Caucasian Individuals Research Articles

DeepParcellation: A novel deep learning method for robust brain magnetic resonance imaging parcellation in older East Asians.

Accurate parcellation of cortical regions is crucial for distinguishing morphometric changes in aged brains, particularly in degenerative brain diseases. Normal aging and neurodegeneration precipitate brain structural changes, leading to distinct tissue contrast and shape in people aged >60 years. Manual parcellation by trained radiologists can yield a highly accurate outline of the brain; however, analyzing large datasets is laborious and expensive. Alternatively, newly-developed computational models can quickly and accurately conduct brain parcellation, although thus far only for the brains of Caucasian individuals. To develop a computational model for the brain parcellation of older East Asians, we trained magnetic resonance images of dimensions 256 × 256 × 256 on 5,035 brains of older East Asians (Gwangju Alzheimer's and Related Dementia) and 2,535 brains of Caucasians. The novel N-way strategy combining three memory reduction techniques inception blocks, dilated convolutions, and attention gates was adopted for our model to overcome the intrinsic memory requirement problem. Our method proved to be compatible with the commonly used parcellation model for Caucasians and showed higher similarity and robust reliability in older aged and East Asian groups. In addition, several brain regions showing the superiority of the parcellation suggest that DeepParcellation has a great potential for applications in neurodegenerative diseases such as Alzheimer's disease.

Muscle measurements in daily clinical practice: correlations between ultrasound, bioelectrical impedance analysis and hand grip strength.

Muscle ultrasound is gaining importance as a measurement tool to evaluate sarcopenia in daily clinical practice. This study sought to collect reference values of the biceps brachii (BB) in healthy subjects, and to correlate them to bioelectrical impedance analysis (BIA) and hand grip strength (HGS). Ultrasound was used to measure muscle thickness (MT), cross-sectional area (CSA) and muscle stiffness (EG). Lean mass (LM), fat mass (FM) and phase angle (PhA) were measured by BIA. HGS was measured using a Jamar dynamometer. Intra-rater reliability was calculated using intraclass correlation (ICC). Correlations were investigated using Pearson correlation (PCC). One-hundred-twenty-three Caucasian individuals (51 male and 72 female subjects) between 18 and 69 years old were included. ICC for ultrasound was 0.99 (CI 0.98-0.99). LM, PhA and HGS showed significant correlations with MT and CSA in the entire population (PCC>0.684). These correlations were more significant and stronger in male than in female subjects (PCC>0.419 and >0.279 resp.). Significant correlations with respect to FM and EG were seen exclusively in female subjects. Significant correlations were observed between parameters of muscle quantity measured by ultrasound, BIA and HGS. Intra-rater reliability was excellent. Future studies in larger populations are needed to clarify the observed gender differences.

Een vergelijking tussen spierechografie, impedantieanalyse en handknijpkracht bij gezonde personen

A comparison between muscle ultrasound, impedancemetry and hand grip strength in healthy individuals The pathophysiology of sarcopenia remains incompletely understood, but a muscle ultrasound gains interest as a potential diagnostic tool. The goal of this study was to compare the age- and gender-related effects on muscle parameters derived from an ultrasound, bioelectrical impedancemetry (BIA) and hand grip strength (HGS) in order to gather information about sarcopenia and to strengthen the position of the muscle ultrasound. Healthy subjects were included. Ultrasonographic measurements of muscle thickness (MT), cross-sectional area (CSA) and muscle stiffness (EG) were taken at 75% of the distance between the acromioclavicular joint and the elbow crease, distally. BIA was performed to measure muscle mass (MM), fat mass (FM) and phase angle (PhA). HGS was measured using a Jamar® dynamometer. Associations, age- and gender-related effects were investigated by a Pearson correlation and simple, linear regression analysis. 123 Caucasian individuals (51 men and 72 women) between the ages of 18 and 69 were included. Age showed significant correlations with FM, PhA and HGS. HGS declined with increasing age in both men and women. Only men showed a declining MT. PhA declined with increasing age in both men and women, and FM increased. Analysis of gender- and age-related effects suggests an important role for qualitative parameters in age-related decline of HGS. The absence of significant correlations with respect to a muscle ultrasound is probably a consequence of the limited study population.

Reference Axes for Tibial Component Rotation in Total Knee Arthroplasty: Computed Tomography-Based Study of 1,351 Tibiae.

Many anatomic landmarks have been described for setting tibial component rotation intraoperatively. There is no consensus as to which axis is best for reducing outliers and preventing malrotation. The SOMA (Stryker Orthopaedic Modeling and Analytics) database (Stryker) was used to identify 1,351 computed tomography (CT) scans of the entire tibia. Several reference axes for the tibia (including the Mayo axis, Akagi line, Insall line, anterior condylar axis [ACA], posterior condylar axis [PCA], lateral tibial cortex [LTC], Cobb axis, tibial crest line [TCL], and transmalleolar axis [TMA]) were constructed according to published guidelines. The Berger method served as the reference standard. The Mayo method (involving a line connecting the medial and middle one-thirds of the tibial tubercle and the geometric center of the tibia) and the Insall line (involving a line connecting the posterior cruciate ligament [PCL] insertion and the intersection of the middle and medial one-thirds of the tibial tubercle) both had low variability relative to the Berger method (7.8° ± 1.0° and 5.1° ± 2.2°, respectively) and a low likelihood of internal rotation errors (0.7% and 1.8%, respectively). No clinically significant gender-based differences were found (<0.7° for all). The same was true for ethnicity, with the exception of consistently greater tibial intorsion in Asian versus Caucasian individuals (mean difference in TCL position, +4.5° intorsion for Asian individuals; p < 0.001). This CT-based study of 1,351 tibiae (which we believe to be the largest study of its kind) showed that the Mayo and Insall methods (both of which reference the medial and middle one-thirds of the tibial tubercle) offer an ideal balance of accuracy, low variability, and a reduced likelihood of internal rotation errors. Setting rotation on the basis of distal landmarks (tibial shaft and beyond) may predispose surgeons to substantial malrotation errors, especially given the differences in tibial torsion found between ethnic groups in this study. Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Dyslipidemia in Patients with Type 2 Diabetes Mellitus (DM2) According to Ethnicity: A Systematic Review

Background: The role of dyslipidemia as a significant risk factor for cardiovascular disease (CVD) in patients diagnosed with type 2 diabetes mellitus (DM2) is well established. There are few studies examining the prevalence of dyslipidemia among different ethnic groups. This review aims to analyze literature that has studied dyslipidemia and ethnicity. Should treatment guidelines reflect ethnicity? Method: Systemic narrative synthesis and data extraction was performed using the Preferred Reporting Items for Systematic Review (PRISMA) guidelines. Studies were selected between January 2010 and January 2022 using PubMed, Medline, and Google Scholar. The quality of the studies was assessed through Joanna Briggs Institute (JBI) checklist. Results: Four relevant studies were retrieved from different countries. Asians, mainly Indians and Filipinos, have high triglycerides (TG) levels and low High-Density Lipoproteins (HDL) levels which can partially explain the high incidence of coronary heart disease (CHD) in this group. Indians have high concentrations of small LDL particles, which are more atherogenic than large LDL particles (25). Asians are more sensitive to statin treatment, and lower doses can achieve the same therapeutic target as white Caucasian individuals. Proprotein convertase subtilisin/Kexin type 9 (PCSK9) injectable therapies effectively lower cholesterol among all ethnic groups and may be a suitable alternative when statins are not tolerated. Conclusions - There are differences in dyslipidemia patterns among various ethnic groups compared to white Caucasians. South Asians have more atherogenic dyslipidemia than other ethnic minorities. Such differences might require tailored guidelines to address these ethnic differences.

Novel First-Trimester Prediction Model for Any Type of Preterm Birth Occurring before 37 Gestational Weeks in the Absence of Other Pregnancy-Related Complications Based on Cardiovascular Disease-Associated MicroRNAs and Basic Maternal Clinical Characteristics.

The goal of the study was to establish an efficient first-trimester predictive model for any type of preterm birth before 37 gestational weeks (spontaneous preterm birth (PTB) or preterm prelabor rupture of membranes (PPROM)) in the absence of other pregnancy-related complications, such as gestational hypertension, preeclampsia, fetal growth restriction, or small for gestational age. The retrospective study was performed in the period from 11/2012 to 3/2020. Peripheral blood samples were collected from 6440 Caucasian individuals involving 41 PTB and 65 PPROM singleton pregnancies. A control group with 80 singleton term pregnancies was selected on the basis of equal sample-storage time. A combination of only six microRNAs (miR-16-5p, miR-21-5p, miR-24-3p, miR-133a-3p, miR-155-5p, and miR-210-3p; AUC 0.812, p < 0.001, 70.75% sensitivity, 78.75% specificity, cut-off > 0.652) could predict preterm delivery before 37 gestational weeks in early stages of gestation in 52.83% of pregnancies with a 10.0% FPR. This predictive model for preterm birth based on aberrant microRNA expression profile was further improved via implementation of maternal clinical characteristics (maternal age and BMI at early stages of gestation, infertility treatment with assisted reproductive technology, occurrence of preterm delivery before 37 gestational weeks in previous pregnancy(ies), and presence of any kind of autoimmune disease (rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid syndrome, type 1 diabetes mellitus, or other autoimmune disease)). With this model, 69.81% of pregnancies destined to deliver before 37 gestational weeks were identified with a 10.0% FPR at early stages of gestation. When other clinical variables as well as those mentioned above—such as positive first-trimester screening for early preeclampsia with onset before 34 gestational weeks and/or fetal growth restriction with onset before 37 gestational weeks using the Fetal Medicine Foundation algorithm, as well as positive first-trimester screening for spontaneous preterm birth with onset before 34 gestational weeks using the Fetal Medicine Foundation algorithm—were added to the predictive model for preterm birth, the predictive power was even slightly increased to 71.70% with a 10.0% FPR. Nevertheless, we prefer to keep the first-trimester screening for any type of preterm birth occurring before 37 gestational weeks in the absence of other pregnancy-related complications as simple as possible.

HLA-G expression in Merkel cell carcinoma and the correlation with Merkel cell polyomavirus infection.

Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine cutaneous carcinoma with a high mortality rate. The MCC etiology is not fully understood. Merkel cell-associated polyomavirus (MCPyV) was found in MCC patients, indicating a risk factor for the tumor. Caucasian, elderly, and immunocompromised individuals are more likely to develop this tumor. HLA-G consists of a non-classical class I (Ib) HLA molecule with an immunoregulatory function and was associated with tumor escape in different types of tumors, nonetheless, never been studied in MCC. The purpose of this study was to evaluate the HLA-G expression and also to detect the MCPyV in MCC patients and correlate it with the clinical course of the disease. Forty-five MCC patients were included in a retrospective study. Formalin-fixed paraffin-embedded cutaneous skin biopsies were used by immunohistochemistry and RT-PCR to verify the HLA-G expression and MCPyV infection. HLA-G expression was found in 7 (15.6%), while the presence of MCPyV was detected in 28 (62.2%) of the studied patients. No significant association was found between HLA-G expression and MCPyV infection (p = 0.250). The presence of MCPyV was associated with areas of low sunlight exposure (p = 0.042) and the HLA-G expression with progression to death (p = 0.038). HLA-G expression was detected in MCC patients, as well as the MCPyV presence was confirmed. These markers could represent factors with a possible impact on patient survival; however, further studies with a greater number of patients are needed, to better elucidate the possible role in disease progression.

Temperament traits mediate the relationship between CACNA1C polymorphisms and bipolar disorder in cisgender women.

The influence of temperament traits on bipolar disorder (BD) has been investigated. Both temperament traits and BD are partially genetically determined and seem to be influenced by variations in the CACNA1C gene. These variations presented a significant interactive effect with biological sex, although studies that evaluate this relationship are scarce. Here, we assessed the mediation effect of temperament traits on the relationship between two polymorphisms in the CACNA1C gene (rs1006737 and rs4765913) and BD according to sex. This is a cross-sectional study consisting of 878 Caucasian individuals (508 women and 370 men), aged 18-35, enrolled in a population-based study in the city of Pelotas, Southern Brazil. BD diagnosis was evaluated using the clinical interview MINI 5.0, and temperament traits were assessed via the application of the Affective and Emotional Composite Temperament Scale (AFECTS). Mediation models were tested using the modeling tool PROCESS (version 3.3) for SPSS. Bootstrapping-enhanced mediation analyses in women indicated that traits anger (39%) and caution (27%) mediated the association between the rs4765913 SNP and BD, while traits volition (29%), anger (35%), and caution (29%) mediated the association between the AA haplotype (rs1006737-rs4765913) and the BD. No effect was encountered for cisgender men. Our model revealed that paths from CACNA1C SNPs to BD are mediated by specific temperament traits in women, reinforcing the definition of temperament traits as endophenotypes.

S292 Socioeconomic Status: An Important Determinant for Follow-Up for Surveillance Colonoscopy After Endoscopic Mucosal Resection

Introduction: Alabama had significantly higher incidence of colorectal cancer (CRC)at 43.5 compared to the US rate 39.5, and African Americans have higher rate of CRC compared to Caucasian individuals. There is compelling evidence that surveillance colonoscopy after high-risk adenoma polypectomy can reduce the risk of developing CRC.Our objective was to identify risk factors associated with poor follow up after undergoing colonoscopy with endoscopic mucosal resection (EMR). Methods: We performed retrospective chart review of patients who had EMR at our facility between June 2016-March 2022.Patient demographics, referral, procedural and census data were collected. Census data obtained was used to evaluate income, median household income, and educational attainment. Patients were divided into two groups; poor and good follow up. Poor follow up was defined as those who failed to follow up and/or presented for surveillance colonoscopy >1 month after the recommended timeframe. Results: Initial chart review included 520 eligible patients;73 were excluded due to lack of referral data, and 59 with recent EMR whose recommended surveillance colonoscopy has not passed. Of the included 388 patients, 293 (75.5%) had poor follow up and 95 (24.5%) had good follow up. Descriptive statistics of the various characteristics and comparisons of the of two groups is presented in Table. Compared to individuals with good follow up, there was a significant association of poor follow up with patients whose index colonoscopy was performed at an outside hospital (p=0.003) and if the index colonoscopy was their first colonoscopy (p=0.04). Additionally, census data revealed lower median home values were associated with poor follow up ($168,382) when compared to good follow up ($185,034). There was a trend to poor follow up in patients with obesity (80.5%), former alcohol use (88.9%), patients insured by Medicaid (88.9%), and minority populations including African American, and Hispanic/other ethnicities (77.1%,90.9%, respectively). Conclusion: Our study illustrates that social economic status has significant impact on surveillance colonoscopy after EMR, and outside hospital referral are more likely to have poor follow up compared to in house referrals. Given the potential impact this data has for reducing risk of developing CRC in lower social economic individuals, further studies are needed to validate this finding and stratify predictors of poor follow up. Table 1. - Descriptive characteristics and comparison of poora vs goodb follow up in patients who underwent EMR at UAB between June 2016-March 2022 Overall Follow-up p value N=388 Poor n=293 (75.5%) Good n=95 (24.5%) Age (years), mean (SD) 63 (10.4) 64 (10.4) 62 (10.4) 0.23c Sex Male 52.1% 75.3% 24.8% 0.89d Female 47.9% 75.8% 24.2% Race/Ethnicity Caucasian 67.8% 73.8% 26.2% 0.38d African American 28.1% 77.1% 22.9% Other 2.8% 90.9% 9.1% Type of insurance Private 45.9% 74.7% 25.3% 0.39d Medicare 47.4% 75.0% 25.0% Medicaid 4.6% 88.9% 11.1% Uninsured 2.1% 75.0% 25.0% BMI less than 24.9 – Underweight/ Normal 24.8% 72.8% 27.2% 0.11d between 25.0 and 29.9 – Overweight 32.4% 70.0% 30.0% more than 30.0 – Obese 42.9% 80.5% 19.5% ASA classification 1 0.8% 66.7% 33.3% 0.84d 2 60.2% 75.5% 24.5% 3 38.5% 75.8% 24.2% 4 0.5% 50.0% 50.0% Smoking Current 25.0% 76.3% 23.7% 0.79d Former 26.8% 73.1% 26.9% Never 47.7% 76.2% 23.8% Alcohol Current 46.1% 72.6% 27.4% 0.25d Former 6.9% 88.9% 11.1% Never 46.4% 76.1% 23.9% Drugs Current 3.4% 84.6% 15.4% 0.85d Former 4.4% 70.6% 29.4% Never 87.9% 75.4% 24.6% Employment Employed 29.9% 74.1% 25.9% 0.99d Unemployed 6.9% 74.1% 25.9% Retired 28.4% 75.5% 24.6% Disabled 10.1% 76.9% 23.1% First colonoscopy Yes 17.0% 75.8% 24.2% 0.04d* No 44.6% 69.9% 30.1% Outside Hospital Referral Yes 31.7% 86.2% 13.8% 0.003d* No 67.8% 70.7% 29.3% Time of procedure Morning 57.9% 72.9% 27.1% 0.16d Afternoon 42.0% 79.1% 20.9% ASA=American Society of Anesthesiologists; BMI=body mass index; EMR= endoscopic mucosal resection; SD=standard deviation; UAB=University of Alabama at Birmingham.*Statistically significant at 0.05 level (two-tailed test).aPoor follow up included patients that did not receive surveillance colonoscopy within recommended timeframe or patients who were lost to follow up.bGood follow up is defined as undergoing surveillance colonoscopy within the recommended timeframe.cUnpaired t-test.dChi-square test.

Blood Pressure Responses Following Maximum Oxygen Consumption Test In African American, Hispanic, And Caucasian Individuals: A Pilot Study

Blood Pressure Responses Following Maximum Oxygen Consumption Test In African American, Hispanic, And Caucasian Individuals: A Pilot Study

34092 The distribution of nevi and melanoma in Caucasian and SOC individuals

There is a paucity of literature comparing the bodily distribution of melanocytic nevi vs. melanoma and racial differences in melanoma distribution. We conducted a cross-sectional study of 211 patients who presented for voluntary skin examination from 3/2017-8/2018. Demographic data were obtained before the examination. Nevi were verified by dermoscopy and mapped by location. Data were compared with 2000-2017 melanoma data reported by the Surveillance, Epidemiology, and End Results (SEER) program. Patients self-identified as Hispanic (64.9%), Caucasian (19.2%), American Indian or Alaskan Native (7.2%), Asian (1.9%), and other (1.4%). The greatest differences in distribution of nevi and melanoma were observed at the lower limb/hip (17.3% of melanomas vs. 6.6% of nevi; P < .0001), upper limb and shoulder (26% of melanomas vs. 34.1% of nevi), foot (0.8% of melanomas vs. 2.8% of nevi), and hand (0.2% of melanomas vs. 2.6% of nevi). Caucasians had higher incidence (per 100,000) of melanomas of the face/neck (4,400; 95% CI 3,700-5,100; P < .0001), trunk (9,200; 95% CI 8,500-9,800), and upper extremity (6,800; 95 % CI 6,100-7,500) vs. skin of color (SOC) patients. SOC patients had higher incidence of melanomas of the lower extremity (11,000; 95 % CI 10,000-11,000), acral locations (6,800; 95% CI 5,600-8,000), and feet (5,900; 95% CI 5,100-6,500). Distribution of nevi differed significantly from melanoma by body region. Caucasians had higher incidence of upper-body melanomas while SOC patients had higher incidence of lower-body and acral melanomas. These differences suggest divergent evolutionary pathways of nevi and melanoma in various body regions and across different races.

Osteoarthritis And Hispanics: A Comparative Analysis Of Pain, Function, And Pain Catastrophizing

BACKGROUND: Osteoarthritis (OA) of the knee afflicts over 54 million Americans including 3.1 million Hispanics. Several studies provide treatment guidelines for OA in a stepwise fashion, beginning with physical therapy and only intensifying treatment after 6 months of therapy or identification of radiographic severity (K-L grade of 2 or greater). This approach correlates well with worsening patient symptoms in the non-Hispanic Caucasian individual (NHWP)4. To date, no association between pain, function, and K-L grade has been established in the Hispanic population. Additionally, no comparative analysis of pain catastrophizing for knee OA in Hispanic persons and NHWP has been reported. PURPOSE: Characterize Hispanic patients with knee OA on basis of pain (VAS), function (WOMAC), and radiographic severity (K-L grade) and compare findings to those of NHWP. METHODS: With IRB approval, we conducted a convenient sampling of 90 patients. Patients were considered if they presented with knee pain and were given a primary diagnosis of OA. Patients who met our inclusion criteria were administered PCS, WOMAC, VAS and demographic questionnaires. K-L grade was determined using WBAPE radiographs. RESULTS: 75 patients were analyzed. 54 Hispanic (30% M: F), 25 NHWP (36% M: F). On average, Hispanic patients report greater pain scores than non-Hispanics (p < 0.05). Additionally, Hispanic patients reported greater functional impairment (p < 0.05). There was minimal difference in pain catastrophizing scores between Hispanic (10.9 +/- 10.7 and Caucasian patients (6.5 +/- 5.6). The differences in average K-L grade were insignificant 1.97 and 2.06, respectively. The correlation between VAS and K-L as well as WOMAC and K-L in Hispanics was weak (R < 0.7). CONCLUSION: Hispanics demonstrated greater pain scores with greater functional impairment without demonstrating significantly different scores in pain catastrophizing. These same patients demonstrated a weak correlation between pain, function, and radiographic score, questioning the utility of K-L grade in management of these patients.

Corynebacterium glucuronolyticum in men with and without urethritis syndrome: An underrecognized pathogen or a bona fide commensal?

BackgroundBy analysing the largest collection of Corynebacterium glucuronolyticum (C. glucuronolyticum) isolates from a single centre thus far, we aimed to appraise a potential causal link between an infrequently isolated species and the urethritis syndrome in men. MethodsA total of 1055 Caucasian male individuals with or without urethritis syndrome were included in this single-centre case-control study. Group-wise comparisons were pursued by analysing sociodemographic, behavioural and microbiological specificities between the two groups. C. glucuronolyticum isolates from urethral specimens were identified using the analytical profile index biotyping system (API Coryne) and additionally confirmed by MALDI-TOF mass-spectrometry, with subsequent determination of their antimicrobial sensitivity profiles. Statistical significance was set at p < 0.05 (two-tailed). ResultsC. glucuronolyticum was isolated in 5.08% of study participants with urethritis syndrome and 3.60% of those without it (p = 0.303). In the urethritis group, the species was more frequently found as a sole isolate (p = 0.041) and after prior infection with Chlamydia trachomatis (p = 0.025). The most frequent presentation of urethritis included a clear discharge in small or moderate amounts, without any pathognomonic findings. The resistance rates were 62.22% for clindamycin, 42.22% for tetracycline and 26.67% for ciprofloxacin. ConclusionsOur study provides major insights on the relevance of urethral C. glucuronolyticum in non-gonococcal urethritis, with significant implications for further aetiological research and management approaches.

Native T1 and T2 reference values for maltese healthy cohort.

Cardiac Magnetic Resonance (CMR) is increasingly being used for diagnosing various cardiac conditions. Parametric mapping enables quantitative myocardial characterization by directly measuring myocardial T1 and T2 values. However, reference values of parametric mapping are not standardized across different vendors and scanners, causing drawbacks for clinical implementation of this technique across different sites. We assessed the reference ranges of native T1 and T2 values in a healthy Maltese cohort to establish a local parametric mapping service. Healthy subjects [n = 51; mean age 36.0 (range 19-59) years] with normal cardiac function on CMR were recruited. Subjects underwent uniform parametric mapping pulse sequences [MOLLI 5b(3b)3b for native T1 mapping, and gradient echo single shot FLASH readout for T2 mapping] on a 3T Siemens MAGNETOM Vida scanner. Native T1 and T2 values were measured by placing a region of interest within the interventricular septum at midventricular level. Intra- and inter-observer variability were assessed using Bland-Altman plots. Mean ± 1.96 SD was used as a reference range. Mean native T1 and T2 values were 1200.1 ± 30.7ms and 39.5 ± 1.8ms, respectively. There was no significant bias in repeated measurements by the same and different observers. For the first time in Malta, we established the native T1 and T2 parametric mapping reference values for healthy Caucasian Maltese individuals. This will assist cardiologists to establish diagnosis, disease progression, and response to treatment of various myocardial diseases locally.

Independent replication of advanced brain age in mild cognitive impairment and dementia: detection of future cognitive dysfunction

We previously developed a novel machine-learning-based brain age model that was sensitive to amyloid. We aimed to independently validate it and to demonstrate its utility using independent clinical data. We recruited 650 participants from South Korean memory clinics to undergo magnetic resonance imaging and clinical assessments. We employed a pretrained brain age model that used data from an independent set of largely Caucasian individuals (n = 757) who had no or relatively low levels of amyloid as confirmed by positron emission tomography (PET). We investigated the association between brain age residual and cognitive decline. We found that our pretrained brain age model was able to reliably estimate brain age (mean absolute error = 5.68 years, r(650) = 0.47, age range = 49–89 year) in the sample with 71 participants with subjective cognitive decline (SCD), 375 with mild cognitive impairment (MCI), and 204 with dementia. Greater brain age was associated with greater amyloid and worse cognitive function [Odds Ratio, (95% Confidence Interval {CI}): 1.28 (1.06–1.55), p = 0.030 for amyloid PET positivity; 2.52 (1.76–3.61), p < 0.001 for dementia]. Baseline brain age residual was predictive of future cognitive worsening even after adjusting for apolipoprotein E e4 and amyloid status [Hazard Ratio, (95% CI): 1.94 (1.33–2.81), p = 0.001 for total 336 follow-up sample; 2.31 (1.44–3.71), p = 0.001 for 284 subsample with baseline Clinical Dementia Rating ≤ 0.5; 2.40 (1.43–4.03), p = 0.001 for 240 subsample with baseline SCD or MCI]. In independent data set, these results replicate our previous findings using this model, which was able to delineate significant differences in brain age according to the diagnostic stages of dementia as well as amyloid deposition status. Brain age models may offer benefits in discriminating and tracking cognitive impairment in older adults.

Protocols of Standard of Care for Adult Patients with Primary Antibody Deficiencies Will Improve Timing of Diagnosis, Survival, and Quality of Life.

The majority of primary immunodeficiencies (PIDs) are antibody deficiencies (PADs), and not all of them are rare diseases; As an example, Caucasian individuals suffer from selective IgA deficiency at a frequency of 1:500. In addition to infections, symptomatic patients with PAD are more likely to develop neoplastic, autoimmune, and allergic diseases. In the event that PAD is neglected or delayed for more than ten years, complications develop, eventually resulting in death. No studies have been conducted to devise and report detailed ready-to-use protocols for managing PAD to date. This study aimed to propose protocols and guidelines for the adult PAD patients' standard care. Preparing the protocol, we considered the frequency and type of laboratory tests, imaging, endoscopic examinations, specialist consultations, and standardized recommendations for further care in the place of residence. As a result of the proposed monitoring scheme, patients can be provided with complete care in terms of their underlying conditions and comorbidities, as well as early detection of complications. This protocol will serve as a guide for physicians dealing with these patients and enable comparisons of patient groups across a variety of treatment centers, even far away from each other.A national consultant in the field of clinical immunology verified the protocol mainly developed by Polish experts from reference immunology centres for adults.

Neuroblastoma suppressor of tumorigenicity 1 is a circulating protein associated with progression to end-stage kidney disease in diabetes.

Circulating proteins associated with transforming growth factor-β (TGF-β) signaling are implicated in the development of diabetic kidney disease (DKD). It remains to be comprehensively examined which of these proteins are involved in the pathogenesis of DKD and its progression to end-stage kidney disease (ESKD) in humans. Using the SOMAscan proteomic platform, we measured concentrations of 25 TGF-β signaling family proteins in four different cohorts composed in total of 754 Caucasian or Pima Indian individuals with type 1 or type 2 diabetes. Of these 25 circulating proteins, we identified neuroblastoma suppressor of tumorigenicity 1 (NBL1, aliases DAN and DAND1), a small secreted protein known to inhibit members of the bone morphogenic protein family, to be most strongly and independently associated with progression to ESKD during 10-year follow-up in all cohorts. The extent of damage to podocytes and other glomerular structures measured morphometrically in 105 research kidney biopsies correlated strongly with circulating NBL1 concentrations. Also, in vitro exposure to NBL1 induced apoptosis in podocytes. In conclusion, circulating NBL1 may be involved in the disease process underlying progression to ESKD, and its concentration in circulation may identify subjects with diabetes at increased risk of progression to ESKD.

Genome-wide associations of aortic distensibility suggest causality for aortic aneurysms and brain white matter hyperintensities

Aortic dimensions and distensibility are key risk factors for aortic aneurysms and dissections, as well as for other cardiovascular and cerebrovascular diseases. We present genome-wide associations of ascending and descending aortic distensibility and area derived from cardiac magnetic resonance imaging (MRI) data of up to 32,590 Caucasian individuals in UK Biobank. We identify 102 loci (including 27 novel associations) tagging genes related to cardiovascular development, extracellular matrix production, smooth muscle cell contraction and heritable aortic diseases. Functional analyses highlight four signalling pathways associated with aortic distensibility (TGF-β, IGF, VEGF and PDGF). We identify distinct sex-specific associations with aortic traits. We develop co-expression networks associated with aortic traits and apply phenome-wide Mendelian randomization (MR-PheWAS), generating evidence for a causal role for aortic distensibility in development of aortic aneurysms. Multivariable MR suggests a causal relationship between aortic distensibility and cerebral white matter hyperintensities, mechanistically linking aortic traits and brain small vessel disease.

Robustness of Distinctive Facial Features in Prader-Willi Syndrome: A Stereophotogrammetric Analysis and Association with Clinical and Biochemical Markers in Adult Individuals.

Simple SummaryPrader-Willi syndrome (PWS) is a rare genetically determined neurodevelopmental disorder usually associated with a peculiar facial appearance. There is poor information concerning the relationships between the facial dysmorphism in PWS and other manifestations of the disease and its treatment. This exploratory study aimed to investigate this aspect, since this knowledge might aid in both diagnosis and monitoring of the disease. Three-dimensional facial images of fifteen Caucasian adult individuals with PWS were acquired through stereophotogrammetry; linear distances and angles were then calculated and compared with those of groups of healthy subjects matched for sex and age, obtained using the same noninvasive procedure. Individuals with PWS were evaluated for endocrine/metabolic dysfunction and nocturnal respiratory function, and their associations with facial features were tested. Some facial characteristics did not show any associations with other manifestations of PWS; therefore, they could constitute robust distinctive facial features and contribute to the diagnosis of the disorder. Conversely, other facial characteristics showed relationships with clinical and biochemical markers of PWS, suggesting their potentially useful role in the clinical monitoring and management of the disease. Further studies are needed to confirm these findings.Background: Prader-Willi syndrome (PWS) is a rare genomic imprinting disorder associated to a complex neurodevelopmental phenotype and a distinctive facial appearance. The study investigated the relationships between the quantitative facial dysmorphism in PWS and clinical and biochemical markers of the disease and its treatment. Methods: Facial images of 15 Caucasian adult individuals with PWS (8 males, 42 ± 5 years; 7 females, 37 ± 8 years; BMI 38.87 ± 8.92 kg/m2) were acquired through stereophotogrammetry. From the 3D coordinates of 38 landmarks, linear distances and angles were calculated; they were expressed as z-score values by referring to 403 healthy subjects matched for age and sex and compared by Student’s t-test with Bonferroni correction for multiple testing. Patients underwent auxological and biochemical assessment of endocrine/metabolic dysfunction and nocturnal respiratory function. An exploratory correlation analysis was performed to investigate their associations with the facial phenotype; uncorrected p-values were used. Results and Conclusions: Individuals with PWS showed decreased bifrontal diameter, facial depths, palpebral fissures, mandibular ramus length, lower vermillion height, and modified relative position of exocanthia and nasion. Since these characteristics did not show any associations with clinical and biochemical markers of PWS, they could constitute robust distinctive facial features and contribute to the diagnosis of the disorder. Individuals with PWS showed also a larger mandibular width with smaller gonial angles, thinner upper vermillion, greater inclination of the orbit relative to the Frankfurt plane, and a smaller angle of the auricles versus the facial midplane. Relationships between these facial anthropometric features and body composition, glucidic metabolism indexes, nocturnal hypoxemia episodes, or duration of GH treatment were found, suggesting their potentially useful role in the clinical monitoring and management of the disease. However, they need to be confirmed by subsequent dedicated studies.

Ethnic differences on long term outcomes of polypoidal choroidal vasculopathy after predominantly bevacizumab monotherapy

BackgroundA 3-year single-centre, retrospective, comparative, non-randomized cohort study to describe the long-term outcomes of treatment-naïve, Caucasian and non-Caucasian eyes with polypoidal choroidal vasculopathy (PCV) after treatment with predominantly Bevacizumab monotherapy or in combination with rescue photodynamic therapy (PDT).MethodsDemographics, visual outcomes, optical coherence tomography (OCT) and treatment data were collected up to 3 years after the first visit. Stratified analysis according to ethnicity and baseline vision was performed to identify factors predictive of long-term visual improvement and maintenance.ResultsA total of 89 eyes with PCV were identified, of which 14 received rescue verteporfin PDT. There was an equal distribution between Caucasian and non-Caucasian individuals. Non-Caucasians present at a younger age (67.3 vs. 76.0 years, p = 0.002), have a higher proportion of foveal involvement (80.9%, vs.54.2% p = 0.007), choroidal hyperpermeability (50% vs 25.8%, p = 0.013) and lower baseline visual acuity (53.1 vs. 63.3 letters, p = 0.008). Mean visual acuity (VA) gain was + 8.9 letters and + 5.0 letters at 1 and 3 years of follow-up, respectively. Non-Caucasian individuals had a lower mean final visual acuity (VA) (54.7 vs. 70.5, respectively; P < 0.001) and net gain in VA (+ 2.0 vs. + 7.6 letters, p = 0.581) compared to Caucasian individuals. The mean total number of injections given over 3 years was 14.ConclusionsMost patients treated with predominantly Bevacizumab anti-vascular endothelial growth factor (VEGF) monotherapy achieved sustained visual acuity gains out to 3 years. Due to ethnic-specific differences in presenting PCV phenotypes, non-Caucasians presented with lower baseline VA and had poorer long-term visual outcomes.