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The detection of the first synonymous variant of CEP290 gene and the demonstration of its effect on splicing by a functional study are likely to contribute to the molecular etiology of MKS.This retrospective chart review assesses the impact of introduction of an adolescent young adult oncology navigator (AYAON) on first contact with oncology psychosocial services (OPS) for adolescents and young adults (AYAs) newly diagnosed with cancer. All AYAs newly diagnosed at a single adult oncology center between 17 and 29 years of age from July 2016 to July 2018 were reviewed. AYA contact with the AYAON was associated with an increase in contact with OPS. Following the introduction of the AYAON, there was a clinically significant decrease in the time to first OPS contact for newly diagnosed AYAs with cancer.Background The aim of this study was to analyze patient satisfaction with telehealth in a rural county on the United States-Mexico border after rapid expansion of telehealth services during the COVID-19 pandemic. Materials and Methods Chiricahua Community Health Centers, Inc., a federally qualified health center in southeastern Arizona, conducted phone surveys with 562 patients to measure various outcomes related to patient satisfaction and experience with telehealth between June and August 2020. Data from patient surveys were analyzed within the following age categories less then 18 years (37%), 18-34 years (19%), 35-54 years (15%), and 55+ years (29%). Results and Discussion Patients were overall satisfied with telehealth (87%) and believed the quality of care was just as good as or better than in-person appointments (88%). Many would be willing to try telehealth in the future (54%). Distance/convenience (odds ratio [OR] = 5.01, 95% confidence interval [CI] 2.80-8.97), ease of scheduling (OR = 3.82, 95% CI 1.30-11.21), and protection from potential exposure to coronavirus (OR = 3.01, 95% CI 1.57-5.75) were all strongly predictive of overall satisfaction scores. Adults within the 35-54 (OR = 0.29, 95% CI 0.10-0.81) and 55+ (OR = 0.37, 95% CI 0.14-0.95) age groups were overall less satisfied with telehealth compared with younger adults 18-34 years. Underlying health conditions and primary language were not correlated with satisfaction in using telehealth. Conclusions Telehealth may be an effective tool for overcoming barriers and providing rural patients with access to health care without compromising patient satisfaction.Objective To describe real-world outcomes for youth using the Tandem tslim X2 insulin pump with Control-IQ technology ("Control-IQ") for 6 months at a large pediatric clinic. Methods Youth with type 1 diabetes, who started Control-IQ for routine care, were prospectively followed. Data on system use and glycemic control were collected before Control-IQ start, and at 1, 3, and 6 months after start. Mixed models assessed change across time; interactions with baseline hemoglobin A1c (HbA1c) and age were tested. Results In 191 youth (median age 14, 47% female, and median HbA1c 7.6%), percent time with glucose levels 70-180 mg/dL (time-in-range [TIR]) improved from 57% at baseline to 66% at 6 months (P 70%) doubled from 23.5% at baseline to 47.8% at 3 months, sustaining at 46.7% at 6 months (P  less then  0.001). Glucose management indicator (approximation of HbA1c) improved from 7.5% at baseline to 7.1% at 3 months and 7.2% at 6 months (P  less then  0.001). Those with higher baseline HbA1c experienced the most substantial improvements in glycemic control. Percent time using the Control-IQ feature was 86.4% at 6 months, and less then 4% of cohort discontinued use. Conclusion The Control-IQ system clinically and significantly improved glycemic control in a large sample of youth. System use was high at 6 months, with only a small proportion discontinuing use, indicating potential for sustaining results long term.Background Port-wine stains (PWS) on proximal limbs respond better to pulsed dye laser (PDL) than PWS on distal limbs. Objective To investigate whether the superiority of PDL efficacy on the proximal limbs is related to variations in blood perfusion. Methods Patients with untreated PWS on the extremities underwent three sessions of PDL. Blood perfusion of the selected sites on both the proximal and distal limbs, as well as control sites, was detected by laser speckle imaging before treatment. After treatment was completed, the therapeutic effect was evaluated both objectively and subjectively. Results A total of 19 patients were included. Seventeen of them presented with PWS on the upper extremities and 2 patients on the lower extremities. The mean speckle flow imaging value of the PWS on the upper arms and thighs was significantly lower [80.51 ± 16.96 perfusion unit (PU), control 66.36 ± 13.18 PU] than that on the hands and feet (155.68 ± 71.86 PU, control 72.82 ± 18.97 PU). Meanwhile, the average blanching rate on the proximal and distal limbs was 48.33% and 22.12%, respectively. Significant correlations were identified between blood perfusion and PDL efficacy (r = -0.351, p = 0.031). Conclusions PWS in the proximal limbs responded better to PDL than PWS on distal limbs. This variation in efficacy may be attributed to differences in blood perfusion. Clinical trial registration no. ChiCTR-OCB-15007326.The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 genome editing system has been broadly adopted for high-throughput genetic screens. However, the application of genome-wide single guide RNA (sgRNA) libraries can be challenging. We generated a custom sgRNA library, an order of magnitude smaller than genome-wide alternatives, to facilitate the genetic screening of RNA binding proteins (RBPs). click here We demonstrated the utility of our reagent in a genetic screen for RBPs that conveyed cellular resistance or sensitivity to oxidative stress induced by paraquat. This identified that CSDE1 and STRAP, proteins that interact with each other, convey sensitivity to oxidative stress and that Pumilio homologues (PUM1 and PUM2) convey resistance. Targeting eIF4-E1 and -A1 protected cells from high-dose paraquat, whereas eIF4E2 targeted cells did less well. We also found that G3BP1 promoted sensitivity to a low dose of paraquat but protected cells at a higher dose. Our study highlights the use of genetic screens to identify roles of RBPs and identifies novel genes regulating sensitivity to oxidative stress.Bacterial flagella are the best-known rotational organelles in the biological world. The spiral-shaped flagellar filaments that extend from the cell surface rotate like a screw to create a propulsive force. At the base of the flagellar filament lies a protein motor that consists of a stator and a rotor embedded in the membrane. The stator is composed of two types of membrane subunits, PomA (similar to MotA in Escherichia coli) and PomB (similar to MotB in E. coli), which are energy converters that assemble around the rotor to couple rotation with the ion flow. Recently, stator structures, where two MotB molecules are inserted into the center of a ring made of five MotA molecules, were reported. This structure inspired a model in which the MotA ring rotates around the MotB dimer in response to ion influx. Here, we focus on the Vibrio PomB plug region, which is involved in flagellar motor activation. We investigated the plug region using site-directed photo-cross-linking and disulfide cross-linking experiments.d explain the role of the plug region in blocking the rotation of the stator unit.Antimicrobial peptides (AMPs) are one of the key immune responses that can eliminate pathogenic bacteria through membrane perturbation. As a successful skin commensal, Staphylococcus epidermidis can sense and respond to AMPs through the GraXRS two-component system and an efflux system comprising the VraG permease and VraF ATPase. GraS is a membrane sensor known to function in AMP resistance through a negatively charged, 9-residue extracellular loop, which is predicted to be linear without any secondary structure. An important question is how GraS can impart effective sensing of AMPs through such a small unstructured sequence. In this study, we verified the role of graS and vraG in AMP sensing in S. epidermidis, as demonstrated by the failure of the ΔgraS or ΔvraG mutants to sense. Deletion of the extracellular loop of VraG did not affect sensing but reduced survival with polymyxin B. Importantly, a specific region within the extracellular loop, termed the guard loop (GL), has inhibitory activity since sensingponse system in a clinically relevant S. epidermidis strain. Furthermore, we provide evidence for a unique sensory scheme that would rely on the detoxification function of a permease to effect information processing.Listeria ivanovii (Liv) is an intracellular Gram-positive pathogen that primarily infects ruminants but also occasionally causes enteric infections in humans. Albeit rare, this bacterium possesses the capacity to cross the intestinal epithelium of humans, similar to its more frequently pathogenic cousin, Listeria monocytogenes (Lmo). Recent studies in Lmo have shown that specific glycosyl modifications on the cell wall-associated glycopolymers (termed wall teichoic acid [WTA]) of Lmo are responsible for bacteriophage adsorption and retention of the major virulence factor internalin B (InlB). However, the relationship between InlB and WTA in Liv remains unclear. Here, we report the identification of the unique gene liv1070, which encodes a putative glucosyltransferase in the polycistronic WTA gene cluster of the Liv WSLC 3009 genome. We found that in-frame deletion of liv1070 led to loss of the glucose substitution on WTA, as revealed by ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) analyseria monocytogenes, strains develop resistance to bacteriophage attack due to loss of glycosylated surface receptors, which subsequently results in disconnection of one of the bacterium's major virulence factors, InlB. However, the situation in L. ivanovii remains unclear. Here, we show that L. ivanovii acquires phage resistance following deletion of a unique glycosyltransferase. This deletion also leads to dysfunction of InlB, making the resulting strain unable to invade host cells. Overall, this study suggests that the interplay between phage, bacteria, and the host may be a feature common to the genus Listeria.Bis-(3'-5')-cyclic-dimeric GMP (c-di-GMP) is an important bacterial regulatory signaling molecule affecting biofilm formation, toxin production, motility, and virulence. The genome of Bacillus anthracis, the causative agent of anthrax, is predicted to encode ten putative GGDEF/EAL/HD-GYP-domain containing proteins. Heterologous expression in Bacillus subtilis hosts indicated that there are five active GGDEF domain-containing proteins and four active EAL or HD-GYP domain-containing proteins. Using an mCherry gene fusion-Western blotting approach, the expression of the c-di-GMP-associated proteins was observed throughout the in vitro life cycle. Of the six c-di-GMP-associated proteins found to be present in sporulating cells, four (CdgA, CdgB, CdgD, and CdgG) contain active GGDEF domains. The six proteins expressed in sporulating cells are retained in spores in a CotE-independent manner and thus are not likely to be localized to the exosporium layer of the spores. Individual deletion mutations involving the nine GGDEF/EAL protein-encoding genes and one HD-GYP protein-encoding gene did not affect sporulation efficiency, the attachment of the exosporium glycoprotein BclA, or biofilm production.
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