand, Nrf2 has also been shown to enhance the resistance of cancer cells to chemotherapeutic agents. We believe that maximum efficacy with minimum side effects for any particular therapy can be achieved if the treatment strategy regulates the circadian rhythm. In this review, we discuss the various molecular mechanisms interlinking the circadian rhythm with the Nrf2 pathway and contributing to breast cancer pathogenesis, we also talk about how these two pathways work in close association with the cell cycle which is another oscillatory system, and whether this interplay can be exploited to overcome drug resistance during chemotherapy.