Effect of Iron/Folic Acid Supplementation on the Outcome of Malaria Episodes Treated with Sulfadoxine-Pyrimethamine

Folic acid supplementation may potentially alter the efficacy of sulfadoxine-pyrimethamine (SP) treatment in children with malaria. However, there is lack of evidence fromrandomized controlled trials and effects of folic acid supplementation on clinical efficacy of SP therapy remainmoderately understood among children. In a doublemasked, placebo-controlled trial among preschool children in Pemba Island (Tanzania), iron and folic acid supplementation (Fe/FA) showed an increased risk of hospitalizations and death. In the present paper, we evaluated if folic acid supplementation reduced the efficacy of malaria treatment and thereby contributed to observed adverse effects. During the study, 1648 children had confirmed malarial episodes and received either sulphadoxinepyrimethamine(SP) treatment and iron folic acid or SP treatment and placebo. These children were evaluated for recovery and incidence of hospitalization during the next 15, 30, and 140 days. Two groups did not differ in malarial episode or hospitalization rate on subsequent 15, 30, and 140 days. Altered efficacy of SP by folic acid was not observed and did not contribute to adverse events in the previous trial.This trial is registered with Controlled-trials.com ISRCTN59549825

Molecular characterization of a pericentric inversion of chromosome 3 in a 3-generation family with short stature

Die molekulare Charakterisierung von balanciert auftretenden Chromosomenveränderungen, die mit einem spezifischen klinischen bild einhergehen, haben in vielen Fällen zur Identifizierung Krankheitsverursachender Gene geführt. Ziel der vorliegenden Arbeit war die positionale Klonierung eines Gens in einer 3-Generationen Familie, in der eine perizentrische Inversion mit Kleinwuchs assoziiert ist. Mittels der Fluoreszenz in situ Hybridisierung (FISH) wurden beide Bruchpunkte der Inversion 46,XX,inv(3)(p24.1q26.1) kartiert. BAC CTD-2000B5 und BAC RP11-12N13 überspannen neben anderen Vektoren den 3p bzw. 3q Bruchpunkt. Zur weiteren Eingrenzung wurden Restriktionsfragmente bzw. Long range PCRFragmente dieser BACs als FISH Sonden eingesetzt und die Bruchpunktregionen darüber auf ein 2.9 kb Segment in 3p und ein 5.3 kb Segment in 3q eingegrenzt. Die in silico Analyse der genomischen Sequenz ergab einen Anteil von ca. 30% an repetitiven Elementen (3p:LTR3A, MER67C, L2, MER67D; 3q: LTR16C, MER20, MLT2B1, LTR1B). Beide Bruchpunkte kartieren innerhalb dieser Bereiche. Keiner der beiden Bruchpunkte befindet sich innerhalb eines bekannten Gens. Die in silico Analyse ergab allerdings ein putatives Gen in 3q26.1 mit 12 Exons, einer 1.952 bp großen mRNA und einem ORF von 652 Aminosäuren. Der Bruchpunkt befindet sich in Intron 2. Das putative Gen ist homolog zu PSAT1 auf Chromosom 9. Nach RT-PCR Analyse ergab sich bisher kein Hinweis auf eine Expression im Gehirn bzw. Testis. Weitere Untersuchungen müssen zeigen, ob dieses Gen, bzw. flankierende Gene in 3p bzw. 3q durch die Inversion in ihrer Funktion beeinträchtigt sind.Chromosomal rearrangements associated with a disease phenotype have often led to the identification of novel disease genes. Here we report a 3-generation family in which short stature is being associated with a heterozygous pericentric inversion of 46, XX,inv(3)(p24.1q26.1). We used fluorescence in situ hybridization (FISH) to physically characterize the breakpoint regions. FISH analyses showed that among others the Bacterial artificial chromosome (BAC) CTD-2000B5 and BAC clone RP11-12N13 were spanning the 3p and 3q breakpoints, respectively. In order to further narrow down the breakpoint regions subcloned fragments of the breakpoint spanning BACs as well as long range PCR products were used as probes for FISH. The breakpoints were thus located within a region of 2.9 kb and 5.3 kb on p and q respectively. Analysis of the genomic sequence surrounding the inversion breakpoints revealed 30% repetitive elements containing LTR33A, MER67C, L2 and MER67D elements on p region and LTR16C, MER20, MLT2B1, LTR1B, simple repeats and low copy repeats on q region. We determine that the breakpoints occurred between these repetitive regions. Neither of the inversion breakpoints was found to disrupt a validated gene, however, a novel putative gene was identified at 3q26.1 by in silico analysis. The putative gene has 12 exons, a 1.952 bp mRNA showing a single ORF with 652 amino acids. The breakpoint was found to disrupt the 2nd intron of this putative gene. This gene shows homology to PSAT1 on chromosome 9. No transcript was identified so far in cDNA of human brain and testis. Further expression studies could shed some light on the nature of this putative gene.von Dutta Usha Ran

Health related behaviour changes in pregnant women during COVID-19 pandemic

Background: Pregnancy associated anxiety and depression is very well known for its prevalence. Pandemic like COVID-19 all the more is additive to the levels of anxiety and depression during pregnancy, especially for mothers who are concerned about feto-maternal wellbeing. This study makes an effort to analyze the health-related behavior changes and psychological impact of pregnant women after COVID-19 outbreak. Methods: Cross sectional, questionnaire-based study conducted on pregnant ladies visiting labor room and out-patients department RIMS, Ranchi from April 2020 to September 2020. Results: Most patients were primigravida and turned up only in third trimester. Pregnancy complications like heart disease, GDM, jaundice, PIH were present in 28% of participants. 48% participants had no family income during pandemic. The 92% women wore masks, 80% practiced social distancing, 72% practiced frequent handwashing, 72% practiced frequent handwashing during pandemic, 80% had no regular antenatal check-up. Almost 64% participants showed mild to moderate anxiety, 34% had moderate depression and 40% had moderate stress. Four percentages had severe anxiety, 2% had severe depression and 12% had severe stress. Usage of mask was inversely related to GAD7 scores, but had no correlation with EPDS scores. Rest parameters like frequent handwashing, social distancing, stressful behavior, not going out and frequent handwashing were directly related to GAD 7 and EPDS score. Conclusions: Mental health and preventive behavior of respondents could be attributed to socio demographic, social, situational, economic status, family conditions and perception of severity of Covid19

Study to determine feto maternal outcomes of programmed labor in a tertiary care hospital of Jharkhand

Background: Programmed labor aims to minimize duration and inconvenience of labor both for patient and obstetrician. The present study attempts to provide labor analgesia by using infusion paracetamol in place of conventional ketamine and tramadol. Methods: This study was conducted in the labor room of department of obstetrics and gynecology, RIMS, Ranchi from March 2019 to February 2020. 50 primigravida and 50 multigravidas were studied, with singleton pregnancy, cephalic presentation presenting with spontaneous onset of labor with Gestational age of 37-41 week. Results: 30% of patients were greater than 40 weeks gestation.65% of primigravida experienced severe pain, but only 20% of multigravidas had severe pain.60%primigravidas and 60% multigravidas (of 20% who had severe pain) experienced adequate pain relief with labor analgesia. 60 % primigravida presented with <4 cm cervical dilatation, whereas 40% multigravidas had <4 cm dilatation. 60% primigravida had shortened active phase (3.5 hrs), 60% multigravidas (2.5 hrs) which is suggestive of benefit of obstetrical analgesia in programmed labor. 90% patients had third stage labor less than 3 minutes. Only one multigravida landed in postpartum hemorrhage. All neonates had Apgar score greater than 8. There was no perinatal mortality. Only one primigravida landed in caesarean section due to arrest in second stage. 2 multigravidas had instrumental delivery. Maternal side effects like tachycardia, nausea, cervical and vaginal tears were more in primigravida. Conclusions: Participants with good response to obstetrical analgesia fared better than rest. Response was more satisfactory in primigravida in terms of labor progress

Study to detect infection and diagnose chorioamnionitis to aid in management of cases of preterm premature rupture of membranes in a tertiary care centre of Jharkhand

Background: The present study undertaken is to identify the risk factors causing Preterm premature rupture of membranes (pPROM) and to study fetal and maternal outcome associated with pPROM, to diagnose and manage chorioamnionitis associated with pPROM and to evaluate levels of C reactive protein (CRP). Methods: This study was conducted in the department of obstetrics and gynaecology, Rajendra institute of medical sciences from March 2019 to February 2020.50 cases of confirmed preterm premature rupture of membrane before 35 weeks of pregnancy were taken as cases and 50 cases of normal pregnancy (28-40 weeks) were taken as controls. Results: Highest incidence of premature rupture of membrane was among 20–25-year (68%) age groups. Incidence of premature rupture of membrane was more in low socioeconomic status (72%). Maximum incidence of premature rupture of membrane in 31-33 weeks gestational age (52%). Most cases of premature rupture of membrane in 24–48-hour group (38%). Most of study group (90%) and control group (80%) delivered by vaginal route. 11 study cases with clinical chorioamnionitis had elevated CRP (43.5 mg/l). One presented with clinical chorioamnionitis. CRP was most sensitive (92%). Total maternal morbidity was due to puerperal pyrexia (22%). Four patients with neonatal sepsis had CRP>6 mg/l. CRP and presence of polymorphs in gastric aspirate have 100% association with septicemia in neonates. Conclusions: Preterm premature rupture of membrane can be associated with adverse foetal and maternal outcome if immediate measures are not taken

Impact of micronutrient fortification of yoghurt on micronutrient status markers and growth – a randomized double blind controlled trial among school children in Bangladesh

BACKGROUND: Interventions providing foods fortified with multiple micronutrients can be a cost-effective and sustainable strategy to improve micronutrient status and physical growth of school children. We evaluated the effect of micronutrient-fortified yoghurt on the biochemical status of important micronutrients (iron, zinc, iodine, vitamin A) as well as growth indicators among school children in Bogra district of Bangladesh. METHODS: In a double-masked randomized controlled trial (RCT) conducted in 4 primary schools, 1010 children from classes 1–4 (age 6–9 years) were randomly allocated to receive either micronutrient fortified yoghurt (FY, n = 501) or non-fortified yoghurt (NFY, n = 509). For one year, children were fed with 60 g yoghurt everyday providing 30% RDA for iron, zinc, iodine and vitamin A. Anthropometric measurements and blood/urine samples were collected at base-, mid- and end-line. All children (FY, n = 278, NFY, n = 293) consenting for the end-line blood sample were included in the present analyses. RESULTS: Both groups were comparable at baseline for socio-economic status variables, micronutrient status markers and anthropometry measures. Compliance was similar in both the groups. At baseline 53.4% of the population was anemic; 2.1% was iron deficient (ferritin <15.0 μg/L and TfR > 8.3 mg/L). Children in the FY group showed improvement in Hb (mean difference: 1.5; 95% CI: 0.4-2.5; p = 0.006) as compared to NFY group. Retinol binding protein (mean diff: 0.05; 95% CI: 0.002-0.09; p = 0.04) and iodine levels (mean difference: 39.87; 95% CI: 20.39-59.35; p < 0.001) decreased between base and end-line but the decrease was significantly less in the FY group. Compared to NFY, the FY group had better height gain velocity (mean diff: 0.32; 95% CI: 0.05-0.60; p = 0.02) and height-for-age z-scores (mean diff: 0.18; 95% CI: 0.02-0.33; p = 0.03). There was no difference in weight gain velocity, weight-for-age z-scores or Body Mass Index z-scores. CONCLUSION: In the absence of iron deficiency at baseline the impact on iron status would not be expected to be observed and hence cannot be evaluated. Improved Hb concentrations in the absence of a change in iron status suggest improved utilization of iron possibly due to vitamin A and zinc availability. Fortification improved height gain without affecting weight gain. TRIAL REGISTRATION: ClinicalTrial.gov: NCT0098073

ARHGEF9 disease: Phenotype clarification and genotype-phenotype correlation.

ObjectiveWe aimed to generate a review and description of the phenotypic and genotypic spectra of ARHGEF9 mutations.MethodsPatients with mutations or chromosomal disruptions affecting ARHGEF9 were identified through our clinics and review of the literature. Detailed medical history and examination findings were obtained via a standardized questionnaire, or if this was not possible by reviewing the published phenotypic features.ResultsA total of 18 patients (including 5 females) were identified. Six had de novo, 5 had maternally inherited mutations, and 7 had chromosomal disruptions. All females had strongly skewed X-inactivation in favor of the abnormal X-chromosome. Symptoms presented in early childhood with delayed motor development alone or in combination with seizures. Intellectual disability was severe in most and moderate in patients with milder mutations. Males with severe intellectual disability had severe, often intractable, epilepsy and exhibited a particular facial dysmorphism. Patients with mutations in exon 9 affecting the protein's PH domain did not develop epilepsy.ConclusionsARHGEF9 encodes a crucial neuronal synaptic protein; loss of function of which results in severe intellectual disability, epilepsy, and a particular facial dysmorphism. Loss of only the protein's PH domain function is associated with the absence of epilepsy

Embolization of Cyanoacrylate glue in systemic circulation in a case of hepatocellular carcinoma: an autopsy report

We report a case of embolism of the sclerosant dye with subsequent formation of foreign-body giant cell reaction within the veins of pulmonary and portal circulation in an autopsy case of hepatocellular carcinoma developing over an underlying primary biliary cirrhosis

Neonatal mortality within 24 hours of birth in six low- and lower-middle-income countries.

OBJECTIVE: To estimate neonatal mortality, particularly within 24 hours of birth, in six low- and lower-middle-income countries. METHODS: We analysed epidemiological data on a total of 149 570 live births collected between 2007 and 2013 in six prospective randomized trials and a cohort study from predominantly rural areas of Bangladesh, Ghana, India, Pakistan, the United Republic of Tanzania and Zambia. The neonatal mortality rate and mortality within 24 hours of birth were estimated for all countries and mortality within 6 hours was estimated for four countries with available data. The findings were compared with published model-based estimates of neonatal mortality. FINDINGS: Overall, the neonatal mortality rate observed at study sites in the six countries was 30.5 per 1000 live births (range: 13.6 in Zambia to 47.4 in Pakistan). Mortality within 24 hours was 14.1 per 1000 live births overall (range: 5.1 in Zambia to 20.1 in India) and 46.3% of all neonatal deaths occurred within 24 hours (range: 36.2% in Pakistan to 65.5% in the United Republic of Tanzania). Mortality in the first 6 hours was 8.3 per 1000 live births, i.e. 31.9% of neonatal mortality. CONCLUSION: Neonatal mortality within 24 hours of birth in predominantly rural areas of six low- and lower-middle-income countries was higher than model-based estimates for these countries. A little under half of all neonatal deaths occurred within 24 hours of birth and around one third occurred within 6 hours. Implementation of high-quality, effective obstetric and early newborn care should be a priority in these settings