Bolus Feeding Via Gastric Versus Oral Routes in Very Preterm Neonates.

BACKGROUND: We intend to investigate the association of bolus orogastric tube (BOG) and nipple bottle (N) feedings with postnatal growth in very premature neonates (VPN: gestational age between 28 and 33 weeks). MATERIAL AND METHODS: The days of life (DOL) to achieve full combined oral and gastric enteral nutrition (FEN) and attain body weight (BW) of 2200 g (Wt22) and the length of hospitalization (LOH) were retrospectively associated with clinical and BOG and N feeding-related variables via multivariate regression analyses. Correlations were performed to ascertain the strength of associations. RESULTS: In a cohort of 127 VPN, FEN demonstrated negative associations with gestational age (GA) and LOH and Wt22 with birth weight (BW). FEN showed positive associations with nil by mouth and intravenous fluid-nutrition days and with DOL to start and achieve full nipple feeding. LOH was associated with days on antibiotics and DOL to start and achieve full nipple feeding. Wt22 was associated with DOL to achieve full nipple feeding. The start day of BOG feeding had no independent associations and weak, highly significant positive correlations with Wt22, LOH, and FEN. CONCLUSION: Bolus orogastric tube feeding has no independent implications for postnatal growth, duration of hospitalization, or chronological age to attain full enteral nutrition in VPN unless combined with nipple feeding to provide enteral nutrition. Oral bottle feeding accelerates postnatal catch-up growth and full enteral nutrition acquisition while reducing hospitalization duration. Initiating nipple feeding at 32 weeks of postmenstrual age may be safe in stable VPN. Antibiotic therapy increases hospitalization duration.

An Overview of Targeted Genome Editing Strategies for Reducing the Biosynthesis of Phytic Acid: an Anti-nutrient in Crop Plants.

Anti-nutrients are substances either found naturally or are of synthetic origin, which leads to the inactivation of nutrients and limits their utilization in metabolic processes. Phytic acid is classified as an anti-nutrient, as it has a strong binding affinity with most minerals like Fe, Zn, Mg, Ca, Mn, and Cd and impairs their proper metabolism. Removing anti-nutrients from cereal grains may enable the bioavailability of both macro- and micronutrients which is the desired goal of genetic engineering tools for the betterment of agronomic traits. Several strategies have been adopted to minimize phytic acid content in plants. Pursuing the molecular strategies, there are several studies, which result in the decrement of the total phytic acid content in grains of major as well as minor crops. Biosynthesis of phytic acid mainly takes place in the seed comprising lipid-dependent and lipid-independent pathways, involving various enzymes. Furthermore, some studies show that interruption of these enzymes may involve the pleiotropic effect. However, using modern biotechnological approaches, undesirable agronomic traits can be removed. This review presents an overview of different genes encoding the various enzymes involved in the biosynthetic pathway of phytic acid which is being targeted for its reduction. It also, highlights and enumerates the variety of potential applications of genome editing tools such as TALEN, ZFN, and CRISPR/Cas9 to knock out the desired genes, and RNAi for their silencing.

Microtubule-associated protein MAP1LC3C regulates lysosomal exocytosis and induces zinc reprogramming in renal cancer cells.

Microtubule-associated protein 1 light chain 3 gamma (MAP1LC3C or LC3C) is a member of the microtubule-associated family of proteins that are essential in the formation of autophagosomes and lysosomal degradation of cargo. LC3C has tumor-suppressing activity, and its expression is dependent on kidney cancer tumor suppressors, such as von Hippel-Lindau protein and folliculin. Recently, we demonstrated that LC3C autophagy is regulated by noncanonical upstream regulatory complexes and targets for degradation postdivision midbody rings associated with cancer cell stemness. Here, we show that loss of LC3C leads to peripheral positioning of the lysosomes and lysosomal exocytosis (LE). This process is independent of the autophagic activity of LC3C. Analysis of isogenic cells with low and high LE shows substantial transcriptomic reprogramming with altered expression of zinc (Zn)-related genes and activity of polycomb repressor complex 2, accompanied by a robust decrease in intracellular Zn. In addition, metabolomic analysis revealed alterations in amino acid steady-state levels. Cells with augmented LE show increased tumor initiation properties and form aggressive tumors in xenograft models. Immunocytochemistry identified high levels of lysosomal-associated membrane protein 1 on the plasma membrane of cancer cells in human clear cell renal cell carcinoma and reduced levels of Zn, suggesting that LE occurs in clear cell renal cell carcinoma, potentially contributing to the loss of Zn. These data indicate that the reprogramming of lysosomal localization and Zn metabolism with implication for epigenetic remodeling in a subpopulation of tumor-propagating cancer cells is an important aspect of tumor-suppressing activity of LC3C.

Immediate Postnatal Microbial Colonization in Sick Term Neonates Admitted to NICU: Prevalence, Microbiota, and Associated Characteristics.

OBJECTIVE: The immediate postnatal rectal (RC) and nasopharyngeal colonization (NPC), their prevalence, taxa, and associated characteristics were investigated in sick term infants admitted to the neonatal intensive care unit. STUDY DESIGN: In a retrospective cohort single center study, nasopharyngeal (NPCx) and rectal (RCx) microbial cultures were obtained within 20 minutes of birth in mild-to- moderate sick term infants. Associations between the colonization and maternal-neonatal variables, including early neonatal course, were analyzed via logistic regression analysis. RESULTS: A total of 154 term infants were admitted for respiratory distress, hypoglycemia, maternal chorioamnionitis (CHO), and suspected neonatal sepsis; out of which, 80 (52%) were NPCx-positive (+) infants. The duration of rupture of membrane (ROM) was higher (15.5 ± 10.0 vs. 11.3 ± 11.0 hours, p = 0.02), while the respiratory support requirement (16.3 vs. 29.7%, p = 0.04) and occurrence of maternal group B Streptococcus (GBS) colonization lower (15.0 vs. 35.1%, p = 0.01) in NPCx+ infants. ROM increased (odds ratio [OR]: 1.04, 95% confidence interval [CI]: 1.01-1.07), and maternal GBS colonization decreased the odds of positive nasopharyngeal cultures (OR: 0.31, 95% CI: 0.14-0.72). The major microorganisms isolated were Staphylococcus epidermidis (41%), α hemolytic Streptococcus (AHS; 16%), Escherichia coli (13%), and GBS (1.06%). Among the enrolled infants, 44 (28.5%) were RCx positive. The need for (11.4 vs. 27.3%, p = 0.03) and days on respiratory support (0.2 ± 0.6 vs. 0.8 ± 2.5, p = 0.03) were lower and the occurrence of CHO higher (41.0 vs. 23.2%, p = 0.04) in the RCx positive infants. Cesarean section (CS) was performed less frequently (18.2 vs. 55.5%, p = 0.001) and decreased the odds of having positive rectal cultures (OR: 0.21, 95% CI: 0.08-0.51). In total, 80% of the RCx positive infants isolated E. coli, and 6.8% Klebsiella. CONCLUSION: In sick term neonates, early NPC is dominated by SE and RC by E. coli. NPC is supported by ROM and declines by maternal GBS colonization, whereas RC decreases with CS. NPC is more common than RC in this population. KEY POINTS: · Early neonatal nasopharyngeal microbial colonization in sick term neonates, dominated by Staphylococcus epidermidis, is enhanced by the rupture of membrane and diminishes by maternal GBS colonization.. · Cesarean section decreases the rectal colonization, which is composed of E. coli as the predominant microorganism.. · The microbiota of early postnatal colonization in sick term neonates differs from that reported in healthy term infants..

A Rare Case Report of 17q23.1q23.2 Microdeletion With Homozygosity of 11p11.2q13.4 in a Newborn.

We present the case of a newborn with 17q23.1q23.2 microdeletion and additional homozygosity of 11p11.2q13.4. In the literature, 17q23.1q23.2 microdeletion syndrome is a novel syndrome reported in nine patients. Our patient is a full-term baby boy admitted to a neonatal intensive care unit for hypoglycemia, respiratory distress, presumed sepsis, and thrombocytopenia. General appearance revealed microcephaly, micrognathia, ankyloglossia, small mouth, and high arch palate. The patient also presented with hypotonia, poor feeding, and poor weight gain in the first week of life followed by hypertonia and tremors from the second week of life. The phenotypic and clinical presentation lead to the genetic investigation of microarray which revealed 17q23.1q23.2 microdeletion and additional homozygosity of 11p11.2q13.4.

Genome-wide profiling of drought-tolerant Arabidopsis plants over-expressing chickpea MT1 gene reveals transcription factors implicated in stress modulation.

Drought, a major abiotic limiting factor, could be modulated with in-built reprogramming of plants at molecular level by regulating the activity of plant developmental processes, stress endurance and adaptation. The transgenic Arabidopsis thaliana over-expressing metallothionein 1 (MT1) gene of desi chickpea (Cicer arietinum L.) was subjected to transcriptome analysis. We evaluated drought tolerance of 7 days old plants of Arabidopsis thaliana in both wild-type (WT) as well as transgenic plants and performed transcriptome analysis. Our analysis revealed 24,737 transcripts representing 24,594 genes out of which 5,816 were differentially expressed genes (DEGs) under drought conditions and 841 genes were common in both genotypes. A total of 1251 DEGs in WT and 2099 in MT1 were identified in comparison with control. Out of the significant DEGs, 432 and 944 were upregulated, whereas 819 and 1155 were downregulated in WT and MT1 plants, respectively. The physiological and molecular parameters involving germination assay, root length measurements under different stress treatments and quantitative expression analysis of transgenic plants in comparison to wild-type were found to be enhanced. CarMT1 plants also demonstrated modulation of various other stress-responsive genes that reprogrammed themselves for stress adaptation. Amongst various drought-responsive genes, 24 DEGs showed similar quantitative expression as obtained through RNA sequencing data. Hence, these modulatory genes could be used as a genetic tool for understanding and delineating the mechanisms for fine-tuning of stress responses in crop plants.

microRNA 166: an evolutionarily conserved stress biomarker in land plants targeting HD-ZIP family.

MicroRNAs (miRNAs) are significant class of noncoding RNAs having analytical investigating and modulatory roles in various signaling mechanisms in plants related to growth, development and environmental stress. Conserved miRNAs are an affirmation of land plants evolution and adaptation. They are a proof of indispensable roles of endogenous gene modulators that mediate plant survival on land. Out of such conserved miRNA families, is one core miRNA known as miR166 that is highly conserved among land plants. This particular miRNA is known to primarily target HD ZIP-III transcription factors. miR166 has roles in various developmental processes, as well as regulatory roles against biotic and abiotic stresses in major crop plants. Major developmental roles indirectly modulated by miR166 include shoot apical meristem and vascular differentiation, leaf and root development. In terms of abiotic stress, it has decisive regulatory roles under drought, salinity, and temperature along with biotic stress management. miR166 and its target genes are also known for their beneficial synergy with microorganisms in leguminous crops in relation to lateral roots and nodule development. Hence it is important to study the roles of miR166 in different crop plants to understand its defensive roles against environmental stresses and improve plant productivity by reprogramming several gene functions at molecular levels. This review is hence a summary of different regulatory roles of miR166 with its target HD-ZIP III and its modulatory and fine tuning against different environmental stresses in various plants.

Evaluation and Risk Assessment of Congenital Anomalies in Neonates.

Congenital anomalies (CA) are a large heterogeneous group of disorders of abnormal morphogenesis or biochemistry which present at birth and carry widely variable implications for morbidity and mortality. They are the leading cause of infant mortality in the USA, with an incidence of 3-4% of all births. CA are the fourth leading cause of neonatal mortality worldwide, with an estimated 295,000 deaths annually. The enormous variability in the clinical presentation in terms of severity, time of occurrence, course, complications, management, and outcomes makes the evaluation of CA complicated, highly specific, and individualized. The anomalies can impart tremendous physical, social, and emotional distress on the patient with massive emotional, social, financial, and medical implications for the family and society. The diagnosis may remain elusive despite rigorous, elaborate, and extensive investigations in many cases. While the enormous strides in genetic testing and gene modification therapy have an encouraging impact on the diagnosis and treatment, the risk assessment of recurrence in the family and population of CA remains obscure in most cases due to the lack of information and referable evidence.

Genome-wide association study for phosphate deficiency responsive root hair elongation in chickpea.

Root hairs (RHs) are single-celled elongated epidermal cells and play a vital role in nutrient absorption, particularly for immobile minerals like phosphorus (P). As an adaptive response to P deficiency, an increase in RH length enhances root-soil contact and absorptive area for P absorption. Genetic variations have been reported for RH length and its response to P deficiency in plants. However, only a few association studies have been conducted to identify genes and genetic loci associated with RH length. Here, we screened desi chickpea accessions for RH length and its plasticity under P deficiency. Further, the genome-wide association study (GWAS) was conducted to identify the genetic loci associated with RH length in P deficient and sufficient conditions. Although high variability was observed in terms of RH length in diverse genotypes, majority of the accessions showed typical response of increase in RH length in low P. Genome-wide association mapping identified many SNPs with significant associations with RH length in P-sufficient and P-deficient conditions. A few candidate genes for RH length in P deficient (SIZ1-like and HAD superfamily protein) and sufficient (RSL2-like and SMAP1-like) conditions were identified which have known roles in RH development and P deficiency response or both. Highly associated loci and candidate genes identified in this study would be useful for genomic-assisted breeding to develop P-efficient chickpea.

Placental histopathology in late preterm infants: clinical implications.

BACKGROUND: The etiopathogenesis of late preterm (LPT) birth is undetermined. Placental histopathology, which reflects an adverse intrauterine environment and is reportedly associated with preterm labor and neonatal morbidities, has not been studied in LPT infants. PURPOSE: We investigated placental pathological lesion as markers of an adverse intrauterine environment during LPT labor. METHODS: This retrospective case-control study compared placental histopathological and clinical variables between LPT and term neonates. Placental variables included chorioamnionitis, funisitis, hemorrhage, abruption, infarction, calcification, and syncytial knots. Maternal variables included age, substance abuse, pregnancyassociated diabetes mellitus and hypertension, duration of rupture of membrane, antibiotic use, and magnesium sulfate, whereas, those of neonates included gestational age, birth weight, race, sex, and Apgar scores. Standard statistical proedures were applied to analyze the data. RESULTS: Chorioamnionitis (50% vs. 17.8%, P<0.001) and funisitis (20% vs. 4.4%, P=0.002) were more common in term infants. Placental infarction rate was insignificantly higher in LPT infants (25.6% vs. 14.3%, P=0.08). The mothers in the LPT group were older (30.4 years vs. 28.1 years, P=0.05; odds ratio [OR], 1.06; 95% confidence interval [CI], 0.998-1.12, P=0.056) and more often suffered from hypertension (28.9 vs. 12.9 %, P=0.02), and received magnesium sulfate (48.9 vs. 20%, P< 0.001; OR, 2.86; 95% CI, 1.12-7.29, P<0.05). Duration of rupture of membrane was higher in term infants (13.6 hours vs. 9.1 hours, P<0.001). Chorioamnionitis (OR, 0.33; 95% CI, 0.13-0.79; P<0.05) was associated with a lower risk of LPT delivery. CONCLUSION: Placental infection is not a risk factor for LPT births. There is a nonsignificant predominance of vascular anomalies in LPT placentas. Higher maternal age, magnesium sulfate therapy, and maternal hypertension are clinical risk factors for LPT labor.

Cetirizine as a Causative Agent for Drug Induced Methemoglobinemia: A Case Report and Review.

A case of methemoglobinemia (MHb) in a teenage woman, triggered by an acute ingestion of approximately 120 to 180 mg of cetirizine, allegedly, with no suicidal intent is described. The patient presented with anxiety and tremors and rapidly developed central cyanosis unresponsive to oxygen supplementation. There was a history of recurrent, spontaneously remitting, unprovoked "blue discoloration of hands." Investigations confirmed the diagnosis of MHb, and the patient responded to ascorbic acid and methylene blue, although the baseline methemoglobin level remained slightly high. The exact enzymatic deficiency could not be ascertained as the patient refused to undergo complete testing. To the best of our knowledge, this is the first documentation of cetirizine as a causative agent for drug induced MHb. Cetirizine, a selective histamine H1 receptor antagonist is eliminated via oxidation and conjugation processes, which use pathways other than cytochrome P450 enzyme system. The metabolism could potentially create by-products, like superoxide or hydrogen peroxide, which could act as strong reducing agents and oxidize hemoglobin into ferric containing methemoglobin. In this case, an unusually high systemic load of the drug speculatively saturated and overwhelmed the protective enzyme systems, which resulted in clinical manifestation of MHb.

Complications associated with the current sequential pharmacological management of early postnatal hypotension in extremely premature infants.

Early postnatal hypotension in premature infants is treated with escalating doses of vasopressor-inotropes (VI), followed by hydrocortisone if VI therapy fails. The adverse effects of this standard clinical practice have not been well reported. In a retrospective case-control study, we compared the complications associated with VI and hydrocortisone (HCVI) treatments in extremely low-birth-weight infants (≤1000 g) with contemporaneous normotensive medication-naïve controls via standard univariate and multivariate analyses. Birth weight, gestational age, and receipt of antenatal steroids did not differ between VI (n = 74) and control (n = 124) groups, while the occurrence of gestational diabetes mellitus and risks for patent ductus arteriosus, intraventricular-periventricular hemorrhage, spontaneous intestinal perforation, ventriculomegaly, and bronchopulmonary dsyplasia were higher in VI. Infants in the HCVI group (n = 69) had lower birth weight, gestational age, and receipt of antenatal steroids and higher risks for intraventricular-periventricular hemorrhage, bronchopulmonary dysplasia, air leaks, and patent ductus arteriosus than controls. Whereas the occurrences of spontaneous intestinal perforation, ventriculomegaly, and maternal diabetes mellitus did not differ, that of maternal hypertension trended to be lower in HCVI recipients (P = 0.06). In conclusion, hypotensive extremely low-birth-weight infants treated with VI or with HCVI are susceptible to intraventricular-periventricular hemorrhage, bronchopulmonary dysplasia, and patent ductus arteriosus. Furthermore, those who receive inotropes are at risk for spontaneous intestinal perforation and ventriculomegaly. Maternal diabetes mellitus increases the occurrence of hypotension, which responds to VI. Maternal hypertension does not contribute to VI responsive and tends to decrease the occurrence of VI-refractory hypotension.

Sirenomelia and maternal chlamydia trachomatis infection: a case report and review.

Background: Sirenomelia is a lethal congenital anomaly, presenting with fusion of lower extremities and malformed perineum. The pathogenesis is unclear, and "defective blastogenesis" is the proposed mechanism. Chlamydia trachomatis (CT) is an obligate intracellular pathogen which reportedly invades placenta and may result in fetal demise. It has documented cytopathogenic effects, specifically, cellular disruption, tissue dysgenesis, and genomic instability.Case report: An infant with sirenomelia was born as a product of 30 weeks of pregnancy, which was normal except for a persistent maternal CT infection. The infant expired shortly after birth.Conclusion: Fetal invasion by CT, conceivably, may induce structural anomalies, such as sirenomelia by virtue of its cytopathic effects. We intend to draw attention to such a possibility by reporting this case. This association, however, is speculative and more cases of sirenomelia with CT positive mothers need to be described in order to make definite conclusions about such a relationship.

The Association of Adolescent Facebook Behaviours with Symptoms of Social Anxiety, Generalized Anxiety, and Depression.

OBJECTIVE: Social media use and especially Facebook use is highly prevalent among adolescents. We study the association of symptoms of social anxiety, generalized anxiety, and depression with behaviours performed by adolescents when logged onto Facebook. METHOD: We surveyed 102 adolescents about social anxiety symptoms using the Leibowitz Social Anxiety Scale for Children and Adolescents and symptoms of generalized anxiety, depression, and general distress using the Mini Mood and Anxiety Symptom Questionnaire. We created a comprehensive Facebook behaviour scale and a Facebook behaviour repetitive scale to measure extent of engagement on Facebook. Multivariate linear regression analyses were used to study predictors from demographics, Facebook characteristics, and symptoms of social anxiety, generalized anxiety, and depression to the outcomes of Facebook behaviour and Facebook repetitive behaviour. RESULTS: We found that increased total number of Facebook friends, increased time spent per day on Facebook, and increased anxious arousal symptoms were each significantly associated with increased Facebook behaviour and increased repetitive Facebook behaviour. Social anxiety symptoms, depressive symptoms, and general distress were each not associated with Facebook behaviour and repetitive Facebook behaviour. CONCLUSIONS: Increased adolescent generalized anxiety symptoms were associated with increased Facebook behaviour and repetitive Facebook behaviour. As adolescent Facebook use is quite prevalent, mental health and primary care health professionals should inquire about adolescent Facebook use and behaviours, particularly when treating those with generalized anxiety symptoms.

OBJECTIF: L'utilisation des médias sociaux, et en particulier de Facebook, est hautement prévalente chez les adolescents. Nous étudions l'association des symptômes d'anxiété sociale, d'anxiété généralisée et de dépression avec les comportements adoptés par les adolescents lorsqu'ils sont connectés à Facebook. MÉTHODE: Nous avons interrogé 102 adolescents relativement aux symptômes d'anxiété sociale à l'aide de l'échelle d'anxiété sociale de Leibowitz pour enfants et adolescents, et aux symptômes d'anxiété généralisée, de dépression, et de détresse générale au moyen du mini questionnaire des symptômes de l'humeur et d'anxiété. Nous avons créé une échelle détaillée des comportements sur Facebook et une échelle répétitive des comportements sur Facebook afin de mesurer l'étendue de l'emploi de Facebook. Des analyses de régression linéaire multivariée ont servi à étudier les prédicteurs tirés des données démographiques, des caractéristiques de Facebook, et des symptômes d'anxiété sociale, d'anxiété généralisée et de dépression pour les résultats des comportements sur Facebook et des comportements répétitifs sur Facebook. RÉSULTATS: Nous avons constaté qu'un plus grand nombre total d'amis Facebook augmentait le temps passé par jour sur Facebook, et que chacun des symptômes accrus d'éveil de l'anxiété était significativement associé à des comportements accrus sur Facebook et à des comportements répétitifs accrus sur Facebook. Les symptômes d'anxiété sociale, de dépression et de détresse générale n'étaient pas chacun associés aux comportements sur Facebook et aux comportements répétitifs sur Facebook. CONCLUSIONS: Les symptômes accrus d'anxiété généralisée chez les adolescents étaient associés à un comportement accru sur Facebook et à un comportement répétitif sur Facebook. Comme l'utilisation de Facebook par les adolescents est très prévalente, les professionnels de la santé mentale et des soins de première ligne devraient se renseigner sur les comportements sur Facebook des adolescents qui l'utilisent, en particulier lorsque ceux-ci sont traités pour des symptômes d'anxiété généralisée.

Poxviruses Evade Cytosolic Sensing through Disruption of an mTORC1-mTORC2 Regulatory Circuit.

Viruses employ elaborate strategies to coopt the cellular processes they require to replicate while simultaneously thwarting host antiviral responses. In many instances, how this is accomplished remains poorly understood. Here, we identify a protein, F17 encoded by cytoplasmically replicating poxviruses, that binds and sequesters Raptor and Rictor, regulators of mammalian target of rapamycin complexes mTORC1 and mTORC2, respectively. This disrupts mTORC1-mTORC2 crosstalk that coordinates host responses to poxvirus infection. During infection with poxvirus lacking F17, cGAS accumulates together with endoplasmic reticulum vesicles around the Golgi, where activated STING puncta form, leading to interferon-stimulated gene expression. By contrast, poxvirus expressing F17 dysregulates mTOR, which localizes to the Golgi and blocks these antiviral responses in part through mTOR-dependent cGAS degradation. Ancestral conservation of Raptor/Rictor across eukaryotes, along with expression of F17 across poxviruses, suggests that mTOR dysregulation forms a conserved poxvirus strategy to counter cytosolic sensing while maintaining the metabolic benefits of mTOR activity.

A comparative analysis of ante- and postnatal clinical characteristics of extremely premature neonates suffering from refractory and non-refractory hypotension: Is early clinical differentiation possible?

BACKGROUND: About 25% of hypotensive ELBW infants are refractory to intravascular volume expansion and inotropic drugs (VI) and require hydrocortisone (HC). Such neonates suffer from complications of prolonged hypotension and extended therapy with VI. ELBW infants with refractory hypotension (RH) are clinically and biochemically indistinguishable from those who respond to VI. OBJECTIVE: Early identification and differentiation of ELBW infants susceptible to steroid dependent hypotension from those who respond to inotropic medications. METHODS: In a retrospective study the ante- and postnatal clinical characteristics of ELBW infants who received hydrocortisone (HC) for refractory hypotension (RH) were compared to those who responded to volume-inotropes (VI). RESULTS: Infants in HC group had lower birth weight (BW, 675±121g) and gestational age (GA, 25.1±1.3weeks) and higher mean airway pressure and oxygen requirements, all independent of antenatal steroid (ANS) exposure. The receipt of ANS (p 0.01) and occurrences of maternal diabetes mellitus (GDM, p 0.01) were lower in HC group. ANS (OR 0.5, 95% CI 0.2-0.9, p 0.01) and GDM (OR 0.3, 95% CI 0.09-0.9, p 0.04) reduced the risk for RH. HC group had higher risk for IVH (OR 2.1, 95% CI 1.02-4.2 p=0.04) which declined in the multivariate analysis. A trend towards lower risk of ventriculomegaly (VM) was noted in HC group (OR 0.3, 95% CI 0.1-1.1), which became significant after controlling for BW (OR 0.2 95% CI 0.07-0.9, p 0.04). Similar trend was noted for maternal hypertension. CONCLUSION: Hypotension in ELBW infants who are ≤25wks of GA and unexposed to ANS and GDM is refractory to VI therapy. Such neonates may benefit from an initial therapy with, or earlier institution of hydrocortisone. The trend towards a higher risk for VM with VI therapy needs validation in future studies.

Postnatal Transitional Weight Loss and Adverse Outcomes in Extremely Premature Neonates.

The early postnatal weight loss (EPWL) is highly variable in the extremely low birth weight infants (birth weight <1000 g, ELBW). It is reported to be unassociated with adverse outcomes within a range of 3-21% of birth weight. Its wide range might have contributed to this lack of association. The aim of our paper is to study the effects of maximum EPWL, graded as low, medium and large on clinical outcomes in ELBW infants. In a retrospective cohort observational study EPWL was measured as maximum weight loss from birth weight (MWL) in ELBW infants and grouped as low (5-12%) moderate (18.1-12%) and high (18-25%). The clinical course and complications of infants were compared between the groups. Gestational age (GA) was highest and surfactant administration, peak inspiratory pressure requirement, fluid intake, urinary output, oxygen dependent days and the number of oxygen dependent infants at age 28 days were lower in the low MWL compared to the high MWL group. However, all these significant P-values declined after controlling for GA. Diabetes mellitus and pregnancy associated hypertension were not noted in mothers in high MWL group, whereas 38% of mothers in low MWL group suffered from the latter (P=0.05). Maximum postnatal transitional weight loss, assessed in the range of low, moderate and high, is not associated with adverse outcomes independent of gestational age in ELBW infants. Maternal hypertension decreases EPWL in them.

Isolated Placental Inflammation and Vasculopathy: Clinical Implications in the Extremely Low Birth Weight Infants.

The predictive values of placental histopathologies are compromised by a non-segregation of common anomalies. The effects of isolated pure placental inflammation (PI) and vasculopathy-coagulopathy (PV) were compared with normal (NL) placentas in extremely premature infants (ELBW, birth weight < 1000 g). PI infants required lower peak inspiratory pressure on day 3. More infants in PV were oxygen dependence on day 28. PV had an increased risk of intraventricular-periventricular hemorrhage (IVH, OR 4.9, 95% CI 1-24.7, p = 0.05). NL infants were unexposed to PPROM or maternal hypertension, had highest requirement for surfactant, did not develop IVH and periventricular leukomalacia (PVL) and none of them were Caucasian. CONCLUSIONS: In ELBW infants (1) pure placental vasculopathy-coagulopathy is a risk factor for IVH, (2) a non- pathological intrauterine environment is nonconducive to IVH and PVL, (3) pure placental inflammation is protective for acute pulmonary disease, (4) Caucasian mothers are more susceptible to adverse intrauterine environment.

The endosomal sorting complex required for transport pathway mediates chemokine receptor CXCR4-promoted lysosomal degradation of the mammalian target of rapamycin antagonist DEPTOR.

G protein-coupled receptor (GPCR) signaling mediates many cellular functions, including cell survival, proliferation, and cell motility. Many of these processes are mediated by GPCR-promoted activation of Akt signaling by mammalian target of rapamycin complex 2 (mTORC2) and the phosphatidylinositol 3-kinase (PI3K)/phosphoinositide-dependent kinase 1 (PDK1) pathway. However, the molecular mechanisms by which GPCRs govern Akt activation by these kinases remain poorly understood. Here, we show that the endosomal sorting complex required for transport (ESCRT) pathway mediates Akt signaling promoted by the chemokine receptor CXCR4. Pharmacological inhibition of heterotrimeric G protein Gαi or PI3K signaling and siRNA targeting ESCRTs blocks CXCR4-promoted degradation of DEPTOR, an endogenous antagonist of mTORC2 activity. Depletion of ESCRTs by siRNA leads to increased levels of DEPTOR and attenuated CXCR4-promoted Akt activation and signaling, consistent with decreased mTORC2 activity. In addition, ESCRTs likely have a broad role in Akt signaling because ESCRT depletion also attenuates receptor tyrosine kinase-promoted Akt activation and signaling. Our data reveal a novel role for the ESCRT pathway in promoting intracellular signaling, which may begin to identify the signal transduction pathways that are important in the physiological roles of ESCRTs and Akt.

Effect of dietary administration of letrozole and tamoxifen on gonadal development, sex differentiation and biochemical changes in common carp (Cyprinus carpio L.).

The effect of letrozole and tamoxifen on the specific growth rate (SGR; % day(-1)), gonado-somatic index (GSI), total haemoglobin (g%), gonadal and serum protein as well as lipid, sex differentiation and 17ß-oestradiol levels were studied in sexually undifferentiated Cyprinus carpio fingerlings 30 days post fertilisation (30 dpf) for 60 days. Results showed decreased GSI with tamoxifen treatment whereas letrozole increased it. There were reduced protein, lipid, triglyceride and cholesterol levels after treatment with tamoxifen and letrozole during gonadal development. Tamoxifen (200mgkg(-1) feed) induced 82.5% masculinisation, whereas letrozole in the same dose produced 98.5% males. Gonadal 17ß-oestradiol significantly declined from 86.0±1.41pg per 100mg (control) to 45.5±1.94pg per 100mg with tamoxifen and 36.0±0.72pg per 100mg with letrozole treatment. Similarly, serum 17ß-oestradiol levels also decreased after tamoxifen and letrozole treatments. Testicular development in 37.8% of fish treated with tamoxifen and letrozole was found to be more advanced (spermatocytes) than in the control (spermatogonium); however, there was reduced ovarian growth and increased atresia. It was concluded that letrozole and tamoxifen both significantly affect sex differentiation and gonadal maturity in C. carpio leading to the production of sex-reversed males, yet the effect of letrozole was more potent.