Infertility and Social Issue Have the Most Significant Impact on Health-related Quality of Life among Polycystic Ovarian Syndrome Women in South India.

Background: Infertility can have a significant impact on the identity of women. Individual women, who are infertile, experience tragic emotions, as well as those who are sad for great losses, like the death of a loved one. In this case, the woman is experiencing the loss of the ability to procreate. Aim: In the present study, our major concern was to implement the health-related quality of life (HRQOL) Questionnaire on South Indian polycystic ovarian syndrome (PCOS) women to assess the impact of various clinical features of polycystic ovary syndrome on the HRQOL of South Indian women diagnosed. Settings and Design: A total of 126 females in the first phase and 356 females in the second phase between the age group of 18-40 years characterised under the Rotterdam criteria were selected for the study. Materials and Methods: The study was carried out in three different phases which included a one-to-one interview, group discussion and questionnaire session. In our study, we found that all the females who attend the study showed positivity for all the domains developed in the previous study and suggested that further domain can be developed. Statistical Analysis Used: Suitable statistical methods were used with Graph pad PRISM (version 6). Results: Hence, in our study, we developed a further new sixth domain called as 'social impact domain'. Among South Indian PCOS women, we found that infertility and social issue have the most significant impact on HRQOL. Conclusion: The revised questionnaire by including the sixth domain called 'Social issue' is likely to be useful in measuring the quality of health of female having PCOS in regard to South Indian population.

Glycine encephalopathy.

Inherited neurotransmitter diseases are a subset of rare neurometabolic disorders characterized by hereditary deficiencies in neurotransmitter metabolism or transport. Non-ketotic hyperglycinaemia (NKH), called glycine encephalopathy, is an autosomal recessive glycine metabolism disorder characterized by an abnormal accumulation of glycine in all bodily tissues, including the CNS. The SLC6A9 gene, which codes for the GLYT1 protein, a biochemical abnormality in the GCS, and dihydrolipoamide dehydrogenase enzymes, which function as a GCS component, are responsible for the neonatal form's symptoms, which include progressive encephalopathy, hypotonia, seizures, and occasionally mortality in the first few days of life. By changing the MAPK signalling pathways, glycine deprivation in the brain damages neurons by increasing NMDA receptor activation, increasing intracellular Ca levels, and leading to DNA breakage and cell death in the neuron region. In addition to the previously mentioned clinical diagnosis, NKH or GE would be determined by MLPA and 13C glycine breath tests. Pediatricians, surgeons, neurologists, and geneticists treat NKH and GE at the newborn period; there is no cure for either condition.

Understanding the Role of NRF2 Signalling in Cancer.

Nuclear factor erythroid 2 (NFE 2) - related factor 2 (NFE2L2 or NRF2) is one of the transcription factors predominantly related to the expression of antioxidant genes. NRF2 plays a pivotal role in controlling redox potential in several tumor characteristics, including cancer cell metabolism, stem-cell-like characteristics, tumor aggressiveness, invasion, and metastasis. Further, it was recently discovered that the noncanonical pathway of NRF2 activation was involved in carcinogenesis. Cancerrelated changes (e.g., metabolic flexibility) that support cancer progression were found to be redox and NRF2 dependent. The pro or antineoplastic effects of NRF2 are essentially based on the specific molecular characteristics of the type of cancer. Therefore, systematic investigation of NRF2 signaling is necessary to clarify its role in cancer etiology. Understanding the role of NRF2 in triggering gene expressions in different types of cancer is quite challenging, which might be useful to target those genes for better clinical outcomes. To decipher the role of NRF2 in tumor formation and progression, largescale genomic and transcriptomic studies are required to correlate the clinical outcomes with the activity of the NRF2 expression system. This review attempts to give insights into the understanding of the role of NRF2 in cancer.

Genetics of human male infertility.

Infertility is defined as a failure to conceive in a couple trying to reproduce for a period of two years without conception. Approximately 15 percent of couples are infertile, and among these couples, male factor infertility accounts for approximately 50 percent of causes. Male infertility is a multifactorial syndrome encompassing a wide variety of disorders. In more than half of infertile men, the cause of their infertility is unknown (idiopathic) and could be congenital or acquired. Infertility in men can be diagnosed initially by semen analysis. Seminograms of infertile men may reveal many abnormal conditions, which include azoospermia, oligozoospermia, teratozoospermia, asthenozoospermia, necrospermia and pyospermia. The current estimate is that about 30 percent of men seeking help at the infertility clinic are found to have oligozoospermia or azoospermia of unknown aetiology. Therefore, there is a need to find the cause of infertility. The causes are known in less than half of these cases, out of which genetic or inherited disease and specific abnormalities in the Y chromosome are major factors. About 10-20 percent of males presenting without sperm in the ejaculate carry a deletion of the Y chromosome. This deleted region includes the Azoospermia Factor (AZF) locus, located in the Yq11, which is divided into four recurrently deleted non-overlapping subregions designated as AZFa, AZFb, AZFc and AZFd. Each of these regions may be associated with a particular testicular histology, and several candidate genes have been found within these regions. The Deleted in Azoospermia (DAZ) gene family is reported to be the most frequently deleted AZF candidate gene and is located in the AZFc region. Recently, a partial, novel Y chromosome 1.6-Mb deletion, designated "gr/gr" deletion, has been described specifically in infertile men with varying degrees of spermatogenic failure. The DAZ gene has an autosomal homologue, DAZL (DAZ-Like), on the short arm of the chromosome 3 (3p24) and it is possible that a defective autosomal DAZL may be responsible for the spermatogenic defect. The genetic complexity of the AZF locus on the long arm of the Y chromosome could be revealed only with the development of sequence tagged sites. Random attacks on the naked mitochondrial DNA (mtDNA) of sperm by reactive oxygen species or free radicals will inevitably cause oxidative damage or mutation to the mitochondrial genome with pathological consequences and lead to infertility in males. The key nuclear enzyme involved in the elongation and repair of mtDNA strands is DNA polymerase gamma, mapped to the long arm of chromosome 15 (15q25), and includes a CAG repeat region. Its mutation affects the adenosine triphosphate production. The introduction of molecular techniques has provided great insight into the genetics of infertility. Yet, our understanding of the genetic causes of male infertility remains limited.

A386G transition in DAZL gene is not associated with spermatogenic failure in Tamil Nadu, South India.

The DAZ-like (DAZL) gene located on the short arm of autosomal chromosome 3 (3p24), an essential master gene for the premeiotic development of male and female germ cells, is the father of the Y-chromosome DAZ gene cluster and encodes for RNA-binding proteins. Reported instances of positive association of DAZL gene mutations with infertility in men have been found in a Taiwanese population but not in Caucasians. There is no study from Tamil Nadu, South India, to demonstrate the role of DAZL gene in male infertility; we, therefore, analyzed a total of 287 men, including 147 infertile and 140 normozoospermic fertile controls from rural areas of Tamil Nadu, South India, to assess the phenotypic effect of DAZL mutations in this region of the world. Interestingly, all our samples showed absence of the A386G (T54A) mutation that was found to be associated with spermatogenic failure in the Taiwanese population. Therefore, we suggest that the A386G (T54A) mutation is not associated with male infertility in Tamil Nadu, South India.