Multi-omics and machine learning for the prevention and management of female reproductive health.

Females typically carry most of the burden of reproduction in mammals. In humans, this burden is exacerbated further, as the evolutionary advantage of a large and complex human brain came at a great cost of women's reproductive health. Pregnancy thus became a highly demanding phase in a woman's life cycle both physically and emotionally and therefore needs monitoring to assure an optimal outcome. Moreover, an increasing societal trend towards reproductive complications partly due to the increasing maternal age and global obesity pandemic demands closer monitoring of female reproductive health. This review first provides an overview of female reproductive biology and further explores utilization of large-scale data analysis and -omics techniques (genomics, transcriptomics, proteomics, and metabolomics) towards diagnosis, prognosis, and management of female reproductive disorders. In addition, we explore machine learning approaches for predictive models towards prevention and management. Furthermore, mobile apps and wearable devices provide a promise of continuous monitoring of health. These complementary technologies can be combined towards monitoring female (fertility-related) health and detection of any early complications to provide intervention solutions. In summary, technological advances (e.g., omics and wearables) have shown a promise towards diagnosis, prognosis, and management of female reproductive disorders. Systematic integration of these technologies is needed urgently in female reproductive healthcare to be further implemented in the national healthcare systems for societal benefit.

Comparative Evaluation of Serum High-sensitivity C-Reactive Protein and Complete Hemogram Indices in Subjects with and without Apical Periodontitis: A Prospective Interventional Study.

INTRODUCTION: This study aimed to compare the levels of high-sensitivity C-reactive protein (hsCRP) and complete hemogram (CH) parameters before and after root canal treatment in patients with apical periodontitis (AP) and healthy controls. METHODS: Twenty-five patients with asymptomatic AP in a single permanent tooth were recruited along with age- and sex-matched healthy controls. Baseline serum hsCRP and CH parameters were recorded in both groups. Root canal treatment was performed in teeth with AP, and biochemical parameters were re-evaluated at the 6-month follow-up. Mann-Whitney and chi-square tests were used to analyze data quantitatively and qualitatively, respectively. Spearman correlation was applied to explore the relation between hsCRP with AP and periapical healing. Multivariate linear regression tests were used to assess the effect of independent variables such as age, sex, body mass index, and periapical index score on levels of hsCRP. RESULTS: A baseline comparison between patients with AP (3.37 ± 2.69 mg/L) and controls (1.69 ± 2.2 mg/L) revealed a significant difference in hsCRP levels. However, all CH parameters were within the reference range. A total of 22 patients in the AP group completed follow-up, and based on the periapical index score and clinical presentations, 72.2% of patients were classified as healed. At follow-up, hsCRP significantly reduced to 1.79 ± 1.65 mg/L in the AP group. A significant correlation between AP and hsCRP was observed. CONCLUSIONS: Patients with AP had a significantly higher inflammatory burden than healthy controls, which significantly reduced after root canal treatment. No significant change was detected in CH indices.

Heme oxygenase-1 in osteosarcoma.

AIM OF STUDY: The present study was planned to analyze serum heme oxygenase-1 levels in osteosarcoma patients. MATERIALS AND METHODS: Twenty five histopathologically confirmed cases of osteosarcoma localized without metastasis of all the ages attending the Orthopedic Clinics were included in the study group and twenty five patients having musculoskeletal pain (age and sex matched) served as control. Five ml of venous blood was collected aseptically from antecubital vein and serum was be separated by centrifugation and analyzed the same day. Routine biochemistry investigations were performed as per standard enzymatic methods by autoanalyzer. Serum Heme oxygenase-1 was analyzed by enzyme-linked immunosorbent assay. RESULTS: In osteosarcoma patients, serum HO-1 levels were increased as compared to patients having musculoskeletal pain (P < 0.05). Workers have found that HO-1 induction in prostate cancer cell lines (PC3) cells restored the proliferation of osteoblasts, which was inhibited during co-culture with parental prostate cancer cell line PC3 cells. However, no concrete data are available on blood levels of HO in osteosarcoma. Major role of HO-1 is the protection against oxidative injury, additionally, it regulates cell proliferation, modulates inflammatory response and facilitates angiogenesis. CONCLUSION: Findings of the present study suggests that pharmacological agents that regulate HO activity or HO-1 gene silencing may become powerful tools for preventing the onset or progression of various cancers and sensitize them to anticancer therapies.

Serum iron, Folate, Ferritin and CD4 Count in HIV Seropositive Women.

HIV infects cluster of differentiation 4 (CD4) T-lymphocytes, monocytes and macrophages resulting in decreased number and function of CD4 cells, changes that affect both cell mediated and humoral immunity. Hematological abnormalities are a common complication of human immune virus (HIV) infection and these abnormalities increase as the disease advances. Anemia is the most common haematological abnormality in HIV seropositive patients and its incidence is strongly associated with the progression of the disease. The aim of present study was to assess the haematological profile of HIV seropositive women and compare them with CD4 count. Two hundred seropositive females (age 18-25 years) attending antiretroviral therapy clinic were selected. Routine gynaecological and haematological investigations were carried out, study samples were drawn and serum iron, folate and ferritin were analysed by chemiluminiscence and CD4 count was determined by using flow-cytometry. Anemia was prevalent in seropositive women especially in those with low CD4 levels. Serum folate and ferritin levels were significantly lower in females with lower CD4 levels. Serum iron levels were higher at low CD4 levels. The mean CD4 count in HIV seropositive anaemic women were lower as compared to non anaemics suggesting that anaemia improves with higher CD4 cell counts. Plasma folate and ferritin levels are sensitive predictor of anaemia in early HIV infections and these patients should have a regular monitoring of their folate and ferritin levels especially with lower CD4 levels.

Evaluation of Homocysteine, Vitamin B12 and Folic Acid Levels During all the Trimesters in Pregnant and Preeclamptic Womens.

BACKGROUND: Folate, vitamin B12 and vitamin B6 are required for homocysteine metabolism and their deficiency can result in increased homocysteine concentration. Homocysteine concentrations have been found to be increased in late pregnancy toward nonpregnant values. OBJECTIVE: To study folate, vitamin B12 and homocysteine levels in cord blood and maternal blood in preeclampsia. MATERIALS AND METHODS: One hundred fifty pregnant women attending Out Patient Department of Department of Obstetrics and Gynaecology were recruited for the study. Grouped as: GROUP I (control): Fifty normotensive women with singleton pregnancy immediately after delivery; GROUP II (study): Fifty (age and gestation matched women with singleton pregnancy) women with preeclampsia immediately after delivery; GROUP III (study): Fifty normotensive pregnant women were recruited in first trimester (8-12 weeks) that were followed in second (24-28 weeks) and third trimester (32-36 weeks). Homocysteine, vitamin B12 and folic acid levels were investigated by competitive immunoassay using direct chemiluminiscence technology. RESULTS: Homocysteine and folic acid levels were higher in maternal blood of hypertensive pregnant women as compared to normotensive pregnant women (p<0.001, p>0.05 respectively). Vitamin B12 levels were lower in maternal blood of hypertensive pregnant women as compared to normotensive pregnant women. Levels of homocysteine were higher in cord blood of hypertensive pregnant women as compared to normotensive pregnant women (p<0.01). Levels of vitamin B12 and folic acid was lower in cord blood of preeclamptic women as compared to normotensive pregnant women (p<0.001, p<0.01 respectively). A negative correlation was found between homocysteine and folic acid levels of mothers in group II that was statistically significant. CONCLUSION: Elevated homocysteine and folate and vitamin B12 deficiency during pregnancy may be a risk factor for preeclampsia and future risk of cardiovascular risk.

Biomarkers in Preeclamptic Women with Normoglycemia and Hyperglycemia.

The present study was planned to assess IGF-1, leptin and cholinesterase levels in maternal blood of both normoglycaemics and hyperglycaemics preeclampsia. Twenty five normotensive pregnant women at the time of delivery were selected in as group I and sub grouped according to blood glucose less than or more than 85 mg/dL as I A (<85mg/dL) and I B (>85mg/dL). Study group (group II, n=25) comprised of preeclamptic women and was further divided into group II A (<85mg/dL) and group II B (>85mg/dL). Routine biochemical investigations along with IGF-1, leptin and cholinesterase levels were analyzed in maternal and cord blood of preeclamptic and normotensive pregnant women. Serum IGF-1 levels were significantly lower in preeclamptic women and more so in those with hyperglycemia. Cord blood IGF-1 levels were nearly doubled in hyperglycemic preeclamptics as compared to normoglycemic preeclamptics. Leptin levels were higher in preeclamptic women and more in hyperglycemic preeclamptics. Cholinesterase levels were lowered in preeclamptic mothers and higher in hyperglycemics. Cord blood cholinesterase levels were reduced in preeclamptics, more so in hyperglycaemics as compared to group I. Diet recommendation, avoidance of excessive weight gain and healthy life style, exercise and nutritional interventions may be beneficial in these women.

Homocysteine, a biomarker of osteosarcoma.

AIM OF STUDY: The present study was planned to analyze the status of serum homocysteine (hcy), folate, and Vitamin B 12 in patients with osteosarcoma. MATERIALS AND METHODS: The present study was conducted on 60 orthopedics patients who were divided into two groups, group I with 30 patients of osteosarcoma and group II with 30 patients with musculoskeletal pain. RESULTS: The present study indicated that serum folate and hcy levels were increased in osteosarcoma patients and decreased Vitamin B 12 in osteosarcoma patients when compared to controls. CONCLUSION: Lowered serum Vitamin B 12 levels are possibly due to increased metabolic demand of the tumor. Raised hcy levels could be due to the contribution from rapidly proliferating cells. The present study suggests that these parameters can serve as useful markers for diagnosis and follow-up of disease.

Plasma malondialdehyde (MDA) and anti-oxidant status in diabetic retinopathy.

Hyperglycaemia and dyslipidaemia in diabetes mellitus induce increased lipid peroxidation and peroxyl radical formation is an important mechanism in genesis of micro-angiopathy. We took up a study on oxidative stress as measured by lipid peroxidation marker, malondialdehyde (MDA) and antioxidant enzyme status in type 2 diabetes mellitus patients with and without retinopathy and compared them with a control non-diabetic group. MDA was significantly elevated (p < 0.001) in both the diabetic groups whereas antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT) and reduced glutathione (GSH), etc, were significantly decreased (p < 0.001) which might be helpful in risk assessment of various complications of diabetes mellitus. The study included 100 subjects of age group 50-70 years, out of which 50 patients were non-insulin dependent diabetes mellitus (NIDDM) with retinopathy and rest 50 age and sex matched apparently healthy individuals (control group). The status of fasting blood sugar (FBS), postprandial blood sugar (PPBS), total cholesterol (TC), triglyceride (Tg), HDL-cholesterol, LDL-cholesterol, VLDL- cholesterol, GPx, GR, CAT, SOD, MDA were determined. The results showed significant increase (p < 0.001) in FBS, PPBS, TC, TG, LDL-C, VLDL-C, CAT, MDA while HDL-C, GSH, GPx, GR and SOD were found to be decreased significantly (p < 0.001). The data suggest that alteration in anti-oxidant status and MDA may help to predict the risk of diabetic retinopathy.

Niveles de homocisteína, vitamina B12 y ácido fólico en sangre materna y de cordón umbilical en la hipertensión inducida por el embarazo / Study of maternal and cord blood levels of homocysteine, vitamin B12 and folic acid in pregnancy induced hypertension

Los datos relativos a los factores de riesgo cardiovascular en la sangre del cordón umbilical de los recién nacidos hijos de madres con preeclampsia son muy limitados. El presente estudio fue diseñado para investigar la relación entre la concentración de homocisteína, vitamina B12 y ácido fólico en el suero materno y en el suero venoso del cordón umbilical de los respectivos neonatos. Para este estudio se seleccionaron cincuenta mujeres con hipertensión inducida por el embarazo (grupo II) para comparar sus niveles de homocisteína, vitamina B12 y ácido fólico con los de cincuenta embarazadas normotensas (grupo I). Los valores medios de homocisteína y ácido fólico fueron mayores en la sangre materna de las embarazadas hipertensas que en la sangre de las normotensas (p < 0.001 y p > 0.05, respectivamente). El valor medio de vitamina B12 fue menor en la sangre materna de las embarazadas hipertensas, en comparación con la sangre de las normotensas (p > 0.05). Los valores promedio de homocisteína y ácido fólico fueron mayores en la sangre del cordón umbilical de las embarazadas hipertensas que en la sangre del cordón de las normotensas (p < 0.001 y p < 0.01, respectivamente). El valor promedio de la vitamina B12 fue menor en la sangre del cordón umbilical de las embarazadas hipertensas en comparación con la sangre del cordón de las normotensas (p < 0.01). Se encontró una asociación positiva entre la homocisteína fetal y la edad gestacional del feto en el momento del parto en el grupo II. Se observó una asociación negativa entre los niveles de homocisteína y ácido fólico de las madres en el grupo II, que fue estadísticamente significativa

Niveles de homocisteína, vitamina B12 y ácido fólico en sangre materna y de cordón umbilical en la hipertensión inducida por el embarazo / Study of maternal and cord blood levels of homocysteine, vitamin B12 and folic acid in pregnancy induced hypertension

Los datos relativos a los factores de riesgo cardiovascular en la sangre del cordón umbilical de los recién nacidos hijos de madres con preeclampsia son muy limitados. El presente estudio fue diseñado para investigar la relación entre la concentración de homocisteína, vitamina B12 y ácido fólico en el suero materno y en el suero venoso del cordón umbilical de los respectivos neonatos. Para este estudio se seleccionaron cincuenta mujeres con hipertensión inducida por el embarazo (grupo II) para comparar sus niveles de homocisteína, vitamina B12 y ácido fólico con los de cincuenta embarazadas normotensas (grupo I). Los valores medios de homocisteína y ácido fólico fueron mayores en la sangre materna de las embarazadas hipertensas que en la sangre de las normotensas (p < 0.001 y p > 0.05, respectivamente). El valor medio de vitamina B12 fue menor en la sangre materna de las embarazadas hipertensas, en comparación con la sangre de las normotensas (p > 0.05). Los valores promedio de homocisteína y ácido fólico fueron mayores en la sangre del cordón umbilical de las embarazadas hipertensas que en la sangre del cordón de las normotensas (p < 0.001 y p < 0.01, respectivamente). El valor promedio de la vitamina B12 fue menor en la sangre del cordón umbilical de las embarazadas hipertensas en comparación con la sangre del cordón de las normotensas (p < 0.01). Se encontró una asociación positiva entre la homocisteína fetal y la edad gestacional del feto en el momento del parto en el grupo II. Se observó una asociación negativa entre los niveles de homocisteína y ácido fólico de las madres en el grupo II, que fue estadísticamente significativa (AU)

Fluoride levels and osteosarcoma.

CONTEXT: Osteosarcoma is a rare malignant bone tumor, commonly occurring in the age group of 10 to 24 years. Recent reports have indicated that there is a link between fluoride exposure and osteosarcoma. AIMS: The present study was planned to analyze serum levels of fluoride in patients of osteosarcoma and fluoride content of their drinking water. SETTINGS AND DESIGN: The present study was carried out comparing 10 patients of osteosarcoma and 10 healthy volunteers (who served as controls). MATERIALS AND METHODS: Serum and drinking water fluoride levels were estimated by ion selective electrode. STATISTICAL ANALYSIS USED: The data were computed as mean ± SD and Student's t test was applied. RESULTS: Both, the serum and drinking water fluoride levels, were significant by higher in patients with osteosarcoma as compared to controls (P > 0.05, P > 0.001, respectively). CONCLUSIONS: These results suggest a link between fluoride exposure and osteosarcoma.

Birth weight, cord blood lipoprotein and apolipoprotein levels in Indian newborns.

OBJECTIVES: Primordial prevention of chronic disease is of clinical and public health importance. Considering the fetal onset of atherosclerosis, we aimed to determine the cord blood level of lipoproteins and apolipoproteins as well as their correlation with birth weight and gestational age. METHODS: This cross-sectional study comprised 100 healthy Indian newborns. Ten ml. of cord blood was collected from placental end of umbilical vein. Serum was separated by centrifugation and analyzed on the same day for lipid profile including total cholesterol (TC), triglycerides (TG), high density lipoprotein- cholesterol (HDL-C), very low density lipoproteincholesterol (VLDL) and low density lipoprotein-cholesterol (LDL-C), apolipoproteins A-I and B (ApoA-I, ApoB). Atherogenic index (AI) was calculated as the ratio of ApoB to ApoA-I. RESULTS: Cord blood of female newborns had higher TC, HDL-C, LDL-C, Apo A-I, Apo B and AI as compared to male newborns, whereas TG and VLDL-C were higher in male than in female newborns. Significant positive correlation was observed between cord blood Apo A-I and HDL-C (r= 0.45, p<0.01), and between cord blood Apo-B and LDL-C (r= 0.44, p<0.01). Non-significant inverse correlation was observed between Apo A-I and ApoB with gestational age. There was a significant inverse correlation between TG and gestational age (r= -0.197, p <0.05). Positive non-significant correlation was observed between AI and birth weight (r=0.046, p>0.05). CONCLUSIONS: These findings are another confirmatory evidence for the association of prenatal factors with cord blood lipid profile, and can serve as starting point for studying lipid transport system changes during early life.

Serum markers in pre-eclampsia.

Preeclampsia occurs approximately in 10% of pregnancies and remains a leading cause of maternal and neonatal mortality and morbidity worldwide, particularly in developing countries. The condition is usually diagnosed in late pregnancy by the presence of hypertension with proteinuria and/ or edema. Prevention of any disease process requires knowledge of its etiology and pathogenesis, as well as the availability of methods for prediction of those at high risk for this disorder. Numerous clinical, biophysical, and biochemical tests have been proposed for prediction or early detection of preeclampsia. This review will explore the current tests available in the evaluation of hypertensive complications of pregnancy.

Thyroid hormones in pregnancy and preeclampsia.

OBJECTIVE: There is a state of hypothyroxinemia in normal pregnancy and in preeclampsia, when biochemically raised TSH occurs. Identification of changes in thyroid hormones in preeclampsia might be of help in preventing the occurrence of preeclampsia. MATERIAL AND METHODS: The present study was carried out in a hundred women with preeclampsia, 100 age- and parity matched normotensive pregnant women and 50 age-matched healthy non-pregnant women. Thyroid hormones [total T3,T4 and TSH], serum albumin and uric acid were analyzed in these subjects. RESULTS: Women with preeclampsia had higher TT3, TT4 levels as compared to non pregnant women [p<0.05], but preeclamptic TT3, TT4 levels were lower compared to normotensive pregnant women [p<0.05, p<0.01]. TSH levels were higher in both preeclamptic & normotensive pregnant women compared to nonpregnant women [p<0.001] and levels were lower in normotensive pregnant women as compared to nonpregnant women [p<0.001]. A significant negative correlation was observed between birth weight and TSH levels [r=-0.296, p<0.001] serum albumin and TSH levels in preeclamptic women [r=-0.781, p<0.01]. Also, a significant positive correlation was observed between birth weight and albumin [r=0.298, p<0.001]; birth weight and serum uric acid levels [r=-0.46, p<0.01], and serum albumin and TT3 & TT4 levels [r=0.409 & r=0.35, p<0.01 respectively]. CONCLUSION: These findings indicate that there is state of hypothyroxinemia in normal pregnancy and in preeclampsia. Identification of changes in thyroid hormones in preeclampsia might be of help in preventing the occurrence of preeclampsia.

Biomarkers of periodontitis in oral fluids.

Matrix metalloproteinases (MMPs), the key enzymes responsible for matrix degradation, are derived from polymorphonuclear leukocytes during the early stages of periodontitis. The present study determined the levels of GCF matrix metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) and salivary MMP-8 in patients with gingivitis and periodontitis and in healthy controls. Levels of crevicular MMP-2, MMP-9 and salivary MMP-8 were determined by ELISA in subjects with healthy gingiva (n = 15), gingivitis (n = 18) and periodontitis (n = 20). Significantly higher salivary MMP-8 and crevicular MMP-9 were observed in cases of periodontitis compared to gingivitis and healthy adults. On the other hand, crevicular MMP-2 levels in periodontitis subjects were lower than those in gingivitis and healthy subjects. The three MMP levels were highly correlated to probing depth, and bleeding on probing. Salivary MMP-8, crevicular MMP- 2 and 9 may serve as biomarkers of periodontal disease and aid in early detection of periodontitis or gingivitis.

Salivary vitamins E and C in oral cancer.

Lipid peroxidation may be involved in cancer and essential nutrients that can scavenge free radicals, such as vitamins E and C, operate in concert. Levels of antioxidant vitamins E and C were estimated in 50 patients with oral cancer and 24 healthy persons served as control. Significantly lower levels of vitamins E and C were observed in oral cancer patients as compared to controls (P < 0.011). Antioxidant nutrients may be utilized to a greater extent in oral cancer patients to counteract free radical-mediated cell disturbances, resulting in a reduction in salivary antioxidant levels.

Plasma tocopherol levels: a preliminary reference range.

Alpha-tocopherol level was measured spectrofluorometrically in 279 healthy volunteers to establish reliable reference values and to compare possible sex and age-related differences. In the present study, men had higher tocopherol levels than women (p<0.05) and older subjects had lower values. This study provides reference values for alpha-tocopherol that may assist it evaluating the anti-oxidant defense.

Antioxidant status in neonatal jaundice before and after phototherapy.

Phototherapy has been related to increased oxidative stress and lipid peroxidation. In the present study, thirty full term jaundiced neonates with appropriate weight were analyzed before and after completion of phototherapy for malondialdehyde (MDA), reduced glutathione (GSH), total thiols, vitamin C and superoxide dismutase (SOD) levels in hemolysate and albumin levels in plasma. These parameters were analyzed in cord blood samples of 20 healthy neonates as control. It was observed that levels of MDA were elevated significantly (p<0.001) in patients as compared to controls and that the levels increased significantly after phototherapy (p<0.001). Levels of SOD were also found to be increased significantly as compared to controls and the levels rose after phototherapy (p<0.001). On the other hand, the levels of non-enzymatic antioxidants such as GSH, total thiols and vitamin C were significantly low (p<0.001) as compared to controls and the levels decreased significantly after phototherapy (p<0.001). The plasma albumin levels also were found to be decreased significantly after phototherapy (p<0.01). Therefore, phototherapy increases oxidative stress and should be used with care.