Comparison of Vaginal Birth Rate between Induction of Labour and Expectant Management at 40 Weeks in Women with a Previous Caesarean Section: A Pilot Randomized Controlled Trial.

Background: The optimum time of labour induction among women with a previous caesarean without any pregnancy complication and eligible and willing for vaginal delivery is not specified. This study compares the vaginal birth rates between induction at 40 weeks and expectant management till 41 weeks. Method: We conducted this parallel design nonblinded, randomized controlled trial in a tertiary care teaching institution in South India on women with a previous lower segment caesarean section eligible for a trial of labour with singleton foetus without any pregnancy complication at recruitment. We screened 1886 women. Sixty women underwent block (of 6 each) randomization into two groups of thirty each at 40 weeks. We induced the women in the intervention group at 40 weeks with oxytocin or a single 24-hour application of a Foley catheter followed by oxytocin infusion and amniotomy. The expectant group underwent maternal and foetal surveillance and induction at 41 weeks with the same protocol if not delivered by then. We compared the primary outcome of the proportion of vaginal birth rate with a chi-square test. Result: Data from all sixty women were analyzed. Twenty (66.67%) in the induction compared to ten (33.33%) in the expectant group delivered vaginally. This difference was significant (RR 2.0, 95% CI: 1.13-3.52; P = 0.016). One woman in the expectant group had scar dehiscence. Conclusion: Among women with a previous caesarean scar, labour induction at 40 weeks has a significantly higher vaginal birth rate than those managed expectantly till 41 weeks. More extensive trials are feasible and recommended. Trial Registry. The trial was prospectively registered with the clinical trial registry of India. This trial is registered with CTRI/2018/09/015719 (date of registration 14th September 2018).

Chemical inhibitors of hexokinase-2 enzyme reduce lactate accumulation, alter glycosylation processing, and produce altered glycoforms in CHO cell cultures.

Chinese hamster ovary (CHO) cells, predominant hosts for recombinant biotherapeutics production, generate lactate as a major glycolysis by-product. High lactate levels adversely impact cell growth and productivity. The goal of this study was to reduce lactate in CHO cell cultures by adding chemical inhibitors to hexokinase-2 (HK2), the enzyme catalyzing the conversion of glucose to glucose 6-phosphate, and examine their impact on lactate accumulation, cell growth, protein titers, and N-glycosylation. Five inhibitors of HK2 enzyme at different concentrations were evaluated, of which 2-deoxy- d-glucose (2DG) and 5-thio- d-glucose (5TG) successfully reduced lactate accumulation with only limited impacts on CHO cell growth. Individual 2DG and 5TG supplementation led to a 35%-45% decrease in peak lactate, while their combined supplementation resulted in a 60% decrease in peak lactate. Inhibitor supplementation led to at least 50% decrease in moles of lactate produced per mol of glucose consumed. Recombinant EPO-Fc titers peaked earlier relative to the end of culture duration in supplemented cultures leading to at least 11% and as high as 32% increase in final EPO-Fc titers. Asparagine, pyruvate, and serine consumption rates also increased in the exponential growth phase in 2DG and 5TG treated cultures, thus, rewiring central carbon metabolism due to low glycolytic fluxes. N-glycan analysis of EPO-Fc revealed an increase in high mannose glycans from 5% in control cultures to 25% and 37% in 2DG and 5TG-supplemented cultures, respectively. Inhibitor supplementation also led to a decrease in bi-, tri-, and tetra-antennary structures and up to 50% lower EPO-Fc sialylation. Interestingly, addition of 2DG led to the incorporation of 2-deoxy-hexose (2DH) on EPO-Fc N-glycans and addition of 5TG resulted in the first-ever observed N-glycan incorporation of 5-thio-hexose (5TH). Six percent to 23% of N-glycans included 5TH moieties, most likely 5-thio-mannose and/or 5-thio-galactose and/or possibly 5-thio-N-acetylglucosamine, and 14%-33% of N-glycans included 2DH moieties, most likely 2-deoxy-mannose and/or 2-deoxy-galactose, for cultures treated with different concentrations of 5TG and 2DG, respectively. Our study is the first to evaluate the impact of these glucose analogs on CHO cell growth, protein production, cell metabolism, N-glycosylation processing, and formation of alternative glycoforms.

Cottonseed hydrolysate supplementation alters metabolic and proteomics responses in Chinese hamster ovary cell cultures.

Hydrolysates are used as media supplements although their role is not well characterized. In this study, cottonseed hydrolysates, which contained peptides and galactose as supplemental substrates, were added to Chinese hamster ovary (CHO) batch cultures, enhancing cell growth, immunoglobulin (IgG) titers, and productivities. Extracellular metabolomics coupled with tandem mass tag (TMT) proteomics revealed metabolic and proteomic changes in cottonseed-supplemented cultures. Shifts in production and consumption dynamics of glucose, glutamine, lactate, pyruvate, serine, glycine, glutamate, and aspartate suggest changes in tricarboxylic acid (TCA) and glycolysis metabolism following hydrolysate inputs. Quantitative proteomics revealed 5521 proteins and numerous changes in relative abundance of proteins related to growth, metabolism, oxidative stress, protein productivity, and apoptosis/cell death at day 5 and day 6. Differential abundance of amino acid transporter proteins and catabolism enzymes such as branched-chain-amino-acid aminotransferase (BCAT)1 and fumarylacetoacetase (FAH) can alter availability and utilization of several amino acids. Also, pathways involved in growth including the polyamine biosynthesis through higher ornithine decarboxylase (ODC1) abundance and hippo signaling were upregulated and downregulated, respectively. Central metabolism rewiring was indicated by glyceraldehyde-3-phosphate dehydrogenase (GAPDH) downregulation, which corresponded with re-uptake of secreted lactate in the cottonseed-supplemented cultures. Overall, cottonseed hydrolysate supplementation modified culture performance by altering cellular activities critical to growth and protein productivity including metabolism, transport, mitosis, transcription, translation, protein processing, and apoptosis. HIGHLIGHTS: Cottonseed hydrolysate, as a medium additive, enhances Chinese hamster ovary (CHO) cell culture performance. Metabolite profiling and tandem mass tag (TMT) proteomics characterize its impact on CHO cells. Rewired nutrient utilization is observed via glycolysis, amino acid, and polyamine metabolism. Hippo signaling pathway impacts cell growth in the presence of cottonseed hydrolysate.

Soil-Transmitted Helminth Infections among Antenatal Women in Primary Care Settings in Southern India: Prevalence, Associated Factors and Effect of Anti-Helminthic Treatment.

Community-based studies from India on prevalence of soil-transmitted helminth (STH) infections have reported estimates as high as 50% in children. However, prevalence estimates during pregnancy in India are lacking. We aimed to describe the burden, associated factors of STH and cure rate after deworming in primary care settings. Pregnant women were recruited from four urban and five rural centers in Puducherry, South India, from December 2019 to April 2022. One stool sample was collected from each participant before deworming and one repeat sample was collected from STH positive woman after three weeks of deworming. The samples were processed with saline; iodine wet mount, and microscopic concentration techniques. Cure rate (CR) was assessed using Kato-Katz thick smear. Of 650 women included, 49 (7.5%, 95% CI 5.6-9.8) had one of the STH infections; the prevalence of Ascaris lumbricoides, hookworm and Strongyloides was 5.4%, 1.8% and 0.3%, respectively. The prevalence of any STH was higher among ages 26-30 years (9.1%), working women (8.3%), multigravida (8.3%), urban setting (8.3%), those who did not wash their hands before food (9%) and anemic women (8.9%), compared to their counterparts, but not statistically significant. The CR for hookworm was 100% and Ascaris lumbricoides was 88.6%. To conclude, the prevalence of STH was low among pregnant women compared to school aged children. Continued deworming activities along with improved sanitation could further reduce the burden.

A systematic review on the effects of acrylamide and bisphenol A on the development of Drosophila melanogaster.

The current global scenario has instigated a steady upsurge of synthetic chemicals usage thereby creating a toxic environment unsuitable for animals and humans. Acrylamide and bisphenol A are some of the most common toxins found in the atmosphere due to their extensive involvement in numerous industrial processes. Acrylamide, an occupational hazard toxin has been known to cause severe nerve damage and peripheral neuronal damage in both animals and humans. General sources of acrylamide exposure are effluents from textile and paper industries, cosmetics, and thermally processed foods rich in starch. Bisphenol A (BPA) is generally found in food packaging materials, dental sealants, and plastic bottles. It is highly temperature-sensitive that can easily leach into the food products or humans on contact. The genotoxic and neurotoxic effects of acrylamide and bisphenol A have been widely researched; however, more attention should be dedicated to understanding the developmental toxicity of these chemicals. The developmental impacts of toxin exposure can be easily understood using Drosophila melanogaster as a model given considering its short life span and genetic homology to humans. In this review, we have discussed the toxic effects of acrylamide and BPA on the developmental process of Drosophila melanogaster.

A proteomics approach to decipher a sticky CHO situation.

Chinese hamster ovary (CHO) cells serve as protein therapeutics workhorses, so it is useful to understand what intrinsic properties make certain host cell lines and clones preferable for scale up and production of target proteins. In this study, two CHO host cell lines (H1, H2), and their respective clones were evaluated using comparative TMT-proteomics. The clones obtained from host H1 showed increased productivity (6.8 times higher) in comparison to clones from host H2. Based on fold-change analyses, we observed differential regulation in pathways including cell adhesion, aggregation, and cellular metabolism among others. In particular, the cellular adhesion pathway was downregulated in H1, in which podoplanin, an antiadhesion molecule, was upregulated the most in host H1 and associated clones. Phenotypically, these cells were less likely to aggregate and adhere to surfaces. In addition, enzymes involved in cellular metabolism such as isocitrate dehydrogenase (IDH) and mitochondrial-d-lactate dehydrogenase ( d-LDHm) were also found to be differentially regulated. IDH plays a key role in TCA cycle and isocitrate-alpha-ketoglutarate cycle while d-LDHm aids in the elimination of toxic metabolite methylglyoxal, involved in protein degradation. These findings will enhance our efforts towards understanding why certain CHO cell lines exhibit enhanced performance and perhaps provide future cell engineering targets.

Epigenetic comparison of CHO hosts and clones reveals divergent methylation and transcription patterns across lineages.

In this study, we examined DNA methylation and transcription profiles of recombinant clones derived from two different Chinese hamster ovary hosts. We found striking epigenetic differences between the clones, with global hypomethylation in the host 1 clones that produce bispecific antibody with higher productivity and complex assembly efficiency. Whereas the methylation patterns were found mostly inherited from the host, the host 1 clones exhibited continued demethylation reflected by the hypomethylation of newly emerged differential methylation regions (DMRs) even at the clone development stage. Several interconnected biological functions and pathways including cell adhesion, regulation of ion transport, and cholesterol biosynthesis were significantly altered between the clones at the RNA expression level and contained DMR in the promoter and/or gene-body of the transcripts, suggesting epigenetic regulation. Indeed, expression changes of epigenetic regulators were observed including writers (Dnmt1, Setdb1), readers (Mecp2), and erasers (Tet3, Kdm3a, Kdm1b/5c) involved in CpG methylation, histone methylation, and heterochromatin maintenance. In addition, we identified putative transcription factors that may be readers or effectors of the epigenetic regulation in these clones. By combining transcriptomics with DNA methylation data, we identified potential processes and factors that may contribute to the variability in cell physiology between different production hosts.

Prevalence and association of depressive symptoms with spiritual intelligence among older adults: A community-based study in rural Puducherry, South India.

INTRODUCTION: Depression is more common among older adults, but there is a paucity of information about its association with spiritual intelligence. This study aimed to determine the prevalence and association of depressive symptoms with spiritual intelligence among older adults. MATERIALS AND METHODS: This community-based cross-sectional analytical study was conducted among 292 older adults in a rural area of Puducherry, India. A structured questionnaire was used to collect each participant's socio-demographic and behavioral factors; the presence of depressive symptoms was assessed by using Geriatric Depression Scale (short form), spiritual intelligence by the Spiritual Intelligence Self-Report Inventory-24 questionnaire and activities of daily living by Katz Index of Independence scale. Proportion for prevalence estimate, bivariate and multivariable log binomial regression analysis were done. RESULTS: The prevalence of depressive symptoms was 64.1 % (187/292; 95 % CI 58.3-69.3). Of total, 103 (35.3 %) had low, 92 (31.55 %) had moderate and 97 (33.2 %) had high spiritual intelligence. About 11 % (32/292) were partially or fully dependent. Depressive symptoms showed a significant association with marital status, education, sleep pattern, relationship with family members and spiritual intelligence in bivariate analysis. Depressive symptoms were high among those with low spiritual intelligence and disturbed sleep pattern with Adjusted Prevalence Ratio of 1.33 (95 %CI 1.26-1.4) and 1.06 (95 %CI 1.0-1.14) respectively. CONCLUSION: Majority of the older adults had depressive symptoms and significantly more among those with low spiritual intelligence and disturbed sleep. This study gives new evidence on spiritual intelligence among older adults in a community setting and the magnitude of association of depressive symptoms with spiritual intelligence.

Willingness and yield of screening for hepatitis B among outpatients of a tertiary care centre, Puducherry, South India.

India's National Viral Hepatitis Control Programme recommends screening outpatients for hepatitis B at tertiary care centres. We aimed to assess the yield of screening and reasons for refusal for testing. We included adult outpatients at a tertiary care centre, South India during September and October 2019. Participants' willingness to be tested and the reasons for refusal were noted. Fingerstick blood sample was tested for HBsAg using rapid kit. Of a total of 700 participants, 157 (22%, 95% CI: 19.4-25.7%) were unwilling to be tested. Men were more unwilling (26%) compared to women (19%) (aPR 1.90 95% CI: 1.22-2.94; p = 0.004). 'Lack of time' was the most common reason reported for refusal (10%). Of 543 participants tested, 15 (2.8%, 95% CI: 1.6-4.5%) were positive for HBsAg. Similar studies from other regions in India are required for the estimation of yield of opportunistic approach.

Elucidating the impact of cottonseed hydrolysates on CHO cell culture performance through transcriptomic analysis.

In order to evaluate the impact of plant-based hydrolysates on CHO cells, a transcriptomic study was undertaken using cottonseed hydrolysate and Illumina's NextSeq transcriptomics profiling for 2 days of a batch cell culture. While cottonseed hydrolysate extended cell growth and increased antibody titer, significant effects were seen on transcriptomic signatures of supplemented cultures when compared to untreated cultures, evaluated using fold change, gene ontology (GO), and KEGG pathway analysis. Transcription and other factors commonly associated with cell growth such as those of the Atf family and homeobox proteins were upregulated while genes in the Hippo signaling pathway were downregulated. Genes involved in anabolic pathways such as gluconeogenesis and those involving protein folding and translation elongation were upregulated. GO analysis of biological processes for cottonseed-supplemented cultures indicated enrichments in DNA replication, protein processing, and unfolded protein response while molecular functions associated with growth such as GTPases, ATP binding, and aminoacyl t-RNA ligase activity were also enriched. Cellular components associated with structural integrity such as actin cytoskeleton, microtubules, mitochondrion, and Lewy body were enriched. Enriched KEGG pathways include growth-associated pathways such as cell cycle, pI3K-AKT-mTOR, and cancer-related pathways as well as those enhancing glycan metabolism, purine metabolism, amino acid biosynthesis, and protein processing in the endoplasmic reticulum (ER). These transcriptomic profiles provide insights into the roles that hydrolysates such as cottonseed can play in altering CHO cell growth and other physiological characteristics as well as suggesting ways in which CHO cell culture may be modified for enhancing performance in biotechnology applications. KEY POINTS: • Hydrolysate-supplemented cultures increased mammalian cell growth and productivity. • Fold-change analysis revealed upregulation in transcription and translation. • Enriched GOs and KEGG pathways including cell cycle and metabolism were observed.

Radiological and cadaveric study of anatomical safe zone for transoral base of tongue surgery.

The aim of this study is to identify a surgical safe zone in base of tongue surgery. Fifteen Fresh frozen cadavers (30 head and neck regions) were included in the anatomical study. Twenty-two CT-angiogram (CTA) scans of neck were included in the radiological study. Surgical safe zone for base of tongue surgery was studied in cadavers and correlated the same in CTA. Depth of the lingual artery (LA) from the tongue surface and distance of origin of lingual artery from tip of greater cornu of hyoid bone was significantly different when comparing anatomical to radiological study (p < 0.005). On protruded position of tongue, lingual artery appeared more close to the tongue surface and was never encountered posterior to foramen caecum. Preoperative CTA evaluation would over-estimate the depth of LA putting the lingual artery at risk during resection. A surgical safe zone exists posterior to foramen caecum and towards the midline.

Effect of COVID19 pandemic and national lockdown on persons with diabetes from rural areas availing care in a tertiary care center, southern India.

BACKGROUND AND AIMS: COVID-19 pandemic and lockdown measures to contain it have affected health care services globally. This study aims to assess the effect and urban-rural differences of COVID19 pandemic on diabetes care. METHODS: This cross-sectional study was conducted among persons with diabetes (PWDs) registered for care at a diabetes clinic of a tertiary care center in Southern India. We collected following information by telephonic interviews: physician consultations, access to diabetes medications and blood sugar tests, use of telemedicine services, out of pocket expenditure and psychological morbidity. RESULTS: A total of 350 PWDs were interviewed. Majority were male (78%) and from rural areas (79%). One fourth (24%) met any physician for diabetes care at least once during lockdown. PWDs from rural areas mainly consulted a physician in a private clinic (55%) compared to urban areas (26%). Two third (65%) availed medications from private medical shops. Almost half (46%) got their blood sugar tested during and majority of them (81%) reported unsatisfactory glycemic control. Only few (5%) was aware and three utilized telemedicine services. Almost all (99%) spent money (US $ 8.3) for diabetes care. One third (33%) had moderate or high psychological distress. CONCLUSIONS: Majority of PWDs did not consult a physician during lockdown. Cost of care was high. Measures to improve utilisation of telemedicine services and peripheral health facilities are needed.

Expanded Chinese hamster organ and cell line proteomics profiling reveals tissue-specific functionalities.

Chinese hamster ovary (CHO) cells are the predominant production vehicle for biotherapeutics. Quantitative proteomics data were obtained from two CHO cell lines (CHO-S and CHO DG44) and compared with seven Chinese hamster (Cricetulus griseus) tissues (brain, heart, kidney, liver, lung, ovary and spleen) by tandem mass tag (TMT) labeling followed by mass spectrometry, providing a comprehensive hamster tissue and cell line proteomics atlas. Of the 8470 unique proteins identified, high similarity was observed between CHO-S and CHO DG44 and included increases in proteins involved in DNA replication, cell cycle, RNA processing, and chromosome processing. Alternatively, gene ontology and pathway analysis in tissues indicated increased protein intensities related to important tissue functionalities. Proteins enriched in the brain included those involved in acidic amino acid metabolism, Golgi apparatus, and ion and phospholipid transport. The lung showed enrichment in proteins involved in BCAA catabolism, ROS metabolism, vesicle trafficking, and lipid synthesis while the ovary exhibited enrichments in extracellular matrix and adhesion proteins. The heart proteome included vasoconstriction, complement activation, and lipoprotein metabolism enrichments. These detailed comparisons of CHO cell lines and hamster tissues will enhance understanding of the relationship between proteins and tissue function and pinpoint potential pathways of biotechnological relevance for future cell engineering.

Sex, age, and hospitalization drive antibody responses in a COVID-19 convalescent plasma donor population.

Convalescent plasma is a leading treatment for coronavirus disease 2019 (COVID-19), but there is a paucity of data identifying its therapeutic efficacy. Among 126 potential convalescent plasma donors, the humoral immune response was evaluated using a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus neutralization assay with Vero-E6-TMPRSS2 cells; a commercial IgG and IgA ELISA to detect the spike (S) protein S1 domain (EUROIMMUN); IgA, IgG, and IgM indirect ELISAs to detect the full-length S protein or S receptor-binding domain (S-RBD); and an IgG avidity assay. We used multiple linear regression and predictive models to assess the correlations between antibody responses and demographic and clinical characteristics. IgG titers were greater than either IgM or IgA titers for S1, full-length S, and S-RBD in the overall population. Of the 126 plasma samples, 101 (80%) had detectable neutralizing antibody (nAb) titers. Using nAb titers as the reference, the IgG ELISAs confirmed 95%-98% of the nAb-positive samples, but 20%-32% of the nAb-negative samples were still IgG ELISA positive. Male sex, older age, and hospitalization for COVID-19 were associated with increased antibody responses across the serological assays. There was substantial heterogeneity in the antibody response among potential convalescent plasma donors, but sex, age, and hospitalization emerged as factors that can be used to identify individuals with a high likelihood of having strong antiviral antibody responses.

Sex, age, and hospitalization drive antibody responses in a COVID-19 convalescent plasma donor population.

Convalescent plasma is currently one of the leading treatments for COVID-19, but there is a paucity of data identifying therapeutic efficacy. A comprehensive analysis of the antibody responses in potential plasma donors and an understanding of the clinical and demographic factors that drive variant antibody responses is needed. Among 126 potential convalescent plasma donors, the humoral immune response was evaluated by a SARS-CoV-2 virus neutralization assay using Vero-E6-TMPRSS2 cells, commercial IgG and IgA ELISA to Spike (S) protein S1 domain (Euroimmun), IgA, IgG and IgM indirect ELISAs to the full-length S or S-receptor binding domain (S-RBD), and an IgG avidity assay. Multiple linear regression and predictive models were utilized to assess the correlations between antibody responses with demographic and clinical characteristics. IgG titers were greater than either IgM or IgA for S1, full length S, and S-RBD in the overall population. Of the 126 plasma samples, 101 (80%) had detectable neutralizing titers. Using neutralization titer as the reference, the sensitivity of the IgG ELISAs ranged between 95-98%, but specificity was only 20-32%. Male sex, older age, and hospitalization with COVID-19 were all consistently associated with increased antibody responses across the serological assays. Neutralizing antibody titers were reduced over time in contrast to overall antibody responses. There was substantial heterogeneity in the antibody response among potential convalescent plasma donors, but sex, age and hospitalization emerged as factors that can be used to identify individuals with a high likelihood of having strong antiviral antibody levels.

The relationship between residual sphincter damage after primary repair, faecal incontinence, and anal sphincter function in primiparous women with an obstetric anal sphincter injury.

BACKGROUND AND AIMS: Anal sphincter injury has been identified as a primary cause of post-partum fecal incontinence in women with obstetric anal sphincter injury. However, women without obstetric anal sphincter injury may also develop fecal incontinence. The aim is to determine the relationship between fecal incontinence severity; and i) residual anal sphincter injury, quantified by the Starck score, and ii) anal sphincter tone. METHODS: Consecutive case series of prospectively collected data set in a Pelvic Floor Unit within a tertiary teaching hospital in Australia. Population 181 primiparous women with Sultan classification Grade 3 and 4 sphincter injuries. MAIN OUTCOME MEASURES: Sultan classification, anal manometry, pudendal nerve terminal motor latency, St Mark's fecal incontinence score, and Starck ultrasound score. RESULTS: 45% of women reported some degree of fecal incontinence. One third of women with normal external sphincter tone were incontinent. Those with higher Starck score had higher St Mark's scores. A higher Sultan classification correlated with more severe incontinence regardless if the repair was complete. Forceps delivery had a twofold risk of incontinence when compared to non-forceps delivery. CONCLUSION: The importance of an effective anal sphincter repair is confirmed. However, overall there is no direct relationship between residual sphincter damage, anal sphincter tone, and fecal incontinence severity. These data indicate that anal sphincter integrity alone is not the sole mechanism for maintaining fecal continence. Rectal and colonic motor function may also play a role and investigation into these components may provide greater insight into the effect of vaginal delivery upon fecal continence mechanisms.

Do supportive family behaviors promote diabetes self-management in resource limited urban settings? A cross sectional study.

BACKGROUND: Self-management is an essential component of prevention and treatment of type 2 diabetes. Social and family support has been shown to influence self-management behaviors as well as glycemic control and complications. This study was conducted to assess whether diabetes family support improves diabetes self-management and glycemic control in a typical urban population in India. METHODS: A cross-sectional study using a questionnaire that had items from the Summary of Diabetes Self Care Activities Scale (SDSCA), the Diabetes Family Behavior Checklist (DFBC) and some sociodemographic and diabetes related clinical data was conducted. The participants were consecutively sampled from the diabetes outpatient department in a tertiary care hospital in Chennai, south India. RESULTS: A total of 200 consecutive patients from the diabetes outpatient department were interviewed. Diabetes self-management practices were good with respect to avoiding fatty foods and carbohydrates and undergoing regular blood testing for glucose. But the self-management with respect to exercise and foot related care was rare. It was observed that a vast majority of the patients did not report receiving any support from their families. However, in the small proportion who did receive good family support, there is an association between diabetes self-management and diabetes family support (ß = 0.527; p = 0.015). Further, the path model showed that there is a positive statistically significant association between family support score and the diabetes self-management score (ß = 0.254, p < 0.001). However, the negative association between the diabetes self-management score and the mean plasma glucose did not reach statistical significance (ß = - 46.378, p = 0.082). CONCLUSIONS: In the urban south Indian setting, family support was significantly associated with better self-management activities, but better self-management did not reflect as better glycaemic control.

Targeting HIF-2α as therapy for advanced cancers.

Hypoxia-inducible factors (HIF-1α, -2α -3α, and -ß) are key factors that control hypoxia-induced carcinogenic pathways. HIF-1α is predominantly involved in the early stages of cancer, whereas HIF-2α is actively involved in the later stages; in addition, chronic (prolonged) rather than acute (short) hypoxia is a feature of metastasis and chemoresistance that occur during the later stages of cancer. Oncometabolites, onco-miRNAs, glucose deprivation, pseudohypoxia, cytokine/chemokine secretion, and some unique upstream proteins are involved in the signaling switch from HIF-1α to HIF-2α; thus, understanding this signaling switch is critical for the treatment of advanced cancer. In this review, we highlight data relating to HIF-2α rather than HIF-1α signaling in cancer pathways and discuss prospective drugs that target this important factor.

Therapeutical potential of deregulated lysine methyltransferase SMYD3 as a safe target for novel anticancer agents.

INTRODUCTION: SET and MYND domain containing-3 (SMYD3) is a member of the lysine methyltransferase family of proteins, and plays an important role in the methylation of various histone and non-histone targets. Proper functioning of SMYD3 is very important for the target molecules to determine their different roles in chromatin remodeling, signal transduction and cell cycle control. Due to the abnormal expression of SMYD3 in tumors, it is projected as a prognostic marker in various solid cancers. Areas covered: Here we elaborate on the general information, structure and the pathological role of SMYD3 protein. We summarize the role of SMYD3-mediated protein interactions in oncology pathways, mutational effects and regulation of SMYD3 in specific types of cancer. The efficacy and mechanisms of action of currently available SMYD3 small molecule inhibitors are also addressed. Expert opinion: The findings analyzed herein demonstrate that aberrant levels of SMYD3 protein exert tumorigenic effects by altering the epigenetic regulation of target genes. The partial involvement of SMYD3 in some distinct pathways provides a vital opportunity in targeting cancer effectively with fewer side effects. Further, identification and co-targeting of synergistic oncogenic pathways is suggested, which could provide much more beneficial effects for the treatment of solid cancers.

Molecular docking of azole drugs and their analogs on CYP121 of Mycobacterium tuberculosis.

The Mycobacterium tuberculosis genome codes for 20 different cytochromes. These cytochromes are involved in the breakdown of recalcitrant pollutants and the synthesis of polyketide antibiotics and other complex macromolecules. It has been demonstrated that CYP121 is essential for viability of the bacterium by gene knock-out and complementation studies. CYP121 could therefore be a probable target for the development of new drugs for TB. It has been widely reported that orthologs of CYP121 in fungi are inhibited by azole drugs. We evaluated whether these azole drugs or their structural analogs could bind to and inhibit CYP121 of M. tuberculosis using molecular docking. Six molecules with known anti-CYP121 activity were selected from literature and PubChem database was searched to identify structural analogs for these inhibitors. Three hundred and fifty seven molecules were identified as structural analogs and used in docking studies. Fifty three molecules were found to be scored better than the azole drugs and five of them were ranked among the top 12 molecules by two different scoring functions. These molecules may be further tested by in vitro experimentation for their activity against CYP121 of M. tuberculosis.