Genomic insights and advanced machine learning: characterizing autism spectrum disorder biomarkers and genetic interactions.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by altered brain connectivity and function. In this study, we employed advanced bioinformatics and explainable AI to analyze gene expression associated with ASD, using data from five GEO datasets. Among 351 neurotypical controls and 358 individuals with autism, we identified 3,339 Differentially Expressed Genes (DEGs) with an adjusted p-value (≤ 0.05). A subsequent meta-analysis pinpointed 342 DEGs (adjusted p-value ≤ 0.001), including 19 upregulated and 10 down-regulated genes across all datasets. Shared genes, pathogenic single nucleotide polymorphisms (SNPs), chromosomal positions, and their impact on biological pathways were examined. We identified potential biomarkers (HOXB3, NR2F2, MAPK8IP3, PIGT, SEMA4D, and SSH1) through text mining, meriting further investigation. Additionally, we shed light on the roles of RPS4Y1 and KDM5D genes in neurogenesis and neurodevelopment. Our analysis detected 1,286 SNPs linked to ASD-related conditions, of which 14 high-risk SNPs were located on chromosomes 10 and X. We highlighted potential missense SNPs associated with FGFR inhibitors, suggesting that it may serve as a promising biomarker for responsiveness to targeted therapies. Our explainable AI model identified the MID2 gene as a potential ASD biomarker. This research unveils vital genes and potential biomarkers, providing a foundation for novel gene discovery in complex diseases.

Molecular characterization of circadian gene expression and its correlation with survival percentage in colorectal cancer patients.

Colorectal cancer (CRC) is a form of cancer characterized by many symptoms and readily metastasizes to different organs in the body. Circadian rhythm is one of the many processes that is observed to be dysregulated in CRC-affected patients. In this study, we aim to identify the dysregulated physiological processes in CRC-affected patients and correlate the expression profiles of the circadian clock genes with CRC-patients' survival rates. We performed an extensive microarray gene expression pipeline, whereby 471 differentially expressed genes (DEGs) were identified, following which, we streamlined our search to 43 circadian clock affecting DEGs. The Circadian Gene Database was accessed to retrieve the circadian rhythm-specific genes. The DEGs were then subjected to multi-level functional annotation, i.e., preliminary analysis using ClueGO/CluePedia and pathway enrichment using DAVID. The findings of our study were interesting, wherein we observed that the survival percentage of CRC-affected patients dropped significantly around the 100th-month mark. Furthermore, we identified hormonal activity, xenobiotic metabolism, and PI3K-Akt signaling pathway to be frequently dysregulated cellular functions. Additionally, we detected that the ZFYVE family of genes and the two genes, namely MYC and CDK4 were the significant DEGs that are linked to the pathogenesis and progression of CRC. This study sheds light on the importance of bioinformatics to simplify our understanding of the interactions of different genes that control different phenotypes.

Identification of dysregulated canonical pathways associated with pathogenesis and progression of Amyotrophic Lateral Sclerosis-An integrated bioinformatics approach.

The mechanisms responsible for the pathogenesis and progression of Amyotrophic Lateral Sclerosis (ALS) remain poorly understood, making the diagnosis of ALS challenging. We aimed to find the novel gene biomarkers via computationally analyzing microarray expression studies, in three different cell lineages, namely myotube cells, astrocyte cells and oligodendrocyte cells. Microarray gene expression profiles were obtained and analyzed for three cell types: myotube cell lineage (GSE122261), astrocyte, and oligodendrocyte cell lineage (GSE87385). A comprehensive computational pipeline, tailored explicitly for microarray gene expression profiling studies, was devised to analyze the sample groups, wherein the myotube sample group comprised of six control (GSM3462697, GSM3462698, GSM3462699, GSM3462700, GSM3462701, GSM3462702) & six diseased (GSM3462691, GSM3462692, GSM3462693, GSM3462694, GSM3462695, GSM3462696) samples were considered. Similarly, for the astrocyte sample group two samples each for the control (GSM2330040, GSM2330042) and the diseased (GSM2330039, GSM2330041), and for the oligodendrocyte sample group, 2 control (GSM2330043, GSM2330045) samples and two diseased (GSM2330044, GSM2330046) samples were considered for the current study. The in-depth interaction of these DEGs was studied using MCODE and subjected to preliminary functional analysis using ClueGO/CluePedia plug-in. Qiagen's IPA software was employed for enrichment analysis, which generated the key canonical pathways and a list of potential biomarker molecules specific to each sample group. The preliminary analysis yielded 512 DEGs across all 3-sample groups, wherein 139 DEGs belonged to the myotube sample group, 216 DEGs for the astrocyte sample group, and 157 DEGs for the oligodendrocytes sample group. The data suggests growth hormone signaling and its activity, ErbB signaling pathway, and JAK/STAT signaling pathway are some of the pathways that are significantly dysregulated and play a crucial role in the development and progression of ALS. KISS1R and CSHL1 are potential genes that could act as diagnostic biomarkers in myotube cell types. Also, KRAS, TGFB2, JUN, and SMAD6 genes may be used as prognostic biomarkers to differentiate between early and late-stage ALS-diseased patients.

Investigation of differentially expressed genes and dysregulated pathways involved in multiple sclerosis.

Multiple Sclerosis (MS) is a neurodegenerative autoimmune and organ-specific demyelinating disorder, known to affect the central nervous system (CNS). While genetic studies have revealed several critical genes and diagnostic biomarkers associated with MS, the etiology of the disease remains poorly understood. This study is aimed at screening and identifying the key genes and canonical pathways associated with MS. Gene expression profiling of the microarray dataset GSE38010 was used to analyze two control brain samples (control 1; GSM931812, control 2; GSM931813), active inflammation stage samples (CAP1; GSM931815, CAP2; GSM931816) and late subsided stage samples (CP1; GSM931817, CP2; GSM931818) collected from patients ranging between 23 and 54years and both genders. This analysis yielded a list of 58,866 DEGs (29,433 for active-inflammation stage and 29,433 for late-subsided Stage). The interactions between the DEGs were then studied using STRING, Cytoscape software, and MCODE was employed to find the genes that form clusters. Functional enrichment and integrative analysis were performed using ClueGO/CluePedia and MetaCore™. Our data revealed dysregulated key canonical pathways in MS patients. In addition, we identified three hub genes (SCN2A, HTR2A, and HCN1) that may serve as potential biomarkers for the prognosis of MS. Furthermore, the expression patterns of HPCA and PLCB1 provide insights into the progressive stages of MS, indicating that these genes could be used in predicting MS progression. We were able to map potential biomarkers that could be used for the prognosis and diagnosis of MS.

Medical and surgical interventions and outcomes for infants with trisomy 18 (T18) or trisomy 13 (T13) at children's hospitals neonatal intensive care units (NICUs).

OBJECTIVES: To examine characteristics and outcomes of T18 and T13 infants receiving intensive surgical and medical treatment compared to those receiving non-intensive treatment in NICUs. STUDY DESIGN: Retrospective cohort of infants in the Children's Hospitals National Consortium (CHNC) from 2010 to 2016 categorized into three groups by treatment received: surgical, intensive medical, or non-intensive. RESULTS: Among 467 infants admitted, 62% received intensive medical treatment; 27% received surgical treatment. The most common surgery was a gastrostomy tube. Survival in infants who received surgeries was 51%; intensive medical treatment was 30%, and non-intensive treatment was 72%. Infants receiving surgeries spent more time in the NICU and were more likely to receive oxygen and feeding support at discharge. CONCLUSIONS: Infants with T13 or T18 at CHNC NICUs represent a select group for whom parents may have desired more intensive treatment. Survival to NICU discharge was possible, and surviving infants had a longer hospital stay and needed more discharge supports.

Inter-center variation in autopsy practices among regional neonatal intensive care units (NICUs).

OBJECTIVE: To characterize infants who underwent autopsy in regional neonatal intensive care units (NICUs) and examine inter-center variability in autopsy completion. STUDY DESIGN: Retrospective cohort study of infants who died between 2010 and 2016 from 32 participating hospitals in the Children's Hospital Neonatal Database (CHND). Maternal/infant demographics and hospital stay data were collected, along with autopsy rates by center, year, and region. Data analysis utilized bivariate and multivariable statistics. RESULT: Of 6299 deaths, 1742 (27.7%) completed autopsy. Infants who underwent autopsy had higher median birth weight (2 124 g vs. 1 655 g) and gestational age (34 vs. 32 weeks). No differences were seen in sex, length of stay, or primary cause of death. Marked inter-center variability was observed, with 17-fold adjusted difference (p < 0.001) in autopsy rates. CONCLUSION: Patient characteristics do not account for variability in autopsy practices across regional NICUs. Factors such as provider practices and parental preferences should be investigated.

Regulation of key molecules of immunological synapse by T11TS immunotherapy abrogates Cryptococcus neoformans infection in rats.

Cryptococcus neoformans infects and disseminates in hosts with diminished T cell responses. The immunomodulator T11TS (T11 target structure) had profound potential in glioma as well as C. neoformans infected model for disease amelioration. It is been established by our group that T11TS potentiates Calcineurin-NFAT pathway in T cells of C. neoformans infected rats. We investigated the upstream Immunological Synapse (IS) molecules that are vital for the foundation of initial signals for downstream signaling, differentiation and proliferation in T cells. Improved RANTES level in the T11TS treated groups suggests potential recruitment of T cells. Down-regulation of TCRαß, CD3ζ, CD2, CD45 and CD28 molecules by cryptococcus were boosted after T11TS therapy. Heightened expression of inhibitory molecule CTLA-4 in cryptococcosis was dampened by T11TS. The decline of MHC I, MHC II and CD80 expression on macrophages by C. neoformans were enhanced by T11TS. The dampening of positive regulators and upsurge of negative regulators of the IS during cryptococcosis was reversed with T11TS therapy resulting in enhanced clearance of fungus from the lungs as envisaged by our histological studies. This preclinical study with T11TS opens a new prospect for potential immunotherapeutic intervention against the devastating C. neoformans infection with positive aspect for the long-term solution and a safer immunotherapeutic regimen.

Center, Gestational Age, and Race Impact End-of-Life Care Practices at Regional Neonatal Intensive Care Units.

OBJECTIVE: To assess the impact of intercenter variation and patient factors on end-of-life care practices for infants who die in regional neonatal intensive care units (NICUs). STUDY DESIGN: We conducted a retrospective cohort analysis using the Children's Hospital Neonatal Database during 2010-2016. A total of 6299 nonsurviving infants cared for in 32 participating regional NICUs were included to examine intercenter variation and the effects of gestational age, race, and cause of death on 3 end-of-life care practices: do not attempt resuscitation orders (DNR), cardiopulmonary resuscitation within 6 hours of death (CPR), and withdrawal of life-sustaining therapies (WLST). Factors associated with these practices were used to develop a multivariable equation. RESULTS: Dying infants in the cohort underwent DNR (55%), CPR (21%), and WLST (73%). Gestational age, cause of death, and race were significantly and differently associated with each practice: younger gestational age (<28 weeks) was associated with CPR (OR 1.7, 95% CI 1.5-2.1) but not with DNR or WLST, and central nervous system injury was associated with DNR (1.6, 1.3-1.9) and WLST (4.8, 3.7-6.2). Black race was associated with decreased odds of WLST (0.7, 0.6-0.8). Between centers, practices varied widely at different gestational ages, race, and causes of death. CONCLUSIONS: From the available data on end-of-life care practices for regional NICU patients, variability appears to be either individualized or without consistency.

Effects of intraoperative temperatures on postoperative infections in infants and neonates.

BACKGROUND: Perioperative hypothermia has been shown to increase surgical site infection (SSI) rates in adults. We sought to characterize whether intraoperative hypothermia or hyperthermia is associated with postoperative infections in infants. METHODS: We conducted a retrospective review of patients ≤6 months old who underwent surgical procedures from November 2013 to October 2015 at a Level I ACS Children's Surgical Center. The outcome was infections within 30 days after operation, with particular attention to SSI. Data obtained included weight and age at surgery, American Society of Anesthesiologists (ASA) physiologic status, wound class, case length, blood transfusion within 72 h of surgery, and administration of prophylactic antibiotics. Temperatures were classified as hypothermia (T < 36 °C), normothermia (T = 36.0 to 37.9 °C), and hyperthermia (T ≥ 38 °C). RESULTS: The 885 patients had 25 SSIs (2.8%) and 11 nonsurgical site infections (1.2%). On univariate analysis, weight at surgery, higher ASA, perioperative transfusions, and longer case length were associated with higher rate of SSI. Higher median Thigh, higher median T low, and any hyperthermia were associated with higher rate of SSI. On multivariable logistic regression adjusted analyses, hyperthermia at any time during the case was associated with SSI (OR 3.47, [95% CI 1.34, 9.04], p = 0.011). Transfusions were also associated with higher SSI rates (OR 3.60 [95% CI, 1.28, 10.3], p = 0.016). CONCLUSIONS: Intraoperative hyperthermia is associated with increased SSI rates in infants. LEVEL OF EVIDENCE: III.

Association of Neonatologist Continuity of Care and Short-Term Patient Outcomes.

OBJECTIVES: To describe neonatologist continuity of care and estimate the association between these transitions and selected patient outcomes. STUDY DESIGN: We linked Children's Hospitals Neonatal Database records with masked neonatologist daily schedules at 4 centers, which use 2- and 3-week and 1-month "on service" blocks to provide care. After describing the neonatologist transitions, we estimated associations between these transitions and selected short-term patient outcomes using multivariable Poisson, logistic, and linear regression analyses, independent of length of stay (LOS) and case-mix. We also completed analyses after stratifying the cohort by LOS, birthweight, age at admission categories, and selected diagnoses. RESULTS: Stratified by LOS, patient transitions varied between centers in both unadjusted (P < .001) and multivariable analyses (adjusted incidence rate ratio; 95% CI for center B = 3.98 (3.81-4.15), center C = 4.92 (4.71-5.13), center D = 4.2 (4.0-4.4), P < .001), independent of LOS, gestational age, birthweight, surgical intervention, ventilator duration, and mortality. Only central venous line duration (adjusted incidence rate ratio 1.015, 95% CI 1.01-1.02) was minimally and independently associated with the number of transitions. No differences were observed in ventilator duration, oxygen use at neonatal intensive care unit discharge, bloodstream infections, or urinary tract infections. Surviving infants with meconium aspiration, hypoxic ischemic encephalopathy, cerebral infarction, bronchopulmonary dysplasia, and diaphragmatic hernia demonstrated similar findings. CONCLUSIONS: Transitions in neonatologists are frequent in regional neonatal intensive care units but appear unrelated to short-term patient outcomes. Future work to define continuity of care and develop effective strategies that promote longitudinal inpatient management is needed.

Unravelling the apoptotic mechanisms in T-lymphocytes in an animal model for pollen induced airway allergy and studying the impact of specific immunotherapy.

Asthma is a chronic inflammatory disorder of the airways, increasing in prevalence worldwide. Reduced T cell apoptosis may interfere with the down-regulation of an immune response resulting in T cell accumulation contributing to the chronic inflammation of asthma. Most studies focused so far on apoptosis of eosinophils but the detailed role of T lymphocytes apoptosis in allergic diseases is unclear yet. The present experimental study was designed to discern the modulation of various apoptotic proteins of splenic T lymphocytes in a previously established rat model of Alstonia scholaris pollen induced airway allergy. Flowcytometry, immunoblotting, and immunofluorescence imaging techniques were employed for the present investigation. Annexin-V studies registered early apoptotic rate of lymphocytes with allergen sensitization and challenge which was corrected following mucosal immunotherapy. The study demonstrates that allergen sensitization and challenge reduced apoptosis of splenic T-lymphocytes via Fas mediated extrinsic pathway, Bax/Bcl2 regulated intrinsic pathway and also perforin/granzyme mediated pathway which were normalized following allergen specific intranasal immunotherapy. Inadequate T cell apoptosis in asthma appears to interfere with normal T cell elimination, resulting in T cell accumulation, which contributes to chronic inflammation and may be the major underlying cause for tissue damage which can be modulated by intranasal immunotherapy. Thus the apoptosis inducing effect of allergen immunotherapy necessitates more studies to elaborate on its effects on various effector cells of airway inflammation.

T11TS immunotherapy augments microglial and lymphocyte protective immune responses against Cryptococcus neoformans in the brain.

Cryptococcus neoformans, the encapsulated yeast acquired through inhalation, remains localized in lungs, but harbours the CNS in immunocompromised individuals. Several treatment regimes have failed combating this disease totally, but long-term usage of drugs leads to organ damage. As T11-target structure (T11TS) has documented profound immune potentiation, we aimed to investigate the role of microglia, pivotal immune cells of brain in ameliorating cryptococcosis, with T11TS immunotherapy. Murine model with C neoformans infection was prepared by intraperitoneal injection and the brains of rats examined 7 days post-infections for histopathology by PAS and Alcian blue staining corroborated with organ fungal burden evidencing restorative T11TS action on Cryptococcal meningitis. Immunotherapy with three doses of T11TS, a CD2 ligand, in C neoformans infected rats, upregulates toll-like receptors 2, -4 and -9 of microglia, indicating increased phagocytosis of the fungus. Flowcytometric analysis revealed increased numbers of T11TS treated brain infiltrating CD4+ and CD8+ T-lymphocytes along with increased MHC I and MHC II on microglia, activating the infiltrating lymphocytes aiding the killing mechanism. Present study also indicated that T11TS increased production of Th1 inflammatory cytokines conducive to fungal elimination while the inhibitory Th2 cytokines were dampened. This preclinical study is first of its kind to show that T11TS effected profound immune stimulation of microglial activity of C neoformans infected rats eradicating residual fungal burden from the brain and can be a useful therapeutic strategy in fighting against this deadly disease.

T11TS repress gliomagenic apoptosis of bone marrow hematopoietic stem cells.

Combating gliomagenic global immunosuppression is one of the emerging key for improving prognosis in malignant glioma. Apoptosis plays a pivotal role within the adult hematopoietic system particularly in regulating the cells of immune system. Gliomagenic regulation of apoptotic mediators within bone marrow milieu has not been elucidated. We previously demonstrated that administration of membrane glycopeptides T11 target structure (T11TS) not only rejuvenate bone marrow hematopoietic stem cells (BMHSCs) from glioma mediated hibernation by inhibiting gliomagenic overexpression of Ang-1/Tie-2 but also stimulate glioma mediated diminution of expression CD34, c-kit, and Sca-1 markers. In the present study, we investigated the impact of glioma on apoptotic signaling cascades of BMHSCs and consequences following T11TS therapy. Bone marrow smear and Annexin V staining confirm gliomagenic acceleration of apoptotic fate of BMHSCs whereas T11TS treatment in glioma-bearing rats disrupted apoptosis of BMHSCs. Flowcytometry, immunoblotting, and immunofluorescence imagining results revealed multi potent T11TS not only significantly downregulates gliomagenic overexpression of Fas, Fas L, Bid, and caspase-8, the pro-apoptotic extrinsic mediators but also strongly inhibits cytosolic release of cytochrome-c, Apf-1, and Bax to deactivate gliomagenic caspase-9, 3 the key intrinsic apoptotic mediators followed by up modulation of anti-apoptotic Bcl-2 in glioma associated HSCs. T11TS is also able to diminish the perforin-granzyme B mediated apoptotic verdict of BMHSCs during gliomagenesis. The anti-apoptotic action of T11TS on glioma associated BMHSCs provide a crucial insight into how T11TS exerts its immunomodulatory action against glioma mediated immune devastation.

T11TS immunotherapy repairs PI3K-AKT signaling in T-cells: Clues toward enhanced T-cell survival in rat glioma model.

Malignant glioma is the most fatal of astrocytic lineage tumors despite therapeutic advances. Onset and progression of gliomas is accompanied by severe debilitation of T-cell defense and T-cell survival. One of the chief contributors to T-cell survival downstream of activation is the PI3K-AKT pathway. Our prior studies showed that the novel immunotherapeutic molecule T11-target structure (T11TS) blocks T-cell apoptosis in glioma. We also showed activation of immunological synapse components and calcineurin-NFAT pathway following T11TS immunotherapy of glioma-bearing rats. This lead to investigations whether such T-cell activation upon T11TS therapy translates into activation of downstream PI3K/AKT signals which may be related to observed blockade of T-cell apoptosis. For the purpose, we assessed by flowcytometry and immunoblotting, expressions of PI3K, PDK1, AKT, p-AKT, and PTEN in splenic T-cells of normal, experimentally-induced glioma-bearing rats and glioma-bearing rats receiving first, second and third doses of T11TS. We also determined comparative nuclear translocation of NF-κB across groups. We found significant increases in T-cell expressions of PDK1, PI3K, and p-AKT in T11TS-treated animal groups compared to sharp downregulations in glioma. AKT levels remained unchanged across groups. PTEN levels declined sharply after T11TS immunotherapy. T11TS also caused enhanced NF-κB translocation to the T-cell nucleus compared to glioma group. Results showed heightened activation of the PI3K-AKT pathway in glioma-bearing rats following T11TS immunotherapy. These results illustrate the novel role of T11TS immunotherapy in ameliorating the PI3K pathway in T-cells in glioma-bearing animals to enhance T-cell survival, according greater defense against glioma. The study thus has far-reaching clinical outcomes.

Allergen immunotherapy modulates sensitivity of Treg cells to apoptosis in a rat model of allergic asthma.

AIM: To study the apoptosis of Foxp3+ Treg cells following Alstonia scholaris pollen sensitization-challenge and following allergen immunotherapy. MATERIALS & METHODS: Wistar rats were sensitized-challenged with Alstonia scholaris pollen and were further given intranasal immunotherapy. For the analysis of the apoptotic proteins on Treg cells by flow cytometry, multiple gating procedures were followed. RESULTS: Allergen sensitization-challenge increases Annexin-V, Fas, FasL, caspases-8, 9, 3 cytochrome-C, APAF-1, Bax, perforin-1 and granzyme-B on Treg cells which is decreased following intranasal immunotherapy. On the other hand, Bcl-2 expression is decreased in allergy and increased by immunotherapy. CONCLUSION: Apoptosis of Treg cells is increased following allergen sensitization-challenge via extrinsic, intrinsic and perforin/granzyme pathways and allergen immunotherapy decreased the sensitivity to apoptosis of Treg cells.

Antibiotic stewardship in the newborn surgical patient: A quality improvement project in the neonatal intensive care unit.

BACKGROUND: There is significant diversity in the utilization of antibiotics for neonates undergoing surgical procedures. Our institution standardized antibiotic administration for surgical neonates, in which no empiric antibiotics were given to infants with surgical conditions postnatally, and antibiotics are given no more than 72 hours perioperatively. METHODS: We compared the time periods before and after implementation of antibiotic protocol in an institution review board-approved, retrospective review of neonates with congenital surgical conditions who underwent surgical correction within 30 days after birth. Surgical site infection at 30 days was the primary outcome, and development of hospital-acquired infections or multidrug-resistant organism were secondary outcomes. RESULTS: One hundred forty-eight infants underwent surgical procedures pre-protocol, and 127 underwent procedures post-protocol implementation. Surgical site infection rates were similar pre- and post-protocol, 14% and 9% respectively, (P = .21.) The incidence of hospital-acquired infections (13.7% vs 8.7%, P = .205) and multidrug-resistant organism (4.7% vs 1.6%, P = .143) was similar between the 2 periods. CONCLUSION: Elimination of empiric postnatal antibiotics did not statistically change rates of surgical site infection, hospital-acquired infections, or multidrug-resistant organisms. Limiting the duration of perioperative antibiotic prophylaxis to no more than 72 hours after surgery did not increase the rate of surgical site infection, hospital-acquired infections, or multidrug-resistant organism. Median antibiotic days were decreased with antibiotic standardization for surgical neonates.

Modulation of regulatory T cells by intranasal allergen immunotherapy in an experimental rat model of airway allergy.

Allergic airway diseases such as asthma and allergic rhinitis are increasing in prevalence worldwide. The theory of an altered Th1/Th2 balance in allergic diathesis has recently been termed a "procrustean paradigm" as it failed to explain many preclinical findings. Regulatory T cells (Treg) have now been shown to be critical in T-cell homeostasis and in the maintenance of peripheral tolerance to allergens. Allergen specific immunotherapy (SIT) has been shown to induce regulatory T cells in allergic patients. Among various types of SIT, intranasal immunotherapy had not been studied in detail for the treatment of allergic airway diseases. So, there was a need to study the contribution of regulatory T cells and their mechanistic pathways following intranasal immunotherapy in-vivo. It had been previously shown that intranasal allergen immunotherapy using Alstonia scholaris pollen extract abrogates allergic airway inflammation with decline in IgE and Th2 cytokine levels. The present study for the first time offers a multi-targeted approach towards attenuation of airway allergy by the generation of CD4+CD25+Foxp3+T cells and other subsets of Treg cells like Tr1 cells, Th3 cells, CTLA4+Treg cells, and also modulation of various Treg cell surface molecules like GITR, OX40, CD39 and CD73 by intranasal immunotherapy in the same animal model. This animal experiment will thus help to chart out newer molecular targets for treating allergic asthma or rhinitis.

Nutritional Practices and Growth in Premature Infants After Surgical Necrotizing Enterocolitis.

OBJECTIVE: The aim of the study was to describe the nutritional provisions received by infants with surgical necrotizing enterocolitis (NEC) and the associated effects on short-term growth. METHODS: Through the Children's Hospitals Neonatal Database, we identified infants born ≤32 weeks' gestation with surgical NEC from 5 regional neonatal intensive care units for 4 years. Excluded infants had isolated intestinal perforation and died <14 days postoperatively. Infants were stratified by their median parenteral protein dose (low [LP] or high [HP] protein) for the first postoperative week. The primary outcome was postoperative weight growth velocity. Growth (weight, length, and head circumference [HC]) was measured and the effects related to protein dose were estimated using multivariable analyses. RESULTS: There were 103 infants included; the median parenteral protein dose received was 3.27 g ·â€Škg ·â€Šday (LP: 2.80 g ·â€Škg ·â€Šday; HP: 3.87 g ·â€Škg ·â€Šday). Postoperative weight (11.5 ±â€Š6.5 g ·â€Škg ·â€Šday) and linear growth (0.9 ±â€Š0.2 cm/wk) were similar regardless of dose (P > 0.3 between groups for weight and length). Unadjusted and independent associations were identified with HC changes and HP dose (ß = 0.1 cm/wk, P = 0.03) after adjusting for gestational age, the presence of severe bronchopulmonary dysplasia, short bowel syndrome, blood stream infection, severe intraventricular hemorrhage, small for gestational age, and calorie intake. Eventual nonsurvivors received 18% less protein and 14% fewer calories over the first postoperative month. CONCLUSIONS: Postoperative protein doses in infants with surgical NEC appear related to increases in HC. The influence of postoperative nutritional support on risk of adverse outcomes deserves further attention.

T11TS Treatment Augments Apoptosis of Glioma Associated Brain Endothelial Cells, Hint Toward Anti-Angiogenic Action in Glioma.

Malignant glioma continues to be a clinical challenge with an urgent need for developing curative therapeutic intervention. Apoptosis induction in tumor-associated endothelial cells represent a central mechanism that counteracts angiogenesis in glioma and other solid tumors. We previously demonstrated that intraperitoneal administration of sheep erythrocyte membrane glycopeptide T11-target structure (T11TS) in rodent glioma model inhibits PI3K/Akt pathway and Raf/MEK/ERK signaling in glioma-associated brain endothelial cells. In the present study, we investigated whether T11TS treatment influence apoptosis signaling in vivo in glioma-associated brain endothelial cells. Annexin-V/PI staining showed that T11TS treatment in glioma-induced rats increases apoptosis of glioma-associated endothelial cells within glioma milieu compared to brain endothelial cells in glioma induced and control groups. Flowcytometric JC-1 assay revealed that T11TS administration triggers loss of mitochondrial membrane potential in glioma-associated brain endothelial cells. Flowcytometry, immunoblotting, and in situ immunofluoresecnt imaging were employed to investigate the effect of T11TS on apoptotic regulatory proteins in brain endothelial cells. T11TS treatment-upmodulated expression of p53, Bax, Fas, FasL, and FADD in glioma associated endothelial cells and downregulated Bcl-2 protein. T11TS therapy induced cytochrome-c release into cytosol, activated caspase -9, 8, 3, and cleaved Bid in glioma associated brain endothelial cells. The study demonstrates that T11TS induces apoptosis in glioma-associated brain endothelial cells via p53 accumulation and activation of intrinsic as well as Fas-dependent extrinsic pathway. The pro-apoptotic action of T11TS on glioma-associated endothelial cells provides crucial insight into how T11TS exerts its anti-angiogenic function in glioma. J. Cell. Physiol. 232: 526-539, 2017. © 2016 Wiley Periodicals, Inc.