Effect of oropharyngeal colostrum therapy on neonatal sepsis in preterm neonates: A systematic review and meta-analysis.

Various studies have shown that oropharyngeal colostrum application (OPCA) is beneficial to preterm neonates. We performed a systematic review and meta-analysis to assess whether OPCA reduces the incidence of culture-proven neonatal sepsis in preterm neonates. Randomized controlled trials comparing OPCA with placebo or standard care in preterm neonates were included. Medline, Embase, Web of Science, Cumulated Index to Nursing and Allied Health Literature, Scopus, and CENTRAL were searched for studies published up to June 15, 2023. We used the Cochrane Risk of Bias tool, version 2, for risk of bias assessment, the random-effects model (RevMan 5.4) for meta-analysis, and Gradepro software for assessing the certainty of evidence. Twenty-one studies involving 2393 participants were included in this meta-analysis. Four studies had a low risk of bias, whereas seven had a high risk. Oropharyngeal colostrum significantly reduced the incidence of culture-proven sepsis (18 studies, 1990 neonates, risk ratio [RR]: 0.78, 95% confidence interval [95% CI]: 0.65, 0.94), mortality (18 studies, 2117 neonates, RR: 0.73, 95% CI: 0.59, 0.90), necrotizing enterocolitis (NEC) (17 studies, 1692 neonates, RR: 0.59, 95% CI: 0.43, 0.82), feeding intolerance episodes (four studies, 445 neonates, RR: 0.59, 95% CI: 0.38, 0.92), and the time to full enteral feeding (19 studies, 2142 neonates, mean difference: -2 to 21 days, 95% CI: -3.44, -0.99 days). There was no reduction in intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, ventilator-associated pneumonia, neurodevelopmental abnormalities, hospital stay duration, time to full oral feeding, weight at discharge, pneumonia, and duration of antibiotic therapy. The certainty of the evidence was high for the outcomes of culture-positive sepsis and mortality, moderate for NEC, low for time to full enteral feeding, and very low for feeding intolerance. OPCA reduces culture-positive sepsis and mortality (high certainty), NEC (moderate certainty), and time to full enteral feeding (low certainty) in preterm neonates. However, scarcity of data from extremely premature infants limits the generalizability of these results to this population.

Contemporary approaches in the management of uterine leiomyomas.

BACKGROUND: Leiomyomas (fibroids), the most common benign solid tumours in females, originate from the myometrium and are associated with poor quality of life for patients. The current management of uterine leiomyomas mainly includes surgical interventions such as hysterectomy and myomectomy, either by laparoscopy or laparotomy, which have several complications and are not ideal for preserving fertility. Therefore, there is a need to develop or repurpose medical treatments that do not require surgical intervention. OBJECTIVE: Many drugs are used to treat the symptoms associated with uterine fibroids. The main objective of this systematic review is to give an up-to-date account of potential pharmacological agents (non-surgical methods) for the management of uterine leiomyomas. SEARCH STRATEGY: PubMed was searched for scientific and clinical literature using the keyword 'uterine fibroids' along with the drug names described in each section. For example, 'uterine fibroids' and 'ulipristal acetate' were the keywords used to search for literature on ulipristal acetate (UPA). RESULTS: Various preclinical and clinical studies have shown that some drugs and herbal formulations exhibit activity in the management of uterine leiomyomas. Recent studies found that drugs such as UPA, elagolix, EC313, asoprisnol, nutritional supplements and herbal preparations were helpful in treating the symptoms associated with uterine leiomyomas. CONCLUSION: Many drugs show efficacy in patients with symptomatic uterine fibroids. UPA is one of the most studied and prescribed medicines for uterine fibroids; however, its usage has been restricted due to a few recent incidences of hepatic toxicity. Herbal drugs and natural supplements have also shown promising effects on uterine fibroids. The synergistic effects of nutritional and herbal supplements have been reported in certain cases, and should be studied in detail. Further research is warranted to identify the mode of action of the drugs, and to determine the precise conditions that would explain the causes of toxicity in some patients.

Role of Autoerythrocyte Sensitization Test in the Diagnosis of Recurrent Spontaneous Bruising.

Introduction: Psychogenic purpura, also known as autoerythrocyte sensitization syndrome, is a rare condition which is characterized by spontaneous development of painful purpura, or ecchymoses. Skin lesions are usually preceded by stress and emotional trauma. It is usually a diagnosis of exclusion after ruling out history of trauma, drug intake and other bleeding disorders. Autoerythrocyte sensitization test (AEST) and a psychiatric evaluation helps in the diagnosis and treatment. Objective: To demonstrate the importance of AEST in diagnosing the patient of Gardner Diamond syndrome. Materials and Methods: Five suspected cases of autoerythrocyte sensitization syndrome underwent AEST after ruling out other causes of bleeding. Results: Four out of five patients were positive for AEST while one patient was negative. Psychiatric complaints were present in three patients. One patient was lost to follow up. Rest all patients responded well to vitamin C supplementation. Conclusion: Autoerythrocyte sensitization syndrome is a rare disorder and is a diagnosis of exclusion, so a thorough workup of the patient to rule out common causes of bruising is essential. A high index of suspicion on the clinician's part and a simple OPD-based AEST may help in the diagnosis. Psychiatric consultation is important to find out the stress factor and timely management.

Oropharyngeal application of colostrum or mother's own milk in preterm infants: a systematic review and meta-analysis.

CONTEXT: Many preterm neonates often cannot be fed enterally and hence do not receive the benefits of colostrum. Oropharyngeal application of colostrum is a novel way of harnessing the immunological benefits of colostrum. Randomized controlled trials (RCTs) investigating the efficacy of this approach have shown variable results. OBJECTIVE: The aim of this systematic review was to synthesize available data on the effect of oropharyngeal application of colostrum or mother's own milk (CMOM) in preterm infants. DATA SOURCES: Six electronic databases (MEDLINE, Embase, CINAHL, Scopus, Web of Science, and Cochrane Library) were searched until January 13, 2022. Only RCTs comparing oral application of CMOM with placebo/routine care in preterm infants were eligible. Studies enrolling term neonates or administering enteral feeds were excluded. DATA EXTRACTION: Two investigators independently extracted data using a structured proforma. DATA ANALYSIS: The Cochrane Risk of Bias 2 tool was used to assess bias. Random-effects meta-analysis was undertaken using RevMan 5.4 software. From 2787 records identified, 17 RCTs enrolling 4106 preterm infants were included. There was no significant difference between groups in incidence of necrotizing enterocolitis (NEC) stage 2 or higher (RR = 0.65; 95%CI, 0.36-1.20; 1089 participants in 12 trials). Application of CMOM significantly reduced the incidence of sepsis (RR = 0.72; 95%CI, 0.56-0.92; 1511 participants in 15 studies) and any stage of NEC (RR = 0.58; 95%CI, 0.37-0.92; 1616 participants in 16 trials). The CMOM group achieved full enteral feeds 1.75 days sooner (95%CI, 0.3-3.2 days; 1580 participants in 14 studies) and had higher weight at discharge (MD = 43.9 g; 95%CI, 3-85 g; 569 participants in 3 studies). There were no statistically significant differences in other outcomes. CONCLUSIONS: Evidence with low to very low certainty suggests CMOM has a beneficial effect on NEC (any stage), sepsis, and time to full enteral feeds. Given its low cost and minimal risk of harm, routine CMOM use may be considered in preterm neonates. PROSPERO REGISTRATION NUMBER: CRD42021262763.

Diagnosis, Treatment and Prevention of Nutritional Anemia in Children: Recommendations of the Joint Committee of Pediatric Hematology-Oncology Chapter and Pediatric and Adolescent Nutrition Society of the Indian Academy of Pediatrics.

JUSTIFICATION: Anemia in children is a significant public health problem in our country. Comprehensive National Nutrition Survey 2016-18 provides evidence that more than 50% of childhood anemia is due to an underlying nutritional deficiency. The National Family Health Survey-5 has reported an increase in the prevalence of anemia in the under-five age group from 59% to 67.1% over the last 5 years. Clearly, the existing public health programs to decrease the prevalence of anemia have not shown the desired results. Hence, there is a need to develop nationally acceptable guidelines for the diagnosis, treatment and prevention of nutritional anemia. OBJECTIVE: To review the available literature and collate evidence-based observations to formulate guidelines for diagnosis, treatment and prevention of nutritional anemia in children. PROCESS: These guidelines have been developed by the experts from the Pediatric Hematology-Oncology Chapter and the Pediatric and Adolescent Nutrition (PAN) Society of the Indian Academy of Pediatrics (IAP). Key areas were identified as: epidemiology, nomenclature and definitions, etiology and diagnosis of iron deficiency anemia (IDA), treatment of IDA, etiology and diagnosis of vitamin B12 and/or folic acid deficiency, treatment of vitamin B12 and/or folic acid deficiency anemia and prevention of nutritional anemia. Each of these key areas were reviewed by at least 2 to 3 experts. Four virtual meetings were held in November, 2021 and all the key issues were deliberated upon. Based on review and inputs received during meetings, draft recommendations were prepared. After this, a writing group was constituted which prepared the draft guidelines. The draft was circulated and approved by all the expert group members. RECOMMENDATIONS: We recommend use of World Health Organization (WHO) cut-off hemoglobin levels to define anemia in children and adolescents. Most cases suspected to have IDA can be started on treatment based on a compatible history, physical examination and hemogram report. Serum ferritin assay is recommended for the confirmation of the diagnosis of IDA. Most cases of IDA can be managed with oral iron therapy using 2-3 mg/kg elemental iron daily. The presence of macro-ovalocytes and hypersegmented neutrophils, along with an elevated mean corpuscular volume (MCV), should raise the suspicion of underlying vitamin B12 (cobalamin) or folic acid deficiency. Estimation of serum vitamin B12 and folate level are advisable in children with macrocytic anemia prior to starting treatment. When serum vitamin B12 and folate levels are unavailable, patients should be treated using both drugs. Vitamin B12 should preferably be started 10-14 days ahead of oral folic acid to avoid precipitating neurological symptoms. Children with macrocytic anemia in whom a quick response to treatment is required, such as those with pancytopenia, severe anemia, developmental delay and infantile tremor syndrome, should be managed using parenteral vitamin B12. Children with vitamin B12 deficiency having mild or moderate anemia may be managed using oral vitamin B12 preparations. After completing therapy for nutritional anemia, all infants and children should be advised to continue prophylactic iron-folic acid (IFA) supplementation as prescribed under Anemia Mukt Bharat guidelines. For prevention of anemia, in addition to age-appropriate IFA prophylaxis, routine screening of infants for anemia at 9 months during immunization visit is recommended.

Medical postgraduate (MD) program in Laboratory Medicine in India: The Past, Present and Future.

A medical postgraduate course in the field of Laboratory Medicine for the Bachelor of Medicine and Bachelor of Surgery (MBBS) degree holders has existed for more than two decades in India, initiated and offered by the All India Institute of Medical Sciences, New Delhi, which was created under the special Act of Parliament of India 1956. This course has recently been included in the draft of National Medical Commission's Post Graduate Regulation 2021 list of medical courses, and the foundation guidelines have been laid for other medical colleges and teaching hospitals across the country to start this course. This article, written purely in academic interest, describes the past, present and future of this postgraduate training program in India with an aim to answer several doubts regarding this unique and holistic course with a view to providing a direction to those who are willing to become a laboratory physician through this post-graduation.

The spectrum of ABO haemolytic disease of the fetus and newborn in neonates born to group O mothers.

BACKGROUND AND OBJECTIVES: ABO haemolytic disease of the fetus and newborn (HDFN) is a lesser recognized entity; however, the severity may vary in neonates. This prospective observational study was performed to determine the severity and risk of ABO-HDFN in neonates born to O group mothers. MATERIALS AND METHODS: A total of 260 neonates born to non-alloimmunized blood group O mothers were recruited. Blood group O neonates were excluded from the study. Neonatal direct antiglobulin test (DAT) was performed using the column agglutination technique. They were monitored for clinical and laboratory parameters and followed up at 6-8 weeks. The maternal anti-A and anti-B titres (IgM and IgG) were also done. RESULTS: A total of 176 neonates with blood group A (77/260; 29.6%) and B (99/260; 38.1%) were finally included in the study, and 15 (8.5%) of them were DAT positive. Overall, 26.7% (47/176) neonates received phototherapy, 172 (97.7%) survived and none required readmission. The median (inter-quartile range [IQR]) maternal IgG anti-B titre (32 [32-64]) was significantly higher (p < 0.001) than the IgG anti-A titre (16 [8-64]). The maximum total serum bilirubin in neonates had a significant positive association with neonatal birth weight (p = 0.045), positive DAT (p = 0.006) and requirement of phototherapy (p < 0.001). The relative risk (95% CI) of a DAT-positive neonate requiring phototherapy was 4.55 (3.12-6.33). CONCLUSION: The frequency of ABO incompatibility in neonates born to group O mothers was 67.69% (176/260). The maternal IgG titre of ≥64 could be a good predictor for identifying the neonates at risk of developing hyperbilirubinaemia requiring phototherapy.

Withania somnifera - a magic plant targeting multiple pathways in cancer related inflammation.

BACKGROUND: Deregulated inflammatory responses are known to play a pivotal role in cancer initiation and progression. Tumor microenvironment is associated with the presence of a diverse array of inflammatory reactions, which further help tumor growth, metastasis and drug resistance. Withania somnifera is known to curb proliferation of cancer cells and lower inflammatory responses. PURPOSE: In order to minimize the inflammation, cancer treatments often include immunomodulatory drugs. However, given the side effects of both of the cytotoxic cancer drugs and synthetic immunomodulatory agents, there is a need to develop novel anti-inflammatory agents for improved cancer therapy. A number of reports indicate that bioactive phytochemicals derived from W. somnifera exhibit anti-inflammatory capabilities in cancer. A deeper look into the underlying molecular mechanisms implicated in W. somnifera mediated anti inflammation is lacking, which is essential to fully understand the potential of this magical plant in cancer. Therefore, in the present review we are summarizing various reports, which describe mechanistic understanding of W. somnifera in cancer related inflammation. STUDY DESIGN AND METHODOLOGY: In order to gather information on the molecular pathways affected by W. somnifera in cancer related inflammation, 'PubMed' and 'Science Direct' databases were searched using keywords Withania, cancer inflammation, and Withaferin A. Selected literature was analyzed to cover the role of inflammation in cancer, usage and side effects of anti-inflammatory drugs, W. somnifera as an immunomodulatory agent in cancer, molecular pathways modulated by W. somnifera in various preclinical models, and clinical trials using W. somnifera as an anti-inflammatory agent. RESULTS: Upon literature survey we found that both W. somnifera extracts and Withaferin-A, exhibit anti inflammatory activities in various preclinical cancer models. W. somnifera modulates a number of signaling pathways such as NF-kB, JAK-STAT and AP1 to reduce cancer related inflammation. Anti inflammatory properties of W. somnifera might be effective in the treatment of drug resistance in cancers. Based on its promising effects against cancer associated inflammation in preclinical studies, W. somnifera derived products are being tested in clinical trials. CONCLUSION: Several preclinical studies demonstrated anti-inflammatory potential of W. somnifera in a variety of cancers. While a few clinical trials are investigating the role of W. somnifera in various diseases, focused studies on its role in cancer related inflammation are lacking. Additionally, its anti-inflammatory effects offer targeting of senescence associated secretory phenotype (SASP), which is speculated to play a critical role in chemoresistance. Apart from targeting cancer cell proliferation, anti-inflammatory effects of Withania provide double advantage in cancer management. Therefore, clinical trials to target cancer related inflammation using W. somnifera as a drug, should be performed to validate its advantages in cancer therapy.

MRP5 and MRP9 play a concerted role in male reproduction and mitochondrial function.

Multidrug Resistance Proteins (MRPs) are transporters that play critical roles in cancer even though the physiological substrates of these enigmatic transporters are poorly elucidated. In Caenorhabditis elegans, MRP5/ABCC5 is an essential heme exporter because mrp-5 mutants are unviable due to their inability to export heme from the intestine to extraintestinal tissues. Heme supplementation restores viability of these mutants but fails to restore male reproductive deficits. Correspondingly, cell biological studies show that MRP5 regulates heme levels in the mammalian secretory pathway even though MRP5 knockout (KO) mice do not show reproductive phenotypes. The closest homolog of MRP5 is MRP9/ABCC12, which is absent in C. elegans, raising the possibility that MRP9 may genetically compensate for MRP5. Here, we show that MRP5 and MRP9 double KO (DKO) mice are viable but reveal significant male reproductive deficits. Although MRP9 is highly expressed in sperm, MRP9 KO mice show reproductive phenotypes only when MRP5 is absent. Both ABCC transporters localize to mitochondrial-associated membranes, dynamic scaffolds that associate the mitochondria and endoplasmic reticulum. Consequently, DKO mice reveal abnormal sperm mitochondria with reduced mitochondrial membrane potential and fertilization rates. Metabolomics show striking differences in metabolite profiles in the DKO testes, and RNA sequencing shows significant alterations in genes related to mitochondrial function and retinoic acid metabolism. Targeted functional metabolomics reveal lower retinoic acid levels in the DKO testes and higher levels of triglycerides in the mitochondria. These findings establish a model in which MRP5 and MRP9 play a concerted role in regulating male reproductive functions and mitochondrial sufficiency.

Oral Application of Colostrum and Mother's Own Milk in Preterm Infants-A Randomized, Controlled Trial.

OBJECTIVES: To evaluate the effects of oral application of mother's own milk (OMOM) on clinical outcomes in preterm infants of 260/7-306/7 wk gestation. METHODS: In this placebo-controlled randomized trial, subjects received either OMOM or sterile water, beginning at 24-72 h of life, until the infant reached 32 wk postmenstrual age or spoon-feeds were initiated, whichever was earlier. The primary outcome was a composite adverse health outcome, defined as the occurrence of either mortality, late-onset sepsis (LOS), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), or retinopathy of prematurity (ROP). Antibiotic usage and time to full enteral feed were secondary outcomes. Salivary IgA (sIgA) levels at baseline and after 7 d of application in a subset of infants were also compared. RESULTS: A total of 133 neonates (66 colostrum and 67 placebo) were analyzed for the primary outcome. OMOM group had lower incidence of composite adverse health outcome (43.9% vs. 61.2%, RR: 0.70; 95% CI: 0.50-0.99, p = 0.046) and LOS (22.7% vs. 43.3%, RR: 0.73; 95% CI: 0.57-0.93; p = 0.012). There were no significant differences in mortality, NEC, IVH, BPD, ROP, and time to full feeds. The effects were more pronounced in the 290/7-306/7 wk subgroup, in whom the colostrum group also achieved full feeds earlier. There were no differences in the change of sIgA levels from baseline to the seventh day of the application. No adverse effects related to the OMOM application were found. CONCLUSIONS: OMOM decreases the incidence of late-onset sepsis in preterm neonates (260/7-306/7 wk) and is safe. TRIAL REGISTRATION: Clinical Trials Registry-India CTRI/2017/03/008031.

Indian Academy of Pediatrics Revised (2021) Guidelines on Prevention and Treatment of Vitamin D Deficiency and Rickets.

JUSTIFICATION: The emerging literature on prevalence of vitamin D deficiency in India, prevention and treatment strategies of rickets, and extra-skeletal benefits of vitamin D suggest the need for revising the existing guidelines for prevention and treatment of vitamin D deficiency in India. OBJECTIVES: To review the emerging literature on vitamin D prevalence and need for universal vitamin D supplementation. To suggest optimum vitamin D therapy for treatment of asymptomatic and symptomatic vitamin D deficiency, and rickets. To evaluate the extra-skeletal health benefits of vitamin D in children. PROCESS: A National consultative committee was formed that comprised of clinicians, epidemiologists, endocrinologists, and nutritionists. The Committee conducted deliberations on different aspects of vitamin D deficiency and rickets through ten online meetings between March and September, 2021. A draft guideline was formulated, which was reviewed and approved by all Committee members. RECOMMENDATIONS: The group reiterates the serum 25-hydroxy vitamin D cutoffs proposed for vitamin D deficiency, insufficiency, and sufficiency as <12 ng/mL, 12-20 ng/mL and >20 ng/mL, respectively. Vitamin D toxicity is defined as serum 25OHD >100 ng/mL with hypercalcemia and/or hypercalciuria. Vitamin D supplementation in doses of 400 IU/day is recommended during infancy; however, the estimated average requirement in older children and adolescents (400-600 IU/day, respectively) should be met from diet and natural sources like sunlight. Rickets and vitamin D deficiency should be treated with oral cholecalciferol, preferably in a daily dosing schedule (2000 IU below 1 year of age and 3000 IU in older children) for 12 weeks. If compliance to daily dosing cannot be ensured, intermittent regimens may be prescribed for children above 6 months of age. Universal vitamin D supplementation is not recommended in childhood pneumonia, diarrhea, tuberculosis, HIV and non-infectious conditions like asthma, atopic dermatitis, and developmental disorders. Serum 25-hydroxy vitamin D level of >20 ng/mL should be maintained in children with conditions at high-risk for vitamin deficiency, like nephrotic syndrome, chronic liver disease, chronic renal failure, and intake of anticonvulsants or glucocorticoids.

Effectiveness of community-based treatment programs for treatment of uncomplicated severe acute malnourished children aged 6-59 months using locally produced nutrient dense foods: protocol for a multicentric longitudinal quasi-experimental study.

BACKGROUND: Severe acute malnutrition (SAM) is a major underlying cause of mortality among children. Around one third of the world's acutely malnourished children live in India. The WHO recommends community-based management of acute malnutrition (CMAM) for managing children with SAM. In India, different states are implementing community-based SAM treatment programme, hereinafter called CSAM, using varieties of locally produced nutrient dense food items with different nutrient compositions. The study will assess the effectiveness of these state specific CSAM interventions. METHODS: The longitudinal quasi-experimental study will be undertaken in two purposively selected blocks of one district each in the four intervention states and one comparison state. From each state, 200 SAM children identified using weight-for-length/height z-score (WHZ) < - 3 criteria will be enrolled in the study. Their anthropometric data and skinfold thickness will be taken on admission, at sixth week and at discharge by trained field investigators. Other child details, incidence of morbidity and socio-economic details will be collected on admission. To assess food consumption pattern including consumption of locally produced nutrient dense food supplements, dietary assessment, using 24-h dietary recall will be conducted on admission, at sixth week and at discharge. In addition, body composition parameters will be assessed for a sub-set of children using bio-electrical impedance analysis on admission and at discharge to analyse changes in total body water, fat-free mass, and fat mass. Post discharge, all study participants will be followed up monthly until 6 months. Atleast 10% of the sample will be checked for quality assessment. The study's primary outcome is cure rate defined as children attaining WHZ ≥ -2. Secondary outcomes include mean weight gain, mean length of stay, body composition parameters, relapse and mortality rates. Additionally, process evaluation and cost effectiveness analysis will be conducted. DISCUSSION: There is a shortage of robust evidence regarding the effectiveness of locally produced nutrient dense food supplements provided as part of the CSAM intervention in India. This study will contribute to evidence on effective strategies to manage children with uncomplicated SAM in India. The study protocol has all necessary ethical approvals. Written informed consent will be obtained from caregivers of the children. TRIAL REGISTRATION: The study is registered with Clinical Trial Registration of India (Registration No.: CTRI/2020/09/028013 ) Date of registration 24/09/2020.

Prevalence and management of vitamin D deficiency in children with newly diagnosed coeliac disease: cohort study.

BACKGROUND: Coeliac disease (CD) causes deficiency of various micronutrients including vitamin D, and there are no specific guidelines for treatment. AIMS: To determine the prevalence of vitamin D deficiency in children newly diagnosed with CD and the role of oral high-dose vitamin D in its treatment. METHODS: Calcium intake, sun exposure and biochemical and radiological parameters related to vitamin D deficiency were compared between 60 children aged 0-18 years diagnosed with CD and 60 healthy age- and sex-matched controls. The cases with serum 25(OH)D (<20 ng/ml) were given oral vitamin D (60,000 IU/week) and calcium (500 mg/day) for 12 weeks, along with a gluten-free diet (GFD); they were re-evaluated within a week of completion. The primary outcome measure was the serum 25(OH)D level, and secondary measures included serum calcium, phosphorus, alkaline phosphatase, parathormone and clinical and/or radiological rickets. RESULTS: The prevalence of vitamin D deficiency (25(OH)D <20 ng/ml) was significantly greater in the cases (n=38, 63.3%) than in the controls (n=27, 45.0%). Upon treatment, all 38 cases with vitamin D deficiency showed a significant rise in 25(OH)D levels along with normalisation of other biochemical abnormalities. Two children had 25(OH)D levels >100 ng/ml with no other feature suggestive of vitamin D toxicity. CONCLUSIONS: Vitamin D deficiency is more prevalent in children with CD. Administration of oral high-dose vitamin D for 12 weeks along with a GFD leads to a robust response, indicating rapid mucosal recovery. The vitamin D dosage recommended for malabsorption states may be excessive in CD.Abbreviations: ALP: alkaline phosphatase; CaBP: calcium-binding proteins; CD: coeliac disease; GFD: gluten-free diet; PTH: parathormone; RU: reproducibility units; 25(OH)D: 25 hydroxy vitamin D.

Screening and Management of Maternal Malnutrition in Nutritional Rehabilitation Centers as a Routine Service: A Feasibility Study in Kalawati Saran Children Hospital, New Delhi.

BACKGROUND: In India, Nutrition Rehabilitation Centers (NRCs) established at public health facilities provide residential medical nutrition therapy for severe acute malnutrition (SAM) children with complications. A large proportion of their mothers are also malnourished. NRCs do not provide services to such mothers as part of routine practice. However, technical algorithm for delivering Maternal Nutrition (MN) services in facility settings is available. OBJECTIVES: To test the practical feasibility of layering the MN services in NRC as a routine service. METHODS: The MN services were delivered by a nutrition counselor using a triage approach (assess, classify, supplement/counsel/treat). All mothers received diet, micronutrients, and group counseling, those at nutritional risk received individual counseling and SAM mothers also received catch-up diet during their stay. Program data were collected from mothers during January 1 to August 31, 2019 at the NRC in Kalawati Saran Children Hospital. To gain operational insights, a structured interview with nutrition counselor was conducted. RESULTS: Out of 168 mothers, 8% were found to be pregnant and 89% were at nutrition or medical risk. The prevalence of short stature was 18%, severe/thin 21%, overweight/obese 34%, and anemic 72%. Feedback from the nutrition counselor indicated no operational challenges, however, further efforts to ensure that mothers keep coming back for follow-up visits is needed. CONCLUSION: The findings indicated that existing staffs were able to deliver the MN services within the time, cost, and regime of the routine NRC. This paper provides four recommendations for layering the MN services in NRCs.

Clinical Relevance of Methylenetetrahydrofolate Reductase Genetic Testing in Autism: A Case Report of Successful Clinical Outcome.

Autism spectrum disorder is an emerging public health issue. The core features of autism spectrum disorder are persistent impairment in reciprocal social communication and interaction and restricted, repetitive patterns of behavior or interests. We now know that it encompasses disorders previously referred to as early infantile autism, childhood autism, Kanner autism, high-functioning autism, atypical autism, Asperger disorder, childhood disintegrative disorder, and pervasive developmental disorder not otherwise specified. While it is agreed that the etiology of autism spectrum disorder is largely unknown, certain environmental and genetic factors may be responsible for the disease. In particular, emerging evidence has suggested the role of C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene as a possible risk factor. We present the case of a two-year-old boy with high risk for autism who was found on advanced investigation to have heterozygous polymorphism for MTHFR. This prompted us to add folic acid to his therapeutic regime. He was treated with high-dose folic acid along with conventional intervention, and went on to make excellent recovery. We conclude that pharmacological intervention has the potential to improve outcome in a subgroup of autistic children.

Validation of visual estimation of neonatal jaundice in low-income and middle-income countries: a multicentre observational cohort study.

OBJECTIVE: Determine the sensitivity and specificity of neonatal jaundice visual estimation by primary healthcare workers (PHWs) and physicians as predictors of hyperbilirubinaemia. DESIGN: Multicentre observational cohort study. SETTING: Hospitals in Chandigarh and Delhi, India; Dhaka, Bangladesh; Durban, South Africa; Kumasi, Ghana; La Paz, Bolivia. PARTICIPANTS: Neonates aged 1-20 days (n=2642) who presented to hospitals for evaluation of acute illness. Infants referred for any reason from another health facility or those needing immediate cardiopulmonary resuscitation were excluded. OUTCOME MEASURES: Infants were evaluated for distribution (head, trunk, distal extremities) and degree (mild, moderate, severe) of jaundice by PHWs and physicians. Serum bilirubin level was determined for infants with jaundice, and analyses of sensitivity and specificity of visual estimations of jaundice used bilirubin thresholds of >260 µmol/L (need for phototherapy) and >340 µmol/L (need for emergency intervention in at-risk and preterm babies). RESULTS: 1241 (47.0%) neonates had jaundice. High sensitivity for detecting neonates with serum bilirubin >340 µmol/L was found for 'any jaundice of the distal extremities (palms or soles) OR deep jaundice of the trunk or head' for both PHWs (89%-100%) and physicians (81%-100%) across study sites; specificity was more variable. 'Any jaundice of the distal extremities' identified by PHWs and physicians had sensitivity of 71%-100% and specificity of 55%-95%, excluding La Paz. For the bilirubin threshold >260 µmol/L, 'any jaundice of the distal extremities OR deep jaundice of the trunk or head' had the highest sensitivity across sites (PHWs: 58%-93%, physicians: 55%-98%). CONCLUSIONS: In settings where serum bilirubin cannot be measured, neonates with any jaundice on the distal extremities should be referred to a hospital for evaluation and management, where delays in serum bilirubin measurement and appropriate treatment are anticipated following referral, the higher sensitivity sign, any jaundice on the distal extremities or deep jaundice of the trunk or head, may be preferred.

Proteomic Evaluation of the Natural History of the Acute Radiation Syndrome of the Gastrointestinal Tract in a Non-human Primate Model of Partial-body Irradiation with Minimal Bone Marrow Sparing Includes Dysregulation of the Retinoid Pathway.

Exposure to ionizing radiation results in injuries of the hematopoietic, gastrointestinal, and respiratory systems, which are the leading causes responsible for morbidity and mortality. Gastrointestinal injury occurs as an acute radiation syndrome. To help inform on the natural history of the radiation-induced injury of the partial body irradiation model, we quantitatively profiled the proteome of jejunum from non-human primates following 12 Gy partial body irradiation with 2.5% bone marrow sparing over a time period of 3 wk. Jejunum was analyzed by liquid chromatography-tandem mass spectrometry, and pathway and gene ontology analysis were performed. A total of 3,245 unique proteins were quantified out of more than 3,700 proteins identified in this study. Also a total of 289 proteins of the quantified proteins showed significant and consistent responses across at least three time points post-irradiation, of which 263 proteins showed strong upregulations while 26 proteins showed downregulations. Bioinformatic analysis suggests significant pathway and upstream regulator perturbations post-high dose irradiation and shed light on underlying mechanisms of radiation damage. Canonical pathways altered by radiation included GP6 signaling pathway, acute phase response signaling, LXR/RXR activation, and intrinsic prothrombin activation pathway. Additionally, we observed dysregulation of proteins of the retinoid pathway and retinoic acid, an active metabolite of vitamin A, as quantified by liquid chromatography-tandem mass spectrometry. Correlation of changes in protein abundance with a well-characterized histological endpoint, corrected crypt number, was used to evaluate biomarker potential. These data further define the natural history of the gastrointestinal acute radiation syndrome in a non-human primate model of partial body irradiation with minimal bone marrow sparing.

Intramuscular Followed by Oral Vitamin A Supplementation in Neonates with Birth Weight from 750 to 1250 g: A Randomized Controlled Trial.

Multiple intramuscular (IM) injections of vitamin A have been shown to decrease bronchopulmonary dysplasia in very low birth weight (VLBW) neonates. However, this regime is neither practical nor popular. Oral vitamin A has failed to achieve adequate plasma levels. We aimed to investigate if a schedule of initial IM followed by oral supplementation can reduce vitamin A deficiency. This was a blinded, randomized controlled trial, conducted in a level III neonatal unit. Neonates with birth weight from 750 to 1250 g, were enrolled at the age of 24-96 h of life. They were randomly allocated to vitamin A supplementation (VAS) (n = 61) or placebo group (n = 59). VAS group received vitamin A 5000 IU IM on alternate days till establishment of adequate enteral feeds, followed by oral 10,000 IU daily for 28 days. The primary outcome was incidence of vitamin A deficiency (plasma retinol < 200 µg/L) on day 28. A total of 120 neonates with mean (SD) gestation age and birth weight of 31 (2.4) weeks and 1065 (141) g, respectively were enrolled. More than 90% of cases were vitamin A deficient at the baseline. The proportion of vitamin A deficient infants on day 28 of study was significantly lower in VAS group compared to placebo group (4% vs. 61%, p < 0.001). The median (1st-3rd quartile) plasma retinol levels (µg/L) were significantly higher in VAS group compared to placebo [489 (295,627) vs. 184 (156,240), p < 0.001]. We conclude that the IM followed by oral VAS significantly reduced the incidence of vitamin A deficiency in VLBW infants.

Molecular Modeling Studies of Halogenated Imidazoles against 14α- Demethylase from Candida Albicans for Treating Fungal Infections.

BACKGROUND: Imidazole is one of the most explored and marketed azole utilized for the treatment of fungal infections. Lanosterol 14α-demethylase (Cytochrome P450DM) is the active target site for azole antifungals. AIM AND OBJECTIVE: This study emphasized on evaluation of a series of halogenated imidazole analogues using molecular docking studies for anti-Candidal activity. Furthermore, the model was refined by molecular dynamic simulation. METHODS: Halogenated imidazole analogues (PS1-PS30) were obtained from literature for the study. The imidazole analogues were prepared using Chem sketch and molecular docking was performed using Molergo Virtual Docker program and ADMET study was carried out by using Accelry's Accord for Excel programme. RESULTS: The docking study indicated that all the imidazole analogues (PS1-PS30) and standard drugs i.e., Ketoconazole, Miconazole and Clotrimazole possessed interaction with protein residue, heme cofactor and water molecule positioned above Heme cofactor of 14α-demethylase. Further, the ADMET study indicated that most of the halogenated imidazoles possessed good absorption, human intestinal absorption, aqueous solubility and blood brain penetration. CONCLUSION: Halogenated imidazole analogues may be used as potential lead molecules as 14α- demethylase inhibitors.

Premature Expression of Pseudoexfoliation Syndrome With Presenile Cataract in a 28-Year-Old Lady.

PURPOSE: We report a case of premature expression of pseudoexfoliation syndrome with presenile cataract in a 28-year-old lady with primary developmental glaucoma who had undergone glaucoma filtration surgery 26 years ago. METHODS/RESULTS: We report a case of a 28-year-old Indian lady with progressive diminution of vision associated with photophobia in the left eye for 5 years and loss of vision in the right eye since childhood. She underwent glaucoma filtration surgery in the left eye at the age of 2 and was on 2 topical glaucoma medications when she presented to us. Refractive error was -17.00 D with -3.50 D @ 90-degree cylinder in the left eye. The right eye was phthisical. Left eye showed superior diffuse bleb, enlarged but clear cornea with superior Haab's striae, deep and quiet anterior chamber and patent surgical iridectomy at 1 o'clock position. There was diffuse iris atrophy with pseudoexfoliation at the pupillary ruff and over the anterior lens capsule. Lens showed grade 2 nuclear cataract. Intraocular pressure in the left eye was 23 mm Hg. Fundus examination showed 0.9 cupping with an inferior notch and diffuse pallor of the optic disc. Axial length of left eye was 31.44 mm. On the basis of these findings, she was diagnosed with primary developmental glaucoma and high myopia, status after glaucoma filtration surgery with presenile cataract and pseudoexfoliation in the left eye. The topical antiglaucoma medications were augmented. After 1 month, intraocular pressure in the left eye was reduced to 14 mm Hg. She was advised to continue topical glaucoma medications and regular follow-up. CONCLUSIONS: The present case is the first to describe the unusual presentation of pseudoexfoliation in a young individual along with presenile cataract. Simultaneous occurrence of pseudoexfoliation with cataract could be due to previous intraocular surgery, iris trauma, possible low-grade inflammation, and high myopia in a predisposed eye. The clinician should be aware that although a rare condition, pseudoexfoliation can occur in the young and may be associated with presenile cataract.