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The term solid dispersion refers to a group of the solid products consisting of at least two different components, generally a hydrophilic matrix and a hydrophobic drug and matrix can be either crystalline or amorphous. The drug can be dispersed molecularly, in amorphous particles or in crystalline particles. Solid dispersion technologies are particularly promising for improving the aqueous solubility, dissolution rate and bioavailability of BCS Class II drugs as bioavailability of drugs depends on their solubility and permeability. The main objective of the present work was to evaluate the feasibility of the melt granulation technique to improve the dissolution characteristics of a poorly water soluble drug, Glibenclamide. Glibenclamide was chosen as a water-insoluble model drug. Conjugation of Glibenclamide with the different types of carriers was used to increase its Solubility and dissolution rate. Formulation of granules was done by physical mixture and melt granulation technique. The drug carrier interactions were studied by IR spectral analysis. Granules were evaluated by Bulk density, Tapped density, Carr’s index, Hausner ratio and Angle of repose. In-vitro dissolution studies were done on solid dispersion formulations.

Objective: The objective of our retrospective study was to evaluate differences between screening methods (oral administration versus written self-report) for adolescent depression in an outpatient setting Study Design: We analyzed data from 4075 well-child check (WCC) visits from adolescents (ages 12-18 years) at an academic medical center from January 2022 through December 2023. We evaluated the outcomes of depression screening questions from both those asked by staff (oral administration) and those filled out on paper by the patient (written self-report). A composite score of 3 or greater (out of 6) indicates a positive screen for depression. Logistic regression was used to assess for the likelihood of discrepancy between scores. Results: Of the 4518 WCC visits analyzed, 3380 (75%) had completed data for both the orally administered and the written screenings. The scores were equal in 2563 (76%) visits; the written score was greater in 766 (22.6%) visits and the oral score was greater in 51 (1.5%) visits. The screen was positive for depression in 232 (6.8%) visits for the written self-report compared with 66 (2.0%) from the oral administration. Logistic regression analyses showed likelihood of score differences were higher in older age, female gender, Hispanic race/ethnicity, and those with public insurance. Conclusion: This preliminary pilot study shows that there are score differences in depression screening when administered orally by staff versus self-reported in writing, and scores may be higher on the written self-report screening. Limitations of this study include slight differences in the wording of the questions and lack of rigorous protocol guidelines.

The human peripheral leukocyte subset composition depends on genotype variation and pre-natal and post-natal environmental influence diversity. We quantified this composition in adults and neonates, and compared the median values and dispersal ranges of various subsets in them. We confirmed higher frequencies of monocytes and regulatory T cells (Tregs), similar frequencies of neutrophils, and lower frequencies of CD8 T cells, NKT cells, B1 B cells and gamma-delta T cells in neonatal umbilical cord blood. Unlike previous reports, we found higher frequencies of eosinophils and B cells, higher CD4:CD8 ratios, lower frequencies of T cells and iNKT cells, and similar frequencies of CD4 T cells and NK cells in neonates. We characterized monocyte subsets and dendritic cell (DC) subsets in far greater detail than previously reported, using recently described surface markers and gating strategies and observed that neonates had lower frequencies of patrolling monocytes and lower myeloid dendritic cell (mDC):plasmacytoid DC (pDC) ratios. Our data contribute to South Asian reference values for these parameters. We found that dispersal ranges differ between different leukocyte subsets, suggesting differential determination of variation. Further, some subsets were more dispersed in adults than in neonates suggesting influences of postnatal sources of variation, while some show the opposite pattern suggesting influences of developmental process variation. Together, these data and analyses provide interesting biological possibilities for future exploration.

Background Aprepitant, a neurokinin-1 receptor antagonist, in combination with 5 HT-3 antagonist and dexamethasone is recommended in adults receiving moderately and highly emetogenic chemotherapy to reduce chemotherapy-induced vomiting (CIV). Data for use of aprepitant in children is limited and hence aprepitant is not recommended by Pediatric Oncology Group of Ontario guidelines for prevention of CIV in children <12 years. Methods A randomized, double-blind, placebo-controlled trial was conducted at a single center in chemotherapy naïve children (5–18 years) receiving highly emetogenic chemotherapy. All patients received intravenous ondansetron (0.15 mg/kg) and dexamethasone (0.15 mg/kg) prior to chemotherapy followed by oral ondansetron and dexamethasone. Patients randomly assigned to aprepitant arm received oral aprepitant (15–40 kg = days 1–3, 80 mg; 41–65 kg = day 1, 125 mg and days 2–3, 80 mg) 1 h before chemotherapy. Control group received placebo as add-on therapy. Primary outcome measure was the incidence of acute moderate to severe vomiting, which was defined as more than two vomiting episodes within 24 h after the administration of the first chemotherapy dose until 24 h after the last chemotherapy dose in the block. Complete response (CR) was defined as absence of vomiting and retching during the specified phase. Results Of the 96 randomized patients, three were excluded from analysis; 93 patients were analyzed (50 in aprepitant arm and 43 in placebo arm). Acute moderate and severe vomiting was reported in 72 % patients receiving placebo and 38 % patients receiving aprepitant ( p  = 0.001). Complete response rates during acute phase were significantly higher in aprepitant arm (48 vs. 12 %, p  < 0.001). No major adverse effects were reported by patients/guardians. Conclusions This double-blind, randomized, placebo-controlled trial shows that aprepitant significantly decreases the incidence of CIV during acute phase when used as an add-on drug with ondansetron and dexamethasone in children receiving highly emetogenic chemotherapy.

Hospital readmission rate helps to highlight the effectiveness of post-discharge care. There remains a paucity of plausible age-based categorization especially for ages below one year for hospital readmission rates. Data from the 2017 Healthcare Cost and Utilization Project National Readmissions Database was analyzed for ages 0-18 years. Logistic regression analysis was performed to identify predictors for unplanned early readmissions.  Results: We identified 5,529,389 inpatient pediatric encounters which were further divided into age group cohorts. The overall rate of readmissions was identified at 3.2%. Beyond infancy, the readmission rate was found to be 6.7%. Across all age groups, the major predictors of unplanned readmission were cancers, diseases affecting transplant recipients and sickle cell patients. It was determined that reflux, milk protein allergy, hepatitis and inflammatory bowel diseases were significant diagnoses leading to readmission. Anxiety, depression and suicidal ideation depicted higher readmission rates in those older than 13 years. Across ages one to four years, dehydration, asthma and bronchiolitis were negative predictors of unplanned readmission.  Conclusions: Thirty-day unplanned readmissions remain a problem leading to billions of taxpayer dollars lost per annum. Effective strategies for mandatory outpatient follow-up may help the financial aspect of care while also enhancing the quality of care.

Background In recent years, the study of molecular basis of uptake, transport and utilization of grain Fe/Zn (GFe/GZn) in wheat has been an active area of research. As a result, it has been shown that a number of transporters are involved in uptake and transport of Fe. In a recent study, knockout of a transporter gene OsVMT ( VACUOLAR MUGINEIC ACID TRANSPORTER ) in rice was shown to be involved in Fe homoeostasis. Objective In this study, we analysed VMT genes among six monocots and three dicots with major emphasis on wheat VMT genes (TaVMTs), taking OsVMT gene as a reference. Methods and results Using OsVMT gene as a reference, VMT genes were identified and sequence similarities were examined among six monocots and three dicots. Each VMT protein carried one functional domain and 7 to 10 distinct motifs (including 9 novel motifs). The qRT-PCR analysis showed differential expression by all the six TaVMT genes in pairs of contrasting wheat genotypes with high (FAR4 and WB02) and low (K8027 and HD3226) GFe/GZn at two different grain filling stages (14 DAA and 28 DAA). TaVMT1 genes showed up-regulation in high GFe/Zn genotypes relative to low GFe/Zn genotypes, whereas the TaVMT2 genes showed down-regulation or nonsignificant up-regulation in a few cases. Conclusions At 14 DAA, each of the six TaVMT genes exhibited higher expression in wheat genotypes with high GFe and GZn relative to those with low GFe and GZn, suggesting major role of VMT genes in improvement of grain Fe/Zn homoeostasis, thus making TaVMT genes useful for improvement in Fe/Zn in wheat grains.

SuperAgers (SA) are older adults who exhibit cognitive capacities comparable to individuals who are three or more decades younger than them. The current study aimed to identify the characteristics of Indian SA by categorizing 55 older adults into SA and Typical Older Adults (TOA) and comparing their performance with a group of 50 younger participants (YP) (aged 25-50). A total of 105 participants were recruited after obtaining informed written consent. The cognitive abilities of the participants were assessed using Wechsler Adult Intelligence Scale (WAIS)-IV , Color Trails Test, Boston Naming Test (BNT), and Rey Auditory Verbal Learning Test. SA outperformed TOA in all cognitive assessments (  < 0.001) and surpassed YP in BNT and WAIS-IV. SA's delayed recall scores were notably higher (12.29 ± 1.51) than TOA (6.32 ± 1.44). SA excelled in all cognitive domains demonstrating resilience to age-related cognitive decline. This study highlights Indian SuperAgers' exceptional cognitive prowess.

Background: Non-metastatic nm23H1 gene is thought to play a critical role in cell proliferation. Studies of nm23H1 have been done in many other malignancies. But none of these studies took up nm23H1 gene as predictor in the metastases of prostatic carcinoma. Aims and Objectives: To study the expression of nm23H1 in prostatic lesion and to correlate nm23H1 expression with presence of metastases, tumour stage, tumour grade and with PSA level serum. Setting and Design: Tertiary hospital based retrospective and prospective study done in a period of one year from thirty patients having prostatic lesion confirmed by biopsy. Material and Methods: Immunohistochemistry for nm23H1 was performed on unstained coated sections of prostatic lesions to study the relation with prostatic lesion and their correlation with age, PSA level, tumour stage, grading. Clinical data was collected from medical records. Statistical Analysis: SPSS Version 15 analysis software was used. The value were presented in number(%) and Mean ± SD. Results: Majority of patients belong to age group 61 to 70yrs.Gleason score >7 were seen in 55% of patients of adenocarcinoma with and without metastasis. The difference in PSA levels between BPH and adenocarcinoma was significant (P < 0.001). IHC expression for nm23H1 gene showed positive findings in all the cases (P = 1). PSA values >20ng/ml showed maximum % mean expression (98.64%) as compared to PSA levels <10 ng/ml (96.91%). Conclusion: IHC expression of nm23H1 is not an effective tool to distinguish among the cases of BPH, adenocarcinoma of prostate with and without metastasis. Hence nm23H1 gene does not behave like an antimetastatic gene in prostatic lesions.

PurposePolycystic ovarian syndrome (PCOS) is the most common endocrine abnormality among women of reproductive age and is usually associated with oligo-ovulation/anovulation, obesity, and insulin resistance. Hypovitaminosis D may also be a primary factor in the initiation and development of PCOS. However, little is known about the role of genetic variation in vitamin D metabolism in PCOS aetiology. Therefore, we studied the genetic polymorphisms of CYP2R1 and vitamin D binding protein (VDBP) in an Indian population.MethodsSerum vitamin D was measured by ELISA. Genotyping of VDBP single nucleotide polymorphisms (SNPs) rs7041 (HaeIII; G>T) and rs4588 (StyI; A>C) and CYP2R1 SNP rs2060793 (HinfI; A>G) was carried out by restriction fragment length polymorphism in 50 cases of PCOS that were compared with 50 age-matched healthy women.ResultsVitamin D levels were found to be significantly lower in women with PCOS (p = 0.008) than in age-matched controls. There was no significant difference in genotype frequencies of all three polymorphisms (rs7041, rs4588, and rs2060793) between PCOS and control women. In women with a vitamin D deficiency (<20 ng/ml), the GT allele of the VDBP SNP rs7041 (p value =0.04), the VDBP allelic combination Gc1F/1F (T allele of rs4588 and C allele of rs7041) (p value =0.03), and the GA allele of the CYP2R1 SNP rs2060793 (p = 0.05) were associated with an increased risk of developing PCOS.ConclusionsThe present study shows that the GT allele of VDBP SNP rs7041, the VDBP allelic combination (GC1F/1F), and GA allele of CYP2R1 SNP rs2060793 in vitamin D deficient women increase the risk of PCOS.

While infections are a major cause of neonatal mortality in India even in full-term neonates, this is an especial problem in the large proportion (~20%) of neonates born underweight (or small-for-gestational-age; SGA). One potential contributory factor for this susceptibility is the possibility that immune system maturation may be affected along with intrauterine growth retardation. In order to examine the possibility that differences in immune status may underlie the susceptibility of SGA neonates to infections, we enumerated the frequencies and concentrations of 22 leukocyte subset populations as well as IgM and IgA levels in umbilical cord blood from full-term SGA neonates and compared them with values from normal-weight (or appropriate-for-gestational-age; AGA) full-term neonates. We eliminated most SGA-associated risk factors in the exclusion criteria so as to ensure that AGA-SGA differences, if any, would be more likely to be associated with the underweight status itself. An analysis of 502 such samples, including 50 from SGA neonates, showed that SGA neonates have significantly fewer plasmacytoid dendritic cells (pDCs), a higher myeloid DC (mDC) to pDC ratio, more natural killer (NK) cells, and higher IgM levels in cord blood in comparison with AGA neonates. Other differences were also observed such as tendencies to lower CD4:CD8 ratios and greater prominence of inflammatory monocytes, mDCs and neutrophils, but while some of them had substantial differences, they did not quite reach the standard level of statistical significance. These differences in cellular lineages of the immune system possibly reflect stress responses in utero associated with growth restriction. Increased susceptibility to infections may thus be linked to complex immune system dysregulation rather than simply retarded immune system maturation.