Effect of 100% human milk-derived fortifier on growth of premature infants with birth weight of 1000–1500 g

Background: Preterm birth has the highest risk of perinatal morbidity and mortality. Nutrition plays a key role in the growth and development of a preterm infant. Fortification of expressed breast milk is followed to provide an optimal nutrition and a faster catch up growth. The new 100% human milk-derived fortifier (HMDF) can help in providing a safe nutritional option for a premature infant. Objective: The objective of the study was to assess the feed tolerance and impact of a new 100% HMDF on growth outcomes of preterm infants. Materials and Methods: In a single-center study, exclusively human milk-fed preterm infants (1000–1500 g birth weight) were chosen to receive human milk fortified with a new 100% HMDF. The fortifier was initiated when the enteral feed volume reached 100 ml/kg/day and was administered until discharge. The primary outcome of the study was to assess feed tolerance and the secondary endpoints included growth parameters. Results: The cohort study comprised 13 infants with a mean gestational age of 31.64±2.2 weeks and birth weight of 1314.62±110.1 g. During the study period, feed interruptions were nil and none of the infants showed any adverse events of clinical significance. Growth outcomes recorded at the end of the study period showed a mean weight gain of 25.97±7.7 g/day, mean length gain of 0.32±0.23 cm/week, and mean head circumference gain of 0.39±0.20 cm/week. The mean weight growth velocity of the infants was 18.37±5.1 g/kg/day. Conclusion: Preterm infants who received a new 100% HMDF demonstrated feed tolerance and weight gain without any clinically significant record of adverse events. The findings indicate that the new HMDF is a safe option for providing an exclusive human milk-based diet. However, a study with a larger study population may be required to reinforce the findings of this study

A rare cause of recurrent pneumonia: Scimitar syndrome

Scimitar syndrome is characterized by partial or total anomalous pulmonary venous return from the right lung along with hypoplasia ofthe lung. This syndrome has varied presentations, from an asymptomatic state to severe pulmonary hypertension and/or heart failure.Newer diagnostic modalities have improved our understanding of this rare syndrome and hence providing newer treatment options tobe tried. Here, we present a case of a 4-year-old child with recurrent pneumonia with Scimitar syndrome. We are reporting this case inview of the rarity of this syndrome and its presentation as recurrent pneumonia

The loss and gain of functional amino acid residues is a common mechanism causing human inherited disease

Elucidating the precise molecular events altered by disease-causing genetic variants represents a major challenge in translational bioinformatics. To this end, many studies have investigated the structural and functional impact of amino acid substitutions. Most of these studies were however limited in scope to either individual molecular functions or were concerned with functional effects (e.g. deleterious vs. neutral) without specifically considering possible molecular alterations. The recent growth of structural, molecular and genetic data presents an opportunity for more comprehensive studies to consider the structural environment of a residue of interest, to hypothesize specific molecular effects of sequence variants and to statistically associate these effects with genetic disease. In this study, we analyzed data sets of disease-causing and putatively neutral human variants mapped to protein 3D structures as part of a systematic study of the loss and gain of various types of functional attribute potentially underlying pathogenic molecular alterations. We first propose a formal model to assess probabilistically function-impacting variants. We then develop an array of structure-based functional residue predictors, evaluate their performance, and use them to quantify the impact of disease-causing amino acid substitutions on catalytic activity, metal binding, macromolecular binding, ligand binding, allosteric regulation and post-translational modifications. We show that our methodology generates actionable biological hypotheses for up to 41% of disease-causing genetic variants mapped to protein structures suggesting that it can be reliably used to guide experimental validation. Our results suggest that a significant fraction of disease-causing human variants mapping to protein structures are function-altering both in the presence and absence of stability disruption

The sequencing and interpretation of the genome obtained from a Serbian individual

Recent genetic studies and whole-genome sequencing projects have greatly improved our understanding of human variation and clinically actionable genetic information. Smaller ethnic populations, however, remain underrepresented in both individual and large-scale sequencing efforts and hence present an opportunity to discover new variants of biomedical and demographic significance. This report describes the sequencing and analysis of a genome obtained from an individual of Serbian origin, introducing tens of thousands of previously unknown variants to the currently available pool. Ancestry analysis places this individual in close proximity of the Central and Eastern European populations; i.e., closest to Croatian, Bulgarian and Hungarian individuals and, in terms of other Europeans, furthest from Ashkenazi Jewish, Spanish, Sicilian, and Baltic individuals. Our analysis confirmed gene flow between Neanderthal and ancestral pan-European populations, with similar contributions to the Serbian genome as those observed in other European groups. Finally, to assess the burden of potentially disease-causing/clinically relevant variation in the sequenced genome, we utilized manually curated genotype-phenotype association databases and variant-effect predictors. We identified several variants that have previously been associated with severe early-onset disease that is not evident in the proband, as well as variants that could yet prove to be clinically relevant to the proband over the next decades. The presence of numerous private and low-frequency variants along with the observed and predicted disease-causing mutations in this genome exemplify some of the global challenges of genome interpretation, especially in the context of understudied ethnic groups.Comment: 18 pages, 2 figure

A survey-based analysis of the academic job market

Many postdoctoral researchers apply for faculty positions knowing relatively little about the hiring process or what is needed to secure a job offer. To address this lack of knowledge about the hiring process we conducted a survey of applicants for faculty positions: the survey ran between May 2018 and May 2019, and received 317 responses. We analyzed the responses to explore the interplay between various scholarly metrics and hiring outcomes. We concluded that, above a certain threshold, the benchmarks traditionally used to measure research success - including funding, number of publications or journals published in - were unable to completely differentiate applicants with and without job offers. Respondents also reported that the hiring process was unnecessarily stressful, time-consuming, and lacking in feedback, irrespective of outcome. Our findings suggest that there is considerable scope to improve the transparency of the hiring process

Evaluating the Efficacy of a Nursing-Driven versus Provider-Driven Heparin Protocol

At Thomas Jefferson University Hospital patients who require heparin infusions are monitored either by nursing alone or the resident and the nurse together. This project aims to determine: Which protocol more efficiently shortens the time to therapeutic? Are patients therapeutic longer under a certain protocol? Do more patients under either protocol suffer from bleeding complications

The novel KIF1A missense variant (R169T) strongly reduces microtubule stimulated ATPase activity and is associated with NESCAV syndrome

KIF1A is a microtubule-dependent motor protein responsible for fast anterograde transport of synaptic vesicle precursors in neurons. Pathogenic variants in KIF1A have been associated with a wide spectrum of neurological disorders. Here, we report a patient presenting a severe neurodevelopmental disorder carrying a novel de novo missense variant p.Arg169Thr (R169T) in the KIF1A motor domain. The clinical features present in our patient match with those reported for NESCAV syndrome including severe developmental delay, spastic paraparesis, motor sensory neuropathy, bilateral optic nerve atrophy, progressive cerebellar atrophy, epilepsy, ataxia, and hypotonia. Here, we demonstrate that the microtubule-stimulated ATPase activity of the KIF1A is strongly reduced in the motor domain of the R169T variant. Supporting this, in silico structural modeling suggests that this variant impairs the interaction of the KIF1A motor domain with microtubules. The characterization of the molecular effect of the R169T variant on the KIF1A protein together with the presence of the typical clinical features indicates its causal pathogenic effect