Role of mineral nutrients other than iron in pregnancy: under recognized opportunities to improve maternal/fetal outcomes: a literature review.

BACKGROUND: Anemia during pregnancy is an important global health concern, affecting 40% of women worldwide, and iron deficiency shares a significant proportion of the burden. From conception to birth, pregnancy is a period when women undergo metabolic and physiological changes. The nutritional needs are higher during pregnancy; thus, adequate nutrition is essential to maintain fetal growth and development. However, adverse effects due to deficiency in nutrition during pregnancy can result in maternal, fetal and neonatal complications. Despite the multifactorial etiology of anemia, iron deficiency is assumed as the primary cause of anemia during pregnancy and hence, mitigation strategy pivots around it for anemia management. Therefore, excluding other contributors, a single-micronutrient approach with iron supplements remains a myopic approach and this can exacerbate iron deficiency anemia. Micronutrient deficiencies are of particular concern as they may pose a silent threat to the survival and well-being of reproductive-age women and their infants. AIM: Micronutrients, especially trace minerals, play a myriad of roles in pregnancy, and the lack of each one causes adverse complications to both the mother and the fetus. In this review paper, we attempt to piece together available information regarding the adverse effects of abnormal trace mineral levels along with iron deficiency on the mother and the fetus. METHOD: A non-systematic literature search in PubMed, Google Scholar, and the Cochrane databases, for publications on minerals and vitamins during pregnancy and the possible influence of supplements on pregnancy outcomes. CONCLUSION: Micronutrient deficiency exacerbates the pregnancy-induced anemia and other adverse birth outcomes. Micronutrient supplementation during pregnancy can combat anemia as well as reduce a number of adverse pregnancy outcomes in a comprehensive manner.

Organochlorine pesticides induce epithelial as well as inflammatory mediators following exposure to human ovarian surface epithelial cells: An in vitro study.

Although studies have suggested organochlorine pesticides (OCPs) exposure increased the risk of epithelial ovarian cancer, the mechanisms underlying its potential tumorigenic effects in the human ovary are not well understood. In this study, we investigated the impact of dichlorodiphenyldichloroethylene (DDE), endosulfan, and heptachlor exposure on epithelial cadherin (E-cadherin) and proinflammatory mediators in human ovary surface epithelial (HOSE) cells. We found that DDE, endosulfan, and heptachlor exposure resulted in epithelial differentiation accompanied by upregulation of E-cadherin expression and overexpression of proinflammatory cytokines (TNFα, IL-1ß, and IL-6) in HOSE cells. The epithelial differentiation may accelerate HOSE cells to inclusion body formation, a common site for ovarian cancer initiation and persistent exposure to OCPs creates a chronic inflammatory microenvironment that may promote the neoplastic transformation of HOSE cells within the inclusion cyst.

Modulation of mRNA Expression of IL-6 and mTORC1 and Efficacy and Feasibility of an Integrated Approach Encompassing Cognitive Behavioral Therapy Along with Pregabalin for Management of Neuropathic Pain in Postherpetic Neuralgia: A Pilot Study.

OBJECTIVE: This study was designed to explore the efficacy and feasibility of cognitive behavioral therapy (CBT) along with pregabalin and compare it with pregabalin monotherapy for the management of neuropathic pain in post-herpetic neuralgia (PHN) patients and to explore the modulation of messenger RNA (mRNA) expression of interleukin (IL)-6 and mammalian target of rapamycin-1 (mTORC1) genes in these patients. DESIGN: Randomized controlled pilot study. METHODS: The patients aged >18 years of age with an established diagnosis of PHN with evident allodynia and hyperalgesia who had pain for at least 3 months after healing of rash with pain intensity ≥4/10 on NRS-Pain Scale were enrolled. The trial was registered with the Clinical Trials Registry-India (CTRI/2019/03/018014). A detailed baseline assessment regarding type and duration of pain and disability using pain-relevant self-report questionnaires was done. Two mL venous blood samples were collected for gene expression studies at base line and at end of 12 weeks of treatment. Patients were randomized into one of the two groups. Group PR received pregabalin and Group CP received CBT along with pregabalin. The pain intensity was measured using numeric rating scale (NRS)-Pain scale, neuropathic component of the pain by using Neuropathic Pain Symptom Inventory (NPSI) and Pain Detect Questionnaire (PDQ), sleep interference by NRS-Sleep, pain-related catastrophic thoughts by using Pain Catastrophizing Scale (PCS), depression and quality of life using Beck Depression Inventory-II (BDI-II) and Short Form-12 (SF-12), respectively. The research funding was supported by the intramural grant from the institution. RESULTS: A total of 40 patients with 20 in each group were included. Following integrated approach encompassing CBT and Pregabalin, group CP had significant downregulation of mRNA expression of IL-6; however, no such correlation was observed with mTOR expression. A significant decline in the intensity of pain, NPSI scoring for burning, allodynia, and pain-related catastrophizing were observed; also a significant improvement in depressive symptoms and quality of life were observed with the use of CBT. CONCLUSIONS: A significant downregulation of mRNA expression of IL-6 was observed; however, no significant correlation was observed between NRS pain score and ΔCt values of mRNA expression of both mTORC1 gene and IL-6 gene at baseline and at the end of 12th week. In addition, we note a significant decrease in pain intensity, depressive symptoms, and pain-related catastrophizing while improving QOL was observed with the use of CBT as a clinical adjunct along with pregabalin in PHN patients.

Modulation of the Extracellular Signal-Regulated Protein Kinase and Tissue Inhibitors of Matrix Metalloproteases-1 Gene in Chronic Neuropathic Pain.

OBJECTIVES: The aim of this study is to study the modulation of extracellular signal-regulated protein kinase (ERK) and tissue inhibitors of matrix metalloproteases 1 (TIMP 1) gene in patients with neuropathic pain (NP). MATERIALS AND METHODS: In the present, cross-sectional, observational study, 2 ml of venous baseline sample was withdrawn from all the patients with neuropathic (NP) or non NP (NNP) soon after their diagnosis or on their first visit to the pain clinic. A real-time quantitative polymerase chain reaction experiment was conducted to measure the mRNA expression of TIMP1 and ERK genes in blood samples. The Delta Ct, Delta Ct, and fold change analysis of both the genes were conducted between patients with NP and NNP. RESULTS: A total of 285 patients with chronic pain were assessed, out of which, 153 patients had NP and 132 had NNP. The average duration of chronic pain was 11 months for 285 patients. The mRNA expression of TIMP1 gene is significantly down regulated (2.65-fold) (P (-f. 01), and the mRNA expression level of ERK is significantly up regulated (2.03-fold) (P (-f. 01) in NP patients when compared with NNP. CONCLUSION: The mRNA expression of TIMP1 gene is significantly down regulated, and ERK is significantly up regulated in patients with NP. Further, multicentric trials with larger sample size are recommended to confirm this finding.

Significance of MMP-9 and VEGF-C expression in North Indian women with breast cancer diagnosis.

Metastasis accounts for the majority of cancer-associated mortality and renders the targeted therapy fruitless in the patients of breast cancer. Matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF-C) are thought to be involved in tumor progression and metastasis. The aim of this study was to investigate the expression of MMP-9 and VEGF-C at both mRNA and protein levels in breast cancer and to correlate with lymph node metastasis and other clinicopathological characteristics. Biopsy specimens (N = 100) of breast cancer & benign breast disease (N = 100) were investigated for the mRNA expression of MMP-9 and VEGF-C by Real-time PCR and Protein expression by Western blot. Elevated levels of MMP-9 (p < 0.001) and VEGF-C (p < 0.001) expression were detected in breast cancer with corresponding to benign breast disease. Additionally, we found significantly increased levels of MMP-9 and VEGF-C in node-positive group with respect to node-negative group. Moreover, the levels of MMP-9 were significantly increased in larger tumor size (T3/T4) (p < 0.05) as compared to smaller size (T1/T2), which suggests that MMP-9 plays an important role in the progression of breast cancer. VEGF-C expression was associated with the TNM stage of tumor (p < 0.05). Further, a significant positive correlation was established between the mRNA levels of these two genes (p < 0.001). However, we could not obtain any significant correlation between expression of these genes with other clinicopathological parameters like tumor grade, age, menopausal status, and receptor status like ER, PR, and Her2. This study suggests that the high expression of MMP-9 and VEGF-C could act as markers for the tumor presence in breast cancer. In addition, this study recommends that expression of MMP-9 and VEGF-C was significantly associated with lymph node status and may provide valuable diagnosis of lymph node metastasis in breast cancer patients. Further, MMP-9 expression was associated with the tumor size and VEGF-C expression was correlated with the staging of the tumor, although no association was observed with other clinicopathological variables.

PAX1 Methylation Status in Cervical Scrapes as Novel Diagnostic Biomarker in CIN 2/3 and Invasive Squamous Cell Carcinoma.

Objectives: DNA methylation of paired box-1 (PAX-1) gene has been shown to be a potential biomarker for the detection of high-grade cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer. The objective of this pilot study was to quantify and compare methylation percentage of PAX1 gene in benign cervical lesion, pre-invasive and invasive cervical cancer. Methods: A total of 200 screen positive women (VIA, VILI and Pap test) underwent colposcopy. Cervical scrapes taken were taken and stored for DNA analysis and PAX 1 methylation status. Women with Swede score of 5 or more (n = 98) were biopsied. Cervical scrapes and biopsy were taken from women with obvious cervical growth (n = 14), without prior colposcopy. Sixty women were recruited to the study and allocated into three groups on the basis of histopathology, i.e., benign cervix (Group 1; n = 20), CIN 2/3 (Group 2; n = 20) and invasive cervical carcinoma (Group; n = 20). PAX 1 methylation percentage was calculated from the DNA extracted from the cervical scrapes of the women recruited. Results: The mean PAX1 methylation percentage in benign lesions, CIN 2/3 and invasive cancer was 9.58% (SD ± 2.37%), 18.21% (SD ± 2.67%) and 24.34% (SD ± 4.09%), respectively, with p-value of < 0.001. Conclusions: PAX 1 gene methylation has a promising role in identifying high-grade lesions and invasive cancer.

Utilization of Artificial Intelligence in Disease Prevention: Diagnosis, Treatment, and Implications for the Healthcare Workforce.

Artificial intelligence (AI) has been described as one of the extremely effective and promising scientific tools available to mankind. AI and its associated innovations are becoming more popular in industry and culture, and they are starting to show up in healthcare. Numerous facets of healthcare, as well as regulatory procedures within providers, payers, and pharmaceutical companies, may be transformed by these innovations. As a result, the purpose of this review is to identify the potential machine learning applications in the field of infectious diseases and the general healthcare system. The literature on this topic was extracted from various databases, such as Google, Google Scholar, Pubmed, Scopus, and Web of Science. The articles having important information were selected for this review. The most challenging task for AI in such healthcare sectors is to sustain its adoption in daily clinical practice, regardless of whether the programs are scalable enough to be useful. Based on the summarized data, it has been concluded that AI can assist healthcare staff in expanding their knowledge, allowing them to spend more time providing direct patient care and reducing weariness. Overall, we might conclude that the future of "conventional medicine" is closer than we realize, with patients seeing a computer first and subsequently a doctor.

An overview on possible management strategies for coffee white stem borer Xylotrechus quadripes Chevrolat (Coleoptera: Cerambycidae) in Nepal.

The Coffee White Stem Borer (CWSB) is one of the most dreadful and destructive pests of coffee in Asian nations, causing significant production loss each year. CWSB has a narrow host range, with Coffea arabica as their principal host. Once they bore into the stem of C. arabica, the whole plant must be uprooted. The study on the cumulative effects of the invasion of pests in the Nepalese agriculture system is quite vague. Farmers use a variety of methods to combat CWSB, but most of them are ineffective and wasteful. To effectively combat pests, it is important to understand the variety and abundance of natural enemies as well as the botanicals that have pesticide potential. If the management of CWSB in the Nepalese context goes unaddressed, it will prompt an alarming issue to coffee production in Nepal. Hence, it is of utmost necessity to develop rational management strategies of CWSB for promoting organic coffee in Nepal, which has garnered a reputation of excellent quality in the global market. This paper seeks to provide comprehensive information on the CWSB's management technique for using bio-rational compounds to aid Nepalese farmers cultivating organic coffee.

Predictors of Nonconvulsive Seizure and Their Effect on Short-term Outcome.

INTRODUCTION: Nonconvulsive seizures (NCSs) are common in critically ill adult patients with acute neurologic conditions. However, the effect of NCSs on patient outcome remains unclear. In this study, we aimed to determine the effect of NCSs on short-term outcome and to assess the clinical and EEG factors associated with NCSs. METHODS: We retrospectively identified 219 adult patients from the EEG reporting system who underwent continuous EEG (cEEG) monitoring between January 2018 and June 2018. Patients with anoxic brain injury were excluded from the study. Clinical, laboratory, and EEG data were reviewed to determine potentially predictive factors of NCSs. The impact of NCSs on in-hospital mortality, length of stay, and disability on discharge was measured; an modified Rankin scale of three or greater was considered disabled. RESULTS: Of the 219 patients included in our study, a total of 14% (n = 31) had NCSs on continuous EEG, of which 42% (n = 13) had their first seizure discharge recorded during the first hour of continuous EEG monitoring. The presence of clinical seizures before continuous EEG (odds ratio = 1.787; 95% confidence interval = 1.197-2.667, P = 0.0045), history of epilepsy (odds ratio = 1.508; 95% confidence interval = 1.027-2.215, P = 0.035), and comatose state (29 vs. 16%; P = 0.0006) were associated with NCSs. Among EEG characteristics, the presence of interictal epileptiform discharges (P < 0.0001), lateralized rhythmic delta activity (P = 0.02), and lateralized periodic discharges (P < 0.0001) were associated with NCSs. Nonconvulsive seizures were significantly associated with longer in-hospital stay (23.68 ± 24.84 vs. 17.14 ± 20.52; P = 0.036) and disability on discharge (87% [n = 27] vs. 13% [n = 4], P = 0.02). However, there was no significant association between NCS and in-hospital mortality (9.6% [n = 3] vs. 10.6% [n = 20]; P = 0.1). CONCLUSIONS: Nonconvulsive seizures are associated with longer in-hospital stay and disability on discharge but not with in-hospital mortality in adult patients.

Early neurologic decline in acute ischemic stroke patients receiving thrombolysis with large vessel occlusion and mild deficits.

BACKGROUND: We sought to determine the rate of early neurologic decline (END) in patients with acute ischemic stroke (AIS) with large vessel occlusion (LVO) who presented with mild deficits and received intravenous tissue plasminogen activator (IVtPA). METHODS: Among 1022 patients with AIS who received IVtPA from 2014 to 2019, we identified 313 (30.6%) with LVO, of which 94 (30%) presented with National Institute of Health Stroke Scale (NIHSS) score ≤7. Thirteen patients were excluded, leaving 81 for analysis. END was defined as NIHSS worsening of ≥4 points within 24 hours. RESULTS: Among 81 patients with LVO and low NIHSS score, the mean age was 65.8 years (range 25-93) and 41% were female. The mean time to IVtPA from last known well was 2.5 hours (range 0.8-7). LVO sites were as follows: 5 (6%) carotid, 23 (28%) M1, and 53 (65%) M2 occlusions. Among the 81 patients, 28 (34.6%) had END, and these patients were older (70.8 vs 63.2 years, p=0.036). The mean change in NIHSS score at 24 hours in those with END was 10.4 (range 4-22). Patients with END were less likely to be discharged home (25% vs 66%, p=0.004). CONCLUSIONS: Among patients with LVO AIS who received IVtPA, 30% presented with initial mild deficits. END occurred in one-third of LVO patients with initial mild deficits despite receiving IVtPA. Clinicians should be aware that the natural history of LVO with initial mild deficits is not benign and these patients are eligible for rescue thrombectomy in the 24-hour window if they deteriorate.

Lorazepam timing for acute convulsive seizure control (LoTASC).

INTRODUCTION: Guidelines specify early administration of benzodiazepines (BZD) for the management of convulsive status epilepticus. The distinction between acute convulsive seizure and status epilepticus can be misconstrued resulting in BZD administration prior to a patient meeting criteria of status epilepticus. Early BZD administration may theoretically lead to systemic vital instability. Our study aims to assess if administering lorazepam, for convulsive seizures <5 min, causes vital instability. METHODS: This is a retrospective study analyzing patients who presented with a seizure lasting <5 min between 2011 and 2016. Continuous variables of lorazepam receivers versus non- receivers were analyzed using t-test for parametric and Mann-Whitney U test for nonparametric data. Categorical variables were analyzed using Chi-Square Test. Subsequently, subjects were analyzed through univariate and multivariate regression models to determine predictors of vital instability. RESULTS: Out of 1052 subjects initially screened, 165 were included. Of these, 91 (55 %) received lorazepam, and 74 (45 %) did not. Through univariate and multivariate analyses, there was a significantly higher incidence of vital instability (defined as receipt of a vasopressor or intubation) in patients who received lorazepam (OR = 6.76, 95 % CI = 1.48, 30.95) (p = 0.014). This was dose-dependent (p < 0.0001). It was responsible for 22.5 % of the vital instability. Lorazepam administration significantly prolonged the intensive care unit (ICU) length of stay (0 days [IQR 0 - 0] vs [IQR 0-2.3]; p = 0.038). CONCLUSION: Our study suggests that lorazepam administration for acute convulsive seizures not meeting convulsive status epilepticus criteria may lead to iatrogenic vital instability and need for ICU admission.

Down Regulation of KAI1/CD82 in Lymph Node Positive and Advanced T-Stage Group in Breast Cancer Patients.

BACKGROUND: Metastasis represents a deadly aspect of any cancer including breast cancer, given its high prevalence; treatment of metastatic breast cancer remains a clinically unmet need, which necessitates the exploration of metastasis suppressor genes (MSGs). KAI-1/CD82 is an important member of MSGs; the role of KAI1 has been well explored in prostate cancer, however its role in breast cancer is not fully explored and in fact the results of breast cancer studies are contentious. Thus, the present study aimed to investigate expression of KAI1 at both transcriptional and translational levels in the tissue of breast cancer patients and benign breast disease. Further, we analysed the relationship between expression levels of KAI1 and clinicopathological parameters in breast cancer patients. MATERIALS AND METHODS: mRNA expression was studied by Real time PCR and protein expression was analyzed by both Western blot and Immunohistochemistry. RESULTS: The results of the study indicate that KAI1 expression was remarkably decreased in breast cancer both at the gene and the protein levels (P < 0.05) compared to benign breast disease. In addition, KAI1 expression levels were strongly associated with axillary lymph node status and advanced T stage (p < 0.05), however no association was found with tumor grade, age, menopausal status and receptor status like ER, PR and Her2. CONCLUSION: Low expression of KAI1 might be helpful for predicting the lymph node metastasis and T staging, thus predicts malignant prognosis of breast cancer.
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High Resolution Based Quantitative Determination of Methylation Status of CDH1 and VIM Gene in Epithelial Ovarian Cancer.

BACKGROUND: DNA promoter methylation is widely explored epigenetic phenomena, known to effect gene expression and further perturbation in cellular homeostasis. Myriad of studies have leveraged promoter methylation and its potential as biomarker for various types of cancer. Aim of present study is to investigate promoter methylation of CDH1 and VIM gene and etiology of epithelial ovarian cancer (EOC). METHODS: Most of previous studies were qualitative; we have quantitatively assessed methylation levels in 50 EOC cases and control each through high recognition melt (HRM) technique. RESULTS: At 10 % cutoff for CDH1 94% of EOC cases were found to be methylated with mean methylation of 45±13.8, whereas for control mean methylation was found to be 7.3±3.7 amongst 16 % methylation positive control samples. For VIM methylation was detected in 96% of cases with mean of 50.44±11.7 in EOC and in 12% methylation positive samples for control mean methylation was 6.24±4.3. CONCLUSION: In short HRM based DNA methylation can serve as a robust and sensitive diagnostic method for promoter methylation detection and as a biomarker for early epithelial ovarian cancer detection.

Effect of Environmental Exposure and Pharmacogenomics on Drug Metabolism.

BACKGROUND: Pesticides are major xenobiotic compounds and environmental pollutants, which are able to alter drug-metabolizing enzyme as well as pharmacokinetics of drugs. Subsequent to the release of the human genome project, genetic variations (polymorphism) become an integral part of drug development due to their influence on disease susceptibility/ progression of the disease and their impact on drug absorption, distribution, metabolism of active metabolites and finally excretion of the drug. Genetic polymorphisms crucially regulate pharmacokinetics and pharmacodynamics of drugs under the influence of physiological condition, lifestyle, as well as pathological conditions collectively. OBJECTIVE: To review all the evidence concerning the effect of environmental exposure on drug metabolism with reference to pharmacogenomics. METHODS: Scientific data search and review of basic, epidemiological, pharmacogenomics and pharmacokinetics studies were undertaken to evaluate the influence of environmental contaminants on drug metabolism. RESULTS: Various environmental contaminants like pesticides effectively alter drug metabolism at various levels under the influence of pharmacogenomics, which interferes with pharmacokinetics of drug metabolism. Genetic polymorphism of phase I and phase II xenobiotic-metabolizing enzymes remarkably alters disease susceptibility as well as the progression of disease under the influence of various environmental contaminants at various levels. CONCLUSION: Individual specific drug response may be attributed to a large variety of factors alone or in combination ranging from genetic variations (SNP, insertion, deletion, duplication etc.) to physiological setting (gender, age, body size, and ethnicity), environmental or lifestyle factors (radiation exposure, smoking, alcohol, nutrition, exposure to toxins, etc.); and pathological conditions (obesity, diabetes, liver and renal function).