Traviskamper5449

Patient/physician and program-level strategies to improve adherence will play an important role in quality improvement.

Albuminuria screening is an important part of pediatric diabetes care. In our study, pediatric albuminuria screening adherence was suboptimal at 66% in 2019 and deteriorated during the pandemic to 45% in 2020. Program and patient-level adherence to clinical guidelines and barriers to accessing diabetes care during the pandemic merit further study.

Albuminuria screening is an important part of pediatric diabetes care. In our study, pediatric albuminuria screening adherence was suboptimal at 66% in 2019 and deteriorated during the pandemic to 45% in 2020. Program and patient-level adherence to clinical guidelines and barriers to accessing diabetes care during the pandemic merit further study.

Rapid next-generation sequencing (NGS) offers the potential to shorten the diagnostic process and improve the care of acutely ill children. The goal of this study was to report our findings, including benefits and limitations, of a targeted NGS panel and rapid genome sequencing (rGS) in neonatal and pediatric acute clinical care settings.

Retrospective analysis of patient characteristics, diagnostic yields, turnaround time, and changes in management for infants and children receiving either RapSeq, a targeted NGS panel for 4500+ genes, or rGS, at the University of Utah Hospital and Primary Children's Hospital, from 2015 to 2020.

Over a 5-year period, 142 probands underwent rapid NGS 66 received RapSeq and 76 rGS. Overall diagnostic yield was 39%. In the majority of diagnostic cases, there were one or more changes in clinical care management. Of note, 7% of diagnoses identified by rGS would not have been identified by RapSeq.

Our results indicate that rapid NGS impacts acute pediatric care in real-lifeagnosis of patients in neonatal, pediatric, and cardiac intensive care units and impactful change in management. Diagnoses led to significant changes in management for several patients in lower acuity inpatient units supporting further exploration of the utility of rapid sequencing in these settings. This study reviews the limitations of comparing sequencing platforms in the clinical setting and the variables that should be considered in evaluating diagnostic rates across studies.Human pluripotent stem-cell-derived islets (hPSC-islets) are a promising cell resource for diabetes treatment1,2. However, this therapeutic strategy has not been systematically assessed in large animal models physiologically similar to humans, such as non-human primates3. In this study, we generated islets from human chemically induced pluripotent stem cells (hCiPSC-islets) and show that a one-dose intraportal infusion of hCiPSC-islets into diabetic non-human primates effectively restored endogenous insulin secretion and improved glycemic control. Fasting and average pre-prandial blood glucose levels significantly decreased in all recipients, accompanied by meal or glucose-responsive C-peptide release and overall increase in body weight. Notably, in the four long-term follow-up macaques, average hemoglobin A1c dropped by over 2% compared with peak values, whereas the average exogenous insulin requirement reduced by 49% 15 weeks after transplantation. Collectively, our findings show the feasibility of hPSC-islets for diabetic treatment in a preclinical context, marking a substantial step forward in clinical translation of hPSC-islets.Conserved epitopes on the influenza hemagglutinin (HA) stem are an attractive target for universal vaccine strategies as they elicit broadly neutralizing antibodies. Such antibody responses to stem-specific epitopes have been extensively characterized for HA subtypes H1 and H5 in humans. H2N2 influenza virus circulated 50 years ago and represents a pandemic threat due to the lack of widespread immunity, but, unlike H1 and H5, the H2 HA stem contains Phe45HA2 predicted to sterically clash with HA stem-binding antibodies characterized to date. To understand the effect of Phe45HA2, we compared the HA stem-specific B cell response in post hoc analyses of two phase 1 clinical trials, one testing vaccination with an H2 ferritin nanoparticle immunogen ( NCT03186781 ) and one with an inactivated H5N1 vaccine ( NCT01086657 ). In H2-naive individuals, the magnitude of the B cell response was equivalent, but H2-elicited HA stem-binding B cells displayed greater cross-reactivity than those elicited by H5. However, in individuals with childhood H2 exposure, H5-elicited HA stem-binding B cells also displayed high cross-reactivity, suggesting recall of memory B cells formed 50 years ago. Overall, we propose that a one-residue difference on an HA immunogen can alter establishment and expansion of broadly neutralizing memory B cells. These data have implications for stem-based universal influenza vaccination strategies.Currently, licensed seasonal influenza vaccines display variable vaccine effectiveness, and there remains a need for novel vaccine platforms capable of inducing broader responses against viral protein domains conserved among influenza subtypes. We conducted a first-in-human, randomized, open-label, phase 1 clinical trial ( NCT03186781 ) to evaluate a novel ferritin (H2HA-Ferritin) nanoparticle influenza vaccine platform. DDR1-IN-1 mw The H2 subtype has not circulated in humans since 1968. Adults born after 1968 have been exposed to only the H1 subtype of group 1 influenza viruses, which shares a conserved stem with H2. Including both H2-naive and H2-exposed adults in the trial allowed us to evaluate memory responses against the conserved stem domain in the presence or absence of pre-existing responses against the immunodominant HA head domain. Fifty healthy participants 18-70 years of age received H2HA-Ferritin intramuscularly as a single 20-μg dose (n = 5) or a 60-μg dose either twice in a homologous (n = 25) prime-boostvelopment.Aside from PD-L1 expression, biomarkers of response to immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) are needed. In a previous retrospective analysis, we documented that fecal Akkermansia muciniphila (Akk) was associated with clinical benefit of ICI in patients with NSCLC or kidney cancer. In the current study, we performed shotgun-metagenomics-based microbiome profiling in a large cohort of patients with advanced NSCLC (n = 338) treated with first- or second-line ICIs to prospectively validate the predictive value of fecal Akk. Baseline stool Akk was associated with increased objective response rates and overall survival in multivariate analyses, independent of PD-L1 expression, antibiotics, and performance status. Intestinal Akk was accompanied by a richer commensalism, including Eubacterium hallii and Bifidobacterium adolescentis, and a more inflamed tumor microenvironment in a subset of patients. However, antibiotic use (20% of cases) coincided with a relative dominance of Akk above 4.8% accompanied with the genus Clostridium, both associated with resistance to ICI. Our study shows significant differences in relative abundance of Akk that may represent potential biomarkers to refine patient stratification in future studies.Chronic infections caused by microbial biofilms represent an important clinical challenge. The recalcitrance of microbial biofilms to antimicrobials and to the immune system is a major cause of persistence and clinical recurrence of these infections. In this Review, we present the extent of the clinical problem, and the mechanisms underlying the tolerance of biofilms to antibiotics and to host responses. We also explore the role of biofilms in the development of antimicrobial resistance mechanisms.Transcranial direct-current stimulation (tDCS) appears to enhance cognitive function in Alzheimer's disease (AD). Accordingly, over the last two decades, the number of studies using tDCS for AD has grown. This study aimed to provide a quantitative assessment of the efficacy of tDCS in improving cognitive function in patients with AD. We systematically searched the literature until May 2021 to identify relevant publications for inclusion in our systematic review and meta-analysis. Eligible studies were sham-controlled trials assessing the impacts of anodal or cathodal tDCS on cognitive function in patients with AD. The outcome measure of this study was the effects of tDCS on distinct cognitive domains including memory, attention, and global cognitive function. The initial search yielded a total of 323 records. Five other articles were found using manual search of the databases. Of these, 13 publications (14 different studies) with a total of 211 patients of various degrees of AD severity underwent meta-analysis. Meta-analysis revealed the non-significant effects of tDCS on attention (0.425 SMD, 95% CI, -0.254 to 1.104, p = 0.220), and significant positive impacts on the amelioration of general cognitive measures (1.640 SMD, 95% CI, 0.782 to 2.498, p  less then  0.000), and memory (1.031 SMD, 95% CI, 0.688 to 1.373, p  less then  0.000) dysfunction in patients with AD. However, the heterogeneity of the studies were high in all subdomains of cognition (ϰ2 = 22.810, T2 = 0.552, d.f. = 5, I2 = 78.80%, p  less then  0.000 for attention, ϰ2 = 96.29, T2 = 1.727, d.f. = 10, I2 = 89.61%, p  less then  0.000 for general cognition, and ϰ2 = 7.253, T2 = 0.085, d.f. = 5, I2 = 31.06%, p = 0.203 for memory). Improved memory and general cognitive function in patients with AD was shown in this meta-analysis. However, due to the small number of studies and the high heterogeneity of the data, more high-quality studies using standardized parameters and measures are needed before tDCS can be considered as a treatment for AD.Maladaptive coping behaviors are probably involved in post-traumatic stress disorders (PTSD), but underlying mechanisms are incompletely understood. We now report that mice lacking functional insulin-like growth factor I (IGF-I) receptors in orexin neurons of the lateral hypothalamus (Firoc mice) are unresponsive to the anxiolytic actions of IGF-I and develop PTSD-like behavior that is ameliorated by inhibition of orexin neurons. Conversely, systemic IGF-I treatment ameliorated PTSD-like behavior in a wild-type mouse model of PTSD (PTSD mice). Further, systemic IGF-I modified the GABA/Glutamate synaptic structure in orexin neurons of naïve wild-type mice by increasing the dephosphorylation of GABA(B) receptor subunit through inhibition of AMP-kinase (AMPK). Significantly, pharmacological inhibition of AMPK mimicked IGF-I, normalizing fear behavior in PTSD mice. Thus, we suggest that IGF-I enables coping behaviors by balancing E/I input onto orexin neurons in a context-dependent manner. These observations provide a novel therapeutic approach to PTSD through modulation of AMPK.The ability to remember conspecifics is critical for adaptive cognitive functioning and social communication, and impairments of this ability are hallmarks of autism spectrum disorders (ASDs). Although hippocampal ventral CA1 (vCA1) neurons are known to store social memories, how their activities are coordinated remains unclear. Here we show that vCA1 social memory neurons, characterized by enhanced activity in response to memorized individuals, were preferentially reactivated during sharp-wave ripples (SPW-Rs). Spike sequences of these social replays reflected the temporal orders of neuronal activities within theta cycles during social experiences. In ASD model Shank3 knockout mice, the proportion of social memory neurons was reduced, and neuronal ensemble spike sequences during SPW-Rs were disrupted, which correlated with impaired discriminatory social behavior. These results suggest that SPW-R-mediated sequential reactivation of neuronal ensembles is a canonical mechanism for coordinating hippocampus-dependent social memories and its disruption underlie the pathophysiology of social memory defects associated with ASD.