The Peptidoglycan Recognition Protein 1 confers immune evasive properties on pancreatic cancer stem cells.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) has limited therapeutic options, particularly with immune checkpoint inhibitors. Highly chemoresistant 'stem-like' cells, known as cancer stem cells (CSCs), are implicated in PDAC aggressiveness. Thus, comprehending how this subset of cells evades the immune system is crucial for advancing novel therapies. DESIGN: We used the KPC mouse model (LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre) and primary tumour cell lines to investigate putative CSC populations. Transcriptomic analyses were conducted to pinpoint new genes involved in immune evasion. Overexpressing and knockout cell lines were established with lentiviral vectors. Subsequent in vitro coculture assays, in vivo mouse and zebrafish tumorigenesis studies, and in silico database approaches were performed. RESULTS: Using the KPC mouse model, we functionally confirmed a population of cells marked by EpCAM, Sca-1 and CD133 as authentic CSCs and investigated their transcriptional profile. Immune evasion signatures/genes, notably the gene peptidoglycan recognition protein 1 (PGLYRP1), were significantly overexpressed in these CSCs. Modulating PGLYRP1 impacted CSC immune evasion, affecting their resistance to macrophage-mediated and T-cell-mediated killing and their tumourigenesis in immunocompetent mice. Mechanistically, tumour necrosis factor alpha (TNFα)-regulated PGLYRP1 expression interferes with the immune tumour microenvironment (TME) landscape, promoting myeloid cell-derived immunosuppression and activated T-cell death. Importantly, these findings were not only replicated in human models, but clinically, secreted PGLYRP1 levels were significantly elevated in patients with PDAC. CONCLUSIONS: This study establishes PGLYRP1 as a novel CSC-associated marker crucial for immune evasion, particularly against macrophage phagocytosis and T-cell killing, presenting it as a promising target for PDAC immunotherapy.

Associations Between Extreme Temperatures and Cardiovascular Cause-Specific Mortality: Results From 27 Countries.

BACKGROUND: Cardiovascular disease is the leading cause of death worldwide. Existing studies on the association between temperatures and cardiovascular deaths have been limited in geographic zones and have generally considered associations with total cardiovascular deaths rather than cause-specific cardiovascular deaths. METHODS: We used unified data collection protocols within the Multi-Country Multi-City Collaborative Network to assemble a database of daily counts of specific cardiovascular causes of death from 567 cities in 27 countries across 5 continents in overlapping periods ranging from 1979 to 2019. City-specific daily ambient temperatures were obtained from weather stations and climate reanalysis models. To investigate cardiovascular mortality associations with extreme hot and cold temperatures, we fit case-crossover models in each city and then used a mixed-effects meta-analytic framework to pool individual city estimates. Extreme temperature percentiles were compared with the minimum mortality temperature in each location. Excess deaths were calculated for a range of extreme temperature days. RESULTS: The analyses included deaths from any cardiovascular cause (32 154 935), ischemic heart disease (11 745 880), stroke (9 351 312), heart failure (3 673 723), and arrhythmia (670 859). At extreme temperature percentiles, heat (99th percentile) and cold (1st percentile) were associated with higher risk of dying from any cardiovascular cause, ischemic heart disease, stroke, and heart failure as compared to the minimum mortality temperature, which is the temperature associated with least mortality. Across a range of extreme temperatures, hot days (above 97.5th percentile) and cold days (below 2.5th percentile) accounted for 2.2 (95% empirical CI [eCI], 2.1-2.3) and 9.1 (95% eCI, 8.9-9.2) excess deaths for every 1000 cardiovascular deaths, respectively. Heart failure was associated with the highest excess deaths proportion from extreme hot and cold days with 2.6 (95% eCI, 2.4-2.8) and 12.8 (95% eCI, 12.2-13.1) for every 1000 heart failure deaths, respectively. CONCLUSIONS: Across a large, multinational sample, exposure to extreme hot and cold temperatures was associated with a greater risk of mortality from multiple common cardiovascular conditions. The intersections between extreme temperatures and cardiovascular health need to be thoroughly characterized in the present day-and especially under a changing climate.

Atopy and Response to Omalizumab Treatment in Chronic Spontaneous Urticaria.

INTRODUCTION: The possible influence of sensitization to aeroallergens on omalizumab response in chronic spontaneous urticaria (CSU) has been insufficiently investigated. This study's aim was to investigate atopy's influence on omalizumab response in CSU patients. METHOD: Retrospective study of CSU patients followed at a Portuguese Urticaria Center of Reference and Excellence (UCARE), treated with omalizumab for at least 6 months, between 2015 and 2022. At T0, all patients underwent quantification of specific immunoglobulin E (IgE) for total extract of most prevalent aeroallergens (ImmunoCAP Thermo Fisher Scientific®) and were divided in 2 groups, according to their response to omalizumab during the first 16 weeks of treatment: responders (R) (UAS7 <7) versus partial (PR) (UAS7 = 7-15) and nonresponders (UAS7 >15). R were further classified as fast (FR) (4-6 weeks) and slow responders (SR) (12-16 weeks). Total serum IgE, circulating eosinophil, and basophil counts were compared between groups at T0. p < 0.05 was considered statistically significant (SPSS® v25.0). RESULTS: Ninety-six patients (80% female) were studied, mean age 49 ± 14 years. Median CSU duration pre-omalizumab was 3 (0.6-20) years and mean omalizumab treatment duration was 3.7 ± 2.3 years. 38 (40%) had concomitant chronic inducible urticaria and 72 (75%) angioedema. Based on positive results of the specific IgE assay, 35 patients (36%) were considered atopic. Most patients (n = 30; 86%) were sensitized to house dust mites (HDM) (Dermatophagoides farinae = 28, Dermatophagoides pteronyssinus = 27, Blomia tropicalis = 19, Lepidoglyphus destructor = 17), followed by pollens (n = 12; 34%) (mixture of grasses = 10, Olea europaea = 7, Parietaria officinalis = 6), epithelia (n = 9; 26%) (dog = 8, cat = 7), and fungi (Alternaria alternata = 4; 11%). Eight patients (23%) were monosensitized to HDM and 4 (11%) to pollens. No significant association was found between aeroallergen sensitization and CSU duration, concomitant chronic inducible urticaria, or angioedema. Atopic patients featured significantly higher levels of baseline total serum IgE than nonatopic (469 vs. 94 U/mL, respectively; p = 0.0009). Mean baseline counts of eosinophils and basophils were not significantly different between atopic and non-atopic, respectively: eosinophils (128 vs. 121/mm3) and basophils (26 vs. 28/mm3). Regarding response to omalizumab, most patients (58; 60%) were responders: FR - 46 (79%); SR - 12 (21%). There was no significant association between aeroallergen sensitization and omalizumab response or speed of response. CONCLUSIONS: As far as we know, this is the first study exploring the influence of atopy sensitization pattern on omalizumab response in CSU. According to our results, presence of atopy/sensitization pattern does not influence omalizumab response in CSU patients.

The association between probable post-COVID-19 condition and sleep-related parameters: a longitudinal study of non-hospitalised patients.

The long-term effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on sleep remain poorly known. We evaluated the association between probable post-COVID-19 condition and changes in sleep quality and quantity before and after SARS-CoV-2 infection in a consecutive sample of non-hospitalized adults. Individuals were identified with SARS-CoV-2 infection in 2020 at the central laboratory of a tertiary hospital in Porto and followed as outpatients. We included patients diagnosed with SARS-CoV-2 infection ≥3 months before this evaluation, with no missing data on key variables (n = 2445). Participants completed a questionnaire that included sociodemographic, clinical, and infection-related questions. We computed changes in sleep-related parameters referred to 1 month before diagnosis and 1 week before the questionnaire. Multinomial logistic regression models were fitted to compute crude and adjusted odds ratios and 95% confidence intervals (95% CIs). Compared to the pre-infection period, those with probable post-COVID-19 condition reported a greater decrease in hours of sleep, had a 2.60 (95% CI 2.02-3.34) higher adjusted odds of perceiving their sleep quality as worsened and experienced a significant increase in number of days with sleeping disturbances as defined according to multiple items. The association between post-COVID-19 condition and indicators of poor sleep health requires special attention from healthcare professionals and services. It is essential that appropriate multidisciplinary care is provided to mitigate the physical, psychological, social, and professional impact of sleeping problems in these already burdened patients.

Excess mortality in Europe coincides with peaks of COVID-19, influenza and respiratory syncytial virus (RSV), November 2023 to February 2024.

Since the end of November 2023, the European Mortality Monitoring Network (EuroMOMO) has observed excess mortality in Europe. During weeks 48 2023-6 2024, preliminary results show a substantially increased rate of 95.3 (95% CI:  91.7-98.9) excess all-cause deaths per 100,000 person-years for all ages. This excess mortality is seen in adults aged 45 years and older, and coincides with widespread presence of COVID-19, influenza and respiratory syncytial virus (RSV) observed in many European countries during the 2023/24 winter season.

Enhanced Sensitivity in Optical Sensors through Self-Image Theory and Graphene Oxide Coating.

This paper presents an approach to enhancing sensitivity in optical sensors by integrating self-image theory and graphene oxide coating. The sensor is specifically engineered to quantitatively assess glucose concentrations in aqueous solutions that simulate the spectrum of glucose levels typically encountered in human saliva. Prior to sensor fabrication, the theoretical self-image points were rigorously validated using Multiphysics COMSOL 6.0 software. Subsequently, the sensor was fabricated to a length corresponding to the second self-image point (29.12 mm) and coated with an 80 µm/mL graphene oxide film using the Layer-by-Layer technique. The sensor characterization in refractive index demonstrated a wavelength sensitivity of 200 ± 6 nm/RIU. Comparative evaluations of uncoated and graphene oxide-coated sensors applied to measure glucose in solutions ranging from 25 to 200 mg/dL showed an eightfold sensitivity improvement with one bilayer of Polyethyleneimine/graphene. The final graphene oxide-based sensor exhibited a sensitivity of 10.403 ± 0.004 pm/(mg/dL) and demonstrated stability with a low standard deviation of 0.46 pm/min and a maximum theoretical resolution of 1.90 mg/dL.

Stereotactic anatomy of the third ventricle.

PURPOSE: Endoscopic third ventriculostomy (ETV) is a surgical procedure that can lead to complications and requires detailed preoperative planning. This study aimed to provide a more accurate understanding of the anatomy of the third ventricle and the location of important structures to improve the safety and success of ETV. METHODS: We measured the stereotactic coordinates of six points of interest relative to a predefined stereotactic reference point in 23 cadaver brain hemi-sections, 200 normal brain magnetic resonance imaging (MRI) scans, and 24 hydrocephalic brain MRI scans. The measurements were statistically analyzed, and comparisons were made. RESULTS: We found some statistically significant differences between genders in MRIs from healthy subjects. We also found statistically significant differences between MRIs from healthy subjects and both cadaver brains and MRIs with hydrocephalus, though their magnitude is very small and not clinically relevant. Some stereotactic points were more posteriorly and inferiorly located in cadaver brains, particularly the infundibular recess and the basilar artery. It was found that all stereotactic points studied were more posteriorly located in brains with hydrocephalus. CONCLUSION: The study describes periventricular structures in cadaver brains and MRI scans from healthy and hydrocephalic subjects, which can guide neurosurgeons in planning surgical approaches to the third ventricle. Overall, the study contributes to understanding ETV and provides insights for improving its safety and efficacy. The findings also support that practicing on cadaveric brains can still provide valuable information and is valid for study and training of neurosurgeons unfamiliar with the ETV technique.

Two-Year Mortality Predictors in Fragility Fractures-A Medical Records Review Study.

PURPOSE: To evaluate two-year mortality predictors in all subtypes of fragility fractures. METHODS: Medical records review, single-center study with Portuguese patients with fragility fractures; A univariate analysis, with chi-square for categorical variables and parametric t-student and non-parametric Wilcoxon tests for continuous variables, was performed. Posteriorly, a survival analysis, with subsequent Cox regression was conducted to establish independent risk factors/ predictors of two-year mortality in fragility fractures. RESULTS: 758 patients were enrolled in the study. We found a total of 151 deaths within the first two years post-fracture. On Cox regression, older age [OR1.10 CI (1.05-1.11)], male sex [OR1.85 CI(1.24-2.75)], anemia at baseline [OR2.44 CI(1.67-3.57)], malignancy [OR4.68 CI (2.13-10.27)], and multimorbidity [OR1.78 CI(1.11-2.87)] were found as independent predictors for two-year post-fracture mortality. CONCLUSION: Our study suggests that male sex, older age, anemia, malignancy, and multimorbidity are mortality predictors in the first two years after fragility fractures, reinforcing the importance of comorbidity management in preventing or, at least, minimizing adverse outcomes following fragility fractures.

Audiovestibular Involvement in Patients With Systemic Sclerosis.

INTRODUCTION: Audiovestibular dysfunction has been reported in many autoimmune connective tissue diseases, including systemic sclerosis (SSc). OBJECTIVE: To assess the prevalence and features of audiological and vestibular disturbances in SSc patients and evaluate their relationship with disease duration, clinical features, nailfold videocapillaroscopy pattern, and immunologic profiles. METHOD: A matched case-control study was conducted in a rheumatology clinic of a second-level hospital over 24 months. All patients underwent a detailed ear, nose, and throat examination, as well as audiometric and vestibular assessments, including pure tone audiometry, speech audiometry, immittance tests, and the Video Head Impulse Test. RESULTS: Thirty-five SSc patients and 24 healthy controls were included in the study. In the SSc group, subjective hearing loss was reported by 17.1% of patients, vertigo by 14.3%, tinnitus by 11.4%, and dizziness by 5.7%. Sensorineural hearing loss was identified in 42.9% of SSc patients, significantly higher than in the control group ( p = 0.013). There was no correlation between audiological manifestations and clinical symptoms, organ involvement, immunologic characteristics, and treatment. Vestibular dysfunction was detected in 60% of SSc patients, significantly higher than the control group ( p = 0.05). A significant correlation was found between abnormal Video Head Impulse Test and the presence of anti-RNA polymerase III and anti-Th/To antibodies ( p = 0.05 and p = 0.034, respectively). CONCLUSION: Our study revealed an increased prevalence of sensorineural hearing loss and vestibulopathy in SSc patients.

Phenotype of BTK-lacking myeloid cells during prolonged COVID-19 and upon convalescent plasma.

XLA patient with 7-month course of COVID-19 with persistent plasma SARS-CoV-2 load revealed a sustained non-inflammatory profile of myeloid cells in association with contained severity of disease, arguing in favor of the use of BTK inhibitors in SARS-COV-2 infection.

Language performance as a prognostic factor for developing Alzheimer's clinical syndrome and mild cognitive impairment: Results from the population-based HELIAD cohort.

OBJECTIVES: There is limited research on the prognostic value of language tasks regarding mild cognitive impairment (MCI) and Alzheimer's clinical syndrome (ACS) development in the cognitively normal (CN) elderly, as well as MCI to ACS conversion. METHODS: Participants were drawn from the population-based Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) cohort. Language performance was evaluated via verbal fluency [semantic (SVF) and phonemic (PVF)], confrontation naming [Boston Naming Test short form (BNTsf)], verbal comprehension, and repetition tasks. An additional language index was estimated using both verbal fluency tasks: SVF-PVF discrepancy. Cox proportional hazards analyses adjusted for important sociodemographic parameters (age, sex, education, main occupation, and socioeconomic status) and global cognitive status [Mini Mental State Examination score (MMSE)] were performed. RESULTS: A total of 959 CN and 118 MCI older (>64 years) individuals had follow-up investigations after a mean of ∼3 years. Regarding the CN group, each standard deviation increase in the composite language score reduced the risk of ACS and MCI by 49% (8-72%) and 32% (8-50%), respectively; better SVF and BNTsf performance were also independently associated with reduced risk of ACS and MCI. On the other hand, using the smaller MCI participant set, no language measurement was related to the risk of MCI to ACS conversion. CONCLUSIONS: Impaired language performance is associated with elevated risk of ACS and MCI development. Better SVF and BNTsf performance are associated with reduced risk of ACS and MCI in CN individuals, independent of age, sex, education, main occupation, socioeconomic status, and MMSE scores at baseline.

Coarse Particulate Air Pollution and Daily Mortality: A Global Study in 205 Cities.

Rationale: The associations between ambient coarse particulate matter (PM2.5-10) and daily mortality are not fully understood on a global scale. Objectives: To evaluate the short-term associations between PM2.5-10 and total, cardiovascular, and respiratory mortality across multiple countries/regions worldwide. Methods: We collected daily mortality (total, cardiovascular, and respiratory) and air pollution data from 205 cities in 20 countries/regions. Concentrations of PM2.5-10 were computed as the difference between inhalable and fine PM. A two-stage time-series analytic approach was applied, with overdispersed generalized linear models and multilevel meta-analysis. We fitted two-pollutant models to test the independent effect of PM2.5-10 from copollutants (fine PM, nitrogen dioxide, sulfur dioxide, ozone, and carbon monoxide). Exposure-response relationship curves were pooled, and regional analyses were conducted. Measurements and Main Results: A 10 µg/m3 increase in PM2.5-10 concentration on lag 0-1 day was associated with increments of 0.51% (95% confidence interval [CI], 0.18%-0.84%), 0.43% (95% CI, 0.15%-0.71%), and 0.41% (95% CI, 0.06%-0.77%) in total, cardiovascular, and respiratory mortality, respectively. The associations varied by country and region. These associations were robust to adjustment by all copollutants in two-pollutant models, especially for PM2.5. The exposure-response curves for total, cardiovascular, and respiratory mortality were positive, with steeper slopes at lower exposure ranges and without discernible thresholds. Conclusions: This study provides novel global evidence on the robust and independent associations between short-term exposure to ambient PM2.5-10 and total, cardiovascular, and respiratory mortality, suggesting the need to establish a unique guideline or regulatory limit for daily concentrations of PM2.5-10.

Quality of Life of Mothers and Fathers 4 to 6 Months After Birth: The Effect of a Very Preterm Delivery.

OBJECTIVES: The sparse literature on the effect of a preterm delivery on parents' quality of life (QoL) yields inconsistent results, restricting their analysis to mothers. The present study aimed to assess the effect of a very preterm delivery on parents' gender-specific perception of QoL, 4 to 6 months after birth. METHODS: A total of 117 parents of very preterm infants hospitalized at birth in a level III Neonatal Intensive Care Unit, and 214 parents of never hospitalized full-term infants born in a public maternity, both located in the North of Portugal, participated in the study, 4 to 6 months after delivery (November 2013-June 2015). The Portuguese version of the World Health Organization Quality of Life - BREF Inventory was applied and scores were transformed to reflect a 0 to 100 scale. RESULTS: The mean [standard deviation (SD)] of overall QoL ranged between 72.1 (13.3) among mothers of full-term infants and 74.6 (12.5) among mothers of very preterm infants. The perception of QoL was not significantly different among parents of very preterm and full-term infants, according to gender. The highest scores were observed in the psychological and physical dimensions, for both mothers and fathers. CONCLUSIONS FOR PRACTICE: The lack of differences on the perception of QoL among mothers and fathers of very preterm and full-term infants, highlights the need to deeply understand and explore the influence of accommodation mechanisms, the extended family/community and health policies on parental QoL trajectories.

Fiber Loop Mirror Based on Optical Fiber Circulator for Sensing Applications.

In this paper, a different Fiber Loop Mirror (FLM) configuration with two circulators is presented. This configuration is demonstrated and characterized for sensing applications. This new design concept was used for strain and torsion discrimination. For strain measurement, the interference fringe displacement has a sensitivity of (0.576 ± 0.009) pm‧µÎµ-1. When the FFT (Fast Fourier Transformer) is calculated and the frequency shift and signal amplitude are monitored, the sensitivities are (-2.1 ± 0.3) × 10-4 nm-1 µÎµ-1 and (4.9 ± 0.3) × 10-7 µÎµ-1, respectively. For the characterization in torsion, an FFT peaks variation of (-2.177 ± 0.002) × 10-12 nm-1/° and an amplitude variation of (1.02 ± 0.06) × 10-3/° are achieved. This configuration allows the use of a wide range of fiber lengths and with different refractive indices for controlling the free spectral range (FSR) and achieving refractive index differences, i.e., birefringence, higher than 10-2, which is essential for the development of high sensitivity physical parameter sensors, such as operating on the Vernier effect. Furthermore, this FLM configuration allows the system to be balanced, which is not possible with traditional FLMs.

Plerixafor for the Treatment of WHIM Syndrome.

WHIM syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis), a primary immunodeficiency disorder involving panleukopenia, is caused by autosomal dominant gain-of-function mutations in CXC chemokine receptor 4 (CXCR4). Myelokathexis is neutropenia caused by neutrophil retention in bone marrow. Patients with WHIM syndrome are often treated with granulocyte colony-stimulating factor (G-CSF), which can increase neutrophil counts but does not affect cytopenias other than neutropenia. In this investigator-initiated, open-label study, three severely affected patients with WHIM syndrome who could not receive G-CSF were treated with low-dose plerixafor, a CXCR4 antagonist, for 19 to 52 months. Myelofibrosis, panleukopenia, anemia, and thrombocytopenia were ameliorated, the wart burden and frequency of infection declined, human papillomavirus-associated oropharyngeal squamous-cell carcinoma stabilized, and quality of life improved markedly. Adverse events were mainly infections attributable to the underlying immunodeficiency. One patient died from complications of elective reconstructive surgery. (Funded by the National Institutes of Health.).

Medical ethics when moving towards non-anonymous gamete donation: the views of donors and recipients.

Drawing on the views of donors and recipients about anonymity in a country that is experiencing a transition towards non-anonymous gamete donation mandated by the Constitutional Court, we explore how the intersection between rights-based approaches and an empirical framework enhances recommendations for ethical policy and healthcare. Between July 2017 and April 2018, 69 donors and 147 recipients, recruited at the Portuguese Public Bank of Gametes, participated in this cross-sectional study. Position towards anonymity was assessed through an open-ended question in a self-report questionnaire, which was subject to content analysis. Preference for an anonymous donation regime was mentioned by 82.6% of donors and 89.8% of recipients; and all those with children. Instead of the rights-based reasoning used by the Constitutional Court, donors highlighted concerns over future relationships and recipients focused on socioethical values linked with the safeguard of safety, privacy and confidentiality. The remaining participants advocated the choice between anonymity or non-anonymity (double-track policy), invoking respect for their autonomy. The complex, diverse ethical views and reasoning of donors and recipients expand a traditionally dichotomous discussion. Their perspectives challenge the transition towards non-anonymity and international guidelines, raising awareness to the need for their involvement in the design of policies to enable choice according to their values and preferences, and of psychosocial counselling responsive to their socioethical concerns and sensitive to their parental status. Empirical frameworks complement rights-based approaches to uphold justice, fairness and equal respect, and to incorporate utility, beneficence and non-maleficence in policymaking and healthcare in the transition towards non-anonymity.

Heat-related mortality amplified during the COVID-19 pandemic.

Excess mortality not directly related to the virus has been shown to have increased during the COVID-19 pandemic. However, changes in heat-related mortality during the pandemic have not been addressed in detail. Here, we performed an observational study crossing daily mortality data collected in Portugal (SICO/DGS) with high-resolution temperature series (ERA5/ECMWF), characterizing their relation in the pre-pandemic, and how it aggravated during 2020. The combined result of COVID-19 and extreme temperatures caused the largest annual mortality burden in recent decades (~ 12 000 excess deaths [~ 11% above baseline]). COVID-19 caused the largest fraction of excess mortality during March to May (62%) and from October onwards (85%). During summer, its direct impact was residual, and deaths not reported as COVID-19 dominated excess mortality (553 versus 3 968). A prolonged hot spell led mortality to the upper tertile, reaching its peak in mid-July (+ 45% deaths/day). The lethality ratio (+ 14 deaths per cumulated ºC) was higher than that observed in recent heatwaves. We used a statistical model to estimate expected deaths due to cold/heat, indicating an amplification of at least 50% in heat-related deaths during 2020 compared to pre-pandemic years. Our findings suggest mortality during 2020 has been indirectly amplified by the COVID-19 pandemic, due to the disruption of healthcare systems and fear of population in attending healthcare facilities (expressed in emergency room admissions decreases). While lockdown measures and healthcare systems reorganization prevented deaths directly related to the virus, a significant burden due to other causes represents a strong secondary impact. This was particularly relevant during summer hot spells, when the lethality ratio reached magnitudes not experienced since the 2003 heatwaves. This severe amplification of heat-related mortality during 2020 stresses the need to resume normal healthcare services and public health awareness.

Impact of stringent non-pharmaceutical interventions applied during the second and third COVID-19 epidemic waves in Portugal, 9 November 2020 to 10 February 2021: an ecological study.

BackgroundNon-pharmaceutical interventions (NPIs) were implemented worldwide to control the spread of SARS-CoV-2.AimTo evaluate the impact of tiered NPIs and a nationwide lockdown on reduction of COVID-19 incidence during the second and third epidemic waves in Portugal.MethodsSurveillance data on laboratory-confirmed COVID-19 cases were used to conduct an interrupted time series analysis to estimate changes in daily incidence during a second wave tiered NPI period (9 November-18 December 2020), and a third wave lockdown period without (15-21 January 2021) and with school closure (22 January-10 February 2021).ResultsSignificant changes in trends were observed for the overall incidence rate; declining trends were observed for tiered NPIs (-1.9% per day; incidence rate ratio (IRR): 0.981; 95% confidence interval (CI): 0.973-0.989) and a lockdown period without (-3.4% per day; IRR: 0.966; 95% CI: 0.935-0.998) and with school closure (-10.3% per day, IRR: 0.897; 95% CI: 0.846-0.951). Absolute effects associated with tiered NPIs and a lockdown on a subsequent 14-day period yielded 137 cases and 437 cases per 100,000 population potentially averted, respectively.ConclusionOur results indicate that tiered NPIs implemented during the second wave caused a decline in COVID-19 incidence, although modest. Moreover, a third wave lockdown without school closure was effective in reducing COVID-19 incidence, but the addition of school closure provided the strongest effect. These findings emphasise the importance of early and assertive decision-making to control the pandemic.

Gamete and embryo donation for research: what might shape the willingness to donate among gamete donors and recipients?

PURPOSE: Research using gametes and embryos donated by reproductive and third-party donors contributed to substantial, albeit contentious achievements. The views of gamete donors and recipients on donation for research and the underpinning role of attitudes towards research have been seldom explored and are yet to be incorporated into ethical, legal, and regulatory landscapes. From a cultural standpoint, this study adapts and explores psychometric properties of the Portuguese version of the Research Attitudes Questionnaire (RAQ), and analyzes the willingness of gamete donors and recipients to donate gametes and embryos for research and its association with sociodemographic, reproductive characteristics, and attitudes towards research. METHODS: Between July 2017 and June 2018, 71 donors and 165 recipients completed a self-administered questionnaire at the Portuguese Public Bank of Gametes. Willingness to donate and attitudes towards research were measured with a 5-point Likert scale. RAQ psychometric characteristics were explored. RESULTS: Two RAQ components were identified: "trustworthiness of research" and "critical perspective". Most participants were willing to donate gametes and embryos: donors more willing to donate gametes and male recipients more willing to donate gametes and embryos. Higher RAQ scores, indicating a more positive attitude towards research, were observed on the component "trustworthiness of research" among those willing to donate gametes and embryos and on the component "critical perspective" among those willing to donate embryos. CONCLUSION: These findings help foster inclusivity, diversity, and responsiveness of research and call for upstream engagement of male and female gamete donors and recipients, promoting a trustworthy, anticipatory, democratic, and people-centered approach to policies, regulations, and practices in human gamete and embryo research.

Concerns and coping mechanisms during the first national COVID-19 lockdown: an online prospective study in Portugal.

OBJECTIVES: The aim of this study was to explore concerns and coping mechanisms during the first national COVID-19 lockdown in Portugal. The general population provided statements via an open comment box as part of an online prospective study. STUDY DESIGN: This was an Internet-based open cohort study. METHODS: Individuals aged ≥16 years were eligible to participate in this study. Inductive content analysis was performed on completed questionnaires submitted between 23 and 29 March 2020 and 27 April and 3 May 2020 (corresponding with the early and late phases of the first national lockdown, respectively). RESULTS: Data suggest the prominence of behavioural and emotional responses to COVID-19; namely, self-compliance with measures promoted by the government; adopting practices of self-care and supporting/protecting others; and enacting hope (both currently and for the future). Concerns were related to the perception of vulnerabilities for oneself, family and others and to challenging situations presenting in society (e.g. physical and mental health, academic/professional careers, income, social inequality, potential discrimination and stigmatisation, inconsistent information and negative approach to the news), coupled with criticism, scepticism or doubts about government policy and performance of the healthcare system. Expressions of fear and worry and non-compliance with mitigation measures by others (e.g. close relatives, employees and general population) emerged as additional concerns. CONCLUSIONS: Continuous assessment of behavioural and emotional responses to the COVID-19 pandemic is needed to support effective communication and public health policies that are sensitive to the concerns, motivations and expectations of the population. Awareness of changing public opinions enables governments to continue to effectively mobilise the population to take recommended actions to reduce the transmission of COVID-19.