CD8+ T-cell Differentiation and Dysfunction Inform Treatment Response in Acute Myeloid Leukemia.

The interplay between T-cell states of differentiation, dysfunction, and treatment response in acute myeloid leukemia (AML) remains unclear. Here, we leveraged a multimodal approach encompassing high-dimensional flow cytometry and single-cell transcriptomics and found that early memory CD8+ T cells are associated with therapy response and exhibit a bifurcation into two distinct terminal end states. One state is enriched for markers of activation, whereas the other expresses NK-like and senescence markers. The skewed clonal differentiation trajectory towards CD8+ senescence was also a hallmark indicative of therapy resistance. We validated these findings by generating an AML CD8+ single-cell atlas integrating our data and other independent datasets. Finally, our analysis revealed that an imbalance between CD8+ early memory and senescent-like cells is linked to AML treatment refractoriness and poor survival. Our study provides crucial insights into the dynamics of CD8+ T-cell differentiation and advances our understanding of CD8+ T-cell dysfunction in AML.

Kinetics and Fidelity of the Repair of Cas9-Induced Double-Strand DNA Breaks.

The RNA-guided DNA endonuclease Cas9 is a powerful tool for genome editing. Little is known about the kinetics and fidelity of the double-strand break (DSB) repair process that follows a Cas9 cutting event in living cells. Here, we developed a strategy to measure the kinetics of DSB repair for single loci in human cells. Quantitative modeling of repaired DNA in time series after Cas9 activation reveals variable and often slow repair rates, with half-life times up to ∼10 hr. Furthermore, repair of the DSBs tends to be error prone. Both classical and microhomology-mediated end joining pathways contribute to the erroneous repair. Estimation of their individual rate constants indicates that the balance between these two pathways changes over time and can be altered by additional ionizing radiation. Our approach provides quantitative insights into DSB repair kinetics and fidelity in single loci and indicates that Cas9-induced DSBs are repaired in an unusual manner.

Diverse macrophage populations contribute to distinct manifestations of human cutaneous graft-versus-host disease.

BACKGROUND: Graft-versus-host disease (GvHD) is a major life-threatening complication of allogeneic haematopoietic stem cell transplantation (HSCT), limiting the broad application of HSCT for haematological malignancies. Cutaneous GvHD is described as a post-transplant inflammatory reaction by skin-infiltrating donor T cells and remaining recipient tissue-resident memory T cells. Despite the major influence of lymphocytes on GvHD pathogenesis, the complex role of mononuclear phagocytes (MNPs) in tissues affected by GvHD is increasingly appreciated. OBJECTIVES: To characterize the identity, origin and functions of MNPs in patients with acute cutaneous GvHD. METHODS: Using single-cell RNA sequencing and multiplex tissue immunofluorescence, we identified an increased abundance of MNPs in skin and blood from 36 patients with acute cutaneous GvHD. In cases of sex-mismatched transplantation, we used expression of X-linked genes to detect rapid tissue adaptation of newly recruited donor MNPs resulting in similar transcriptional states of host- and donor-derived macrophages within GvHD skin lesions. RESULTS: We showed that cutaneous GvHD lesions harbour expanded CD163+ tissue-resident macrophage populations with anti-inflammatory and tissue-remodelling properties including interleukin-10 cytokine production. Cell-cell interaction analyses revealed putative signalling to strengthen regulatory T-cell responses. Notably, macrophage polarization in chronic cutaneous GvHD types was proinflammatory and drastically differed from acute GvHD, supporting the notion of distinct cellular players in different clinical GvHD subtypes. CONCLUSIONS: Overall, our data reveal a surprisingly dynamic role of MNPs after HSCT. Specific and time-resolved targeting to repolarize this cell subset may present a promising therapeutic strategy in combatting GvHD skin inflammation.

Digital cognitive behavioural therapy for insomnia reduces insomnia in nurses suffering from shift work disorder: A randomised-controlled pilot trial.

Insomnia is a primary symptom of shift work disorder, yet it remains undertreated. This randomised-controlled pilot trial examined the efficacy of a digital, guided cognitive behavioural therapy for insomnia adapted to shift work (SleepCare) in nurses with shift work disorder. The hypothesis was that SleepCare reduces insomnia severity compared with a waitlist control condition. A total of 46 unmedicated nurses suffering from shift work disorder with insomnia (age: 39.7 ± 12.1 years; 80.4% female) were randomised to the SleepCare group or the waitlist control group. The primary outcome measure was the Insomnia Severity Index. Other questionnaires on sleep, mental health and occupational functioning, sleep diary data and actigraphy data were analysed as secondary outcomes. Assessments were conducted before (T0), after the intervention/waitlist period (T1), and 6 months after treatment completion (T2). The SleepCare group showed a significant reduction in insomnia severity from T0 to T1 compared with the control condition (ß = -4.73, SE = 1.12, p < 0.001). Significant improvements were observed in sleepiness, dysfunctional beliefs about sleep, pre-sleep arousal, sleep effort, self-reported sleep efficiency and sleep onset latency. No significant effect was found in actigraphy data. Depressive and anxiety symptoms, cognitive irritation and work ability improved significantly. Overall, satisfaction and engagement with the intervention was high. SleepCare improved insomnia severity, sleep, mental health and occupational functioning. This is the first randomised-controlled trial investigating the efficacy of digital cognitive behavioural therapy for insomnia in a population suffering from shift work disorder with insomnia. Future research should further explore these effects with larger sample sizes and active control conditions.

Relative risk of second malignant neoplasms highest among young adult cancer patients - a population-based registry study in Finland.

BACKGROUND AND PURPOSE: The objective of this study was to explore the incidence of second malignant neoplasms (SMNs) among adult cancer patients in Finland diagnosed with their first primary cancer (FPC) in 1992-2021. MATERIAL AND METHODS: The study used data from the population-based Finnish Cancer Registry (FCR). Risk estimates were calculated using the standardised incidence ratio (SIR), the ratio of observed second cancers compared to the expected numbers assuming the same cancer incidence as the corresponding sex-age-calendar year -split of the general population. RESULTS: A total of 573,379 FPCs were diagnosed during 1992-2021. During the follow-up, 60,464 SMNs were diagnosed. Male cancer patients had neither a decreased nor an increased risk (SIR 1.00 [95% CI, 0.99-1.01]) and female patients had an 8% increased risk (SIR 1.08 [95% CI, 1.06-1.09]) of developing any SMN compared to a FPC in the general population. The highest SIR of any SMN was observed in patients aged 20-39 -years at FPC diagnosis, and the SIR decreased by increasing age at diagnosis. Patients with lymphoid and haematopoietic tissue neoplasms, cancers of the mouth and pharynx, endocrine glands, respiratory and intrathoracic organs, skin, and urinary organs had the highest SIRs, while patients with cancers of the male genital organs and the female breast had the lowest SIRs. INTERPRETATION: Elevated SIRs were observed in cancer patients diagnosed at an early age and for FPCs known to be in large part attributable to lifestyle factors, which highlights the importance of monitoring and encouraging lifestyle changes.

Consensus-based recommendations for the development and expansion of palliative day care clinics in Germany: results of a Delphi study.

BACKGROUND: Needs-based, patient-oriented palliative care includes palliative day care clinics as a specialized semi-inpatient care offer. However, the establishment and development of these facilities has been unsystematic. Research is needed to strengthen their transparency and ensure their accessibility, quality, and structural adequacy. A national Delphi study was conducted to generate appropriate recommendations for the establishment and development of palliative day care clinics in Germany. METHODS: Recommendations were formulated from focus group data on the development and expansion of palliative day care clinics in Germany. Experts on in- and outpatient palliative care rated 28 recommendations for relevance and feasibility, respectively, using a 4-point Likert-type scale. Suggestions for improvement were captured via free text comments. Items were considered consented when more than 80% of the experts scored them 4 (strongly agree) or 3 (somewhat agree), regarding both relevance and feasibility. RESULTS: A total of 23 experts (32% response rate) completed three Delphi rounds. Following the first round, 10 of 28 recommendations were revised according to participants' comments; 1 recommendation was rejected. After the second round, 3 of these 10 recommendations were revised, while 3 were rejected. Consensus was achieved after the third round for 22 of the initial recommendations. CONCLUSIONS: The Delphi-consented recommendations provide a basis for the targeted evidence- and needs-based development of palliative day care clinics. The findings show a need for standards setting and the meaningful integration of these clinics into existing structures. TRIAL REGISTRATION: The present study was prospectively registered on April 20, 2020, with the German Clinical Trials Register (DRKS00021446).

Development and evaluation of regression tree models for predicting in-hospital mortality of a national registry of COVID-19 patients over six pandemic surges.

BACKGROUND: Objective prognostic information is essential for good clinical decision making. In case of unknown diseases, scarcity of evidence and limited tacit knowledge prevent obtaining this information. Prediction models can be useful, but need to be not only evaluated on how well they predict, but also how stable these models are under fast changing circumstances with respect to development of the disease and the corresponding clinical response. This study aims to provide interpretable and actionable insights, particularly for clinicians. We developed and evaluated two regression tree predictive models for in-hospital mortality of COVID-19 patient at admission and 24 hours (24 h) after admission, using a national registry. We performed a retrospective analysis of observational routinely collected data. METHODS: Two regression tree models were developed for admission and 24 h after admission. The complexity of the trees was managed via cross validation to prevent overfitting. The predictive ability of the model was assessed via bootstrapping using the Area under the Receiver-Operating-Characteristic curve, Brier score and calibration curves. The tree models were assessed on the stability of their probabilities and predictive ability, on the selected variables, and compared to a full-fledged logistic regression model that uses variable selection and variable transformations using splines. Participants included COVID-19 patients from all ICUs participating in the Dutch National Intensive Care Evaluation (NICE) registry, who were admitted at the ICU between February 27, 2020, and November 23, 2021. From the NICE registry, we included concerned demographic data, minimum and maximum values of physiological data in the first 24 h of ICU admission and diagnoses (reason for admission as well as comorbidities) for model development. The main outcome measure was in-hospital mortality. We additionally analysed the Length-of-Stay (LoS) per patient subgroup per survival status. RESULTS: A total of 13,369 confirmed COVID-19 patients from 70 ICUs were included (with mortality rate of 28%). The optimism-corrected AUROC of the admission tree (with seven paths) was 0.72 (95% CI: 0.71-0.74) and of the 24 h tree (with 11 paths) was 0.74 (0.74-0.77). Both regression trees yielded good calibration and variable selection for both trees was stable. Patient subgroups comprising the tree paths had comparable survival probabilities as the full-fledged logistic regression model, survival probabilities were stable over six COVID-19 surges, and subgroups were shown to have added predictive value over the individual patient variables. CONCLUSIONS: We developed and evaluated regression trees, which operate at par with a carefully crafted logistic regression model. The trees consist of homogenous subgroups of patients that are described by simple interpretable constraints on patient characteristics thereby facilitating shared decision-making.

Use of Methadone Versus Oxycodone to Facilitate Weaning of Parenteral Opioids in Critically Ill Adult Patients.

BACKGROUND: No previous literature has compared methadone with oxycodone for intravenous (IV) opioid weaning. OBJECTIVE: To determine if a weaning strategy using enteral methadone or oxycodone results in faster time to IV opioid discontinuation. METHODS: This was a single-center, retrospective, cohort medical record review of mechanically ventilated adults in an intensive care unit (ICU) who received a continuous IV infusion of fentanyl or hydromorphone for ≥72 hours and an enteral weaning strategy using either methadone or oxycodone from January 1, 2020, through December 31, 2021. Differences between groups were controlled for using Cox proportional hazards models. The primary outcome was time to continuous IV opioid discontinuation from the initiation of enteral opioids. Secondary outcomes included the primary endpoint stratified for COVID-19, duration of mechanical ventilation, ICU and hospital length of stay, and safety measures. RESULTS: Ninety-three patients were included, with 36 (38.7%) patients receiving methadone and 57 (61.3%) receiving oxycodone. Patients weaned using methadone received IV opioids significantly longer before the start of weaning (P = 0.04). However, those on methadone had a significantly faster time to discontinuation of IV opioids than those on oxycodone, mean (standard deviation) 104.7 (79.4) versus 158.3 hours (171.2), P = 0.04, and, at any time, were 1.89 times as likely to be weaned from IV opioids (hazard ratio, HR 1.89, 95% confidence interval, CI 1.16-3.07, P = 0.01). CONCLUSION AND RELEVANCE: This was the first study showing enteral methadone was associated with a shorter duration of IV opioids without differences in secondary outcomes compared with oxycodone. Prospective research is necessary to confirm this finding.

Prognostic models of in-hospital mortality of intensive care patients using neural representation of unstructured text: A systematic review and critical appraisal.

OBJECTIVE: To review and critically appraise published and preprint reports of prognostic models of in-hospital mortality of patients in the intensive-care unit (ICU) based on neural representations (embeddings) of clinical notes. METHODS: PubMed and arXiv were searched up to August 1, 2022. At least two reviewers independently selected the studies that developed a prognostic model of in-hospital mortality of intensive-care patients using free-text represented as embeddings and extracted data using the CHARMS checklist. Risk of bias was assessed using PROBAST. Reporting on the model was assessed with the TRIPOD guideline. To assess the machine learning components that were used in the models, we present a new descriptive framework based on different techniques to represent text and provide predictions from text. The study protocol was registered in the PROSPERO database (CRD42022354602). RESULTS: Eighteen studies out of 2,825 were included. All studies used the publicly-available MIMIC dataset. Context-independent word embeddings are widely used. Model discrimination was provided by all studies (AUROC 0.75-0.96), but measures of calibration were scarce. Seven studies used both structural clinical variables and notes. Model discrimination improved when adding clinical notes to variables. None of the models was externally validated and often a simple train/test split was used for internal validation. Our critical appraisal demonstrated a high risk of bias in all studies and concerns regarding their applicability in clinical practice. CONCLUSION: All studies used a neural architecture for prediction and were based on one publicly available dataset. Clinical notes were reported to improve predictive performance when used in addition to only clinical variables. Most studies had methodological, reporting, and applicability issues. We recommend reporting both model discrimination and calibration, using additional data sources, and using more robust evaluation strategies, including prospective and external validation. Finally, sharing data and code is encouraged to improve study reproducibility.

An Evaluation of the Relationship Between Medication Regimen Complexity as Measured by the MRC-ICU to Medication Errors in Critically Ill Patients.

Purpose: The purpose of this study was to determine the relationship between medication regimen complexity-intensive care unit (MRC-ICU) score at 24 hours and medication errors identified throughout the ICU. Methods: A single-center, observational study was conducted from August to October 2021. The primary outcome was the association between MRC-ICU at 24 hours and total medication errors identified. During the prospective component, ICU pharmacists recorded medication errors identified over an 8-week period. During the retrospective component, the electronic medical record was reviewed to collect patient demographics, outcomes, and MRC-ICU score at 24 hours. The primary outcome of the relationship of MRC-ICU at 24 hours to medication errors was assessed using Pearson correlation. Results: A total of 150 patients were included. There were 2 pharmacists who recorded 634 errors during the 8-week study period. No significant relationship between MRC-ICU and medication errors was observed (r2 = .13, P = .11). Exploratory analyses of MRC-ICU relationship to major interventions and harm scores showed that MRC-ICU scores >10 had more major interventions (27 vs 14, P = .27) and higher harm scores (15 vs 7, P = .33), although these values were not statistically significant. Conclusion: Medication errors appear to occur independently of medication regimen complexity. Critical care pharmacists were responsible for mitigating a large number of medication errors.

Colposcopic performance in a birth cohort previously eligible for human papillomavirus vaccination.

BACKGROUND: Sweden started subsidized quadrivalent human papillomavirus vaccination for girls aged 13 to 17 in 2007. Since 2012, vaccination has been offered to all girls aged 10 to 12 within a school-based vaccination program, with a coverage of 80% or more. In addition, the vaccine has been offered on-demand as catch-up vaccination for girls aged 13 to 18, with a cumulative coverage of 55% to 60%. Since the first women in Sweden eligible for human papillomavirus vaccination entered the cervical screening program, questions on how to evaluate colposcopic findings among vaccinated women have arisen. Evidence is inconsistent on whether colposcopic features for the detection of cervical lesions are influenced by specific human papillomavirus genotypes and what role they can play in the prevention of invasive cervical cancer in vaccinated women. OBJECTIVE: The primary objective of the study was to compare colposcopic evaluation in vaccinated and unvaccinated women entering the organized cervical screening program. STUDY DESIGN: Women in the 1994 and 1995 birth cohorts who entered the cervical screening program at age 23 in 1 region in Sweden were identified. Colposcopy was performed within 2 to 4 months after a positive screening result in accordance with national guidelines. Colposcopic performance was evaluated according to national guidelines with the Swede score and colposcopic impression. Punch biopsies were taken from colposcopic lesions and as "random biopsies" in the absence of lesions. These biopsies were used as the gold standard for the analysis. An endocervical sample was analyzed for cytologic findings and detection of 14 high-risk human papillomavirus genotypes. All colposcopic imaging was saved digitally for re-review. Vaccination status was obtained through linkage to national vaccination registries. Results were compared between vaccinated and unvaccinated women. RESULTS: In 2018 and 2019, 160 out of 165 (98%) women with a positive screening result attended colposcopy, of which 90 (56%) were vaccinated and 70 (44%) were unvaccinated. Only 7 out of 90 (5%) women in the vaccinated group were human papillomavirus 16/18-positive, compared with 23 out of 70 (33%) in the unvaccinated group (P<.001). There was a total of 61 out of 160 (38%) women with high-grade lesions-33 out of 90 (37%) in the vaccinated group and 28 out of 70 (40%) in the unvaccinated group (P=.697). There was 64% (21/33) of vaccinated women and 75% (21/28) of unvaccinated women with high-grade squamous intraepithelial lesions who had a Swede score of 6 to 10 (indicating high-grade squamous intraepithelial lesions) (P=.124). The sensitivity was slightly higher for the detection of high-grade squamous intraepithelial lesions in unvaccinated women using both colposcopic tests (Swede score, 0.67 vs 0.75; colposcopic impression, 0.67 vs 0.68), but the difference was not statistically significant. CONCLUSION: We found no statistically significant difference between the colposcopic evaluation of vaccinated and unvaccinated women, although human papillomavirus vaccination reduced the prevalence of human papillomavirus 16/18 infection in human papillomavirus-vaccinated women. Our results indicate that colposcopic examination is still a useful tool in vaccinated women entering the organized cervical screening program.

Pseudomonas boanensis sp. nov., a bacterium isolated from river water used for household purposes in Boane District, Mozambique.

A Gram-negative rod with a single polar flagellum was isolated from a freshwater reservoir used for household purposes in Boane District, near Maputo, Mozambique, and designated as strain DB1T. Growth was observed at 30-42 °C (optimum, 30-37 °C) and with 0.5-1.5 % NaCl. Whole-genome-, rpoD- and 16S rRNA-based phylogenies revealed this isolate to be distant from other Pseudomonas species with Pseudomonas resinovorans, Pseudomonas furukawaii and Pseudomonas lalkuanensis being the closest relatives. Phenotypic analyses of strain DB1T showed marked differences with respect to type strains P. resinovorans CCUG 2473T, P. lalkuanensis CCUG 73691T, P. furukawaii CCUG 75672T and Pseudomonas otiditis CCUG 55592T. Taken together, our results indicate that strain DB1T is a representative of a novel species within the genus Pseudomonas for which the name Pseudomonas boanensis is proposed. The type strain is DB1T (=CCUG 62977T=CECT 30359T).

Dynamics from noisy data with extreme timing uncertainty.

Imperfect knowledge of the times at which 'snapshots' of a system are recorded degrades our ability to recover dynamical information, and can scramble the sequence of events. In X-ray free-electron lasers, for example, the uncertainty--the so-called timing jitter--between the arrival of an optical trigger ('pump') pulse and a probing X-ray pulse can exceed the length of the X-ray pulse by up to two orders of magnitude, marring the otherwise precise time-resolution capabilities of this class of instruments. The widespread notion that little dynamical information is available on timescales shorter than the timing uncertainty has led to various hardware schemes to reduce timing uncertainty. These schemes are expensive, tend to be specific to one experimental approach and cannot be used when the record was created under ill-defined or uncontrolled conditions such as during geological events. Here we present a data-analytical approach, based on singular-value decomposition and nonlinear Laplacian spectral analysis, that can recover the history and dynamics of a system from a dense collection of noisy snapshots spanning a sufficiently large multiple of the timing uncertainty. The power of the algorithm is demonstrated by extracting the underlying dynamics on the few-femtosecond timescale from noisy experimental X-ray free-electron laser data recorded with 300-femtosecond timing uncertainty. Using a noisy dataset from a pump-probe experiment on the Coulomb explosion of nitrogen molecules, our analysis reveals vibrational wave-packets consisting of components with periods as short as 15 femtoseconds, as well as more rapid changes, which have yet to be fully explored. Our approach can potentially be applied whenever dynamical or historical information is tainted by timing uncertainty.

Urban health challenges: Lessons from COVID-19 responses.

The COVID-19 pandemic has forced a re-examination of our societies and in particular urban health. We argue that urban health needs to address three inter-related challenge areas - the unequal impacts of climate change, changing patterns of urbanization, and the changing role of the local government - across multiple spatial scales: from individual, households to neighbourhoods, cities, and urban hinterlands. Urban health calls for nimble institutions to provide a range of responses while adapting to crisis situations, and which operate beyond any one spatial scale. We illustrate our argument by drawing on South and Southeast Asian examples where responses to the pandemic have confronted these challenges across scales. A multiscalar definition of urban health offers an opportunity to challenge dominant approaches to urban health in research, policy, and practice.

Drivers of local extinction risk in alpine plants under warming climate.

The scarcity of local plant extinctions following recent climate change has been explained by demographic inertia and lags in the displacement of resident species by novel species, generating an 'extinction debt'. We established a transplant experiment to disentangle the contribution of these processes to the local extinction risk of four alpine plants in the Swiss Alps. Projected population growth (λ) derived from integral projection models was reduced by 0.07/°C of warming on average, whereas novel species additionally decreased λ by 0.15 across warming levels. Effects of novel species on predicted extinction time were greatest at warming < 2 °C for two species. Projected population declines under both warming and with novel species were primarily driven by increased mortality. Our results suggest that extinction debt can be explained by a combination of demographic inertia and lags in novel species establishment, with the latter being particularly important for some species under low levels of warming.

Knowledge, health beliefs and attitudes towards dementia and dementia risk reduction among descendants of people with dementia: a qualitative study using focus group discussions.

BACKGROUND: Individuals with a parental family history of dementia have an increased risk of developing dementia because they share their genes as well as their psychosocial behaviour. Due to this increased risk and their experience with dementia, they may be particularly eager to receive information regarding dementia risk reduction (DRR). This study evaluated the knowledge, beliefs and attitudes towards dementia and DRR among descendants of people with dementia. METHOD: Using a semi-structured topic guide, three focus group discussions were conducted consisting of 12 female (80%) and 3 male (20%) descendants of people with dementia with a mean (± SD) age of 48.8 (± 12) years. Focus group discussions were audio recorded and transcribed. Each transcript was analysed thoroughly, and where appropriate, a code was generated and assigned by two researchers independently. Then, similar codes were grouped together and categorized into themes. RESULTS: The items in the topic guide could only be addressed after participants had been given the opportunity to share their experiences of having a parent with dementia. Participants were unaware or uncertain about the possibility of reducing the risk of developing dementia and therefore hesitant to assess their dementia risk without treatment options in sight. Moreover, participants indicated that their general practitioner only gave some information on heritability, not on DRR. Although participants identified a large number of modifiable risk factors as a group during the group discussions, they were eager to receive more information on dementia and DRR. In the end, participants adopted a more positive attitude towards a DRR programme and provided suggestions for the development of future DRR programmes. CONCLUSIONS: Although the research aim was to evaluate the knowledge, beliefs and attitudes towards dementia and DRR, sharing experiences of having a parent with dementia seemed a prerequisite for considering participants' own risk of developing dementia and participating in a DRR programme. Knowledge of dementia and DRR was limited. Due to unawareness of the possibility of reducing dementia risk, participants were hesitant about assessing their dementia risk. Group discussions positively changed the perception of dementia risk assessment and participants' willingness to participate in a DRR programme.

Five Factor Machiavellianism: Validation of a New Measure.

Numerous scholars have criticized the traditional assessment of Machiavellianism due to insufficient construct coverage, some going so far as to question its distinctness from psychopathy. Tackling these issues, Collison, Vize, Miller, and Lynam developed the Five Factor Machiavellianism Inventory (FFMI), comprising antagonism, agency, and planfulness. We aimed to replicate the MACH-IV psychopathy relations, demonstrate the validity of the FFMI by assessing its relations with the NEO-PI-R and the HEXACO facets, and link the FFMI to a broad range of work-related criteria. We replicated the MACH-IV psychopathy relations and found a very high (rICCS = .91) absolute profile similarity between the FFMI's correlations with the NEO-PI-R in our sample (N = 572) and the correlation profile for the same variables reported by Collison and colleagues. Both the NEO-PI-R and HEXACO-PI-R profiles for the FFMI found in the current study supported its distinctiveness from traditional measures of Machiavellianism, which converged greatly with the correlation profiles for the FFMI-antagonism dimension. A cluster analysis also showed a substantial proportion of Five Factor Machiavellian individuals. In addition, the FFMI displayed positive relations with a broad range of criteria for vocational and work-related success and was clearly distinct from psychopathy.

Autoimmunity to the Follicle-Stimulating Hormone Receptor (FSHR) and Luteinizing Hormone Receptor (LHR) in Polycystic Ovarian Syndrome.

Hyperandrogenemia and ovulatory dysfunction are hallmarks of polycystic ovary syndrome (PCOS), pointing to a deranged hypothalamus-pituitary-ovarian (HPO) axis. An autoimmune etiology of PCOS is suspected in a subset of patients due to the relatively high concordance of PCOS with common autoimmune diseases. For this reason, we tested the hypothesis that natural autoantibodies (aAb) to the follicle-stimulating hormone receptor (FSHR) or luteinizing hormone receptor (LHR) are prevalent in PCOS. To this end, new luminometric assays for quantifying aAb to the FSHR (FSHR-aAb) or LHR (LHR-aAb) were developed using full-length recombinant human receptors as fusion proteins with luciferase as reporter. Prevalence of FSHR-aAb and LHR-aAb was determined in serum samples from healthy controls and PCOS patients. Steroid hormone profiles were compared between patients with and without FSHR-aAb or LHR-aAb. Signal linearity and detection ranges were characterized and both methods passed basic performance quality checks. The analysis revealed a relatively low prevalence, with 4 out of 430 samples positive for FSHR-aAb in the control versus 11 out of 550 samples in the PCOS group, i.e., 0.9% versus 2.0%, respectively. Similarly, there were only 5 samples positive for LHR-aAb in the control versus 2 samples in the PCOS group, i.e., 1.2% versus 0.4%, respectively. Samples positive for FSHR-aAb displayed steroid hormones in the typical range of PCOS patients, whereas the two samples positive for LHR-aAb showed relatively elevated free testosterone in relation to total testosterone concentrations with unclear significance. We conclude that the FSHR and LHR constitute potential autoantigens in human subjects. However, the prevalence of specific autoantibodies to these receptors is relatively low, both in control subjects and in women with PCOS. It is therefore unlikely that autoimmunity to the LHR or FSHR constitutes a frequent cause of hyperandrogenemia or ovulatory dysfunction in PCOS.

Contextualizing the COVID-19 pandemic's impact on food security in two small cities in Bangladesh.

The COVID-19 pandemic is an evolving urban crisis. This research paper assesses impacts of the lockdown on food security and associated coping mechanisms in two small cities in Bangladesh (Mongla and Noapara) during March to May 2020. Due to restrictions during the prolonged lockdown, residents (in particular low-income groups) had limited access to livelihood opportunities and experienced significant or complete loss of income. This affected both the quantity and quality of food consumed. Coping strategies reported include curtailing consumption, relying on inexpensive starchy staples, increasing the share of total expenditure allocated to food, taking out loans and accessing relief. The pandemic has exacerbated the precariousness of existing food and nutrition security in these cities, although residents with guaranteed incomes and adequate savings did not suffer significantly during lockdown. While coping strategies and the importance of social capital are similar in small and large cities, food procurement and relationships with local governments show differences.

THE CHRONIC KIDNEY DISEASE RISK ANALYSIS IN PATIENTS WITH ARTERIAL HYPERTENSION AND COEXISTENT HYPERURICEMIA.

OBJECTIVE: The aim: Is the analysis of chronic kidney disease risk in patients with arterial hypertension and coexistent hyperuricemia. PATIENTS AND METHODS: Materials and methods:We observed 40 patients with arterial hypertension and coexistent hyperuricemia (I group), 35 - with arterial hypertension (II group) and 30 practically healthy people (control). The duration of hypertension was 4,3 ± 2,31 years and 4,0 ± 2,11 years (p = 0,9247) for I and II group respectively, of hyperuricemia - 4,1 ± 0,35 years for I group. Categories of albuminuria (А1, А2, А3) and glomerular filtration rate (G1, G2, G3A, G3B, G4, G5) were determined in all observed patients. Clinical, anthropometric, biochemical, immunoassay, statistical (SPSS 21, Graph Pad) methods were used. RESULTS: Results:The categories of albuminuria and glomerular filtration rate in patients from the I group demonstrated that A1G1 was confirmed in 3 persons, A1G2 - 5, A2G1 - 7, A2G2 - 20, A1G3A - 1, A1G3B - 1, A2G3A - 2, A2G3B - 1. Among patients from the II group category A1G1 was defined in 7, A1G2 - 2, A2G1 - 16, A2G2 - 10 persons. The percent of low chronic kidney disease risk was on 5,7 % higher in hypertensive persons comparable with comorbid persons. High and very high risk was confirmed in 10 % persons from I group and nobody from the ІІ group. CONCLUSION: Conclusions:Chronic kidney disease risk is increased in patients with arterial hypertension and coexistent hyperuricemia. This indicates an association between elevated uric acid levels and chronic kidney disease progression.