Prevalence of Urinary Tract Infection in Infants with Unexplained Acute Fever: A cross sectional study

Background: Urinary tract infection (UTI) is one of the most common bacterial infections in infancy, with a high risk of recurrence, and maybe an indicator of underlying urinary tract abnormality. It is often misdiagnosed due to irregular and unrelated symptomatology in the absence of directed screening. Knowledge of baseline risk of urinary tract infection can help clinicians make informed diagnostic and therapeutic decisions. Objectives: The objectives of the study were to know the prevalence of UTI in infants with unexplained acute fever and to know other features of UTI besides fever. Methods: This was an observational, descriptive, cross sectional study. The study was conducted in private tertiary care hospital in Kolkata involving 110 infants attending the out-patient department of Paediatrics, KPC Medical College and Hospital from January 2020, to June 2020. Urine specimens were collected using midstream clean-catch urine (CCU) method and tested by urinalysis and culture. Template was generated in MS excel sheet and analysis was done on SPSS software. Results: Urine sample was successfully obtained from 110 infants, of which 66 (60%) were males, 44 (40%) were females. UTI was maximum present in age group 61-365 days (12.73%). In gender maximum UTI was present in males (11.82%). Majority of cases present with the temperature 38.30C to 38.90C (37.27%). Fever (100%) and Failure to thrive (70.91%) were the commonest presentation of cases selected for the study. Gastroenteritis was the most common illness observed in 33 (30%) infants. Conclusions: Prevalence rates of UTI varied by age, gender, race, and circumcision status. Prevalence estimates can help clinicians make informed decisions regarding diagnostic testing in children presenting with signs and symptoms of urinary tract infection

Controlled transient respiratory arrest along with rapid right ventricular pacing for improving balloon stability during balloon valvuloplasty in pediatric patients with congenital aortic stenosis - A retrospective case series analysis

Rapid right ventricular pacing is safe, effective, and established method to provide balloon stability during balloon aortic valvuloplasty (BAV). Controlled transient respiratory arrest at this point of time may further reduce left ventricular stroke volume, providing an additional benefit to maintain balloon stability. Two groups were studied. Among the 10 patients, five had rapid pacing alone (Group A), while the other five were provided with cessation of positive pressure breathing as well (Group B). The outcomes of BAV in the two groups of patients were studied. One patient in Group A had failed balloon dilatation even after the fourth attempt, while in Group B there were no failures. The peak systolic gradient reduction was higher in Group B (70.05% in comparison to 52.16% of group A). In Group A, five subjects developed aortic regurgitation (grade 2 in four and grade 3 in one, while no grade 3 aortic regurgitation developed in any patient in Group B). Controlled transient respiratory arrest along with rapid ventricular pacing may be effective in maintaining balloon stability and improve the outcome of BAV

Ciglitazone, a PPARγ agonist, ameliorates diabetic nephropathy in part through homocysteine clearance

Diabetes and hyperhomocysteinemia (HHcy) are two independent risk factors for glomeruloslerosis and renal insufficiency. Although PPARγ agonists such as ciglitazone (CZ) are known to modulate diabetic nephropathy, the role of CZ in diabetes-associated HHcy and renopathy is incompletely defined. We tested the hypothesis that induction of PPARγ by CZ decreases tissue Hcy level; this provides a protective role against diabetic nephropathy. C57BL/6J mice were administered alloxan to create diabetes. Mice were grouped to 0, 1, 10, 12, and 16 wk of treatment; only 12- and 16-wk animals received CZ in drinking water after a 10-wk alloxan treatment. In diabetes, PPARγ cDNA, mRNA, and protein expression were repressed, whereas an increase in plasma and glomerular Hcy levels was observed. CZ normalized PPARγ mRNA and protein expression and glomerular level of Hcy, whereas plasma level of Hcy remained unchanged. GFR was dramatically increased at 1-wk diabetic induction, followed by hypofiltration at 10 wk, and was normalized by CZ treatment. This result corroborated with glomerular and preglomerular arteriole histology. A steady-state increase of RVR in diabetic mice became normal with CZ treatment. CZ ameliorated decrease bioavailability of NO in the diabetic animal. Glomerular MMP-2 and MMP-9 activities as well as TIMP-1 expression were increased robustly in diabetic mice and normalized with CZ treatment. Interestingly, TIMP-4 expression was opposite to that of TIMP-1 in diabetic and CZ-treated groups. These results suggested that diabetic nephropathy exacerbated glomerular tissue level of Hcy, and this caused further deterioration of glomerulus. CZ, however, protected diabetic nephropathy in part by activating PPARγ and clearing glomerular tissue Hcy

Differential Recognition of Phosphorylated Transactivation Domains of p53 by Different p300 Domains

Histone acetyltransferases form crucial links in transducing extrinsic signals to actual initiation of transcription. A multitude of stress signal integrations occur through the interaction of p300 with p53 phosphorylated at different residues of the transactivation domain. How such interactions activate different gene expression programs remains largely unknown. p300 contains at least five domains that are known to interact with p53, but their role in transcription regulation is not known. We measured the binding affinity of various phosphorylated transactivation domains towards several p53 binding domains of p300 by fluorescence anisotropy. The binding affinities of different phosphorylated transactivation domains of p53 towards different domains of p300 vary by several orders of magnitude, indicating that interactions of different post-translationally modified forms of p53 may occur through different domains of p300. Thus, different post-translationally modified p53 fragments may form transcription-initiating complexes of different configurations, leading to the activation of different promoters and pathways

H2S Protects Against Methionine–Induced Oxidative Stress in Brain Endothelial Cells

Homocysteine (Hcy) causes cerebrovascular dysfunction by inducing oxidative stress. However, to date, there are no strategies to prevent Hcy-induced oxidative damage. Hcy is an H2S precursor formed from methionine (Met) metabolism. We aimed to investigate whether H2S ameliorated Met-induced oxidative stress in mouse brain endothelial cells (bEnd3). The bEnd3 cells were exposed to Met treatment in the presence or absence of NaHS (donor of H2S). Met-induced cell toxicity increased the levels of free radicals in a concentration-dependent manner. Met increased NADPH-oxidase-4 (NOX-4) expression and mitigated thioredxion-1(Trx-1) expression. Pretreatment of bEnd3 with NaHS (0.05 mM) attenuated the production of free radicals in the presence of Met and protected the cells from oxidative damage. Furthermore, NaHS enhanced inhibitory effects of apocynin, N-acetyl-l-cysteine (NAC), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), Nω-nitro-l-arginine methyl ester (L-NAME) on ROS production and redox enzymes levels induced by Met. In conclusion, the administration of H2S protected the cells from oxidative stress induced by hyperhomocysteinemia (HHcy), which suggested that NaHS/H2S may have therapeutic potential against Met-induced oxidative stress. Antioxid. Redox Signal. 11, 25–33

Integrin alpha 10, a Novel Therapeutic Target in Glioblastoma, Regulates Cell Migration, Proliferation, and Survival

New, effective treatment strategies for glioblastomas (GBMs), the most malignant and invasive brain tumors in adults, are highly needed. In this study, we investigated the potential of integrin alpha 10 beta 1 as a therapeutic target in GBMs. Expression levels and the role of integrin alpha 10 beta 1 were studied in patient-derived GBM tissues and cell lines. The effect of an antibody-drug conjugate (ADC), an integrin alpha 10 antibody conjugated to saporin, on GBM cells and in a xenograft mouse model was studied. We found that integrin alpha 10 beta 1 was strongly expressed in both GBM tissues and cells, whereas morphologically unaffected brain tissues showed only minor expression. Partial or no overlap was seen with integrins alpha 3, alpha 6, and alpha 7, known to be expressed in GBM. Further analysis of a subpopulation of GBM cells selected for high integrin alpha 10 expression demonstrated increased proliferation and sphere formation. Additionally, siRNA-mediated knockdown of integrin alpha 10 in GBM cells led to decreased migration and increased cell death. Furthermore, the ADC reduced viability and sphere formation of GBM cells and induced cell death both in vitro and in vivo. Our results demonstrate that integrin alpha 10 beta 1 has a functional role in GBM cells and is a novel, potential therapeutic target for the treatment of GBM