Hollisfrandsen3999

The unity of the components of gerontology provides scientific background for improving public policy aimed on adapting socio-economic development to the demographic processes of population aging.Gaucher disease, the most prevalent metabolic storage disorder, is caused by mutations in the glucocerebrosidase gene GBA1, which lead to the accumulation of glucosylceramide (GlcCer) in affected cells. Gaucher disease type 1 (GD1), although defined as a nonneuronopathic subtype, is accompanied by an increased risk of Parkinson's disease. To gain insights into the association of progressive accumulation of GlcCer and the Parkinson's disease phenotypes, we generated dopaminergic (DA) neurons from induced pluripotent stem cells (iPSCs) derived from a GD1 patient and a healthy donor control, and measured GlcCer accumulation by liquid chromatography-mass spectrometry. We tested two DA neuron differentiation methods a well-established method that mimics a step-wise developmental process from iPSCs to neural progenitor cells, and to DA neurons; and a synthetic mRNA-based method that overexpresses a transcription factor in iPSCs. GD1-specific accumulation of GlcCer was detected after 60 days of differentiation by the former method, whereas it was detected after only 10 days by the latter method. With this synthetic mRNA-based rapid differentiation method, we found that the metabolic defect in GD1 patient cells can be rescued by the overexpression of wild-type GBA1 or the treatment with an inhibitor for GlcCer synthesis. Furthermore, we detected the increased phosphorylation of α-synuclein, a biomarker for Parkinson's disease, in DA neurons derived from a GD1 patient, which was significantly decreased by the overexpression of wild-type GBA1. These results suggest that synthetic mRNA-based method accelerates the analyses of the pathological mechanisms of Parkinson's disease in GD1 patients and possibly facilitates drug discovery processes.

Few reports have examined dental arch morphology (DAM) after dental implant placement in cleft patients and its actual state is unclear.

To analyze the presence of changes in DAM and influencing factors in cleft lip and/or palate (CLP) patients who receive implant treatment in the alveolar cleft region.

Subjects comprised 20 CLP patients in whom maxillary dental arch width (DAW) was evaluated before and after implant treatment based on computed tomography data. First, widths between the canines (W3), between the first premolars (W4), between the second premolars (W5), and between the first molars (W6) were measured before and after surgery. Changes in distance were analyzed using the Wilcoxon signed-rank test, revealing a significant increase in W6. Analysis of Co-Variance was performed with the difference in W6 after implant treatment as the response variable, and the following six items as explanatory variables sex; cleft type; age at alveolar bone graft; time to implantation after bone grafting; number of implants; and time after completion of the observation period.

The reduction in W6 was larger in the order of complete bilateral CLP, complete unilateral CLP, and unilateral cleft lip and alveolus, and the change decreased with an increasing number of implants.

Implant treatment of the alveolar cleft region may result in a slight reduction in width of the dental arch after treatment completion.

Implant treatment of the alveolar cleft region may result in a slight reduction in width of the dental arch after treatment completion.Angiotensin II (AngII), the effector peptide of the renin angiotensin system and has an important role in regulating cardiovascular hemodynamics and structure. AngII is an important biomarker for certain diseases that are associated with cardiovascular disorders, i.e., influenza, SARS-CoV-2, tumors, hypertension, etc. However, AngII presents in blood in very low concentrations and they are not stable due to their reactivity, therefore spontaneous detection of AngII is a big challenge. In this study, AngII-imprinted spongy columns (AngII-misc) synthesized for AngII detection from human serum, and characterized by surface area measurements (BET), swelling tests, scanning electron microscopy (SEM), FTIR studies. AngII binding studies were achieved from aqueous environment and maximum binding capacity was found as 0.667 mg/g. It was calculated that the AngII-miscs recognized AngII 8.27 and 14.25 times more selectively than competitor Angiotensin I and Vasopressin molecules. Newly produced AngII-misc binds 60.5 pg/g AngII from crude human serum selectively. It has a great potential for spontaneous detection of AngII from human serum for direct and critical measurements in serious diseases, that is, heart attacks, SARS-CoV-2, etc.

Systemic lupus erythematosus is a chronic autoimmune disease with varied and unpredictable levels of disease activity. The ability to self-manage lupus is important in controlling disease activity. Our objective was to determine levels of patient activation toward self-management in lupus.

We used baseline results from the MyLupusGuide

study that had recruited 541 lupus patients from ten centers. We used the Patient Activation Measure (PAM), a validated self-reported tool designed to measure activation towards self-management ability, as our primary variable and examined its association with demographic, disease-related, patient-provider communication and psychosocial variables captured in our study protocol. Univariable and multivariable linear regressions were performed using linear mixed models, with a random effect for centers.

The average age was 50±14 years, 93% were female, 74% were Caucasian and the average disease duration was 17±12 years. The mean PAM score was 61.2±13.5 with 36% of participants scoring in the two lower levels, indicating low activation. Variables associated with low activation included being single, lower physical health status, lower self-reported disease activity, lower self-efficacy, use of more emotional coping and less distraction and instrumental coping strategies, and perceived lack of clarity in patient-doctor communication.

Low patient activation was observed in more than one third of lupus patients indicating a large proportion of patients perceived that they are lacking in lupus self-management skills. These results highlight a modifiable gap in perceived self-management ability among patients with lupus.

Low patient activation was observed in more than one third of lupus patients indicating a large proportion of patients perceived that they are lacking in lupus self-management skills. These results highlight a modifiable gap in perceived self-management ability among patients with lupus.

Hemophilia A (HA) is an inherited X-linked recessive coagulation disorder caused by factor VIII (F8) deficiency. F8 rearrangements involving intron 22 (int22) and intron 1 (int1) account for almost half of severe HA phenotype also a hotspot exon 14 provides numerous mutational patterns. This study aims to identify F8 gene mutations among Egyptian HA patients.

DNA samples from 60 HA patients were screened for int22 and int1 rearrangements using simplified inverse shifting PCR (IS-PCR) followed by exon 14 sequencing. Also, four uncharacterized patients were studied by targeted exome sequencing.

In 33.3% of the studied patients, we identified three int22 rearrangements, three exon 14 mutations (two frameshift; one novel (NM_000132.3c.2734_2735delAA, p.(N912Ffs*6)), a second reported mutation (NM_000132.3c.3091_3094delAGAA, p.(K1031Lfs*9)), and one nonsense mutation (NM_000132.3c.2440C>T, p.(R814*)). All identified mutations were detected in patients with severe HA phenotype. Targeted exome sequencing could not detect any known pathogenic variants.

Intron 22 rearrangement and exon 14 mutations correlate with most severe hemophilia A Egyptian patients.

Intron 22 rearrangement and exon 14 mutations correlate with most severe hemophilia A Egyptian patients.

We evaluated the pregnancy experience of women receiving care in the Division of Rheumatology at a major academic center in New York City during the COVID-19 pandemic.

A web-based COVID-19 survey was emailed to 26,045 patients followed in the Division of Rheumatology at a single center in New York City. Women aged 18 to 50 were asked about pregnancy. We compared the COVID-19 experience between pregnant and non-pregnant women, and also explored the impact of the pandemic on prenatal care and perinatal outcomes.

Of 7,094/26,045 respondents, 1,547 were women aged 18 to 50, with 61 (4%) reporting being pregnant during the pandemic. The prevalence of self-reported COVID-19 was similar in pregnant and non-pregnant women (8% vs.9% respectively, p=0.76). Among women with COVID-19, pregnant women had shorter duration of symptoms (p <0.01) and were more likely to experience loss of smell or taste (p=0.02) than non-pregnant women. Approximately three-fourths of women had a systemic rheumatic disease, with no differences when stratified by pregnancy or COVID-19 status. 67% of pregnant women noted changes to prenatal care during the pandemic, and 23% of postpartum women stated the pandemic affected delivery.

Among women followed in the Division of Rheumatology at a major center in New York City, pregnancy was not associated with increased self-reported COVID-19. Pregnancy was associated with a shorter duration of COVID-19 symptoms and a higher prevalence of loss of smell or taste. The COVID-19 pandemic impacted pre-natal care for the majority of pregnant patients.

Among women followed in the Division of Rheumatology at a major center in New York City, pregnancy was not associated with increased self-reported COVID-19. Pregnancy was associated with a shorter duration of COVID-19 symptoms and a higher prevalence of loss of smell or taste. The COVID-19 pandemic impacted pre-natal care for the majority of pregnant patients.Although tracheal involvement of lung cancer is frequently seen, endotracheal metastasis of colon cancer is a rare entity. Since endotracheal lesion gives no symptom until tracheal lumen nearly occluded, the diagnosis of endotracheal metastasis could be challenging. F-18 fluorodeoxyglucose positron emission tomography/computed tomography may be crucial to detect this unusal distant metastasis of colon cancer. Herein, we report FDG avid endotracheal lesion that was confirmed as metastasis from colon cancer in 56-year-old female patient.Bacterial lipolytic enzymes of family IV are homologs of the mammalian hormone-sensitive lipases (HSL) and have been successfully used for various biotechnological applications. The broad substrate specificity and ability for enantio-, regio-, and stereoselective hydrolysis are remarkable features of enzymes from this class. Many crystal structures are available for esterases and lipases, but structures of enzyme-substrate or enzyme-inhibitor complexes are less frequent although important to understand the molecular basis of enzyme-substrate interaction and to rationalize biochemical enzyme characteristics. Tebipenem Pivoxil manufacturer Here, we report on the structures of a novel family IV esterase isolated from a metagenomic screen, which shows a broad substrate specificity. We solved the crystal structures in the apo form and with a bound substrate analogue at 1.35 and 1.81 Å resolution, respectively. This enzyme named PtEst1 hydrolyzed more than 60 out 96 structurally different ester substrates thus being substrate promiscuous. Its broad substrate specificity is in accord with a large active site cavity, which is covered by an α-helical cap domain.