ASSOCIATION OF THYROID DYSFUNCTION IN WOMEN PRESENTING WITH MENSTRUAL PROBLEMS.

Background; Menstrual disorders frequently affect the quality of life of adolescents and young adult women, especially those who suffer dysmenorrhoea and heavy menstruation. Different studies have associated thyroid dysfunction with menstrual problems. This study was conducted to document the frequency of hypothyroidism in women with menstrual problems. Objective; To determine frequency of thyroid dysfunction in women having menstrual problems at a tertiary care hospital.  Material and methods; All the study cases (227) who meet inclusion and exclusion criteria of my study were taken from OPD of the Department of Gynecology and Obstetrics, Nishtar Hospital Multan.  Once registered, 5 ml venous blood sample was taken and sent to the central laboratory of the Nishtar Hospital Multan for serum TSH and T4 levels by a pathologist having minimum 5 years experience after post-graduation.   Hypothyroidism was determined on laboratory report after serum analysis for TSH and T4. Data was analyzed by using SPSS Version 20. Results; Mean age of our study cases was noted to be 24.08± 4.65 years. Of these 227 study cases, 134 (59 %) were married while 93 (41%) were unmarried. Mean body mass index (BMI) of our study cases was 22.31 ± 2.70 kg/m2 , 160 (70.5%) were normal weight, 51 (22.5%) were overweight and 16 (7%) were obese. Secondary amenorrhea was noted in 25 (11%), oligomenorrhea in 42 (18.5%),  polymenorrhea in 16 (7%), heavy menstrual bleeding in 59 (26%) and irregular menstrual bleeding in 85 (37.5%). Mean serum TSH level of our study cases was 4.85 ± 0.91 mIU/L while mean T4 level was noted to be 86.90 ± 38.81 nmol/L and hypothyroidism was noted in 176 (77.5%) of our study cases. Overt hypothyroidism was noted in 75 (33 %) and subclinical hypothyroidism in 101 (44.5%) of our study cases. Conclusion; Very high frequency of thyroid dysfunction was noted in women having menstrual problems in our study. Thyroid dysfunction was significantly associated with residential status, obesity, poor socioeconomic status, level of education and type of menstrual problem. Our study results suggest that women presenting with menstrual problems must be screened for thyroid hormones for proper management of these patients. Keywords; Thyroid dysfunction, Menstrual problems, subclinical hypothyroidism, overt hypothyroidism. DOI: 10.7176/JMPB/67-06 Publication date:August 31st 202

FREQUENCY OF ANEMIA AMONG WOMEN PRESENTING WITH SHORT INTER-PREGNANCY INTERVAL AT A TERTIARY CARE HOSPITAL.

Background; The time interval between pregnancies is considered to be an important and modifiable risk factor in terms of adverse perinatal outcomes. This study was done to  determine the frequency of anemia in pregnant women having short interpregnancy interval. Materials and methods; All the pregnant women with short interpregnancy interval were registered from Department of Gynecology and Obstetrics, Nishtar Hospital Multan, Pakistan. Examination was done including general physical examination. Those with interpregnancy interval less than 6 months were included in study. Detailed history was taken regarding parity, duration of pregnancy. Duration of gestation was estimated according to patients last menstrual period. Three ml venous blood sample was drawn and sent to the pathology laboratory of Nishtar Hospital Multan for Hb levels analysis. Data was entered and analyzed by SPSS version 20. Results; Mean age of our study cases was noted to be 27.83 ± 4.95 years (with minimum age of our study cases was 21 years while maximum age was noted to be 38 years). Of these 90 study cases, 51 (56.7%) were from rural areas, 73 (81.1%) were normal weight 11(12.2%) were overweight and 6 (6.7%) were obese. Seventy eight (86.7%) were illiterate. Of these 90 study cases, 73 (81.1%) were having poor socioeconomic status, 11 (12.2%) were diabetic and 17 (18.9%) were hypertensive. Mean body mass index (BMI) of our study cases was noted to be 22.31 ± 2.07 Kg/m2. Mean gestational age of our study cases was noted to be 24.02 ± 8.31 weeks. Mean Hb level was noted to 10.67 ± 0.893 g/dl (with minimum Hb level was 9.6 g/dl while maximum Hb level was 12.5 g/dl). Mean interpregnancy interval was 4.23 ± 0.98 months (with minimum interpregnancy interval was 2.5 months while maximum interpregnancy interval was 6 months). Anemia was noted in 74 (82.2%) our study cases and only 23 (25.6%) of our study cases were taking iron supplements. Conclusion; Short interpregnancy interval less than 6 months is related with adverse pregnancy outcomes. Very high frequency of anemia was noted in our study cases having interpregnancy interval less than 6 months. Anemia was significantly associated with residential status, hypertension and iron supplementation. Birth spacing is an issue which women should have some control over. Educational interventions, including birth control, should be applied during prenatal visits and following delivery.Keywords; Short interpregnancy Interval, anemia, hemoglobin.DOI: 10.7176/JMPB/67-05Publication date:August 31st 202

Human linker histones: interplay between phosphorylation and O-β-GlcNAc to mediate chromatin structural modifications

Eukaryotic chromatin is a combination of DNA and histone proteins. It is established fact that epigenetic mechanisms are associated with DNA and histones. Initial studies emphasize on core histones association with DNA, however later studies prove the importance of linker histone H1 epigenetic. There are many types of linker histone H1 found in mammals. These subtypes are cell specific and their amount in different types of cells varies as the cell functions. Many types of post-translational modifications which occur on different residues in each subtype of linker histone H1 induce conformational changes and allow the different subtypes of linker histone H1 to interact with chromatin at different stages during cell cycle which results in the regulation of transcription and gene expression. Proposed O-glycosylation of linker histone H1 promotes condensation of chromatin while phosphorylation of linker histone H1 is known to activate transcription and gene regulation by decondensation of chromatin. Interplay between phosphorylation and O-β-GlcNAc modification on Ser and Thr residues in each subtype of linker histone H1 in Homo sapiens during cell cycle may result in diverse functional regulation of proteins. This in silico study describes the potential phosphorylation, o-glycosylation and their possible interplay sites on conserved Ser/Thr residues in various subtypes of linker histone H1 in Homo sapiens

Impact of tobacco price and taxation on affordability and consumption of tobacco products in the Southeast Asia Region : a systematic review

Introduction: The objective of the review was to study the impact of tobacco taxes or prices on affordability and/or consumption of tobacco products in WHO-South East Asia Region (SEAR) countries, overall, and by socioeconomic status; and change in consumption of one tobacco product for a given change in price/tax on other tobacco product. Methods: The searches were run on five databases (Medline, Embase, Cinahl, EconLit, Tobacconomics) using keywords such as ‘tobacco’, ‘tax’, ‘price’, ‘impact’ with their synonyms. Additionally, first 100 articles through google search and e-reports from targeted sources were also reviewed. Studies illustrating the impact of prices/taxes on consumption/affordability of tobacco products in SEAR, available in English language, with no limitation on time were included in the review. After two steps of screening, data from 28 studies were extracted using a structured, and pre-tested data extraction form. Results: Out of the total twenty-eight studies, twelve studies reported an inverse association between price and consumption/affordability while 11 studies reported no or positive association between price and consumption/affordability of tobacco products. Five studies had unclear interpretations. Majority of studies estimated that the less affluent group were more price responsive as compared to the more affluent group. Some studies indicated increased consumption of one product in response to price rise of other product, although, the findings were inconsistent. Conclusions: The findings of our review support the use of tobacco tax and price measures as effective tools to address the tobacco epidemic. Our findings however also emphasise the importance of increasing tobacco product taxes and prices sufficiently to outweigh the effects of income growth, in order for the measures to be effective in reducing the affordability and consumption of tobacco products

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

A sociological study about the causes and consequences of milk adulteration: A case study of district Faisalabad

Extraordinary nourishing significance of milk as well as comparative lower price related to other diets containing protein made it a particular portion of dietetics amongst the inhabitants around the globe. Conversely, the amplified demand of milk globally made it disposed to gigantic intensities of deceitful actions. It is a highly risky product for falsified deeds for getting economic gains where culprits can intensify nutrition protection threats and reduce nutritious worth by deliberated contamination along with the deficiency of maintenance, negligence in deprived cleanliness circumstances, no refrigeration conveniences. Current study was directed to expose the causes, harmful consequences and solutions for the prevention of this menace. For this purpose, 60 respondents from supply chain conveniently and 150 respondents from consumer chain systematically. Due to adulteration in milk, it became considerably low nutritious levels which also be lethal for community well-being exposed through current milk adulteration outrages which caused risky issues related to socio-economic conditions in addition to psychological and serious health concerns related to stomach, eye sight, cardiac, renal, and lever failure due to hazardous additives used as adulterants in milk

Serine 204 phosphorylation and O-<it>β</it>-GlcNAC interplay of IGFBP-6 as therapeutic indicator to regulate IGF-II functions in viral mediated hepatocellular carcinoma

Abstract Hepatocellular carcinoma is mainly associated with viral hepatitis B and C. Activation of cell growth stimulator IGF-II gene is observed in tumor formation especially in viral associated hepatocellular carcinoma. Elevated IGF-II levels are indicator of increased risk for cholangiocellular and hepatocellular carcinomas through over saturation of IGF-II binding capacities with IGF receptors leading to cellular dedifferentiation. In HCV, core protein is believed to trans-activate host IGF-II receptor through PKC pathway and the inhibition of tumor cell growth can be achieved by blocking IGF-II pathway either at transcriptional level or increasing its binding with IGFBPs (Insulin like growth factor proteins) at C-terminal, so that it is not available in free form. IGFBP-6 is a specific inhibitor of IGF-II actions. Affinity of IGFBPs with IGFs is controlled by post-translational modifications. Phosphorylation of IGFBPs inhibits IGFs action on target cells while O-glycosylation prevents binding of IGFBP-6 to glycosaminoglycans and cell membranes and resulting in a 10-fold higher affinity for IGF-II. O-glycosylation and phosphorylation operate the functional expression of cellular proteins, this switching on and off the protein expression is difficult to monitor in vivo. By using neural network based prediction methods, we propose that alternate O-β-GlcNAc modification and phosphorylation on Ser 204 control the binding of IGFBP-6 with IGF-II. This information may be used for developing new therapies by regulating IGFBP-6 assembly with IGF-II to minimize the risk of viral associated hepatocellular carcinoma. We can conclude that during HCV/HBV infection, O-β-GlcNAc of IGFBP-6 at Ser 204 diminish their binding with IGF-II, increase IGF-II cellular expression and promote cancer progression which can lead to hepatocellular carcinoma. Furthermore, this site can be used for developing new therapies to control the IGF-II actions during viral infection to minimize the risk of hepatocellular carcinoma.</p

Serine 204 phosphorylation and O-β-GlcNAC interplay of IGFBP-6 as therapeutic indicator to regulate IGF-II functions in viral mediated hepatocellular carcinoma

Hepatocellular carcinoma is mainly associated with viral hepatitis B and C. Activation of cell growth stimulator IGF-II gene is observed in tumor formation especially in viral associated hepatocellular carcinoma. Elevated IGF-II levels are indicator of increased risk for cholangiocellular and hepatocellular carcinomas through over saturation of IGF-II binding capacities with IGF receptors leading to cellular dedifferentiation. In HCV, core protein is believed to trans-activate host IGF-II receptor through PKC pathway and the inhibition of tumor cell growth can be achieved by blocking IGF-II pathway either at transcriptional level or increasing its binding with IGFBPs (Insulin like growth factor proteins) at C-terminal, so that it is not available in free form. IGFBP-6 is a specific inhibitor of IGF-II actions. Affinity of IGFBPs with IGFs is controlled by post-translational modifications. Phosphorylation of IGFBPs inhibits IGFs action on target cells while O-glycosylation prevents binding of IGFBP-6 to glycosaminoglycans and cell membranes and resulting in a 10-fold higher affinity for IGF-II. O-glycosylation and phosphorylation operate the functional expression of cellular proteins, this switching on and off the protein expression is difficult to monitor in vivo. By using neural network based prediction methods, we propose that alternate O-β-GlcNAc modification and phosphorylation on Ser 204 control the binding of IGFBP-6 with IGF-II. This information may be used for developing new therapies by regulating IGFBP-6 assembly with IGF-II to minimize the risk of viral associated hepatocellular carcinoma. We can conclude that during HCV/HBV infection, O-β-GlcNAc of IGFBP-6 at Ser 204 diminish their binding with IGF-II, increase IGF-II cellular expression and promote cancer progression which can lead to hepatocellular carcinoma. Furthermore, this site can be used for developing new therapies to control the IGF-II actions during viral infection to minimize the risk of hepatocellular carcinoma

Socio-Economic Status (SES) differences in changing affordability of tobacco products from 2011-12 to 2018-19 in India

INTRODUCTION We studied the change in affordability of tobacco products, an important determinant of tobacco use, across the different socio-economic status (SES) in India. METHODS We calculated affordability in the form of relative income price (RIP-cost of tobacco products relative to income) for years 2011-12 and 2018-19 using three different denominators, i.e., per capita Gross Domestic Product (GDP) and Net State Domestic Product (NSDP) at national and state levels, respectively; monthly per capita consumer expenditure (MPCE); and individual wages. We investigated RIP for cigarettes, bidis and smokeless tobacco (SLT) across different SES groups (caste groups, type of employment and education). RESULTS RIP increased marginally for cigarettes, bidis and remained almost constant for SLT across casual workers. However, when RIP was adjusted with SES variables, there was no significant change (p>0.05) in affordability of products for casual workers in year 2018-19 as compared to 2011-12. For regular workers, cigarettes and bidis became marginally less affordable (βvariables SLT reported no change in affordability. There was a marginal increase in affordability for all products when RIP was calculated with GDP. CONCLUSION Although implementation of GST has increased the price of tobacco products, it is still not sufficient to reduce the affordability of tobacco products, particularly SLT and especially for the lower SES group