Duration of face mask exposure matters: evidence from Swiss and Brazilian kindergartners' ability to recognise emotions.

Wearing facial masks became a common practice worldwide during the COVID-19 pandemic. This study investigated (1) whether facial masks that cover adult faces affect 4- to 6-year-old children's recognition of emotions in those faces and (2) whether the duration of children's exposure to masks is associated with emotion recognition. We tested children from Switzerland (N = 38) and Brazil (N = 41). Brazil represented longer mask exposure due to a stricter mandate during COVID-19. Children had to choose a face displaying a specific emotion (happy, angry, or sad) when the face wore either no cover, a facial mask, or sunglasses. The longer hours of mask exposure were associated with better emotion recognition. Controlling for the hours of exposure, children were less likely to recognise emotions in partially hideen faces. Moreover, Brazilian children were more accurate in recognising happy faces than Swiss children. Overall, facial masks may negatively impact children's emotion recognition. However, prolonged exposure appears to buffer the lack of facial cues from the nose and mouth. In conclusion, restricting facial cues due to masks may impair kindergarten children's emotion recognition in the short run. However, it may facilitate their broader reading of facial emotional cues in the long run.

Unmet needs in mental healthcare for women with clinically significant symptoms of perinatal depression and/or anxiety during the COVID-19 pandemic.

OBJECTIVE/BACKGROUND: Unmet needs in perinatal mental healthcare are an important public health issue particularly in the context of a stressful life event such as the COVID-19 pandemic but data on the extent of this problem are needed. AIM: The aim of this study is to determine the (1) proportion of women with clinically significant symptoms of perinatal depression, anxiety or comorbid symptoms of depression and anxiety, receiving mental healthcare overall and by country and (2) factors associated with receiving mental healthcare. METHOD: Women in the perinatal period (pregnancy or up to 6 months postpartum) participating in the Riseup-PPD-COVID-19 cross-sectional study, reported on sociodemographic, social support health-related factors, and COVID-19 related factors, and on symptoms of depression (Edinburgh Postnatal Depression Scale [EPDS]) and anxiety (Generalised Anxiety Disorder [GAD-7]) using self-report questionnaires. Clinically significant symptoms were defined as EPDS ≥ 13 for depression and GAD-7 ≥ 10 for anxiety. Mental healthcare was defined as self-reported current mental health treatment. RESULTS: Of the 11 809 participants from 12 countries included in the analysis, 4 379 (37.1%) reported clinically significant symptoms of depression (n = 1 228; 10.4%; EPDS ≥ 13 and GAD-7 ⟨ 10), anxiety (n = 848; 7.2%; GAD-7 ≥ 10 and EPDS ⟨ 13) or comorbid symptoms of depression and anxiety (n = 2 303; 19.5%; EPDS ≥ 13 and GAD-7 ≥ 10). Most women with clinically significant symptoms of depression, anxiety, or comorbid symptoms of depression and anxiety were not receiving mental healthcare (89.0%). Variation in the proportion of women with clinically significant symptoms of depression and/or anxiety reporting mental healthcare was high (4.7% in Turkey to 21.6% in Brazil). Women in the postpartum (vs. pregnancy) were less likely (OR 0.72; 95% CI 0.59-0.88), whereas women with previous mental health problems (vs. no previous mental health problems) (OR 5.56; 95% CI 4.41-7.01), were more likely to receive mental healthcare. CONCLUSION: There are high unmet needs in mental healthcare for women with clinically significant symptoms of perinatal depression and/or anxiety across countries during the COVID-19 pandemic. Studies beyond the COVID-19 pandemic and covering the whole range of mental health problems in the perinatal period are warranted to understand the gaps in perinatal mental healthcare.

The effect of limited healthcare access on poor outcomes among hospitalized COVID-19 patients in Honduras: A single center cohort study.

Background: The COVID-19 pandemic has had a severe impact on the Latin American subcontinent, particularly in areas with limited hospital resources and a restricted Intensive Care Unit (ICU) capacity. This study aimed to provide a comprehensive description of the clinical characteristics, outcomes, and factors associated with survival of COVID-19 hospitalized patients in Honduras. Research question: What were the characteristics and outcomes of COVID-19 patients in a large referral center in Honduras? Study design and methods: This study employed a retrospective cohort design conducted in a single center in San Pedro Sula, Honduras, between October 2020 to March 2021. All hospitalized cases of confirmed COVID-19 during this timeframe were included in the analysis. Univariable and multivariable survival analysis were performed using Kaplan-Meier curves and Cox proportional hazards model aiming to identify factors associated with decreased 30 day in-hospital survival, using a priori-selected factors. Results: A total of 929 confirmed cases were identified in this cohort, with males accounting for 55.4 % of cases. The case fatality rate among the hospitalized patients was found to be 50.1 % corresponding to 466 deaths. Patients with comorbidities such as hypertension, diabetes, obesity, chronic kidney disease, chronic obstructive pulmonary disease and cardiovascular disease had a higher likelihood of mortality. Additionally, non-survivors had a significantly longer time from illness onset to hospital admission compared to survivors (8.2 days vs 4.7 days). Among the cohort, 306 patients (32.9 %) met criteria for ICU admission. However, due to limited capacity, only 60 patients (19·6 %) were admitted to the ICU. Importantly, patients that were unable to receive level-appropriate care had lower likelihood of survival compared to those who received level-appropriate care (hazard ratio: 1.84). Interpretation: This study represents, the largest investigation of in-hospital COVID-19 cases in Honduras and Central America. The findings highlight a substantial case fatality rate among hospitalized patients. In this study, patients who couldn't receive level-appropriate care (ICU admission) had a significantly lower likelihood of survival when compared to those who did. These results underscore the significant impact of healthcare access during the pandemic, particularly in low- and middle-income countries.

A New Set of in Silico Tools to Support the Interpretation of ATM Missense Variants Using Graphical Analysis.

Establishing the pathogenic nature of variants in ATM, a gene associated with breast cancer and other hereditary cancers, is crucial for providing patients with adequate care. Unfortunately, achieving good variant classification is still difficult. To address this challenge, we extended the range of in silico tools with a series of graphical tools devised for the analysis of computational evidence by health care professionals. We propose a family of fast and easy-to-use graphical representations in which the impact of a variant is considered relative to other pathogenic and benign variants. To illustrate their value, the representations are applied to three problems in variant interpretation. The assessment of computational pathogenicity predictions showed that the graphics provide an intuitive view of prediction reliability, complementing and extending conventional numerical reliability indexes. When applied to variant of unknown significance populations, the representations shed light on the nature of these variants and can be used to prioritize variants of unknown significance for further studies. In a third application, the graphics were used to compare the two versions of the ATM-adapted American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines, obtaining valuable information on their relative virtues and weaknesses. Finally, a server [ATMision (ATM missense in silico interpretation online)] was generated for users to apply these representations in their variant interpretation problems, to check the ATM-adapted guidelines' criteria for computational evidence on their variant(s) and access different sources of information.

Predictors of screen exposure among infants under 2 years of age during the COVID-19 pandemic.

Contradicting pediatric societies' recommendations, studies show that screen exposure begins at the first year of life for many children worldwide, with parental needs, educational purposes, and parental stress emerging as associated factors. However, the COVID-19 pandemic has likely worsened this scenario. This study aims to: 1) estimate the average daily screen exposure time for Brazilian infants aged 0-23 months during the COVID-19 pandemic based on caregiver report; 2) analyze the correlation between average exposure time, parental motivations for exposure, parental burnout levels and infant age; and 3) test the predictive role of parental motivations, burnout, and infant age on infant screen exposure. For this purpose, 139 parents (living in Brazil) answered online to questionnaires on infant screen exposure, parental motivations for exposure (four subscales: Parental Needs; Educational; Child's Desires/Family Routine; Behavioral Control), and parental burnout (Total score; four subscales: Emotional Exhaustion; Contrast; Feelings of Being Fed Up; Emotional Distancing). On average, infants were exposed to screens for 131 min/day. Higher scores on the four parental motivation subscales and higher parental burnout (specifically the Contrast subscale) correlated with longer exposure times. Furthermore, the motivation subscales Parental Needs and Child's Desires/family routine, the burnout subscale Contrast and infant age predicted greater screen exposure, while the burnout scale Feelings of Being Fed Up predicted less exposure. Our results suggest that infants in Brazil were exposed to substantial amounts of screen time during the pandemic. Interventions aiming to reduce screen time must consider parental motivations and parental burnout/mental health along with infant age.

Associations of height, body mass index, and weight gain with breast cancer risk in carriers of a pathogenic variant in BRCA1 or BRCA2: the BRCA1 and BRCA2 Cohort Consortium.

INTRODUCTION: Height, body mass index (BMI), and weight gain are associated with breast cancer risk in the general population. It is unclear whether these associations also exist for carriers of pathogenic variants in the BRCA1 or BRCA2 genes. PATIENTS AND METHODS: An international pooled cohort of 8091 BRCA1/2 variant carriers was used for retrospective and prospective analyses separately for premenopausal and postmenopausal women. Cox regression was used to estimate breast cancer risk associations with height, BMI, and weight change. RESULTS: In the retrospective analysis, taller height was associated with risk of premenopausal breast cancer for BRCA2 variant carriers (HR 1.20 per 10 cm increase, 95% CI 1.04-1.38). Higher young-adult BMI was associated with lower premenopausal breast cancer risk for both BRCA1 (HR 0.75 per 5 kg/m2, 95% CI 0.66-0.84) and BRCA2 (HR 0.76, 95% CI 0.65-0.89) variant carriers in the retrospective analysis, with consistent, though not statistically significant, findings from the prospective analysis. In the prospective analysis, higher BMI and adult weight gain were associated with higher postmenopausal breast cancer risk for BRCA1 carriers (HR 1.20 per 5 kg/m2, 95% CI 1.02-1.42; and HR 1.10 per 5 kg weight gain, 95% CI 1.01-1.19, respectively). CONCLUSION: Anthropometric measures are associated with breast cancer risk for BRCA1 and BRCA2 variant carriers, with relative risk estimates that are generally consistent with those for women from the general population.

The multifaceted genomic history of Ashaninka from Amazonian Peru.

Despite its crucial location, the western side of Amazonia between the Andes and the source(s) of the Amazon River is still understudied from a genomic and archaeogenomic point of view, albeit possibly harboring essential information to clarify the complex genetic history of local Indigenous groups and their interactions with nearby regions,1,2,3,4,5,6,7,8 including central America and the Caribbean.9,10,11,12 Focusing on this key region, we analyzed the genome-wide profiles of 51 Ashaninka individuals from Amazonian Peru, observing an unexpected extent of genomic variation. We identified at least two Ashaninka subgroups with distinctive genomic makeups, which were differentially shaped by the degree and timing of external admixtures, especially with the Indigenous groups from the Andes and the Pacific coast. On a continental scale, Ashaninka ancestors probably derived from a south-north migration of Indigenous groups moving into the Amazonian rainforest from a southeastern area with contributions from the Southern Cone and the Atlantic coast. These ancestral populations diversified in the variegated geographic regions of interior South America, on the eastern side of the Andes, differentially interacting with surrounding coastal groups. In this complex scenario, we also revealed strict connections between the ancestors of present-day Ashaninka, who belong to the Arawakan language family,13 and those Indigenous groups that moved further north into the Caribbean, contributing to the early Ceramic (Saladoid) tradition in the islands.14,15.

Social cognition in individuals with schizophrenia, autism spectrum disorder and controls / Cognição social em indivíduos saudáveis, com esquizofrenia e com transtorno do espectro do autismo

ABSTRACT Objective: The aim of this study was to compare the social cognition profiles of male adults with ASD (n = 15), SCHZ (n = 16) and controls (n = 20). Change the second sentence of the abstract. Methods: A cross-sectional assessment of social cognition domains with emotional face perception with eye tracking was performed, and two IQ measures (Verbal IQ and Performance IQ) (Wechsler Adult Intelligence Scale), and the DSM-IV Structured Clinical Interview were applied. Results: There were no significant differences in terms of average performance in social cognition tests or eye tracking tasks between the ASD and SCHZ groups. However, both had lower performances in most cases when compared to the control group. In the social cognition tasks, individuals in the control group performed better than both clinical groups. Conclusion: Although differences were identified between individuals with ASD and SCHZ, it was not possible to determine patterns or to differentiate the clinical groups.

RESUMO Objetivo: O objetivo deste estudo foi comparar os perfis de cognição social de adultos do sexo masculino com TEA (n = 15), SCHZ (n = 16) e controles (n = 20). Métodos: Foram aplicadas uma avaliação transversal dos domínios de cognição social com percepção emocional com rastreamento ocular, duas medidas de QI (QI verbal e QI de desempenho) (Escala de Inteligência Adulta de Wechsler) e a Entrevista Clínica Estruturada DSM-IV. Resultados: Não houve diferenças significativas em termos de desempenho médio em testes de cognição social ou tarefas de rastreamento ocular entre os grupos ASD e SCHZ. No entanto, ambos tiveram desempenhos mais baixos na maioria dos casos, quando comparados ao grupo controle. Nas tarefas de cognição social, os indivíduos do grupo controle tiveram melhor desempenho do que ambos os grupos clínicos. Conclusão: Embora tenham sido identificadas diferenças entre indivíduos com TEA e SCHZ, não foi possível determinar padrões ou diferenciar os grupos clínicos.

A cross-country study on the impact of governmental responses to the COVID-19 pandemic on perinatal mental health.

This study aimed to analyse the role of governmental responses to the coronavirus disease 2019 (COVID-19) outbreak, measured by the Containment and Health Index (CHI), on symptoms of anxiety and depression during pregnancy and postpartum, while considering the countries' Inequality-adjusted Human Development Index (IHDI) and individual factors such as age, gravidity, and exposure to COVID-19. A cross-sectional study using baseline data from the Riseup-PPD-COVID-19 observational prospective international study (ClinicalTrials.gov: NCT04595123) was carried out between June and October 2020 in 12 countries (Albania, Brazil, Bulgaria, Chile, Cyprus, Greece, Israel, Malta, Portugal, Spain, Turkey, and the United Kingdom). Participants were 7645 pregnant women or mothers in the postpartum period-with an infant aged up to 6 months-who completed the Edinburgh Postnatal Depression Scale (EPDS) or the Generalised Anxiety Disorder Assessment (GAD-7) during pregnancy or the postpartum period. The overall prevalence of clinically significant depression symptoms (EPDS ≥ 13) was 30%, ranging from 20,5% in Cyprus to 44,3% in Brazil. The prevalence of clinically significant anxiety symptoms (GAD-7 ≥ 10) was 23,6% (ranging from 14,2% in Israel and Turkey to 39,5% in Brazil). Higher symptoms of anxiety or depression were observed in multigravida exposed to COVID-19 or living in countries with a higher number of deaths due to COVID-19. Furthermore, multigravida from countries with lower IHDI or CHI had higher symptoms of anxiety and depression. Perinatal mental health is context-dependent, with women from more disadvantaged countries at higher risk for poor mental health. Implementing more restrictive measures seems to be a protective factor for mental health, at least in the initial phase of the COVID-19.

Sexual dysfunction, depression, and marital dissatisfaction among Brazilian couples.

BACKGROUND: Health professionals treating sexual dysfunction and relational dissatisfaction recognize that they are multifactorial phenomena, and depression can be bidirectionally associated with both. AIM: The purpose of this study was to investigate sexual dysfunction in heterosexual couples in relation to the quality of their marital relationship and depression symptoms. METHODS: The sample consisted of 100 heterosexual couples recruited in Brazil. Both partners of each couple completed the Golombok-Rust Inventory of Sexual Satisfaction and the Golombok-Rust Inventory of Marital Satisfaction, which were translated and adapted, and the Beck Depression Inventory, which was validated for the Brazilian population. Both partners completed their questionnaires separately, and the couple's surveys were linked to preserve conjugal data for dyadic analysis. The Actor-Partner Interdependence Model was used to understand how sexual dysfunction in couples is related to depression and relationship quality among and between partners. RESULTS: Sexual dysfunction was found to be strongly associated with dissatisfaction in the relationship (husbands, ß = 0.57, P < 0.001; wives, ß = 0.60, P < 0.001), and a positive association was found between depressive symptoms and marital dissatisfaction (husbands, ß = .32, P < .001; wives ß = .40, P < .001). CLINICAL IMPLICATION: The results suggest that it is important for health professionals to be aware of the dyadic impact of struggles with both sex and the relationship and the presence of depression symptoms in patients who seek care for sexual complaints or depression and who are in a marital relationship. STRENGTHS AND LIMITATIONS: The different results found for men and women may shed light on the biopsychosocial dimensions of human sexuality. When treated as a purely physical experience, sex is myopic. In this study we demonstrated psychosocial aspects associated with gender and sexuality, and the partner's variables were found to have a greater impact on women than they did on the men. A limitation of this study is that the sample is not generalizable as it is not demographically representative of all socioeconomic groups in Brazil. Furthermore, the participants in this sample did not have clinical levels of depression, so the results cannot be extended to couples in which one or both spouses have depressive disorder. CONCLUSION: It was found that sexual dysfunction is strongly associated with the quality of the couple relationship, and that the quality of relationship plays a mediating role between depression and marital quality, especially for the women.

Saúde mental de puérperas durante a pandemia de Covid-19 no Brasil / Postpartum women mental health during the Covid-19 pandemic in Brazil / Salud mental de mujeres posparto durante la pandemia de Covid-19 en Brasil

Estudos internacionais têm reportado níveis elevados de sintomas de depressão e ansiedade em mulheres no período perinatal em resultado da atual pandemia. O presente estudo avaliou a sintomatologia de depressão e ansiedade em puérperas durante a pandemia de COVID-19 no Brasil. Participaram 625 mulheres, com idades entre 18 e 44 anos (M = 31.6; DP = 5.3), que tinham um bebê até 6 meses de idade. Foram administrados o Questionário de Transtorno de Ansiedade Generalizada (GAD-7) e a Escala de Depressão Pós-Natal de Edimburgo (EPDS). Os resultados mostraram níveis clinicamente significativos de depressão (EPDS ≥13) em 47.4% das participantes, níveis clinicamente significativos de ansiedade generalizada (GAD-7 ≥10) em 41.8% dos casos, e sintomas comórbidos em 33.1% da amostra. Registrou-se uma correlação positiva significativa entre os sintomas de depressão e ansiedade. Além disso, mais dias de vida do bebê, idade mais jovem da mãe e menor nível de escolaridade estavam associados a níveis potencialmente clínicos de sintomas. Assim, é prioritária a definição de programas de prevenção e intervenção na saúde mental perinatal durante o atual período pandêmico, com continuidade para o futuro.

International studies have reported high levels of depression and anxiety symptoms in perinatal women due to the ongoing pandemic. The present study examined symptoms of depression and anxiety in postpartum women during the COVID-19 pandemic in Brazil. Participants were 625 women, aged between 18 and 44 years (M = 31.6; SD = 5.3), who had an infant up to 6 months of age. The Generalized Anxiety Disorder Questionnaire (GAD-7) and the Edinburgh Postnatal Depression Scale (EPDS) were administered. Results showed clinically significant levels of depression (EPDS ≥13) in 47.4% of the participants, clinically significant levels of generalized anxiety (GAD-7 ≥10) in 41.8% of the cases, and comorbid symptoms in 33.1% of the participants. There was a significant positive correlation between symptoms of depression and anxiety. Furthermore, infant's older age, mother's younger age, and lower educational level were associated with potentially clinical levels of symptoms. Thus, prevention and intervention programs targeting perinatal mental health during the ongoing pandemic and beyond should be developed and prioritized.

Estudios internacionales han reportado altos niveles de síntomas de depresión y de ansiedad en mujeres em el período perinatal como consecuencia de la actual pandemia. El presente estudio examinó los síntomas de depresión y ansiedad en mujeres posparto durante la pandemia de COVID-19 en Brasil. Las participantes fueron 625 mujeres, con edades entre 18 y 44 años (M = 31.6; SD = 5.3), que tenían un hijo de hasta 6 meses de edad. Se administró el Cuestionario de Trastorno de Ansiedad Generalizada (GAD-7) y la Escala de Depresión Postnatal de Edimburgo (EPDS). Los resultados mostraron niveles clínicamente significativos de depresión (EPDS ≥13) en el 47.4 % de las participantes, niveles clínicamente significativos de ansiedad generalizada (GAD-7 ≥10) en el 41.8 % de los casos y síntomas comórbidos en el 33.1 % de las participantes. Hubo una correlación positiva significativa entre los síntomas de depresión y ansiedad. Además, más días de vida del bebé, menor edad de la madre y menor nivel educativo se asociaron con niveles potencialmente clínicos de síntomas. Por lo tanto, se debe priorizar la definición de programas de prevención e intervención dirigidos a la salud mental perinatal durante la pandemia en curso, con continuidad para el futuro.

Decomposing the Intraurban Malnutrition Gap Between Poor and Non-poor Children in Colombia : Decomposing the Intraurban Malnutrition Gap Between Poor and Non-poor Children in Colombia.

In Colombia, although it can be said that, on average children living in urban areas have better quality of life than their rural peers, it is also true that within cities, there are high levels of socioeconomic inequality. Our objective is to identify the contribution of the factors that explain the gap in stunting and excess weight between poor and non-poor children under 5 years of age in urban areas of Colombia. We use data from the 2015 National Nutritional Status Survey, and two nonlinear decomposition techniques based on the classical decomposition method developed by Blinder-Oaxaca. With a sample of 6877 observations, the results show that the intraurban gap of stunting between poor and non-poor children in urban areas is 4.8 percentage points. Its main determinants are the mother's educational level (46.5%), affiliation to the health system by the mother (19.4%), and assisted delivery in a medical institution (16.6%). For excess weight, the gap is - 2.1 percentage points, and its main determinants are the mother's educational level (39.2%) and birth attended by a physician (21.8%). This study suggests the coexistence of a double burden of malnutrition (DBM) in children under 5 years of age living in urban areas of Colombia. Stunting is associated with low-income levels while excess weight is associated with higher income levels. The identification of the main determinants of DBM and its relative importance, constitutes a contribution for public policy makers aimed at reducing socioeconomic gaps.

Association between ADHD symptoms and inhibition-related brain activity using functional near-infrared spectroscopy (fNIRS).

Attention deficit hyperactivity disorder (ADHD) is associated with deficits in inhibitory functions including interference control, inhibition of prepotent/automatic responses and suppression of already initiated responses. This study used functional near-infrared spectroscopy (fNIRS) to investigate the neural basis of these three forms of inhibition assessed by a recently developed behavioral protocol combining the Stroop-matching/stop-signal task in twenty-five young adults with inattention, impulsivity and/or hyperactivity symptoms. The severity of ADHD symptoms was measured using the Adult ADHD Self-Report Scale (ASRS). The concentration of oxygenated hemoglobin (HbO) was assessed in the dorsolateral prefrontal cortex (DLPFC), inferior frontal gyrus (IFG) and temporoparietal regions (TP) during the Stroop-matching/stop-signal task. Correlations yielded significant associations between ASRS scores and HbO concentration in frontal regions during blocks with stop-signal tasks, namely the right IFG, the left DLPFC and the left IFG. This study revealed that different types of inhibition involve unique frontal and temporoparietal activities and linked frontal dysfunction during the suppression of ongoing responses to the severity of ADHD symptoms.

Biallelic germline mutations in MAD1L1 induce a syndrome of aneuploidy with high tumor susceptibility.

Germline mutations leading to aneuploidy are rare, and their tumor-promoting properties are mostly unknown at the molecular level. We report here novel germline biallelic mutations in MAD1L1, encoding the spindle assembly checkpoint (SAC) protein MAD1, in a 36-year-old female with a dozen of neoplasias. Functional studies demonstrated lack of full-length protein and deficient SAC response, resulting in ~30 to 40% of aneuploid blood cells. Single-cell RNA analysis identified mitochondrial stress accompanied by systemic inflammation with enhanced interferon and NFκB signaling both in aneuploid and euploid cells, suggesting a non-cell autonomous response. MAD1L1 mutations resulted in specific clonal expansions of γδ T cells with chromosome 18 gains and enhanced cytotoxic profile as well as intermediate B cells with chromosome 12 gains and transcriptomic signatures characteristic of leukemia cells. These data point to MAD1L1 mutations as the cause of a new variant of mosaic variegated aneuploidy with systemic inflammation and unprecedented tumor susceptibility.

A Large Case-Control Study Performed in Spanish Population Suggests That RECQL5 Is the Only RECQ Helicase Involved in Breast Cancer Susceptibility.

Around 50% of the familial breast cancer (BC) cases are estimated to be caused by germline variants in known low-, moderate-, and high-risk susceptibility genes, while the other half is of unknown genetic origin. In the present study, we wanted to evaluate the role of the RECQ helicases, some of which have been studied in the past as candidates, with unclear results about their role in the disease. Using next-generation sequencing (NGS) technology, we analyzed the whole coding sequence of BLM, RECQL1, RECQL4, RECQL5, and WRN in almost 2000 index cases from BC Spanish families that had previously tested negative for the known BC susceptibility genes (BRCAX) and compared the results with the controls extracted from gnomAD. Our results suggest that BLM, RECQL1, RECQL4, and WRN do not play a major role in BC susceptibility. However, in the combined analysis, joining the present results with those previously reported in a series of 1334 BC Spanish patients and controls, we found a statistically significant association between Loss of Function (LoF) variants in RECQL5 and BC risk, with an OR of 2.56 (p = 0.009; 95% CI, 1.18-4.98). Our findings support our previous work and places the RECQL5 gene as a new moderate-risk BC gene.

The lifetime costs of perinatal depression and anxiety in Brazil.

BACKGROUND: Each year, an estimated 860,000 Brazilian women experience depression and anxiety perinatally. Despite well-known devastating impacts of these conditions on mothers and children, they remain neglected in low- and middle-income countries. Knowing the costs of untreated perinatal depression and anxiety can inform decision-making. METHODS: Simulation modelling is used to examine lifetime costs of perinatal depression and anxiety for a hypothetical cohort of women and their children, followed until children are aged 40 years. Costs are measured from a societal perspective, including healthcare expenditure, productivity and health-related quality of life losses; 2017 data are taken from country-specific sources. Present values are calculated using a discount rate of 3 %. RESULTS: Lifetime cost of perinatal depression and anxiety in Brazil are USD 4.86 billion or R$ 26.16 billion, including costs linked to poorer quality of life (USD 2.65 billion), productivity loss (USD 2.16 billion) and hospital care (USD 0.05 billion). When the costs associated with maternal suicide are included, total costs increase to USD 4.93 billion. LIMITATIONS: Several costs could not be included in the analysis because of a lack of data. The study is reliant of longitudinal data on associations between perinatal depression and anxiety and impacts on mothers and children. Therefore, no causality can be inferred. CONCLUSION: Our findings illustrate the economic rationale for investment in this area. This is the first study that estimates the costs of perinatal mental health problems in a low- or middle-income country setting.

Rates of depressive and anxiety symptoms in the perinatal period during the COVID-19 pandemic: Comparisons between countries and with pre-pandemic data.

BACKGROUND: The COVID-19 pandemic was a significant threat to perinatal mental health. This study examined differences in clinically significant depression, anxiety, and co-morbid symptoms among pregnant and postpartum women across several countries and compared prevalence of perinatal depression and anxiety before and during the pandemic in each participating country. METHODS: Participants were 3326 pregnant and 3939 postpartum women (up to six months postpartum) living in Brazil, Chile, Cyprus, Greece, Israel, Portugal, Spain, Turkey, and the United Kingdom. An online survey was completed between June 7th and October 31st 2020, and included the Edinburgh Postnatal Depression Scale (EPDS) and the Generalized Anxiety Disorder Screener (GAD-7). The pre-pandemic studies were identified through literature review. RESULTS: Prevalence of clinically significant depression (EPDS≥13), anxiety (GAD-7 ≥ 10), and co-morbid (EPDS≥13 and GAD-7 ≥ 10) symptoms was 26.7 %, 20 % and 15.2 %, in pregnant women, and 32.7 %, 26.6 % and 20.3 %, in postpartum women, respectively. Significant between-country differences were found in all mental health indicators in both perinatal periods. Higher levels of symptoms were observed during (versus before) the pandemic, especially among postpartum women. LIMITATIONS: Participants were mostly highly educated and cohabiting with a partner. The online nature of the survey may have limited the participation of women from vulnerable socio-economically backgrounds. CONCLUSIONS: Our findings expand previous literature on the negative impact of the COVID-19 pandemic on perinatal mental health, by highlighting that this may be influenced by country of residence. Mental health care policies and interventions should consider the unique needs of perinatal women in different parts of the world.

OGG1 Inhibition Triggers Synthetic Lethality and Enhances The Effect of PARP Inhibitor Olaparib in BRCA1-Deficient TNBC Cells.

Background: PARP1 plays a critical role in the base excision repair (BER) pathway, and PARP1 inhibition leads to specific cell death, through a synthetic lethal interaction, in the context of BRCA1/2 deficiency. To date, up to five different PARP inhibitors (PARPi), have been approved, nevertheless, the acquisition of resistance to PARPi is common and there is increasing interest in enhancing responses and expand their use to other tumour types. Methods: We hypothesized that other BER members could be additional synthetic lethal partners with mutated BRCA genes. To test this, we decided to evaluate the glycosylase OGG1 as a potential candidate, by treating BRCA1 proficient and deficient breast cancer cells with PARPi olaparib and the OGG1 inhibitor TH5478. Results: Knocking out BRCA1 in triple-negative breast cancer cell lines causes hypersensitivity to the OGG1 inhibitor TH5487. Besides, TH5487 enhances the sensitivity to the PARP inhibitor olaparib, especially in the context of BRCA1 deficiency, reflecting an additive interaction. Discussion: These results provide the first evidence that OGG1 inhibition is a promising new synthetic lethality strategy in BRCA1-deficient cells, and could lead to a new framework for the treatment of hereditary breast and ovarian cancer.