Gynaecologists' views on the management of Vaginal Vault Prolapse: A qualitative study.

Objective: This study examined gynaecologists' experience and views on the management of vaginal vault prolapse (VVP) using laproscopic sarcocolpopexy (LSCP) versus open sarcocolpopexy (OSCP). Methods: In a qualitative study conducted at the University of Surrey and Homerton University Hospital, UK, from 2016 to 2017, semi-structured interviews were conducted with 15 consultants experienced in minimal access surgery or urogynecology. Interviews were recorded and transcripts were analyzed using the qualitative description (QD) approach. Results: Eight broad themes emerged: VVP management, LSCP for management of VVP, OSCP and vaginal surgery with or without mesh use in VVP management, laparoscopic training and support as well as surgeons' attitude towards LSCP. All participants acknowledged the importance of LSCP in the management of post-hysterectomy VVP as benefits outweighed risks in their view. OSCP was considered suitable in very specific circumstances. Vaginal surgery could be an excellent alternative to OSCP bearing in mind long-term efficacy and sexual activity in young women. Most participants agreed with national recommendations to avoid use of mesh in vaginal surgery for VVP and expressed the view that it should be done in specialised centres by trained surgeons who do such operations. Conclusions: This study showed that the acceptability of LSCP was dependent on participants' experience and consideration of the balance between patient's goals and potential risks. It provides useful guidance for future large-scale projects.

Minocycline, levodopa and MnTMPyP induced changes in the mitochondrial proteome profile of MPTP and maneb and paraquat mice models of Parkinson's disease.

Mitochondrial dysfunction is the foremost perpetrator of the nigrostriatal dopaminergic neurodegeneration leading to Parkinson's disease (PD). However, the roles played by majority of the mitochondrial proteins in PD pathogenesis have not yet been deciphered. The present study investigated the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and combined maneb and paraquat on the mitochondrial proteome of the nigrostriatal tissues in the presence or absence of minocycline, levodopa and manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin (MnTMPyP). The differentially expressed proteins were identified and proteome profiles were correlated with the pathological and biochemical anomalies induced by MPTP and maneb and paraquat. MPTP altered the expression of twelve while combined maneb and paraquat altered the expression of fourteen proteins. Minocycline, levodopa and MnTMPyP, respectively, restored the expression of three, seven and eight proteins in MPTP and seven, eight and eight proteins in maneb- and paraquat-treated groups. Although levodopa and MnTMPyP rescued from MPTP- and maneb- and paraquat-mediated increase in the microglial activation and decrease in manganese-superoxide dismutase expression and complex I activity, dopamine content and number of dopaminergic neurons, minocycline defended mainly against maneb- and paraquat-mediated alterations. The results demonstrate that MPTP and combined maneb and paraquat induce mitochondrial dysfunction and microglial activation and alter the expression of a bunch of mitochondrial proteins leading to the nigrostriatal dopaminergic neurodegeneration and minocycline, levodopa or MnTMPyP variably offset scores of such changes.

Prevalence of psychiatric morbidity amongst the community dwelling rural older adults in northern India.

BACKGROUND & OBJECTIVES: The population of elderly is growing globally and so are the physical illnesses and psychiatric morbidity. This study was planned to assess the prevalence and patterns of psychiatric morbidity amongst rural older adults in Lucknow, north India. METHODS: A survey was conducted in subjects aged 60 yr and above to identify the cases of psychiatric morbidity in rural population from randomly selected two revenue blocks of Lucknow district, Uttar Pradesh, India. All subjects were screened through Hindi Mental Status Examination (HMSE) and Survey Psychiatric Assessment Schedule (SPAS) to identify for the suspected cases of cognitive and the psychiatric disorders, respectively. The subjects screened positive on HMSE and SPAS were assessed in detail on Cambridge Mental Disorder of the Elderly Examination-Revised (CAMDEX-R) and Schedule for Clinical Assessment in Neuropsychiatry (SCAN), to diagnose cognitive disorders and psychiatric disorders (other than the cognitive), respectively on the basis of International Classification of Diseases-10 (ICD-10) diagnostic guidelines. RESULTS: The overall prevalence of psychiatric morbidity in rural older adults was found to be 23.7 per cent (95% CI=21.89-25.53). Mood (affective) disorders were the commonest (7.6%, 95% CI=6.51-8.80), followed by mild cognitive impairment (4.6%, 95% CI=3.72-5.53), mental and behavioural disorders due to substance use (4.0%, 95% CI=3.17-4.87) and dementia (2.8%) [Alzheimer's disease (2.4%, 95% CI=1.81-3.16) and vascular (0.4%, 95% CI=0.16-0.73)]. INTERPRETATION & CONCLUSIONS: Overall prevalence of psychiatric morbidity amongst rural elderly in this study was found to be less in comparison to those reported in earlier studies from India. However, prevalence pattern of different disorders was found to be similar. Therefore, it appears that a stringent methodology, refined case criteria for diagnosis and assessment by trained professionals restrict false diagnosis.

Should women with high body mass index be denied fertility treatments?

Obesity is an emerging global epidemic with a negative impact on fertility. Almost all guidelines and policies have a stringent limit of body mass index (BMI) to access fertility services which has promoted a debate amongst fertility practitioners globally. Proponents of placing such a limit point to the negative impact of elevated BMI on the outcome of fertility treatment, its cost effectiveness and the risk it poses to the intending mother and unborn child. Opponents of placing a restriction base their arguments on the lack of conclusive, robust evidence regarding the variables along with the ethical dilemmas of promoting discrimination and stigmatization by denying a couple their basic right of parenthood. In this review, we analyse these medical and ethical dilemmas in the light of current evidence. The focus is on female infertility.

Role of secondary mediators in caffeine-mediated neuroprotection in maneb- and paraquat-induced Parkinson's disease phenotype in the mouse.

Maneb and paraquat are known to induce Parkinson's disease (PD) phenotype, however, caffeine offers neuroprotection. Nitric oxide (NO) acts an important mediator in PD phenotype and tyrosine kinase (TK), nuclear factor kappa B (NF-kB), p38 mitogen activated protein kinase (p38 MAPK) are known to regulate its production. The present study aimed to elucidate the role of caffeine in the regulation of NO production and microglial activation and their subsequent contribution in dopaminergic neuroprotection. The animals were treated with caffeine and/or maneb and paraquat along with controls. In a few sets of experiments, the animals were also treated with aminoguanidine, an inhibitor of inducible NO synthase, pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-kB, genistein, an inhibitor of TK or SB202190, an inhibitor of p38 MAPK. Tyrosine hydroxylase (TH)-immunoreactivity and anti-integrin αM (OX-42) staining were performed to assess the number of dopaminergic neurons and activation of microglia, respectively. NO was measured in terms of nitrite, however, the expressions of p38 MAPK, interleukin (IL)-1ß, NF-kB and TK were checked by western blot analyses. Maneb and paraquat induced the number of degenerating dopaminergic neurons, microglial cells, nitrite content, expressions of IL-1ß, p38 MAPK, NF-kB and TK and caffeine co-treatment reduced the level of such alterations. Reductions were more pronounced in the animals co-treated with aminoguanidine, PDTC, genistein or SB202190. The results obtained thus demonstrate that caffeine down-regulates NO production, neuroinflammation and microglial activation, which possibly contribute to neuroprotection.

Melatonin or silymarin reduces maneb- and paraquat-induced Parkinson's disease phenotype in the mouse.

Oxidative stress is reported as one of the most widely accepted mechanisms of maneb (MB)- and paraquat (PQ)-induced nigrostriatal dopaminergic neurodegeneration leading to the Parkinson's disease (PD) phenotype. The study investigated the effects of silymarin, an antioxidant of plant origin, and melatonin, an indoleamine produced in all species, in MB- and PQ-induced mouse model of PD. The mice were treated intraperitoneally daily with silymarin (40mg/kg) or melatonin (30mg/kg) along with respective controls for 9wk. Subsets of these animals were also treated with MB (30mg/kg) and PQ (10mg/kg), twice a week, for 9wk, 2hr after silymarin/melatonin treatment. Locomotor activities along with striatal dopamine content, tyrosine hydroxylase (TH) immunoreactivity, number of degenerating neurons, lipid peroxidation and nitrite content were estimated. Additionally, mRNA expression of vesicular monoamine transporter, cytochrome P-450 2E1 (CYP2E1), and glutathione-S-transferase A4-4 (GSTA4-4), catalytic activities of CYP2E1 and GSTA4-4 and protein expressions of unphosphorylated and phosphorylated p53 (p53 and P-p53), Bax and caspase 9 were measured in control and MB- and PQ-treated mice with either silymarin or melatonin treatments. Silymarin/melatonin significantly offset MB- and PQ-mediated reductions in locomotor activities, dopamine content, TH immunoreactivity, VMAT 2 mRNA expression and the expression of p53 protein. Silymarin/melatonin attenuated the increases in lipid peroxidation, number of degenerating neurons, nitrite content, mRNA expressions of cytochrome P-450 2E1 (CYP2E1) and GSTA4-4, catalytic activities of CYP2E1 and GST and P-p53, Bax and caspase 9 protein expressions. The results demonstrate that silymarin and melatonin offer nigrostriatal dopaminergic neuroprotection against MB- and PQ-induced PD by the modulation of oxidative stress and apoptotic machinery.

Expanding perfusion across disciplines: the use of thrombelastography technology to reduce risk in an obstetrics patient with Gray Platelet Syndrome--a case study.

It is important that our speciality continues to push its boundaries. Our perfusion team has invested time lecturing to non-cardiac specialties about perfusion-led technology. This resulted in working closely with the obstetrics team to treat a pregnant patient with the bleeding disorder Gray Platelet Syndrome. In the first instance, we used our Thromboelastograph (TEG) platelet mapping programme to assess the patient. These results agreed with the platelet aggregation tests, showing a degree of platelet inhibition, but it was the overall clotting profile (basic thrombelastograph), showing a borderline hyper-coagulable state, that was of most interest and commonly seen in pregnancy. We believe a TEG result within acceptable limits could help re-adjust the risk of spinal haematomas following regional anaesthesia, thereby, reducing the risks of difficult intubation and general anaesthetic exposure to the baby. The case study describes both basic and platelet mapping thrombelastographs and their potential role in not only this patient with Gray Platelet Syndrome, but any obstetric patient where there are bleeding concerns.

Comparative evolutionary analyses of beta globin gene in eutherian, dinosaurian and neopterygii taxa.

BACKGROUND & OBJECTIVES: Comparative genomics and evolutionary analyses of conserved genes have enabled us to understand the complexity of genomes of closely related species. For example: ß-globin gene present in human hemoglobin is one such gene that has experienced many genetic changes in many related taxa and produced more than 600 variants. One of the variant, HBS causes sickle-cell anemia in humans but offers protection against severe malaria due to Plasmodium falciparum. In the present study, we characterized and performed evolutionary comparative analyses of the ?-globin gene in different related and unrelated taxa to have a comprehensive view of its evolution. METHODS: DNA and protein sequences of ß-globin gene were downloaded from NCBI and characterized in detail in nine eutherian (Homo sapiens, Pan troglodytes, Macaca mulatta, Mus musculus, Rattus norvegicus, Bos taurus, Canis familiaris, Equus caballus, Oryctolagus cuniculus), a dinosaurian (Gallus gallus) and a neopterygii (Danio rerio) taxa. Three more eutherian (Papio anubis, Ovis aries and Sus scrofa) taxa were included for an analysis at the protein level but not included at the gene level owing to lack of genomic information. Computational and phylogenetic analyses were performed using evolutionary comparative approach. RESULTS: Results of comparative and phylogenetic analyses revealed less conservation of genetic architecture of ß-globin compared to its protein architecture in all eutherian taxa. Both dinosaurian and neopterygii taxa served as outgroups and varied at gene and protein levels. INTERPRETATION & CONCLUSION: Most remarkably, all primates from eutherian taxa including P. anubis showed only nine codon position differences and an absolute similarity between H. sapiens and P. troglodytes. Absolute conservation of coding region in Equus caballus (horse) was observed. The results were discussed with an inference on the role of evolutionary forces in maintaining such close similarities and variations across closely related taxa. Further, the need to utilize more comparative approaches in understanding the disease causing genes' evolution in closely related taxa is hoped for.

When Should We Freeze Embryos? Current Data for Fresh and Frozen Embryo Replacement IVF Cycles.

Recent years have seen a dramatic rise in the number of frozen-thawed embryo replacement (FER) cycles. Along with the advances in embryo cryopreservation techniques, the optimization of endometrial receptivity has resulted in outcomes for FER that are similar to fresh embryo transfer. However, the question of whether the Freeze all strategy is for all is nowadays a hot topic. This review addresses this issue and describes current evidence based on randomized controlled trials and observational studies. To date, it is reasonable to perform FER in cases with a clear indication for the benefits of such strategy including impending ovarian hyperstimulation syndrome (OHSS) or preimplantation genetic testing for aneuploidy (PGT-A); however, this strategy does not fit for all. This review analyses the pros and cons of the freeze all strategy highlighting the need to follow a personalized plan in embryo transfer, avoiding a freeze all methodology for all patients in an unselected manner.

Proteomics in Parkinson's disease: current trends, translational snags and future possibilities.

Proteomic technologies are widely used to understand the molecular mechanism of Parkinson's disease (PD) and to develop biomarkers for its early diagnosis. The differential expression patterns of brain, cerebrospinal fluid and blood proteins of patients or chemically induced animal models are used to identify protein fingerprints for developing diagnostic and therapeutic strategies for PD. A number of differentially expressed proteins associated with energy metabolism, oxidative stress, signal transduction, electron transport and detoxification pathways are identified using proteomic strategies. Proteomics immensely contributed to the detection of qualitative and quantitative changes of expressed proteins and their post-translational modifications. An update on proteomics-driven research for developing early biomarkers and understanding the molecular aspects of PD, along with their translational snags, challenges and future possibilities, are discussed in this review.

Novel microbial route to synthesize silver nanoparticles using spore crystal mixture of Bacillus thuringiensis.

Metallic nanoparticles are traditionally synthesized by wet chemical techniques, where the chemicals used are often toxic and flammable. In the present study, the spore crystal mixture of Bacillus thuringiensis was used for the synthesis of silver nanoparticles. Nanoparticles were characterized using UV-Vis absorption spectroscopy, XRD and TEM. X-ray diffraction and TEM analysis showed the average particle size of 15 nm and mixed (cubic and hexagonal) structure. This is for the first time that any bacterial spore crystal mixture was used for the synthesis of nanoparticles. Further, these biologically synthesized nanoparticles were found to be highly toxic against different multi drug resistant human pathogenic bacteria.

Omics in mechanistic and predictive toxicology.

High-throughput omics strategies delineate the molecular mechanism of toxicity, predict the toxicity of newer drugs and chemicals, and identify individuals at high risks on the basis of expression patterns of messenger ribonucleic acids, genes, and proteins, and detection of intermediary metabolites. Despite being a developing country, India is one of the fastest growing nations in the usages and applications of omics technologies. Several differentially expressed genes and proteins under various pathological and toxicant-exposed conditions have been identified, and many association studies on genetic polymorphisms with toxicant-induced diseases have been conducted for the predictive and mechanistic purposes. To date, omics-driven approaches have identified some novel fingerprints associated with disease risk/protection and prediction of toxicity of newer chemicals. Although the contributions of such findings in the mechanistic toxicology have been immense, predictive values of these findings in toxicology have been limited. In this review, the current status of omics-based research and its future possibilities at the Indian Institute of Toxicology Research (IITR), Lucknow, India, have been discussed.

Subverting Heteronormativity: An Intervention to Foster Positive Attitudes Toward Homosexuality Among Indian College Students.

Prejudice against gay and lesbian persons remains largely an unaddressed issue in India. This experimental study involved designing, implementing, and assessing the effectiveness of an intervention to foster positive attitudes toward the homosexual community among Indian college students. The experimental group (n = 60) received a three-component module including perspective taking, education, and direct contact with gay and lesbian persons. Attitudes toward homosexuals, empathy, and self-esteem were measured using standardized questionnaires 15 days before the intervention and immediately following the intervention. No intervention was carried out with the control group (n = 55). Their attitudes were measured 15 days apart, parallel to the experimental group. Results showed that attitudes toward homosexuality improved significantly in the experimental group. The control group also showed a significant, but small, improvement in attitudes. Further, levels of empathy were found to increase only in the experimental group. Limitations, future directions, and implications of the study are discussed.

Salinity induced lipid production in microalgae and cluster analysis (ICCB 16-BR_047).

This work aimed to gain mechanistic insights into the salt stress mediated enhanced lipid accumulation in microalgae. Two freshwater microalgae were isolated from North Guwahati Assam, and were identified as Chlorella sorokiniana CG12(KR905186) and Desmodesmus GS12(KR905187). The effects of various salts such as NaCl, KCl, MgCl2 and CaCl2 were investigated where CaCl2 exhibited the maximum effect on lipid enhancement up to 40.02% and 44.97% in CG12 and GS12, respectively. Furthermore, the substantial increase was observed in oleic acid content up to 64.18% and 53.46% in CG12 and GS12 in the presence of 25mM and 5mM CaCl2, respectively. Cluster analysis revealed the correlation between lipid profile alterations by varying concentration of salts. Based on the outcomes of the present study, it is hypothesized that Ca2+ plays a decisive role in the cell signaling under salt stress conditions and subsequently enhances the synthesis of lipid molecules.

Levels of salivary thiocyanate and its relation with occurrence of micronuclei using exfoliative cytology in smokers and nonsmokers.

AIMS: To evaluate the levels of salivary thiocyanate and its relation with the occurrence of micronuclei (MN) using exfoliative cytology in smokers and nonsmokers. MATERIALS AND METHODS: One hundred and twenty patients were divided into 3 groups: nonsmoker group 1 (control), smokers group 2, and smokers group 3. Their saliva was collected and analyzed for thiocyanate levels, and exfoliative cytology was evaluated for the presence of MN. STATISTICAL ANALYSIS USED: Fisher's exact test and ANOVA test were used. RESULTS: It was seen that as the grade of smoking increased, the levels of salivary thiocyanate and occurrence of MN increased. CONCLUSIONS: Detection and quantification of "biomarkers" such as salivary thiocyanate and MN in noninvasive and painless procedures such as oral exfoliative cytology can be an upcoming research domain in the field of cancer prevention and therapeutics.

Caregiver Burden and Quality of Life of Key Caregivers of Patients with Dementia.

BACKGROUND: Dementia is the most devastating cognitive disorder of the elderly and needs extra attention to care. Therefore, this study was conducted to identify the caregiver burden of dementia key caregivers and their Quality of Life (QOL). MATERIALS AND METHODS: Sample consisted of purposively selected 24 dementia key caregivers fulfilling the inclusion criteria from the in-patient of the Department of Geriatric Mental Health, King George's Medical University, Lucknow, Uttar Pradesh, India. Zarit Burden Interview and World Health Organization QOL-BREF were administered. Mean, standard deviation, t-test, Chi-square with Yate's correction were used to analyze the data. RESULTS: All key caregivers felt mild to moderate level of burden. Gender-wise significant difference was found on burden area of expectation (P < 0.05). Mean scores on physical, psychological, social relationship, and environmental QOL were found to be on lower side. A negative correlation was found between burden and QOL. CONCLUSION: Professional help and supportive psychotherapy can be provided to the key caregivers of dementia patients to reduce their burden, strengthen the coping skill and thus improve their QOL.

Effects of beta-cyfluthrin on white and sepia mutants of Drosophila melanogaster.

The effects of sublethal concentrations of a synthetic pyrethroid, beta-cyfluthrin (Bulldock 025 SC) were investigated in the F1 generations of white and sepia mutants of Drosophila melanogaster after various cross combinations of the parents which were exposed separately to the insecticide mixed diet for 24 hours. The experiment was carried out under the laboratory conditions at a temperature of 25+/-5 degrees C and 60+/-5% relative humidity. The insecticide had deleterious effect on the growth and development of both the mutant flies. Larval, pupal and total developmental periods were found to be increased as compared to controls, whereas the number of adult emerged decreased in all the treatment sets. Larval period index (LPI), pupal period index (PPI) and growth index (GI) were observed to be decreased in the entire cross combinations. Maximum effects were observed in those sets where both the sexes were treated, crossed and F1 generation was studied on the treated food having sublethal concentration of the insecticide, followed by similar treatment sets but on the fresh untreated food. Females were found to be resistant as compared to the males, whereas white mutant files were more susceptible to the test insecticide beta-cyfluthrin as compared to sepia mutant flies.

Immobilisation of Fenugreek ß-amylase on chitosan/PVP blend and chitosan coated PVC beads: a comparative study.

A Box-Behnken design of Response Surface Methodology (RSM) was utilised for optimisation of parameters affecting immobilisation of Fenugreek ß-amylase on chitosan coated PVC (polyvinyl chloride) beads and beads made from chitosan/PVP (polyvinylpyrrolidone) blend, which resulted in 85.2% and 81% immobilisation efficiency, respectively. Immobilisation resulted in shift of pH optima while the optimum temperature remained unaffected. Enhancement in thermal stability of the enzyme was observed on conjugation with both the matrices. The immobilised enzyme appeared suitable for industrial applications due to the non-toxic nature of chosen matrices, ease of immobilisation procedure, enhanced stability and reusability with retention of 72% and 60% residual activity after 10 uses for the enzyme immobilised on chitosan coated PVC beads and on the beads of chitosan/PVP blend, respectively.

α-Amylase immobilization onto functionalized graphene nanosheets as scaffolds: Its characterization, kinetics and potential applications in starch based industries.

α-Amylase is imperative for starch and its deriviatized industries. Functionalized graphene sheets were tailored and optimized as scaffold for α-amylase immobilization using Response Surface Methodology based on Box-Behnken design, with an overall immobilization efficiency of 85.16%. Analysis of variance provided adequacy to the mathematical model for further studies. Native and immobilized functionalized graphene were characterized using transmission and scanning electron microscopy, followed by Fourier transform infrared (FTIR) spectroscopy. Wheat α-amylase conjugated with functionalized graphene sheets were visually evident on transmission and scanning micrographs while the FTIR spectra showed interplay of various chemical interactions and bonding, during and after immobilization. Optimum pH and optimum temperature for immobilized enzyme though remained unchanged but showed broader range whereas Km showed a slight decrease (1.32 mg/mL). It also showed enhanced thermal and storage stability and retained 73% residual activity after 10 uses. These ensemble of properties and non-toxic nature of functionalized graphene, makes it viable to be absorbed commercially in starch processing industries.

Mechanism of Nanotization-Mediated Improvement in the Efficacy of Caffeine Against 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Parkinsonism.

The study aimed to measure the neuroprotective efficacy of caffeine-encapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles over bulk and to delineate the mechanism of improvement in efficacy both in vitro and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinsonism. Caffeine-encapsulated PLGA nanoparticles exhibited more pronounced increase in the endurance of dopaminergic neurons, fibre outgrowth and expression of tyrosine hydroxylase (TH) and growth-associated protein-43 (GAP-43) against 1-methyl-4-phenylpyridinium (MPP+)-induced alterations in vitro. Caffeine-encapsulated PLGA nanoparticles also inhibited MPP(+)-mediated nuclear translocation of nuclear factor-kappa B (NF-κB) and augmented protein kinase B phosphorylation more potentially than bulk counterpart. Conversely, MPTP reduced the striatal dopamine and its metabolites and nigral TH immunoreactivity whereas augmented the nigral microglial activation and nigrostriatal lipid peroxidation and nitrite content, which were shifted towards normalcy by caffeine. The modulations were more evident in caffeine-encapsulated PLGA nanoparticles treated animals as compared with bulk. Moreover, the striatal caffeine and its metabolites were found to be significantly higher in caffeine-encapsulated PLGA nanoparticles-treated mice as compared with bulk. The results thus suggest that nanotization improves the protective efficacy of caffeine against MPTP-induced Parkinsonism owing to enhanced bioavailability, inhibition of the nuclear translocation of NF-κB and activation of protein kinase B phosphorylation.