Bridging the gap: Multi-omics profiling of brain tissue in Alzheimer's disease and older controls in multi-ethnic populations.

INTRODUCTION: Multi-omics studies in Alzheimer's disease (AD) revealed many potential disease pathways and therapeutic targets. Despite their promise of precision medicine, these studies lacked Black Americans (BA) and Latin Americans (LA), who are disproportionately affected by AD. METHODS: To bridge this gap, Accelerating Medicines Partnership in Alzheimer's Disease (AMP-AD) expanded brain multi-omics profiling to multi-ethnic donors. RESULTS: We generated multi-omics data and curated and harmonized phenotypic data from BA (n = 306), LA (n = 326), or BA and LA (n = 4) brain donors plus non-Hispanic White (n = 252) and other (n = 20) ethnic groups, to establish a foundational dataset enriched for BA and LA participants. This study describes the data available to the research community, including transcriptome from three brain regions, whole genome sequence, and proteome measures. DISCUSSION: The inclusion of traditionally underrepresented groups in multi-omics studies is essential to discovering the full spectrum of precision medicine targets that will be pertinent to all populations affected with AD. HIGHLIGHTS: Accelerating Medicines Partnership in Alzheimer's Disease Diversity Initiative led brain tissue profiling in multi-ethnic populations. Brain multi-omics data is generated from Black American, Latin American, and non-Hispanic White donors. RNA, whole genome sequencing and tandem mass tag proteomicsis completed and shared. Multiple brain regions including caudate, temporal and dorsolateral prefrontal cortex were profiled.

Bridging the Gap: Multi-Omics Profiling of Brain Tissue in Alzheimer's Disease and Older Controls in Multi-Ethnic Populations.

INTRODUCTION: Multi-omics studies in Alzheimer's disease (AD) revealed many potential disease pathways and therapeutic targets. Despite their promise of precision medicine, these studies lacked African Americans (AA) and Latin Americans (LA), who are disproportionately affected by AD. METHODS: To bridge this gap, Accelerating Medicines Partnership in AD (AMP-AD) expanded brain multi-omics profiling to multi-ethnic donors. RESULTS: We generated multi-omics data and curated and harmonized phenotypic data from AA (n=306), LA (n=326), or AA and LA (n=4) brain donors plus Non-Hispanic White (n=252) and other (n=20) ethnic groups, to establish a foundational dataset enriched for AA and LA participants. This study describes the data available to the research community, including transcriptome from three brain regions, whole genome sequence, and proteome measures. DISCUSSION: Inclusion of traditionally underrepresented groups in multi-omics studies is essential to discover the full spectrum of precision medicine targets that will be pertinent to all populations affected with AD.

Which Jobs are Unlucky against the Biologic and the Economic Risks Caused by the Covid-19 Pandemic?

Context: Beyond the biological impact of the pandemic in working life, socioeconomic consequences is also important for workers. This study aimed to investigate both biologic and economic impacts of the pandemic. Methods: In this cross-sectional study, a structured questionnaire were applied by telephone to 233 workers who were diagnosed with coronavirus disease-2019 (Covid-19) at hospital. A pretest was applied before the data collection. The outcomes of the study were work-related Covid-19 transmission (WRCT) and pandemic-related economic worsening (PREW). Descriptive statistics is presented. Chi-square test is used in comparison of proportions. Results: Of the 233 workers, 52% were male (n = 120) and the mean age was 37.7 (±9.2) years. WRCT was observed in 73% of health care workers. PREW was 6.7 times higher in private sector (95% confidence interval = 3.1-14.5), especially in self-employed and small business owners. Drivers and sales workers were the unluckiest. Because they were affected in terms of both the WRCT and PREW. Conclusions: Within the framework of occupational health, the economic destructive effects of the Covid-19 pandemic as well as the biological impacts should be considered with a holistic perspective. Protective policies should be developed especially for economically fragile groups against the pandemic such as self-employed, small business owners, and private sector workers.

Facing Pandemic: Burnout in Nurses in Turkey.

OBJECTIVE: Burnout syndrome is a disorder that characterized by emotional exhaustion, depersonalization, and personal lack of accomplishment perception and it is common in nurses. During the coronavirus disease 2019 pandemic, nurses tried to take care of their patients and protect themselves and their families from disease and death. This study examines the factors affecting nurses' burnout in Turkey during the coronavirus disease 2019 pandemic. MATERIAL AND METHODS: Data were collected from 3523 nurses in 69 cities across Turkey by sociodemographic questions and Maslach Burnout Scale with the electronic questionnaire created in the "SurveyMonkey" application between June 9, 2020 and June 21, 2020. To assess the impact of the pandemic on nurses' burnout, nurses were categorized as those working in pandemic units and others. RESULTS: The response rate was 68%, and 3523 nurses from 69 cities across Turkey participated in the survey. Analyses were conducted with 2386 nurses that answered all questions. 76.45% of the nurses were from tertiary hospitals, and 54.9% (n = 1309) worked in pandemic units. Of 2386 participants, 86.13% (n = 2055) were female, the mean age was 33.9 (±8.43), and 58.76% (n = 1402) were married. Of 2386 participants, 54.9% (n = 1309) worked in pandemic units (outpatient clinics, inpatient clinics, and intensive care units). In multivariate linear regression analyses, the emotional exhaustion score was higher in nurses working in pandemic units (P < .05). CONCLUSION: The factors that have been shown to cause burnout in previous studies were similar. However, in this study, it was also seen that the pandemic is a fundamental cause of burnout.

CWH43 Variants Are Associated With Disease Risk and Clinical Phenotypic Measures in Patients With Normal Pressure Hydrocephalus.

Background and Objectives: Variants in the CWH43 gene have been associated with normal pressure hydrocephalus (NPH). We aimed to replicate these findings, identify additional CWH43 variants, and further define the clinical phenotype associated with CWH43 variants. Methods: We determined the prevalence of CWH43 variants by whole-genome sequencing (WGS) in 94 patients with NPH. The odds of having CWH43 variant carriers develop NPH were determined through comparison with 532 Mayo Clinic Biobank volunteers without a history of NPH. For patients with NPH, we documented the head circumference, prevalence of disproportionate enlargement of subarachnoid hydrocephalus (DESH), microvascular changes on MRI quantified by the Fazekas scale, and ambulatory response to ventriculoperitoneal shunting. Results: We identified rare (MAF <0.05) coding CWH43 variants in 15 patients with NPH. Ten patients (Leu533Terfs, n = 8; Lys696Asnfs, n = 2) harbored previously reported predicted loss-of-function variants, and combined burden analysis confirmed risk association with NPH (OR 2.60, 95% CI 1.12-6.03, p = 0.027). Additional missense variations observed included Ile292Thr (n = 2), Ala469Ser (n = 2), and Ala626Val (n = 1). Though not quite statistically significant, in single variable analysis, the odds of having a head circumference above the 75th percentile of normal controls was more than 5 times higher for CWH43 variant carriers compared with that for noncarriers (unadjusted OR 5.67, 95% CI 0.96-108.55, p = 0.057), and this was consistent after adjusting for sex and height (OR 5.42, 95% CI 0.87-106.37, p = 0.073). DESH was present in 56.7% of noncarriers and only 21.4% of carriers (p = 0.016), while sulcal trapping was also more prevalent among noncarriers (67.2% vs 35.7%, p = 0.030). All 8 of the 15 variant carriers who underwent ventriculoperitoneal shunting at our institution experienced ambulatory improvements. Discussion: CWH43 variants are frequent in patients with NPH. Predicted loss-of-function mutations were the most common; we identified missense mutations that require further study. Our findings suggest that congenital factors, rather than malabsorption or vascular dysfunction, are primary contributors to the CWH43-related NPH clinical syndrome.

Radiological Findings in the Case Exposed to Zirconium.

Pneumoconiosis is a lung disease that develops as a result of a tissue reaction that occurs with the accumulation of inorganic particles. Pathoclinical features may vary depending on the type of inhaled particle. Today, fibrotic and nonfibrotic tissue reactions are well defined in some substances. For example, it is known that exposures such as silica, asbestos, beryllium, and talc are associated with fibrosis in the lung, while exposures such as iron, tin, and barium sulfate cause non-fibrogenic changes. However, the pathoclinic and radiological findings of some rare exposures such as zirconium are not widely known. In a 52-year-old dental technician with a 26-year history of zirconium exposure, more prominent parenchymal emphysematous and fibrotic changes were detected in the upper zones of the thorax high-resolution computed tomography. Since zirconium exposure was clearly defined, radiological findings of this case may be useful to current literature.

Clinical Deep Phenotyping of ABCA7 Mutation Carriers.

BACKGROUND AND OBJECTIVES: Putative loss-of-function (pLOF) ABCA7 variants that increase Alzheimer disease (AD) risk were identified; however, deep phenotypic characterization of these variants in mutation carriers is limited. We aimed to obtain deep clinical phenotypes of ABCA7 pLOF mutation carriers from a large retrospectively reviewed series. METHODS: Genotypes were determined for 5,353 individuals evaluated at Mayo Clinic for 6 reported ABCA7 pLOF variants (p.E709fs, p.Trp1214X, p.L1403fs, c.4416+2T>G, p.E1679X, and c.5570+5G>C). Medical records of 100 mutation carriers were reviewed for demographics, clinical phenotypes, and diagnoses. Eleven mutation carriers had autopsy-based neuropathologic diagnoses. RESULTS: We confirmed that ABCA7 pLOF mutations confer AD risk in our series of 2,495 participants with AD and 2,858 cognitively unaffected participants. Clinical review of 100 mutation carriers demonstrated phenotypic variability of clinical presentations with both memory and nonmemory cognitive impairment and a subset presenting with motor symptoms. There was a wide range of age at onset of cognitive symptoms (ages 56-92 years, mean = 75.6). Ten of the 11 autopsied mutation carriers had AD neuropathology. ABCA7 pLOF mutation carriers had higher rates of depression (41.6%) and first-degree relatives with cognitive impairment (38.1%) compared with the general population. DISCUSSION: Our study provides a deep clinical review of phenotypic characteristics of mutation carriers for 6 ABCA7 pLOF mutations. Although memory impairment was the most common initial symptom, nonmemory cognitive and/or motor symptoms were present in a substantial number of mutation carriers, highlighting the heterogeneity of clinical features associated with these mutations. Likewise, although AD neuropathology is the most common, it is not the only autopsy-based diagnosis. Presence of earlier ages at onset, higher rates of depression, and first-degree relatives with cognitive impairment among mutation carriers suggest that these genetic variants may have more aggressive clinical features than AD in the general population. This deep phenotyping study of ABCA7 pLOF mutation carriers provides essential genotype-phenotype correlations for future precision medicine approaches in the clinical setting.

Facing the Pandemic: Burnout in Physicians in Turkey.

OBJECTIVE: During the COVID-19 pandemic, physicians have been working for long hours, with the fear of contracting the disease and infecting their families. Therefore, there are great concerns about the mental health of physicians. In this research, we aimed to reveal the factors that affect the burnout among physicians working during the pandemic. MATERIAL AND METHODS: This is a cross-sectional study involving physicians working during the pandemic in health institutions that admit COVID-19 patients. A questionnaire form consisting of the "Sociodemographic Data Form" and the "Maslach Burnout Inventory (MBI)" was used. The questionnaire was sent to the contact numbers of physicians via the internet. The target population was reached through the communication groups of the Turkish Thoracic Society and other professional associations, the communication groups of health institutions, and also through personal correspondence. Burnout was evaluated with the scores of each participant from the 3 subscales of Emotional Exhaustion (EE), Depersonalization (DP), and Lack of Accomplishment (LA). RESULTS: Of the 1177 physicians who participated in the survey, 893 answered the survey completely. Females comprised 56.70% (n = 506) of the respondents, and the mean age was 38.63 (±11.65). The residents (41%, n = 366) and specialists (31%, n = 277) made up the majority of the physicians. Eighty-six percent (n = 768) of the physicians had difficulty in obtaining personal protective equipment (PPE). It was determined that 81.7% (n = 730) of the 893 physicians were actively working in pandemic units (outpatient clinics, emergencies, inpatient clinics, intensive care units), and burnout was significantly higher in these physicians (P < .01). After excluding other confounding factors by regression analysis, their Maslach total scores and EE scores were found to be significantly high (P = .001). CONCLUSION: Working in pandemic units and facing difficulty in accessing PPE are identified as the most important risk factors for burnout. Hence, we can say that working with PPE, and with the managers' discretion and support, the physicians' burnout can be prevented.

How were Non-COVID pulmonary patients and diseases affected from COVID-19 pandemic period?

OBJECTIVE: This study aimed to focus on non-COVID-19 patients during the process when all physicians focused on COVID-19 patients. Patients with pulmonary diseases in the COVID-19 pandemic period were analyzed. MATERIAL AND METHODS: Non-COVID-19 cases who were hospitalized in the pulmonology clinic, outpatients, and patients who applied to the non-COVID-19 emergency service and requested a pulmonology consultation in the period from March 16, 2020 to May 15, 2020 and in the same period of the previous year (i.e., from March 16, 2019 to May 15, 2019) were included in this study. RESULTS: In the pandemic period, it was found that there was an 84% decrease in outpatient admissions, a 43% decrease in inpatients, and a 75% decrease in emergency services. During the pandemic period, in outpatient setting, male and younger case admissions increased, admissions with chronic obstructive pulmonary disease (COPD), and interstitial lung diseases decreased, whereas the frequency of admission to asthma, pneumonia, and pulmonary thromboembolism increased. In the period of the pandemic, patients with asthma, COPD, and lung cancer were less hospitalized, whereas patients with pulmonary thromboembolism, pneumonia, and pleural effusion were hospitalized more. In non-COVID-19 patient treatments during the pandemic period, usage of a metered dose inhaler increased. CONCLUSION: During the COVID-19 pandemic, non-COVID pulmonary pathologies decreased significantly, and there was a change in the profile of the patients. From now on, to be prepared for pandemic and similar extraordinary situations, to organize hospitals for the epidemic, to determine health institutions to which nonepidemic patients can apply, to make necessary plans in order not to neglect the nonepidemic patients, and to develop digital health service methods, especially telemedicine, would be appropriate.

Burnout in Chest Physicians after Health Care Reforms: A Cross-Sectional Study in Turkey.

OBJECTIVES: The health reform has recently been one of the most important items on the agenda worldwide. The aim of this study is to investigate burnout syndrome in chest physicians and exhibit its connection with reform processes. MATERIALS AND METHODS: In this survey, the "Socio-demographic Data Form" and "Maslach Burnout Inventory" were used. Between September and November 2016, chest physicians were reached with permissions by expertise associations via e-mail groups. A sample size of 352 physicians was included in the study out of 2,349 chest physicians in Turkey. RESULTS: Among 352 physicians, 238 (67.60%) were women, and the mean age was 38.93 (±9.97). Higher burnout scores were determined in young physicians (aged ≤35), residents, those with low income, and those with ≥55 weekly working hours. The performance-based salary system was regarded as a problem by 84.7%, and 83.5% stated that they had not enough leisure time for themselves and their families. More than a half (55.7%) indicated that they would not choose the same specialty if they ever had a chance to choose again. CONCLUSION: We observed that most of chest physicians in Turkey experience burnout syndrome, which might be influenced by reforms in the health care system. The health system and working conditions should be dealt with immediately by health authorities and reformed in accordance with human dignity and rights to life.