Genome-wide association study (GWAS) identified PCOS susceptibility variants and replicates reported risk variants.

BACKGROUND: Genetic predisposition and environmental factors are considered risk factors for polycystic ovary syndrome (PCOS). Genome-wide association studies (GWAS) have been reported from various subpopulations to evaluate SNPs associated with PCOS risk. No PCOS-associated GWAS study has been reported from India so far. PURPOSE: The current study was conducted to identify the PCOS-susceptible loci among the North Indian population and to validate the significant loci reported by previous GWAS studies. METHODS: A total of 272 participants with 134 PCOS patients and 138 age-matched healthy controls were recruited. Genomic DNA was isolated and genotyped by using Infinium Global Screening Array v3.0 microchip considering HWE 10e-5 statistically significant. RESULTS: A total of fifteen markers have been identified as candidate PCOS risk factors. Only two SNPs, namely rs17186366 and rs11171739 have been identified through replication analysis while comparing the previously reported PCOS GWAS data. In-silico analysis was performed to study the functional impact of identified significant genes for gene ontology, pathways related to gene set, and cluster analysis to determine protein-protein interaction among genes or gene products. CONCLUSION: The study suggests that multiple variants play an important role in PCOS pathogenesis and emphasizes the importance of further genetic studies among Indian subpopulations. The study also validates two previously reported SNPs in the Indian population. What this study adds to clinical work Study summarizes the importance of candidate gene markers validated by replication and in-silico functional study, significantly involved in PCOS pathogenesis in the studied population. These markers can be used in the future as diagnostic markers for clinical phenotype identification.

Investigation of the Association of Serum Trace Elements Concentrations and Serum Biochemical Parameters with the Risk of Polycystic Ovary Syndrome: a Case-Control Study.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrinological syndrome characterized by hyperandrogenism of ovarian origin and is often considered a predisposing factor for metabolic disorders. The objective of the study was to investigate serum levels of (a) trace elements (copper (Cu), zinc (Zn), magnesium (Mg), selenium (Se), iron (Fe), chromium (Cr), and manganese (Mn)); and (b) biochemical parameters (glucose, cholesterol, triglycerides, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), albumin, total protein, creatinine, and C-reactive protein (CRP) with risk of PCOS. Another objective was to explore the relationship between serum trace elements and biochemical variables. Serum trace elements were estimated by inductively coupled plasma mass spectrometry (ICP-MS) and biochemical parameters were estimated by colorimetric methods in 99 PCOS cases and 82 controls. Linear and non-linear associations of serum variables with PCOS risk were studied under logistic, probit, GAM, and BKMR model. Statistical analyses were performed using IBM SPSS 22.0 and R package version 4.2.1. All studied serum trace elements (except Zn) are significantly associated with PCOS. Combined effect analysis revealed Mg-Se and Fe-Cu association with PCOS risk. A significant association of cholesterol, HDL-C, LDL-C, CRP, and albumin was observed. Furthermore, linear regression analysis suggests an association between Mg-Cu and Mg-Fe-Mn with HDL-C; Fe and Cr-Cu with albumin; and Cu-Se with cholesterol and LDL-C both.

Genetic Variants of Steroidogenesis and Gonadotropin Pathways and Polycystic Ovary Syndrome Susceptibility: A Systematic Review and Meta-analysis.

Genetic variants are predisposing factors to polycystic ovary syndrome (PCOS), a multifactorial condition that often gets triggered due to various environmental factors. The study investigates the association of the variants of genes that are involved in the steroidogenesis pathway or gonadotropin pathway with the risk of PCOS. Appropriate keywords for predetermined genes were used to search in PubMed, Google Scholar, Science Direct, and Central Cochrane Library up to January 11, 2023. PROSPERO (CRD42022275425). Inclusion criteria: (a) case-control study; (b) genotype or allelic data. Exclusion criteria were: (a) duplicate studies; (b) clinical trials, systematic reviews, meta-analysis or conference abstract, case reports; (c) other than the English language; (d) having insufficient data; e) genetic variants for which meta-analysis has been reported recently and does not have a scope of the update. Various genetic models were applied as per data availability. Overall 12 variants of 7 genes were selected for the analysis. Relevant data were extracted from 47 studies which include 10,584 PCOS subjects and 16,150 healthy controls. Meta-analysis indicates a significant association between TOX3 rs4784165 [ORs = 1.08, 95% CI (1.00-1.16)], HMGA2 rs2272046 [ORs = 2.73, 95% CI (1.97-3.78)], YAP1 rs1894116 [OR = 1.22, 95% CI (1.13-1.33)] and increased risk of PCOS. Whereas FSHR rs2268361 [ORs = 0.84, 95% CI (0.78-0.89)] is associated with decreased PCOS risk. When sensitivity analysis was carried out, the association became significant for CYP19 rs700519 and FSHR rs6165 under an additive model. In addition, C9Orf3 rs3802457 became significantly associated with decreased PCOS risk with the removal of one study. Insignificant association was observed for CYP19A (rs2470152), FSHR (rs2349415, rs6166), C9Orf3 (rs4385527), GnRH1 (rs6185) and risk of PCOS. Our findings suggest association of CYP19A (rs700519), TOX3 (rs4784165), HMGA2 (rs2272046), FSHR (rs6165, rs2268361), C9orf3 (rs3802457), and YAP1 (rs1894116) with risk for PCOS.

A Case Report of Valacyclovir-Associated Neurotoxicity in End-Stage Renal Disease: A Rare but Preventable Side Effect.

Neurotoxicity can develop as a side effect of valacyclovir in patients with renal disease, especially without a renally adjusted dose. We present a 56-year-old female with end-stage renal disease (ESRD) on hemodialysis (HD) who presented to the emergency room (ER) with agitation and confusion and was found to have valacyclovir-associated neurotoxicity (VAN). Five days prior, she had been prescribed the standard treatment of 500 mg valacyclovir twice daily for three days for herpes simplex virus-1 (HSV-1); however, her creatinine clearance was low enough to require a renally adjusted dose. Her condition was worsened from missing a dialysis session due to acute confusion. She was treated with three days of hemodialysis sessions. Improvement in mentation and agitation was observed after the second day of hemodialysis, and a complete resolution of symptoms and return to cognitive baseline occurred two days later. There are reports of daily hemodialysis shortening the neurotoxicity period and resulting in a faster return to normal mentation. This case is important as the dose of valacyclovir must be adjusted in those with kidney disease.

Genetic variants of metabolism and inflammatory pathways, and PCOS risk -Systematic review, meta-analysis, and in-silico analysis.

IMPORTANCE: Identification of genetic risk factors for PCOS susceptibility. OBJECTIVE: To identify genetic risk variants of the genes involved in metabolic or inflammatory pathways. DATA SOURCES: Relevant literature was identified and extracted from PubMed, Central Cochrane Library, Google Scholar, and Science Direct by using a set of keywords related to pre-determined genes up to 06 May 2023. Study selection and synthesis: PRISMA guidelines were followed to design the protocol which is registered in PROSPERO (CRD42023422501). Pooled odds ratio (OR) and 95% confidence interval (95% CI) for different gene variants were calculated under different genetic models (dominant model, recessive model, additive model, and allele model) by using Review Manager software 4.2. MAIN OUTCOMES: Metabolic genetic variants FTO rs9939609, IL-6 rs1800795 and CAPN10 rs3842570, rs2975760, and RAB5B rs705702 are associated with PCOS risk. RESULTS: Forty-four relevant articles have been identified for genes involved in metabolic (n = 23) or inflammatory pathways (n = 21). There is a significant association (p < 0.05) of IL-6 rs1800795 and FTO rs9939609 with increased risk.CAPN10 rs2975760 Ins allele is suggested as a protective factor among only the non-Asian population. Also, a significant association of CAPN10 rs2975760 and RAB5B rs705702 with increased risk among the Asian population is suggested. However, no significant association could be found between CAPN10 rs3792267, rs5030952, and SUMO1P1 rs2272046, and the risk of PCOS in any of the subpopulations analysed. In silico analysis suggests the deleterious effect of IL-6 rs1800795. CONCLUSION: and relevance: The study suggests the role of various genetic variants for genetic predisposition to PCOS among different subpopulations.

Efficacy of Artificial Oocyte Activation in Improving the Reproductive Outcome in Poor Responders: A Single Centre Cohort Study.

Objective: Achieving pregnancy in poor ovarian response patients is a challenge. Failed fertilization after ICSI, despite normal semen parameters is due to defects in oocyte activation. In-vitro activation of oocytes using Ca+2 agents can be useful in increasing the fertilization rates in these patients. This study aimed to evaluate the efficacy of artificial oocyte activation by calcium ionophores in poor responders in improving fertilization, cleavage, implantation and clinical pregnancy rates. Materials and methods: This is a prospective, cohort study conducted on 120 patients having poor ovarian response, (POSEIDON criteria) undergoing in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment at Southend Fertility and IVF, New Delhi from 1st August 2019 to 31st March 2020. Exclusion criterion was patients with partners with abnormal semen parameters. After OPU patients were randomized into two groups, study group (n=50) underwent ICSI-AOA (ICSI followed by artificial oocyte activation) using calcium ionophore- GM508 Cult-Active Solution) while the controls (n=57) were subjected to ICSI only. Results: Comparison of ICSI-AOA and ICSI groups showed: (i) number of fertilized oocytes - 2.42 vs. 2.16, p = 0.049 (ii) No. of cleavage stage embryos 2.32 vs. 1.96, p = 0.008 (iii) No. of grade A embryos 1.52 vs. 1.04, p = 0.009 (iv) fertilization rate - 89.00% vs. 83.04%, p = 0.093 (v) cleavage rate - 96.33% vs. 92.55%, p = 0.165 (vi) implantation rate - 27.14% vs. 11.74%, p = 0.098 (vii) clinical pregnancy rate - 34.3% vs. 20.5%, p = 0.167. Conclusion: The number of fertilized oocytes, grade A embryos and cleavage stage embryos formed after ICSI-AOA were statistically significantly more than ICSI. ICSI-AOA has not shown improvement in fertilization, cleavage, implantation and clinical pregnancy rate. From the present study the conclusive evidence cannot be drawn due to small sample size hence further studies are needed on a larger population.

Carcinoma vulva: Ten years experience in a teaching institution of North India.

Introduction: Vulvar carcinoma is primarily a disease of post-menopausal women. Surgery is a primary treatment strategy. Chemotherapy and radiotherapy are a part of multimodal therapy. Presently, there is a shift towards neoadjuvant chemotherapy or radiotherapy so as to decrease the surgical morbidities. Objective: To study the surgical outcome and prognostic factors in Ca vulva patients. Methodology: A retrospective analysis of 19 vulvar cancer patients, surgically treated at a teaching institution of Punjab (2009-2019). Results: Mean age of the patients was 60.95 years. Ulcerative swelling (89.5%) over labia majora (73.7%) was the main presenting symptom. Radical vulvectomy-bilateral IFLN dissection was performed in 74% patients, hemivulvectomy-unilateral IFLN dissection in 21% patients and wide local excision in one patient. Squamous cell carcinoma was detected in all, and one had verrucous carcinoma. Thirty-seven per cent patients had FIGO stage III disease, 31.5% - stage II and 31.5% - stage I. On HPE, 78.57% (11/14) patients had positive nodes and two had ECS. Only 5/9 (55.5%) cases could receive PORT. Seven patients defaulted follow-up. Two developed nodal metastasis, and seven women developed recurrence. One patient with regional recurrence faced demise during RT course. In 10/19 regular follow-up patients, four are alive and disease free, five patients are on palliative chemoradiation, and one is undergoing adjuvant radiotherapy for regional recurrence. Estimated 5-year overall survival is 83.33%. Conclusion: Tumour stage, nodal positivity and nodal ECS were poor prognostic factors. Radical surgery-extensive groin node dissection causes significant morbidity; hence, studies evaluating the role of neoadjuvant treatment are needed so as to modify current treatment practices. HPV vaccination as a preventive measure and a thorough and extensive evaluation of patients with suspicious signs in vulvar disease is needed.

A Study to Assess Symptom Profile and Break Through Infections Among Health Care Workers Post Covid Vaccination at Tertiary Care Health Facility.

Introduction: Breakthrough infections in fully vaccinated persons pose a major challenge to the ongoing vaccine campaign against SARS-CoV-2 globally. Objectives: To investigate the occurrence of breakthrough infections and the association of Covid symptoms with the vaccination status of health care workers (HCWs). Material and Methods: Done in Government Medical College, Patiala among Covid-positive HCWs who have received one or both doses of Covid vaccine, using pretested semi-structured validated Proforma and telephonic interview from April 1, 2021 to June 15, 2021. Results: Among 3388 HCWs, 115 vaccinated HCWs (1st or 2nd dose) became Covid positive. Among vaccinated Covid positive HCWs, 54 received the first dose and 61 both doses. Breakthrough infections (≥14 days post 2nd dose) occurred in 4.6% (47 of 1021) HCWs. The vaccine is significantly protective as shown by an odds ratio of 0.27; thus, vaccinated HCWs are 73% less likely to get Covid infection as compared to non-vaccinated HCWs. There was no statistically significant difference between symptom profiles of cases whether they took one or both doses of vaccine, except headache. Only tiredness and headache were reported significantly higher in the unvaccinated group in comparison to vaccinated HCWs. Conclusion: Research is needed on tracking the immune response and viral genomic sequence of samples of vaccinated Covid-positive HCWs to have constant vigilance on remerging new strains of the SARS-CoV-2.

Serine biosynthesis as a novel therapeutic target for dilated cardiomyopathy.

AIMS: Genetic dilated cardiomyopathy (DCM) is a leading cause of heart failure. Despite significant progress in understanding the genetic aetiologies of DCM, the molecular mechanisms underlying the pathogenesis of familial DCM remain unknown, translating to a lack of disease-specific therapies. The discovery of novel targets for the treatment of DCM was sought using phenotypic sceening assays in induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) that recapitulate the disease phenotypes in vitro. METHODS AND RESULTS: Using patient-specific iPSCs carrying a pathogenic TNNT2 gene mutation (p.R183W) and CRISPR-based genome editing, a faithful DCM model in vitro was developed. An unbiased phenotypic screening in TNNT2 mutant iPSC-derived cardiomyocytes (iPSC-CMs) with small molecule kinase inhibitors (SMKIs) was performed to identify novel therapeutic targets. Two SMKIs, Gö 6976 and SB 203580, were discovered whose combinatorial treatment rescued contractile dysfunction in DCM iPSC-CMs carrying gene mutations of various ontologies (TNNT2, TTN, LMNA, PLN, TPM1, LAMA2). The combinatorial SMKI treatment upregulated the expression of genes that encode serine, glycine, and one-carbon metabolism enzymes and significantly increased the intracellular levels of glucose-derived serine and glycine in DCM iPSC-CMs. Furthermore, the treatment rescued the mitochondrial respiration defects and increased the levels of the tricarboxylic acid cycle metabolites and ATP in DCM iPSC-CMs. Finally, the rescue of the DCM phenotypes was mediated by the activating transcription factor 4 (ATF4) and its downstream effector genes, phosphoglycerate dehydrogenase (PHGDH), which encodes a critical enzyme of the serine biosynthesis pathway, and Tribbles 3 (TRIB3), a pseudokinase with pleiotropic cellular functions. CONCLUSIONS: A phenotypic screening platform using DCM iPSC-CMs was established for therapeutic target discovery. A combination of SMKIs ameliorated contractile and metabolic dysfunction in DCM iPSC-CMs mediated via the ATF4-dependent serine biosynthesis pathway. Together, these findings suggest that modulation of serine biosynthesis signalling may represent a novel genotype-agnostic therapeutic strategy for genetic DCM.

Resveratrol attenuates arsenic-induced cognitive deficits via modulation of Estrogen-NMDAR-BDNF signalling pathway in female mouse hippocampus.

BACKGROUND: Chronic inorganic arsenic (iAs) exposure induces deleterious effects on CNS including oxidative stress, cognitive deficits and altered brain neurochemistry. Little is known about the association between iAs and estrogen receptor expression in brain regions. AIMS AND OBJECTIVES: Owing to the neuroprotective and estrogenic activities of resveratrol (RES), we examined the combined effects of arsenic trioxide (As2O3) and RES on neurobehavioural functions, estrogen signalling and associated neurochemical changes in mouse hippocampus. MATERIALS AND METHODS: As2O3 alone (2 and 4 mg/kg bw) or along with RES (40 mg/kg bw) was administered orally for 45 days to adult female mice. From days 33 to 45, open field, elevated plus maze and Morris water maze tests were conducted to evaluate locomotion, anxiety and learning and memory. On day 46, animals were euthanized and brain tissue and hippocampi obtained therefrom were processed for atomic absorption spectrophotometry and western blotting respectively. RESULTS: As2O3 alone exposure resulted in enhanced anxiety levels, reduced locomotion and impaired learning and memory. As2O3-induced behavioural deficits were accompanied by downregulation of estrogen receptor (ERα) expression with a concomitant reduction of BDNF and NMDAR 2B levels in the hippocampus. However, the behavioural alterations and expression of these markers were restored in RES-supplemented mice. Moreover, a dose-dependent iAs accumulation was observed in serum and brain tissues of mice receiving As2O3 alone whereas simultaneous administration of As2O3 with RES facilitated iAs efflux. CONCLUSIONS: These results suggest that reduced ERα expression with associated downregulation of BDNF and NMDAR 2B levels could be a mechanism by which iAs induces cognitive impairment; hence, the modulation of estrogen-NMDAR-BDNF pathway by RES represents a potential avenue to recover behavioural deficits induced by this neurotoxin.

Unusual Cases of Pure Malignant Germ Cell Tumors of the Ovary: A Case Series on 10 Years Experience at a Tertiary Care Center.

BACKGROUND: Malignant ovarian germ cell tumors (MOGCTs) are rare female cancers, constituting up to 10% of ovarian cancers. Dysgerminoma is the most common histological variant. Surgical removal of the tumor with optimal debulking is the treatment of choice. Multidrug chemotherapy following surgery offers high remission rates. Considering the prevalence of these tumors in adolescent and young females, fertility-sparing treatment is of paramount importance. METHODS: The data of all patients with ovarian malignancy admitted at a tertiary-care-teaching hospital from September 2009-March 2019 were analyzed. Ten patients of MOGCTs were treated in this period. The clinical features, radiological and biochemical findings, and management and treatment outcome were evaluated. RESULTS: The median age of patients was 23 years. Histological subtypes included immature teratoma (n=3), endodermal sinus tumor (n=4), and dysgerminoma (n=3). Tumor markers namely AFP, ßHCG, and LDH increased in all except the patients with immature teratoma. Two patients with dysgerminoma were in the second trimester of pregnancy. All patients except one underwent surgery followed by BEP chemotherapy. Two patients had developed metastasis within six months of treatment and died. In seven patients, no evidence of disease was reported till date. CONCLUSION: Management of antenatal patients with dysgerminoma by surgery followed by BEP chemotherapy has favorable prognosis. Fertility-sparing surgery with adjuvant chemotherapy offers great advantage in young girls. However, risk stratification based on prognostic factors should be implemented in order to individualize the treatment for achieving higher survival rates. The option for oocyte-cryopreservation prior to surgery must be discussed with patients desiring future fertlity.

Curcumin supplementation shows modulatory influence on functional and morphological features of hippocampus in mice subjected to arsenic trioxide exposure.

Since, oxidative stress has been suggested as one of the mechanisms underlying arsenic-induced toxicity, the present study focused on the role of antioxidant (curcumin) supplementation on behavioral, biochemical, and morphological alterations with context to mice hippocampus (CA1) following arsenic trioxide (As2O3) administration. Healthy male Swiss albino mice were divided into control and experimental groups. As2O3 (2 mg/kg bw) alone or along with curcumin (100 mg/kg bw) was administered to experimental groups by oral route for 45 days whereas the control groups received either no treatment or vehicle for curcumin. Animals were subjected to behavioral study towards the end of the experimental period (day 33-45). On day 46, the brain samples were obtained and subjected either to immersion fixation (for morphometric observations) or used afresh for biochemical test. Behavioral tests (open field, elevated plus maze, and Morris water maze) revealed enhanced anxiety levels and impairment of cognitive functions in As2O3 alone treated groups whereas a trend of recovery was evident in mice simultaneously treated with As2O3 and curcumin. Morphological observations showed noticeable reduction in stratum pyramidale thickness (CA1), along with decrease in density and size of pyramidal neurons in As2O3 alone exposed group as compared to As2O3+Cu co-treated group. Hippocampal glutathione levels were found to be downregulated in animals receiving As2O3 as against the levels of controls and curcumin supplemented animals, thereby, suggestive of beneficial role of curcumin on As2O3 induced adverse effects.

Insights into nonylphenol degradation by UV-activated persulfate and persulfate/hydrogen peroxide systems in aqueous matrices: a comparative study.

Nonylphenol ethoxylates are widely used industrial surfactants. Once released into environment compartments, these chemicals undergo degradation and generate more toxic short chain artificial compound nonylphenol (NP). The latter is a known endocrine disrupting compound and persistent micropollutant. In the present study, the performance of NP degradation in UV-induced PS, PS/Fe2+, PS/H2O2, and PS/H2O2/Fe2+ systems was examined. The effect of concentration of oxidant and activators on the efficiency of target compound decomposition was studied. The trials were conducted in ultrapure water and groundwater to assess the influence of matrix composition. The obtained results indicated that NP degradation by all the systems studied followed a pseudo-first-order kinetics. The application of UV-activated PS at lower concentrations of the oxidant improved NP oxidation in both water matrices. The addition of iron activator at a cost-effective concentration showed slight improvement in the studied PS-based systems. The application of UV-induced dual oxidant PS/H2O2 system demonstrated promising results in NP oxidation. In turn, the addition of Fe2+ to the UV/PS/H2O2 system accelerated the target compound oxidation at an optimized dose of iron activator. The radicals scavenging studies indicated that HO• was the predominant radical in all UV-induced PS-based systems. The results of this research could provide significant information for the removal of NP from different water matrices by means of UV-induced persulfate-based oxidation processes.

UV-assisted chemical oxidation of antihypertensive losartan in water.

Population growth and deteriorating health issues have led to an increase in the consumption of angiotensin receptor blockers (ARBs), such as losartan (LOR), for treating high blood pressure and, as a result, to the frequent detection of these drugs in water and wastewater. The present study focuses on the oxidation of LOR by UV photolysis, UV(/Fe2+)-activated persulfate (PS) and hydrogen peroxide (H2O2) systems. The effects of operating parameters including pH value, reaction time, concentration of oxidant and activator on the efficacy of treatment were studied. The target compound degradation by direct UV photolysis, UV/PS and UV/H2O2 systems proved to be efficient and followed a pseudo-first-order kinetic model. The application of UV/oxidant systems even at lower PS or H2O2 concentrations resulted in more than 95% of LOR degradation in 10 min. In addition, the use of UV/Fe2+-activated oxidant systems led to a further increase in the kobs by improving the LOR oxidation in aqueous solution. The effectiveness of LOR mineralization based on total organic carbon (TOC) removal was also considered. The optimized results of the studied systems obtained in ultrapure water were used in groundwater to assess the effectiveness of LOR decomposition in more complex environmental matrix. Moreover, the acute toxicity of LOR solutions before and after the UV/Fe2+-activated PS and H2O2 oxidation to luminous bacteria (Vibrio fischeri) was investigated.

Comparative study of hemodynamic effects of intrathecal bupivacaine with butorphanol in cardiac and non-cardiac patients.

BACKGROUND AND AIMS: The synergism between intrathecal opioids and low dose local anesthetics makes it possible to achieve reliable spinal anesthesia (SA) with minimal hypotension. The study objective was to compare the hemodynamic effects of reduced dose of 0.5% intrathecal bupivacaine (2mL) with 25 µg butorphanol in cardiac vs non-cardiac patients. MATERIAL AND METHODS: We included sixty patients aged 30-80 years, undergoing infraumbilical surgeries in the study and compared thirty cardiac patients with mild to moderate reduction in left ventricular ejection fraction (LVEF) on 2D echocardiography (Group C) with 30 non-cardiac patients (Group NC) for similar types of surgery. Both the groups received 0.5% bupivacaine 2.0 ml with 25 µg butorphanol. RESULTS: The spinal block characteristics were similar in both groups (P > 0.05). The blood pressure of the patients in the two groups was comparable till 80 min P > 0.05 after which Group NC had significant increase in blood pressure compared to Group C upto 95 min (P < 0.05). Similarly, heart rate was comparable until 90 min (P > 0.05) after which Group NC had significant increase in heart rate versus Group C upto 100 min (P < 0.05). Eight patients in group C and five patients in group NC showed hypotension. Bradycardia was seen in 4 patients in group C in comparison to only one patient in group NC. CONCLUSION: We can safely consider spinal anesthesia with 10 mg bupivacaine and 25µg butorphanol in cardiac patients with mild to moderately reduced ejection fraction presenting for infraumbilical non-cardiac surgeries with the advantage of intraoperative hemodynamic stability and adequate postoperative analgesia.

Persulfate-based photodegradation of a beta-lactam antibiotic amoxicillin in various water matrices.

Amoxicillin (AMX), a widely used beta-lactam antibiotic, belongs to the World Health Organization's list of essential medicines. This subsequently causes its long-term presence in the environment and therefore, affects different environmental compartments. In this research, the degradation and mineralisation of AMX by UVC-activated persulfate-based treatment in various aqueous media was assessed. The degradation of the target compound was in accordance with the pseudo-first-order reaction kinetics in all the UVC-induced systems. The results indicated that AMX degradation in any real water matrices is notably inhibited by the matrix properties. The trials with radical scavengers in ultrapure water proved the existence of [Formula: see text] and HO., but mainly [Formula: see text] contributed to the degradation of AMX in the UVC/[Formula: see text] and UVC/[Formula: see text]/Fe2+ systems. It was shown that the parent compound disappeared during the treatment, but the mineralisation extent referred to the formation of transformation products the main of which were identified. The findings of this study could provide valuable information about the elimination of beta-lactam antibiotics from various environmental and processed waters.

Photo-induced oxidation of ceftriaxone by persulfate in the presence of iron oxides.

The present study focuses on degradation and mineralization of a third generation cephalosporin antibiotic ceftriaxone (CTA) in UVA- and UVC-induced persulfate (PS) system combined with heterogeneous (α-FeO(OH) and Fe3O4) activators. The CTA oxidation efficiency was investigated in buffered solution (pH 7.4) to stimulate the inhibitory properties of environmental and processed water matrices. Irrespective of the studied UV-induced persulfate system, the mineralization was less effective than CTA degradation. In turn, UVC-induced systems proved to be more effective than UVA-induced processes for decomposition of the target compound and removal of TOC. Accordingly, 2-h oxidation in UVA-induced systems resulted in partial decomposition and negligible mineralization of CTA. While the application of UVC-activated persulfate processes resulted in complete CTA degradation during the first 15 min of oxidation with the most efficient kobs of 0.53 min-1 and 38.3% TOC removal obtained in the UVC/PS system at [PS]0 = 500 µM. Groundwater (GW) trials results clearly indicated the inhibitory effect of the GW composition on the effectiveness of CTA degradation in the studied UV-induced PS-based systems, while the potential treatment efficacy in GW proved predictable based on the results obtained in the buffered UW trials. Adjusting the pH to 3 considerably improved the removal of TOC and the use of PS in both of the water matrices studied. The results of radicals scavenging experiments indicated that both SO4- and HO contributed to the CTA decomposition efficacy in the UV-induced persulfate systems, but the former was the predominant radical in all studied processes. The findings of the study strongly suggest that the UV-induced PS systems are promising treatment technologies for the abatement of cephalosporin antibiotics pollution in natural aqueous matrices.

Porous carbons derived from polyethylene terephthalate (PET) waste for CO2 capture studies.

Oxygen augmented carbon adsorbent has been developed using polyethylene terephthalate (PET) waste by first carbonizing at different temperatures (500-800 °C) and then chemically activating using different ratios of KOH: PET (mass ratio 1 to 4). The textural characterization divulges the effect of activation in terms of the development of the high surface area and micropore volume of 1690 m2 g-1 and 0.78 cm3 g-1 respectively, for the optimum sample (PET-3-700). Elemental analysis of PET-3-700 illustrates the presence of 34.33% oxygen and XPS results confirmed the occurrence of oxygen moieties which enhance the basicity of the adsorbent and promote CO2 capture. The CO2 adsorption capacity of prepared carbons was determined thermogravimetrically under dynamic conditions, at different concentrations of CO2 (6-100%) and temperatures. The maximum CO2 uptake capacity of 2.31 mmol g-1 was exhibited by PET-3-700 at an adsorption temperature of 30 °C under 100% pure CO2 flow. Four adsorption-desorption cycles corroborate almost complete regenerability of the prepared adsorbent. Adsorption kinetics at all adsorption conditions was described best by fractional order kinetic model. Freundlich isotherm fit indicates the surface of adsorbent being heterogeneous and low values of isosteric heat shows physisorption behavior of the process. Negative values of thermodynamic parameters indicate exothermic and feasible nature of adsorption process.

Malignant Mixed Germ Cell Tumors of the Ovary: A Series of Rare Cases.

BACKGROUND: Malignant mixed germ cell tumors of ovary are rare aggressive cancers affecting young adolescent girls. The commonest combination reported in literature is dysgerminoma and endodermal sinus tumors but in our study the most common combination was immature teratoma and endodermal sinus tumor which is exteremely rare. Preservation of future fertility is a concern. Fertility sparing surgery followed by combination chemotherapy is the current treatment of choice but treatment must be individualized depending upon the nature of the tumor. METHODS: A retrospective study on five patients with these tumors was conducted on patients at Guru Gobind Singh Medical College and Hospital (Punjab, India) between September 2009 to January 2018. RESULTS: Median age of patients was 15.6 years. Histopathological combination was immature teratoma and endodermal sinus tumor (n=3), endodermal sinus tumor and embryonal carcinoma (n=1), and mature and immature teratoma (n=1). Tumor markers AFP, beta HCG and LDH were raised in all except the patient with mature and immature teratoma. All patients underwent surgery followed by combination chemotherapy. Three patients developed metastasis within six months of treatment and died. In the remaining two, no reccurrence was reported till date. CONCLUSION: Malignant mixed germ cell tumors of ovary are extremely rare tumors and have poor prognosis. Fertility preservation is a concern as these patients are usually young adolescent girls but fertility sparing treatment must be individualized on the basis of tumor type, surgical staging, and availability of combination chemotherapy. Considering high recurrence rate and mortality, total hysterectomy with bilateral salpingo-oophorectomy with complete surgical staging followed by combination chemotherapy should be perfomed at advanced stage and aggressive tumor biology. Preservation of fertility must be held secondary.

Recent Progress in Genome Editing Approaches for Inherited Cardiovascular Diseases.

PURPOSE OF REVIEW: This review describes the recent progress in nuclease-based therapeutic applications for inherited heart diseases in vitro, highlights the development of the most recent genome editing technologies and discusses the associated challenges for clinical translation. RECENT FINDINGS: Inherited cardiovascular disorders are passed from generation to generation. Over the past decade, considerable progress has been made in understanding the genetic basis of inherited heart diseases. The timely emergence of genome editing technologies using engineered programmable nucleases has revolutionized the basic research of inherited cardiovascular diseases and holds great promise for the development of targeted therapies. The genome editing toolbox is rapidly expanding, and new tools have been recently added that significantly expand the capabilities of engineered nucleases. Newer classes of versatile engineered nucleases, such as the "base editors," have been recently developed, offering the potential for efficient and precise therapeutic manipulation of the human genome.