Tag: nevin manimala

Org Biomol Chem. 2022 Apr 14. doi: 10.1039/d2ob00606e. Online ahead of print.

ABSTRACT

The Angiotensin Converting Enzyme 2 (ACE2) assists the regulation of blood pressure and is the main target of the coronaviruses responsible for SARS and COVID19. The catalytic function of ACE2 relies on the opening and closing motion of its peptidase domain (PD). In this study, we investigated the possibility of allosterically controlling the ACE2 PD functional dynamics. After confirming that ACE2 PD binding site opening-closing motion is dominant in characterizing its conformational landscape, we observed that few mutations in the viral receptor binding domain fragments were able to impart different effects on the binding site opening of ACE2 PD. This showed that binding to the solvent exposed area of ACE2 PD can effectively alter the conformational profile of the protein, and thus likely its catalytic function. Using a targeted machine learning model and relative entropy-based statistical analysis, we proposed the mechanism for the allosteric perturbation that regulates the ACE2 PD binding site dynamics at atomistic level. The key residues and the source of the allosteric regulation of ACE PD dynamics are also presented.

PMID:35420112 | DOI:10.1039/d2ob00606e

J Osteopath Med. 2022 Apr 14. doi: 10.1515/jom-2021-0267. Online ahead of print.

ABSTRACT

CONTEXT: Ehlers-Danlos syndromes (EDS) are disorders of connective tissue that lead to a wide range of clinical presentations. While we are beginning to understand the association between EDS and psychological manifestations, it is critical that we further elucidate the relationship between the two. Understanding the correlation between EDS and mental health will better ensure swift diagnosis and effective treatment for patients.

OBJECTIVES: This study aims to systematically examine and report the prevalence of psychiatric disorders in the EDS population.

METHODS: The PubMed database was searched on June 14, 2021 for articles published from January 2011 to June 2021. We included original, evidence-based, peer-reviewed journal articles in English that reported information on psychiatric disorders among EDS patients. Psychiatric disorders and psychological conditions were limited to those included in the “psychology” and “mental disorders” Medical Subject Headings (MeSH) search terms defined by the National Library of Medicine. Publications identified utilizing this search strategy by M.K. were imported into the Covidence system, where they first underwent a title and abstract screening process by three independent reviewers (M.K., K.L., H.G.). During the full-text review, two independent reviewers read the full text of the questionable articles to assess their eligibility for inclusion. Studies were excluded if they did not meet our target objective or if they were not in English or if they were opinion pieces, conference abstracts, or review articles. Data were extracted from the shortlisted studies by reviewers. During the data extraction phase, the quality and risk of publication bias were assessed by two independent reviewers utilizing the National Institutes of Health (NIH) Study Quality Assessment Tools. Any disagreements in study selection, data extraction, or quality assessment were adjudicated via discussion between the two reviewers, utilizing a third reviewer as a decider if necessary.

RESULTS: Out of 73 articles identified, there were no duplicates. A total of 73 records were screened, but only 40 articles were assessed in full text for eligibility. A total of 23 articles were ultimately included, which collectively discussed 12,298 participants. Ten (43.5%) of the included studies were cross-sectional in design, three (13.0%) were case reports, and three (13.0%) were retrospective chart reviews. The remaining seven (30.4%) articles were either case-control, cohort, qualitative, controlled observational, or validation studies. Twelve (52.2%) of the studies reported data on depression disorders, six of which reported prevalence data. Nine (39.1%) of the studies reported data on anxiety disorders, five of which reported prevalence data. Studies that reported nonprevalence data presented odds-ratio, mean scores on psychiatric evaluations, and other correlation statistics. Psychiatric disorders that were most reported in these articles were mood disorders (n=11), anxiety disorders (n=9), and neurodevelopmental disorders (n=7). Although the reports varied, the highest psychiatric prevalence reports in EDS patients involved language disorders (63.2%), attention-deficit/hyperactivity disorder (ADHD) (52.4%), anxiety (51.2%), learning disabilities (42.4%), and depression (30.2%).

CONCLUSIONS: Although mood disorders were cited in more articles, the highest reported prevalence was for language disorders and ADHD. This discrepancy highlights the importance of performing more research to better understand the relationship between EDS and psychiatric disorders.

PMID:35420002 | DOI:10.1515/jom-2021-0267

Pediatr Pulmonol. 2022 Apr 13. doi: 10.1002/ppul.25921. Online ahead of print.

ABSTRACT

OBJECTIVES: To describe the short- and medium-term repeatability of lung clearance index (LCI_2.5 ) in infants and calculate the number of patients needed to enrol in a study (N) using LCI_2.5 as a primary outcome.

METHODS: An 8-month follow-up observational study was employed for assessing short-term [coefficient of repeatability (CR) and intraclass correlation (ICC)] and medium-term repeatability (Bland-Altman method) of LCI_2.5 in infants with cystic fibrosis (CF) or recurrent wheeze (RW) measured by the nitrogen multiple-breath washout test (N₂ -MBW). Using these variability data, the N to reach 90% test power at the level of statistical significance (0.05) was calculated.

RESULTS: Forty infants with CF and 21 with RW were enrolled. Initial N₂ -MBW testing was successful in 33 and 17 patients, respectively. Follow-up data were available for 23 and 11 infants, respectively. Short-term repeatability of LCI_2.5 was high (CR = 1.10 and 1.04 in CF and RW patients, respectively; ICC = 0.88 and 0.83 in CF and RW patients, respectively). The between-subject standard deviation was <13% of the actual LCI_2.5 value. In clinically stable patients, LCI_2.5 did not significantly change during the 8-month follow-up. Mean LCI_2.5 change was -0.08 (1% of baseline) in CF and -0.05 (0.6%) in RW, with 95% limits of agreement being (-1.70; 1.53) in CF and (-1.51; 1.40) in RW patients. N = 23 infants if both intra-group differences of LCI_2.5 and minimal difference to be detected would be 2.0.

CONCLUSION: N₂ -MBW may be a reproducible tool with reasonable test power to detect differences in infant studies. This article is protected by copyright. All rights reserved.

PMID:35419996 | DOI:10.1002/ppul.25921

Transbound Emerg Dis. 2022 Apr 13. doi: 10.1111/tbed.14558. Online ahead of print.

ABSTRACT

Colistin is a critically important antimicrobial for human medicine, and colistin-resistant Escherichia coli are commonly found in poultry and poultry products in Southeast Asia. Here, we aim at disentangling the within-farm and outside-farm drivers of colistin resistance in small-scale chicken farms of the Mekong delta of Vietnam. Nineteen Vietnamese chicken farms were followed up along a whole production cycle, during which weekly antimicrobial use data were recorded. At the beginning, middle and end of each production cycle, commensal E. coli samples from birds were collected, pooled and tested for colistin resistance. Twelve models were fitted to the data using an Expectation-Maximization algorithm and compared. We further tested the spatial clustering of the occurrence of resistance importations from external sources using the local Moran’s I statistic. In the best model, colistin resistance in E. coli from chickens was found to be mostly affected by importations of resistance, and, to a lesser extent, by the use of antimicrobials in the last 1.73 weeks [0.00; 2.90], but not by the use of antimicrobials in day-olds, nor their colistin resistance carriage from hatchery. The occurrence of external source importations proved to be sometimes spatially clustered, suggesting a role of local environmental sources of colistin resistance. This article is protected by copyright. All rights reserved.

PMID:35419995 | DOI:10.1111/tbed.14558

Ther Apher Dial. 2022 Apr 14. doi: 10.1111/1744-9987.13852. Online ahead of print.

ABSTRACT

INTRODUCTION: This study examined the discordance between hemodialysis patients’ reports and their physicians’ estimates of dietary restriction adherence and related factors in Japan.

METHODS: In a cross-sectional survey of 6,644 outpatients, physicians who estimated higher and lower adherence than their patients’ self-reported were categorized as overestimation and underestimation in terms of discordance, respectively. Possible factors included clinical indicators, patient characteristics related to negative stereotypes, and health beliefs related to statistical discrimination.

RESULTS: The concordance rate was .069 based on the weighted kappa coefficient. The coefficients of acceptable serum potassium, prevalence of diabetes, and self-efficacy on overestimates were .663 , -.126, and -.132, respectively. The coefficients of these factors on underestimates were -.589, .338, and .145, respectively. All these coefficients were significant.

CONCLUSIONS: The discordance may be high and is related to physicians’ clinical data reliance, negative stereotypes about patient characteristics, and a lack of understanding of patients’ health beliefs.

PMID:35419948 | DOI:10.1111/1744-9987.13852

J Cosmet Dermatol. 2022 Apr 14. doi: 10.1111/jocd.14987. Online ahead of print.

ABSTRACT

INTRODUCTION: Vitiligo is a skin disease that is associated with impaired skin immune systems and pigment degradation in skin melanocyte cells. Despite the significant impact of the disease on the quality of life of patients, treatment of the disease using effective method such as the transplantation of uncultivated melanocytes was considered by researchers around the world. The goal of this research was to use microneedling to transplant epidermal keratinocyte-melanocyte cells suspension for the treatment of vitiligo patients.

METHODS: In this study, 15 male and female vitiligo in face region patients aged 18 to 45 years were studied. In this study, melanocyte-keratinocyte cells suspension was sprayed. Patients underwent microneedling treatment after spraying the cells. Before and after transplantation, patients were biometrically examined, and the quantity of pigmentation and changes in the transplanted region were documented. Statistical software was used to examine the results.

RESULTS: The color difference between the lesion area and normal skin in one, two, and six months after treatment with cell suspension was significantly reduced compared to before treatment (by 48.95 %). Moreover, the amount of melanin was significantly increased 6 months after treatment compared to before treatment (129.8±4.16 vs. 195.2±3.54, P = 0.000). A significant decrease in skin brightness in the skin of the lesion area was observed compared to normal skin, 6 months after treatment compared to before treatment (43.7±1.44 vs. 27.9±1.24, P = 0.000).

CONCLUSION: Epidermal keratinocyte – melanocyte cells suspension in combination with microneedling could be considered as an effective treatment of vitiligo.

PMID:35419925 | DOI:10.1111/jocd.14987

Cytometry A. 2022 Apr 14. doi: 10.1002/cyto.a.24559. Online ahead of print.

ABSTRACT

Single-cell bioelectrical properties are commonly used for blood cell phenotyping in a label-free manner. However, previously reported inherent single-cell bioelectrical parameters (e.g., diameter D_c , specific membrane capacitance C_sm and cytoplasmic conductivity σ_cy ) of neutrophils, eosinophils and basophils were obtained from only tens of individual cells with limited statistical significance. In this study, granulocytes were separated into neutrophils, eosinophils and basophils based on fluorescent flow cytometry, which were further aspirated through a constriction-microchannel impedance flow cytometry for electrical property characterization. Based on this microfluidic impedance flow cytometry, single-cell values of D_c , C_sm and σ_cy were measured as 10.25 ± 0.66 μm, 2.17 ± 0.30 μF/cm² , and 0.37 ± 0.05 S/m for neutrophils (n_cell = 9 442); 9.73 ± 0.51 μm, 2.07 ± 0.19 μF/cm² , and 0.30 ± 0.04 S/m for eosinophils (n_cell = 2 982); 9.75 ± 0.49 μm, 2.06 ± 0.17 μF/cm² , and 0.31 ± 0.04 S/m for basophils (n_cell = 5 377). Based on these inherent single-cell bioelectrical parameters, neural pattern recognition was conducted, producing classification rates of 80.8% (neutrophil vs. eosinophil), 77.7% (neutrophil vs. basophil) and 59.3% (neutrophil vs. basophil). These results indicate that as inherent single-cell bioelectrical parameters, D_c , C_sm and σ_cy can be used to classify neutrophils from eosinophils or basophils to some extent while they cannot be used to effectively distinguish eosinophils from basophils.

PMID:35419939 | DOI:10.1002/cyto.a.24559

Dermatol Ther. 2022 Apr 13:e15508. doi: 10.1111/dth.15508. Online ahead of print.

ABSTRACT

BACKGROUND: Polycaprolactone (PCL)-based fillers are widely used for skin rejuvenation and wrinkle reduction.

OBJECTIVE: To compare the efficacy and safety of newly developed PCL-based fillers (SYB filler®; SF-01) and widely used existing PCL-based fillers (Ellansé-M®) for correction of moderate-to-severe nasolabial folds.

METHODS: In a randomized, participant-and evaluator-blinded, matched-pair, prospective study, participants were randomized for injections of SF-01 or Ellansé-M® in both nasolabial folds. Efficacy was evaluated using the Wrinkle Severity Rating Scale (WSRS), Global Esthetic Improvement Scale (GAIS), and a 3-dimensional (3D) scanner. All adverse events (AEs) were examined and reported.

RESULTS: At month 12, both SF-01-and Ellansé-M®-treated groups showed statistically significant improvements in the WSRS, GAIS, and 3D scanner scores compared to baseline. The difference in changes in WSRS scores at month 12 between the two groups was 0.08 ± 0.34 compared to baseline. The upper limit of the 95.0% confidence interval was 0.0031, which was lower than the predefined margin for non-inferiority (0.35). All AEs were injection site-related (swelling, pain, and erythema) and disappeared within 30 min after the procedure.

CONCLUSION: SF-01 was non-inferior to Ellansé-M® and demonstrated favorable efficacy and safety at 12 months after correcting moderate-to-severe nasolabial folds.

PMID:35419911 | DOI:10.1111/dth.15508

Dermatol Ther. 2022 Apr 13:e15510. doi: 10.1111/dth.15510. Online ahead of print.

ABSTRACT

AIMS: To characterize moderate to severe psoriasis (PsO) adult patients treated with secukinumab, estimate drug persistence and assess any reasons for treatment discontinuation.

METHODS: Non-interventional, retrospective, longitudinal record-based study including patients diagnosed with PsO who started secukinumab between January 2018 and January 2020. Baseline characteristics were analysed by descriptive statistics; drug persistence and predictive factors were assessed through Kaplan-Meier curves and univariate and multivariate analysis, respectively.

RESULTS: A total of 302 patients were included in the study: mean age was 48.4 years, 41.7% were female, median time since diagnosis was 12.9 years. 51.3% of patients were bio-naïve while 48.7% had previously been treated with biologics. PsO in difficult-to-treat locations (DTL) was present in 82.1% of patients, with scalp PsO in about half of patients. At 5-years follow-up, 84 patients discontinued secukinumab, 45 of which due to loss of efficacy. At week 104, overall treatment persistence was 71.7%. A higher probability of drug persistence was identified among those patients who initiated secukinumab ≥5 years after diagnosis, were bio-naïve or treated with only one previous biologic, had no PsO on DTL, and had diabetes mellitus. The predictive factors for discontinuation identified in our study were the start of secukinumab <5 years after diagnosis (p=.001), the bio-experimented status with ≥2 biologics (p=.007), and the presence of PsO on DTL (p=.014).

CONCLUSIONS: A time since diagnosis of ≥5 years, naïve status or previous use of only one biologic are predictors for secukinumab persistence, whereas the presence of PsO on DTL predicts drug discontinuation.

PMID:35419886 | DOI:10.1111/dth.15510

Clin Endocrinol (Oxf). 2022 Apr 13. doi: 10.1111/cen.14739. Online ahead of print.

ABSTRACT

Ultrasound (US) is the pivotal procedure during the diagnostic work-up of thyroid nodule and several US-based risk stratification systems (RSSs) have been recently developed. Since the performance of RSSs in detecting medullary thyroid carcinoma (MTC) has been rarely investigated, the present systematic review aimed to achieve high evidence about 1) how MTC is classified according to RSSs; 2) if RSSs correctly classify MTC at high risk/suspicion, and 3) if MTC is classified as suspicious at US when RSSs are not used. The review was performed according to MOOSE. The online search was performed by specific algorithm on January 2022. A random-effects model was used for statistical analysis. Twenty-five papers were initially included and their risk of bias was generally low. According to ATA system, 65% of MTCs was assessed at high suspicion and 25% at intermediate suspicion. Considering all RSSs, a 54.8% of MTCs was put in a high-risk/suspicion category. Pooling data from studies without data of RSS the prevalence of ultrasonographically suspicious MTCs was 60%. As conclusion, MTC presentation according to RSSs is partially known and it is classified in a high-risk/suspicion category of RSSs in just over a half of cases. This advises for further studies, ideally supported by international societies, to better define the US presentation of MTC. This article is protected by copyright. All rights reserved.

PMID:35419855 | DOI:10.1111/cen.14739