Positive personality resources as buffers against psychological reactions to uncertainty.

Since March 2020, Russia has been facing three lasting challenges of uncontrollable threat and uncertainty: the COVID-19 pandemic taking place at the global scale, and two national-level ones, the radical amendments to the Constitution and a drop in oil prices and national currency. We used this opportunity to investigate the way personality resources predict individual differences in the cognitive evaluations of uncertainty and emotional responses associated with each situation. We conducted a longitudinal study with 4 measurement waves between April and November 2020 in a sample of Russian-speaking volunteers (N = 219). The assessment of each of the three situations at each measurement occasion included the evaluation of its degree of certainty/uncertainty, general orientation, positive and negative emotions. We used repeated-measures ANOVA to explore the differences in cognitive appraisals and emotional reactions across time and situations, and multilevel modeling with random slopes to investigate the individual differences in the change trends for these variables. The results suggest that individuals with higher levels of personality resources tend to appraise the challenging situations as more certain, have a better sense of orientation in these situations, show more positive emotional responses, and exhibit more positive change trends over time reflecting successful adaptation. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-03879-1.

Meaning of life as a resource for coping with psychological crisis: Comparisons of suicidal and non-suicidal patients.

Introduction: Meaning is an important psychological resource both in situations of accomplishment and in situations of ongoing adversity and psychological crisis. Meaning in life underlies the reasons for staying alive both in everyday and in critical circumstances, fulfilling a buffering function with respect to life adversities. Aim: The aim of the present study was to reveal the role of both meaningfulness, including specific sources of meaning and reasons for living, and meaninglessness (alienation) in patients suffering from profound crisis situations with or without suicidal intentions and behavior. Methods: The sample included 148 patients (all Caucasian) who were referred to a crisis center in Moscow, Russia. Seventy-seven patients (54 females, mean age 32.00 ± 11.98 years) reported a current crisis situation in their life but denied suicidal thoughts or behavior. Twenty-nine patients (21 females, mean age 31.55 ± 13.76 years) reported suicidal ideations but denied suicidal attempts or self-harming behavior. Forty-two patients (31 females, mean age 30.64 ± 11.38 years) had episodes of suicidal attempts or self-harming behavior accompanied by suicidal intentions. There were no significant gender or age differences between groups.Participants completed a number of measures of different aspects of meaning and meaninglessness, well-being, ill-being and psychological resources. For some patients (N = 74), a clinical checklist was completed by their doctors assessing 28 various characteristics associated with the patient's clinical status. Results and discussion: Meaningfulness and reasons for living were more helpful in distinguishing between reactions to profound crisis situations (suicidal intentions versus non-suicidal behavior) than were measures of well-being, ill-being, meaning crisis or personality resources. In both suicidal and non-suicidal crisis patients meaningfulness predicted more positive reasons for living. The relationship between meaningfulness and most reasons for living remained significant after controlling for clinically appraised suicidal "readiness," acute stress and lack of social support. Self-transcendence was the major specific source of meaning predicting higher reasons for living after adjusting for general meaningfulness. Conclusion: The data cast some light on the psychological meaning of suicide. It follows that prevention efforts are to be focused not on eliminating the factors "pushing" one to suicidal behavior, but rather on supporting inner strengths conducive of a positive decision, to be, through enhancing meaningfulness and reasons for living.

An international study on psychological coping during COVID-19: Towards a meaning-centered coping style.

BACKGROUND/OBJECTIVE: This study examined the role of different psychological coping mechanisms in mental and physical health during the initial phases of the COVID-19 crisis with an emphasis on meaning-centered coping. METHOD: A total of 11,227 people from 30 countries across all continents participated in the study and completed measures of psychological distress (depression, stress, and anxiety), loneliness, well-being, and physical health, together with measures of problem-focused and emotion-focused coping, and a measure called the Meaning-centered Coping Scale (MCCS) that was developed in the present study. Validation analyses of the MCCS were performed in all countries, and data were assessed by multilevel modeling (MLM). RESULTS: The MCCS showed a robust one-factor structure in 30 countries with good test-retest, concurrent and divergent validity results. MLM analyses showed mixed results regarding emotion and problem-focused coping strategies. However, the MCCS was the strongest positive predictor of physical and mental health among all coping strategies, independently of demographic characteristics and country-level variables. CONCLUSIONS: The findings suggest that the MCCS is a valid measure to assess meaning-centered coping. The results also call for policies promoting effective coping to mitigate collective suffering during the pandemic.

ANTECEDENTES/OBJETIVO: Este estudio examinó el papel de diferentes estrategias de afrontamiento psicológico en la salud mental y física durante las fases iniciales de la crisis de COVID-19. MÉTODO: 11,227 personas de 30 países representando todos los continentes participaron en el estudio y completaron medidas de malestar psicológico (depresión, estrés y ansiedad), soledad, bienestar, salud física, medidas de afrontamiento centrado en el problema y en la emoción, y una medida denominada Escala del Afrontamiento Centrado en el Sentido (MCCS) que fue desarrollada en este estudio. El análisis de validación de la MCCS se realizó en todos los países, y los datos se evaluaron mediante un modelo multinivel. RESULTADOS: La MCCS mostró una estructura unifactorial en 30 países con buenos resultados de validez test-retest, concurrente y divergente. Los análisis mostraron resultados mixtos en cuanto a las estrategias de afrontamiento centradas en la emoción y en el problema. La MCCS fue el predictor positivo más fuerte de salud física y mental, independientemente de las características demográficas y las variables a nivel de país. CONCLUSIONES: Los resultados sugieren que la MCCS es un insrumento fiable para medir afrontamiento centrado en el sentido. Estos resultados pueden servir para dirigir políticas que promuevan un afrontamiento eficaz con el fin de mitigar el sufrimiento colectivo durante la pandemia.

Correction: A 32 kb Critical Region Excluding Y402H in CFH Mediates Risk for Age-Related Macular Degeneration.

[This corrects the article DOI: 10.1371/journal.pone.0025598.].

A 32 kb critical region excluding Y402H in CFH mediates risk for age-related macular degeneration.

Complement factor H shows very strong association with Age-related Macular Degeneration (AMD), and recent data suggest that multiple causal variants are associated with disease. To refine the location of the disease associated variants, we characterized in detail the structural variation at CFH and its paralogs, including two copy number polymorphisms (CNP), CNP147 and CNP148, and several rare deletions and duplications. Examination of 34 AMD-enriched extended families (N = 293) and AMD cases (White N = 4210 Indian = 134; Malay = 140) and controls (White N = 3229; Indian = 117; Malay = 2390) demonstrated that deletion CNP148 was protective against AMD, independent of SNPs at CFH. Regression analysis of seven common haplotypes showed three haplotypes, H1, H6 and H7, as conferring risk for AMD development. Being the most common haplotype H1 confers the greatest risk by increasing the odds of AMD by 2.75-fold (95% CI = [2.51, 3.01]; p = 8.31×10(-109)); Caucasian (H6) and Indian-specific (H7) recombinant haplotypes increase the odds of AMD by 1.85-fold (p = 3.52×10(-9)) and by 15.57-fold (P = 0.007), respectively. We identified a 32-kb region downstream of Y402H (rs1061170), shared by all three risk haplotypes, suggesting that this region may be critical for AMD development. Further analysis showed that two SNPs within the 32 kb block, rs1329428 and rs203687, optimally explain disease association. rs1329428 resides in 20 kb unique sequence block, but rs203687 resides in a 12 kb block that is 89% similar to a noncoding region contained in ΔCNP148. We conclude that causal variation in this region potentially encompasses both regulatory effects at single markers and copy number.

Genome scan of M. tuberculosis infection and disease in Ugandans.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is an enduring public health problem globally, particularly in sub-Saharan Africa. Several studies have suggested a role for host genetic susceptibility in increased risk for TB but results across studies have been equivocal. As part of a household contact study of Mtb infection and disease in Kampala, Uganda, we have taken a unique approach to the study of genetic susceptibility to TB, by studying three phenotypes. First, we analyzed culture confirmed TB disease compared to latent Mtb infection (LTBI) or lack of Mtb infection. Second, we analyzed resistance to Mtb infection in the face of continuous exposure, defined by a persistently negative tuberculin skin test (PTST-); this outcome was contrasted to LTBI. Third, we analyzed an intermediate phenotype, tumor necrosis factor-alpha (TNFalpha) expression in response to soluble Mtb ligands enriched with molecules secreted from Mtb (culture filtrate). We conducted a full microsatellite genome scan, using genotypes generated by the Center for Medical Genetics at Marshfield. Multipoint model-free linkage analysis was conducted using an extension of the Haseman-Elston regression model that includes half sibling pairs, and HIV status was included as a covariate in the model. The analysis included 803 individuals from 193 pedigrees, comprising 258 full sibling pairs and 175 half sibling pairs. Suggestive linkage (p<10(-3)) was observed on chromosomes 2q21-2q24 and 5p13-5q22 for PTST-, and on chromosome 7p22-7p21 for TB; these findings for PTST- are novel and the chromosome 7 region contains the IL6 gene. In addition, we replicated recent linkage findings on chromosome 20q13 for TB (p = 0.002). We also observed linkage at the nominal alpha = 0.05 threshold to a number of promising candidate genes, SLC11A1 (PTST- p = 0.02), IL-1 complex (TB p = 0.01), IL12BR2 (TNFalpha p = 0.006), IL12A (TB p = 0.02) and IFNGR2 (TNFalpha p = 0.002). These results confirm not only that genetic factors influence the interaction between humans and Mtb but more importantly that they differ according to the outcome of that interaction: exposure but no infection, infection without progression to disease, or progression of infection to disease. Many of the genetic factors for each of these stages are part of the innate immune system.

Complement factor H and hemicentin-1 in age-related macular degeneration and renal phenotypes.

In this study, we investigated the associations of complement factor H (CFH) and hemicentin-1 (HMCN1) with age-related macular degeneration (AMD) and renal function. Three scales, measuring the course of AMD and drusen development, were examined in two samples: the Family Age-Related Macular degeneration Study (FARMS), consisting of families ascertained through a single individual with severe AMD, and an unascertained population-based family cohort, the Beaver Dam Eye Study (BDES), which was also used to assess longitudinal changes in AMD and associations with renal function. Associations were performed by a regression accounting for known risk factors as well as familial and sibling effects. Strong evidence of the association of rs1061170 (Y402H) variation with AMD was confirmed (P = 9.15 x 10(-5) in BDES, P = 0.016 in FARMS). This association was observed in multiple AMD scales, suggesting that its role is not phenotype-specific. Polymorphisms in both CFH and HMCN1 appeared to influence the longitudinal rate of change of AMD. The rs1061170 polymorphism was also associated with a reduction in estimated glomerular filtration rate (eGFR) (P = 0.046). Another CFH polymorphism, rs800292, was similarly associated with eGFR [beta = -0.90 (P = 0.022)]. Associations between rs743137 (P = 0.05) and rs680638 (P = 0.022) in HMCN1 with calculated creatinine clearance progression were also observed. Both genes appear to play a role in both AMD and renal pathophysiology. These findings support evidence for common pathways influencing ocular and renal function and suggest that further work is required on their common determinants.

Linkage and association analysis of candidate genes for TB and TNFalpha cytokine expression: evidence for association with IFNGR1, IL-10, and TNF receptor 1 genes.

Tuberculosis (TB) is a growing public health threat globally and several studies suggest a role of host genetic susceptibility in increased TB risk. As part of a household contact study in Kampala, Uganda, we have taken a unique approach to the study of genetic susceptibility to TB by developing an intermediate phenotype model for TB susceptibility, analyzing levels of tumor necrosis factor-alpha (TNFalpha) in response to culture filtrate as the phenotype. In the present study, we analyzed candidate genes related to TNFalpha regulation and found that interleukin (IL)-10, interferon-gamma receptor 1 (IFNGR1), and TNFalpha receptor 1 (TNFR1) genes were linked and associated to both TB and TNFalpha. We also show that these associations are with progression to active disease and not susceptibility to latent infection. This is the first report of an association between TB and TNFR1 in a human population and our findings for IL-10 and IFNGR1 replicate previous findings. By observing pleiotropic effects on both phenotypes, we show construct validity of our intermediate phenotype model, which enables the characterization of the role of these genetic polymorphisms on TB pathogenesis. This study further illustrates the utility of such a model for disentangling complex traits.

Lymphangiogenesis by blind-ended vessel sprouting is concurrent with hemangiogenesis by vascular splitting.

Development of effective vascular therapies requires the understanding of all modes of vessel formation involved in angiogenesis (here termed "hemangiogenesis") and lymphangiogenesis. Two major modes of vessel morphogenesis include sprouting of a new vessel from a preexisting vessel and splitting of a preexisting parent vessel into two offspring vessels. In the quail chorioallantoic membrane (CAM) during mid-development (embryonic days E6-E9), lymphangiogenesis progressed primarily via blind-ended vessel sprouting. Isolated lymphatic endothelial progenitor cells were recruited to the tips of growing vessels. During concurrent hemangiogenesis, parent blood vessels expanded from the capillary network and split into offspring vessels, accompanied by transient capillary expression of alpha smooth muscle actin (alphaSMA) and recruitment of polarized mural progenitor cells. Lymphatics and blood vessels were identified by confocal/fluorescence microscopy of vascular endothelial growth factor (VEGF) receptor VEGFR-2, alphaSMA (specific to CAM blood vessels), homeobox transcription factor Prox1 (specific to lymphatics), and the quail hematopoetic marker, QH-1. VEGFR-2 was expressed intensely in isolated cells and lymphatics, and moderately in blood vessels. Prox1 was absent from isolated progenitor cells prior to lymphatic recruitment. Exogenous vascular endothelial growth factor-165 (VEGF165) increased blood vessel density and anastomotic frequency without changing endogenous modes of vascular/lymphatic vessel formation or marker expression. Although VEGF165 is a key cellular regulator of hemangiogenesis and vasculogenesis, the role of VEGF165 in lymphangiogenesis is less clear. Interestingly, VEGF165 increased lymphatic vessel diameter and density as measured by novel Euclidean distance mapping, and the antimaturational dissociation of lymphatics from blood vessels, accompanied by lymphatic reassociation into homogeneous networks.