APOE3 Christchurch Heterozygosity and Autosomal Dominant Alzheimer's Disease.

BACKGROUND: Variants in APOE and PSEN1 (encoding apolipoprotein E and presenilin 1, respectively) alter the risk of Alzheimer's disease. We previously reported a delay of cognitive impairment in a person with autosomal dominant Alzheimer's disease caused by the PSEN1 E280A variant who also had two copies of the apolipoprotein E3 Christchurch variant (APOE3 Ch). Heterozygosity for the APOE3 Ch variant may influence the age at which the onset of cognitive impairment occurs. We assessed this hypothesis in a population in which the PSEN1 E280A variant is prevalent. METHODS: We analyzed data from 27 participants with one copy of the APOE3 Ch variant among 1077 carriers of the PSEN1 E280A variant in a kindred from Antioquia, Colombia, to estimate the age at the onset of cognitive impairment and dementia in this group as compared with persons without the APOE3 Ch variant. Two participants underwent brain imaging, and autopsy was performed in four participants. RESULTS: Among carriers of PSEN1 E280A who were heterozygous for the APOE3 Ch variant, the median age at the onset of cognitive impairment was 52 years (95% confidence interval [CI], 51 to 58), in contrast to a matched group of PSEN1 E280A carriers without the APOE3 Ch variant, among whom the median age at the onset was 47 years (95% CI, 47 to 49). In two participants with the APOE3 Ch and PSEN1 E280A variants who underwent brain imaging, 18F-fluorodeoxyglucose positron-emission tomographic (PET) imaging showed relatively preserved metabolic activity in areas typically involved in Alzheimer's disease. In one of these participants, who underwent 18F-flortaucipir PET imaging, tau findings were limited as compared with persons with PSEN1 E280A in whom cognitive impairment occurred at the typical age in this kindred. Four studies of autopsy material obtained from persons with the APOE3 Ch and PSEN1 E280A variants showed fewer vascular amyloid pathologic features than were seen in material obtained from persons who had the PSEN1 E280A variant but not the APOE3 Ch variant. CONCLUSIONS: Clinical data supported a delayed onset of cognitive impairment in persons who were heterozygous for the APOE3 Ch variant in a kindred with a high prevalence of autosomal dominant Alzheimer's disease. (Funded by Good Ventures and others.).

Outcomes and patterns of use of Radium-223 in metastatic castration-resistant prostate cancer.

Introduction: Radium-223 dichloride (Ra-223) is recommended as a treatment option for metastatic castration-resistant prostate cancer (mCRPC) patients with symptomatic bone metastases and no visceral disease, after docetaxel failure, or in patients who are not candidates to receive it. In this study, we aimed to ambispectively analyze overall survival (OS) and prognostic features in mCRPC in patients receiving Ra-223 as per clinical routine practice and identify the most suitable treatment sequence. Patients and methods: This study is observational, multicentric, and ambispective. Eligibility criteria included mCRPC patients treated with Ra-223, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, without visceral metastases, and no more than three cm involved lymph nodes. Results: A total of 145 patients were included; the median age was 73.97 years, and a Gleason score of more than or equal to 7 in 61 (48%) patients; 73 (81%) had previously received docetaxel. The most important benefit was reached by those patients who received Ra-223 in the second-line setting, with a median OS of 17 months (95% CI, 12-21), and by patients who received six cycles of treatment, with a median OS of 19 months (95% CI, 14-21). An alkaline phosphatase (ALP) decrease was also identified as a prognosis marker. When performing the multivariate analysis, the time to develop castration-resistant disease longer than 24 months was the most important prognostic factor to predict the evolution of the patients receiving Ra-223. Ra-223 was well tolerated, with thrombocytopenia, anemia, and diarrhea being the main adverse events. Conclusion: There is a benefit for those patients who received Ra-223 in the second-line setting, regardless of prior use of docetaxel. In addition, a survival benefit for patients presenting with a decline in ALP was observed.

Quality of Life in Patients with Chronic Low Back Pain and Differences by Sex: A Longitudinal Study.

BACKGROUND: The experience of chronic low back pain has a significant impact on the quality of life of affected people, resulting in difficulties in performing basic activities of daily living. AIM: To study the perceived quality of life of people affected by chronic low back pain and the associated factors by sex. METHODS: A prospective, longitudinal and observational design was used. RESULTS: A total of 129 people (58.1% women) with chronic low back pain were studied. The mean pain intensity scores were of moderate severity (6.42 points), with a modest improvement at follow-up (6.17 points). Epidural nerve blocks were the most effective therapeutic intervention in reducing the intensity of pain. Participants described a negative perception of their health with regard to quality of life, with low scores for the two constructs both at baseline (health index, 0.444; perception of health, 38.76 points) and at follow-up (health index, 0.447; perception of health, 40.43 points). Participants had severe functional limitation scores (50.79 points). The results were significantly better among men. There was an inverse relationship between the average pain intensity (ß = -0.304; p < 0.001), functional limitation (ß = -0.466; p < 0.001) and mental health (ß = -0.565; p < 0.001) and quality of life. CONCLUSIONS: The chronification of low back pain complicates people's biopsychosocial adaptation to life. There is a longitudinal inverse association between pain and functional limitation and health-related quality of life.

Non-invasive surveillance of shared pathogens in the Eurasian brown bear (Ursus arctos) human interface.

Multi-host communities are perfect scenarios for the emergence and spread of pathogens, threatening the recovery of endangered, isolated, or inbred populations, such as the brown bear (Ursus arctos) in northwestern Spain. The population recovery in recent years has forced bears to occupy highly anthropized areas, increasing their interaction with human and domestic animals, with potential consequences for global health. During 2022-2023 a survey of parasites, bacteria and viruses shared between wildlife, domestic animals and humans was performed in this population using non-invasive surveillance, i.e., bear fecal samples (n = 73) and sponge-based sampling of trees (n = 42; 14 rubbed trees and 28 control trees). Pathogen detection rates were defined as the percentage of qPCR or culture-positive samples. Generalized linear models were fitted to assess their relationship with environmental variables including dispersion of the human population, and percentage of agricultural and periurban habitats in a 6 km-buffer around each sample. Canine Adenovirus type 1 (45.2%), Giardia spp. (15.1%), Salmonella spp. (12.3%), and extended-spectrum-beta-lactamases (ESBL) Escherichia coli (1.4%) were identified in fecal samples. In contrast, only five sponges from three rubbed and two control trees resulted positive to E. coli (14.3%). The results suggest that several pathogens are common in the Cantabrian brown bear population and that anthropization of the territory modulates their prevalence and richness. The effective design of management programs for bear conservation will require a one-health approach, in which genetic analysis of non-invasive samples can be key tools for the sanitary surveillance at the wildlife-livestock-human interface.

Assessment of Standardized Care Plans for People with Chronic Diseases in Primary Care Settings.

BACKGROUND: Aging populations are driving a shift in emphasis toward enhancing chronic disease care, reflected in Catalonia's regional plan which prioritizes standardized nursing care plans in primary care settings. To achieve this, the ARES-AP program was established with a focus on harmonizing standards and supporting routine nursing clinical decision-making. This study evaluates nurses' perceptions of ARES-AP's standardized care plans for chronic diseases. METHODS: A mixed-methods approach based on an ad hoc questionnaire (n = 141) and a focus group (n = 14) was used. Quantitative data were statistically analysed, setting significance at p < 0.05. Qualitative data were explored via content analysis. RESULTS: ARES-AP training was assessed positively. The resources for motivational interviewing and care plans for the most prevalent chronic diseases were rated very positively. This study identified key factors influencing program implementation, including facilitators such as structured information and nursing autonomy, barriers such as resistance to change, motivators such as managerial support, and suggested improvements such as technological improvements and time management strategies. CONCLUSIONS: This study identifies areas for improvement in implementing standardized nursing care plans, including additional time, motivation, enhanced IT infrastructure, and collaboration among primary care professionals. It enhances understanding of these plans in primary care, especially in managing chronic diseases in aging populations. Further research should assess the program's long-term impact on chronic patients. This study was not registered.

IFITM5-related (type V) osteogenesis imperfecta with evidence of perinatal involvement: A case report.

Osteogenesis imperfecta (OI) is a rare hereditary disorder characterized by bone fragility and frequent fractures. While most cases are attributed to variations in collagen-coding genes COL1A1 and COL1A2, other genes such as IFITM5 have also been associated with the disease, accounting for up to 5 % of cases. Here, we report a case of a 3-month-old female with a femur fracture and limb deformity. X-rays revealed evidence of osteopenia and previous fractures in the arms, clavicle, ribs, and left limb, alongside prenatal bone deformities detected by ultrasound. Initial clinical evaluation suggested progressively deforming (Sillence's type III) osteogenesis imperfecta (OI). Molecular testing led to the diagnosis of IFITM5-related OI, identifying the c.-14C>T (rs587776916) variant. Although this variant has been previously reported in patients with IFITM5-related OI, prenatal involvement had not been associated with this variant.

Building community engagement with caregivers through online interaction and a salutogenic approach in a period of isolation.

Background: Informal caregivers are essential figures that deal with the effects of dependence in the elderly. However, they suffer from poorer health-related quality of life, particularly regarding mental health. Social support is crucial, but this was suspended or dramatically reduced during the Covid-19 pandemic. Salutogenesis theory explores the contributing factors for the promotion and maintenance of health. Considering all these, we offered caregivers the opportunity to join a participatory project aimed at creating communication spaces where they could share experiences, think together about potential solutions, and explore which salutogenic actions they used in their daily basis and how they had changed during Covid-19 restrictions. Methods: We used a qualitative methodology with a socio-constructivist and phenomenological approach and purposive sampling. We organized two focus groups consisting of online semi-structured discussions with seven participants in total. Conversations were videotaped and transcribed and we conducted content thematic analyses using the NVivo software. Results: Caregiving in our setting are primarily women with high levels of education that do not always feel comfortable with this load because it interferes with their personal and professional lives. The pandemic increased caregivers feelings of loneliness, resignation, and burden, directly affecting their mental health. Furthermore, the disappearance of prevention programs and the difficulties to access healthcare services produced negative consequences on the already fragile elderly and their family caregivers. Conclusion: The pandemic and its restrictions exacerbated the problematics affecting informal caregivers. Although these people are aware of their situation and have valued knowledge of how to improve their health, they cannot always put it into practice. We call policymakers to reframe interventions aimed at caregivers by introducing the voice of the community in the planning and to rethink the management of vulnerable people and their carers in other potential health crises.

Positive mental health and sense of coherence among emergency medical service professionals.

Background: Positive mental health (PMH) is a construct used to define and evaluate health from a positive perspective. Healthcare professionals in the emergency ambulance service are more likely to experience mental health disorders than the overall population. The demographic and occupational variables and Sense of Coherence (SOC) can act as predictors of PMH and can serve as protective elements against stress and demanding situations in the work environment. Objective: This study aimed to evaluate PMH and its relationship with demographic and occupational variables and determine if SOC is a predictive variable for PMH in health professionals working in the emergency ambulance service. Methods: A descriptive, cross-sectional, and correlational study was conducted with a sample of 406 healthcare professionals from the emergency ambulance service in eight health regions of Catalonia, Spain. The following variables were analyzed: Age, biological sex, household members, dependents family members, professional category, type of contract, job satisfaction and sense of collaboration with other institutions. The following assessment instruments were used: Positive Mental Health Questionnaire and Sense of Coherence scale. Results: High scores were obtained in Positive Mental Health (PMH). Study participants who reported feeling completely satisfied in their work also showed a significant relationship with all PMH factors: greater satisfaction with their personal life, in their helpful prosocial attitude toward others, in their capability to deal effectively with stress and navigate conflict scenarios, in their ability to solve problems and self-realization, greater empathy and ability to understand the feelings of others, greater ability to establish interpersonal relationships. Comprehensibility, as a dimension of SOC, was identified as a predictor for some factors of PMH: a greater personal satisfaction, self-control, autonomy, interpersonal skills and total PMHQ. More than 43% of positive mental health in health professionals is explained by higher Meaningfulness and Comprehensibility values of the SOC, the absence of dependent family members and having a non-graduate background. Conclusion: Healthcare workers in the emergency ambulance service had high PMH. Meaningfulness (ME) and Comprehensibility (C), dimensions of SOC, were identified as model predictors of greater PMH, showing higher scores in most of PMH factors. To enhance SOC as a mental health promotion measure, resilience programs should be implemented to help professionals develop skills to face and overcome adverse situations. Educating in stress management thought networks are key elements to strengthen SOC. Managers in emergency medical services play a key role in transforming healthcare work environments to promote positive outcomes in the mental health of their healthcare workers.

New threats in the recovery of large carnivores inhabiting human-modified landscapes: the case of the Cantabrian brown bear (Ursus arctos).

Understanding mortality causes is important for the conservation of endangered species, especially in small and isolated populations inhabiting anthropized landscapes where both natural and human-caused mortality may hinder the conservation of these species. We investigated the mortality causes of 53 free-ranging brown bears (Ursus arctos) found dead between 1998 and 2023 in the Cantabrian Mountains (northwestern Spain), a highly human-modified region where bears are currently recovering after being critically threatened in the last century. We detected natural traumatic injuries in 52.63% and infectious diseases in 39.47% of the 38 bears for which the mortality causes were registered, with 21.05% of these cases presenting signs of both infectious diseases and traumas. More specifically, almost 30% of the bears died during or after intraspecific fights, including sexually selected infanticide (10.53%). In addition, primary infectious diseases such as infectious canine hepatitis, distemper, clostridiosis and colibacillosis caused the death of 15.79% of the bears. The number of direct human-caused deaths (i.e., shooting, poisoning, snare) decreased over the study period. This study also reveals three new mortality causes triggered by pathogens, two of which-Clostridium novyi and verotoxigenic Escherichia coli-not previously described in ursids, and the other one, canine distemper virus, never reported in brown bears as cause of death. New management strategies for the conservation of Cantabrian bears, which are urgently needed due to the rapid expansion of the population, should consider the mortality causes described in this study and must promote further research to elucidate how the high prevalence of infectious diseases may threaten the current recovery of the population.

The effects of rhythmic auditory stimulation on functional ambulation after stroke: a systematic review.

BACKGROUND: Several studies have reported the effect of rhythmic auditory stimulation (RAS) on functional ambulation in stroke patients, yet no systematic overview has yet been published. This study aims to synthesize the available evidence describing changes in stroke patients after RAS intervention for functional ambulation and the use of walking assistive devices, and to find out if the effect of RAS and music-based RAS differs depending on the lesioned area. METHODS: The PubMed, PEDro, Cochrane Central Register of Controlled Trials, Web of Science, Scopus and CINAHL electronic databases were searched for reports evaluating the effect of RAS on walking in stroke patients, applying the PICOS criteria for the inclusion of studies. RESULTS: Twenty one articles were included (948 stroke survivors). Most studies were of good methodological quality according to the PEDro scale, but they had a high risk of bias. The most consistent finding was that RAS improves walking and balance parameters in stroke patients in all phases compared to baseline and versus control groups with conventional treatment. Functional ambulation and the use of walking assistive devices were inconsistently reported. Several studies also suggest that RAS may be as good as other complementary therapies (horse-riding and visual cueing). CONCLUSIONS: Despite the beneficial effects of RAS, the question remains as to whether it is better than other complementary therapies. Given the heterogeneity of the interventions, the interventions in control groups, the varied durations, and the different outcome measures, we suggest that care should be taken in interpreting and generalizing findings. PROSPERO REGISTRATION: CRD42021277940.

Efficacy of heat-inactivated Mycobacterium bovis vaccine delivered to European badgers (Meles meles) through edible bait.

Badgers (Meles meles) are a major tuberculosis (TB) reservoir in Europe, with the potential to transmit infection to cattle. Here we assessed whether a recently described oral tuberculosis vaccine based on heat-inactivated Mycobacterium bovis (HIMB), delivered as edible baits, can protect badgers from infection. Eight badgers were given individually five baits, each one consisting of a ball of peanut butter, natural peanut and oat flakes including a dose of the vaccine containing 5 × 107 colony-forming units. In parallel, a control group of seven badgers did not receive the vaccine. One month and a half later a second dose of the vaccine was offered to the vaccinated group. Ninety-four days after the second dose, all badgers were challenged with M. bovis (103 colony-forming units per animal) delivered endobronchially to the right middle lung lobe. Clinical, immunological, pathological and bacteriological variables were measured throughout the whole study to assess the efficacy of the vaccine. Two vaccinated animals showed high bacterial load of M. bovis and worsening of pathological lesions of TB. Conversely, the other six vaccinated animals showed slight improvement in bacterial load and pathology with respect to the control group. These results suggest that delivering the TB vaccine via food bait can partially protect wild badger populations, although vaccination can lead to either protection or tolerization, likely depending on the animal's immune status and general condition at the time of vaccination. Further optimization of the vaccination trial/strategy is needed to reduce the rate of tolerization, such as altering vaccine dose, number of doses, type of bait, use of adjuvants or route of administration.

Immunogenicity and safety assessment of a SARS-CoV-2 recombinant spike RBD protein vaccine (Abdala) in paediatric ages 3-18 years old: a double-blinded, multicentre, randomised, phase 1/2 clinical trial (ISMAELILLO study).

Background: COVID-19 in paediatric ages could result in hospitalizations and death. In addition, excluding children from vaccination could turn them into reservoirs of the SARS-COV-2. Safe and effective COVID-19 vaccines are urgently needed for large-scale paediatric vaccination. ISMAELILLO study aimed to evaluate safety and immunogenicity of two strengths of a new recombinant receptor-binding domain (RBD) protein vaccine (Abdala) in paediatric population. Methods: A double-blinded, multicentre, randomised, phase 1/2 clinical trial was conducted in nine polyclinics in the province of Camagüey, Cuba. Healthy children and adolescents were stratified according to age (3-11 years old, or 12-18 years old) and they were randomly assigned (1:1; block size four) in two dosage level groups of vaccine to receive three intramuscular doses of 25 µg or 50 µg of RBD, 14 days apart. Main safety endpoint was analyzed as the percentage of serious adverse reactions during vaccination up to 28 days after the third dose (Day 56) in participants who received at least one dose vaccination. The primary immunogenicity endpoint assessed was seroconversion rate of anti-RBD IgG antibody at day 56. The immunogenicity outcomes were assessed in the per-protocol population. This trial is registered with Cuban Public Registry of Clinical Trials, RPCEC00000381. Findings: Between July 15, 2021, and August 16, 2021, 644 paediatric subjects were screened, of whom 592 were enrolled after verifying that they met the selection criteria: firstly 88 were included in Phase 1 of the study and 504 who completed Phase 2. The vaccine was well tolerated. Injection site pain was the most frequently reported local event (143 [8·4%] of 1707 total doses applied), taking place in 66/851 (7·8%) in the 25 µg group and in 77/856 (9·0%) in the 50 µg. The most common systemic adverse event (AE) was headache: 23/851 (2·7%) in the 25 µg group and 19/856 (2·2%) in the 50 µg. Reactogenicity was mild or moderate in severity, represented in 75% of cases by local symptoms, completely resolved in the first 24-48 h. Twenty-eight days after the third dose, seroconversion anti-RBD IgG were observed in 98·2% of the children and adolescents (231/234) for the 50 µg group and 98·7% (224/228) for the 25 µg group without differences between both strength. The specific IgG antibody geometric mean titres (GMT) showed higher titres between participants who received Abdala 50 µg (231·3; 95% CI 222·6-240·4) compared to those who received 25 µg (126·7; 95% CI 121·9-131·7). The mean ACE2 inhibition %, were 59·4% for 25 µg, and for 50 µg, 72·9% (p < 0·01). Both strength elicited neutralising activity against the SARS-CoV-2, specifically (18·3; 95% CI 14·7-22·78) for Abdala 25 µg and (36·4; 95% CI 30·26-43·8) for 50 µg to the selected sample analyzed. Interpretation: Abdala vaccine was safe and well tolerated at both antigenic strength levels tested in participants aged between 3 and 18 years. Regarding immunogenicity, Abdala Vaccine stimulated the production of specific IgG antibodies against the RBD of SARS-CoV-2 as well as the production of ACE2 inhibition titres and neutralising antibodies (Nab) in children and adolescents. Funding: Centre for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba.

Assessing the Student Nurses' Knowledge of Oral Health Care.

Oral health is crucial for the overall well-being and quality of life, and nurses play a significant role in promoting it. This study assessed the oral health knowledge of fourth-grade nursing degree students. Seventy-two students completed a questionnaire covering sociodemographic variables, oral health-related factors, knowledge about oral health, and perceptions of its importance and learning experiences. The results showed that 83.3% of students attended regular dental check-ups for preventive purposes, and 55.6% had visited a dentist during the last year. Most of the students reported experiencing cavities (66.7%) and undergoing orthodontic treatment (54.2%). The average knowledge score in oral health was 6.4 out of 10, and students recognized the importance of oral health in the nursing role. However, their knowledge acquired during their nursing degree scored relatively low, being 2.5 out of 5. Notably, students who valued problem-based learning achieved higher knowledge scores (p < 0.05). Overall, fourth-grade nursing students demonstrated a moderate level of oral health knowledge. Improving oral health education within nursing curricula, particularly through problem-based learning, is essential to enhance their preparedness in addressing oral health issues effectively. This study was not registered.

A Qualitative Approach to Exploring the Impact of the Gay Identity Formation Process.

Background: Most gay men experience difficulty in coming to terms with their sexual orientation, with their health, wellbeing, and quality of life potentially affected by unpleasant experiences often associated with the formation of their gay identity. It is therefore important for nurses to understand the needs of gay men so that they can accompany them and provide quality care during and after the identity formation process. Objective: The aim of the study was to explore and describe the identity formation and coming out experiences of gay men. Methods: A qualitative design with a constructivist naturalist approach was used. Data were collected through in-depth semi-structured interviews with five gay men with experience of the gay identity formation process, and data were analyzed using a thematic analysis method. Results: The results show that the men needed support, as they reported feeling different and alone during the identity formation and coming out process, and that their mental health was affected. Fear of rejection, negative reactions, and disappointing people were the reasons that led the men not to disclose their sexual orientation to family, while those who had come out defined a feeling of liberation. Conclusions: The gay identity formation process has potential impacts on health, wellbeing, and quality of life. Nurses need cultural competence training to be able to understand the needs of gay men, accompany them in the identity formation process, and provide individualized and non-heteronormative care. Nurses also need to participate in dismantling a heterosexist social structure.

Hypertrophic osteopathy in a common dolphin (Delphinus delphis) with concurrent pulmonary Halocercus delphini infestation.

Dolphins are marine mammals that often live in coastal habitats. Common causes of severe skeletal disorders among wild dolphins are congenital vertebral anomalities, collisions with sea vessels, trauma, hunting-related injury, infectious diseases, environmental pollution, and tumors. A free-ranging male, 3-year-old common dolphin (Delphinus delphis) was found dead in the coast of Asturias in northern Spain. Postmortem examination revealed lordosis in the caudal vertebral column, while X-ray imaging and computer tomography showed well-organized palisade-like periosteal proliferation, appearing as florid-like accretions, along the spinous apophysis of 26 lumbar-caudal vertebrae. The transverse apophysis was affected on only a few caudal vertebrae. The cortical layer remained intact. Histology of vertebra tissue showed periosteal proliferation of cancellous bone. The animal was diagnosed with hypertrophic osteopathy. The lungs showed diffuse parasitic granulomatous bronchointerstitial pneumonia caused by Halocercus delphini, consolidation of the pulmonary tissue, congestion, and alveolar edema. The animal was also afflicted by parasitic granulomatous gastritis caused by Anisakis simplex sensu lato and tattoo skin disease. The dolphin suffered from hypertrophic osteopathy associated with pulmonary Halocercus delphini infestation. This syndrome, known as hypertrophic pulmonary osteopathy, has been described in diverse terrestrial mammals, including domestic animals, wildlife and humans, but not in dolphins. This case reports the first description of hypertrophic osteopathy associated to a pulmonary disorder in dolphin, and it provides insights into factors that can induce column malformation in dolphins, suggesting the importance of taking thoracic lesions into account during differential diagnosis.

Sex differences in blood biomarkers and cognitive performance in individuals with autosomal dominant Alzheimer's disease.

INTRODUCTION: Plasma tau phosphorylated at threonine 217 (P-tau217) and neurofilament light (NfL) have emerged as markers of Alzheimer's disease (AD) pathology. Few studies have examined the role of sex in plasma biomarkers in sporadic AD, yielding mixed findings, and none in autosomal dominant AD. METHODS: We examined the effects of sex and age on plasma P-tau217 and NfL, and their association with cognitive performance in a cross-sectional study of 621 Presenilin-1 E280A mutation carriers (PSEN1) and non-carriers. RESULTS: As plasma P-tau217 levels increase, cognitively unimpaired female carriers showed better cognitive performance than cognitively unimpaired male carriers. Yet, as disease progresses, female carriers had a greater plasma NfL increase than male carriers. There were no sex differences in the association between age and plasma biomarkers among non-carriers. DISCUSSION: Our findings suggest that, among PSEN1 mutation carriers, females had a greater rate of neurodegeneration than males, yet it did not predict cognitive performance. HIGHLIGHTS: We examined sex differences in plasma P-tau217 and NfL in Presenilin-1 E280A (PSEN1) mutation carriers and non-carriers. Female carriers had a greater plasma NfL increase, but not P-tau217, than male carriers. As plasma P-tau217 levels increase, cognitively unimpaired female carriers showed better cognitive performance than cognitively unimpaired male carriers. The interaction effect of sex by plasma NfL levels did not predict cognition among carriers.

A CRISPR-Cas9 mutation in sox9b long intergenic noncoding RNA (slincR) affects zebrafish development, behavior, and regeneration.

The role of long noncoding RNAs (lncRNAs) regulators of toxicological responses to environmental chemicals is gaining prominence. Previously, our laboratory discovered an lncRNA, sox9b long intergenic noncoding RNA (slincR), that is activated by multiple ligands of aryl hydrocarbon receptor (AHR). Within this study, we designed a CRISPR-Cas9-mediated slincR zebrafish mutant line to better understand its biological function in presence or absence of a model AHR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The slincRosu3 line contains an 18 bp insertion within the slincR sequence that changes its predicted mRNA secondary structure. Toxicological profiling showed that slincRosu3 is equally or more sensitive to TCDD for morphological and behavioral phenotypes. Embryonic mRNA-sequencing showed differential responses of 499 or 908 genes in slincRosu3 in absence or presence of TCDD Specifically, unexposed slincRosu3 embryos showed disruptions in metabolic pathways, suggesting an endogenous role for slincR. slincRosu3 embryos also had repressed mRNA levels of sox9b-a transcription factor that slincR is known to negatively regulate. Hence, we studied cartilage development and regenerative capacity-both processes partially regulated by sox9b. Cartilage development was disrupted in slincRosu3 embryos both in presence and absence of TCDD. slincRosu3 embryos also displayed a lack of regenerative capacity of amputated tail fins, accompanied by a lack of cell proliferation. In summary, using a novel slincR mutant line, we show that a mutation in slincR can have widespread impacts on gene expression and structural development endogenously and limited, but significant impacts in presence of AHR induction that further highlights its importance in the developmental process.

Mortality Causes in Captive Cantabrian capercaillie (Tetrao urogallus cantabricus) in Spain.

The Cantabrian capercaillie (Tetrao urogallus cantabricus) is one of the most severely threatened subspecies of capercaillie. Its current population range is restricted to a small area of the Cantabrian Mountains (northwestern Spain), with only around 200 individuals remaining. As part of the national strategy for the conservation of the subspecies, the Cantabrian capercaillie Captive Breeding Center of Sobrescobio opened in 2009. Here, we use the information provided by the necropsies performed in this facility on 29 individuals (11 males, 13 females and 5 undetermined; 16 chicks and 13 adults) in order to describe the main mortality causes of captive-bred Cantabrian capercaillies. After necropsy, tissue samples were taken for evaluation using standard methods in histology and microbiology. The majority of the captive animals (18/29, 62.07%) died due to infectious diseases, mainly due to Escherichia coli, Clostridium perfringens, or Aspergillus fumigatus infection. The remaining 11 animals died due to stress-related processes (i.e., rupture of the heart apex and cardiomyopathy or neurogenic shock) (8/29, 27.59%), duodenal obstruction and coelomitis (1/29, 3.45%), perforation of the proventriculus and heart with a briar branch (1/29, 3.45%) or euthanasia due to a valgus leg deformity that prevented proper animal welfare (1/29, 3.45%). Young animals (i.e., younger than 2 months) died mainly due to infectious diseases (14/16, 87.5%), while stress-related causes were responsible for most adult deaths (7/13, 53.85%). We additionally report that two free-ranging adult males died due to exertional myopathy. This study provides relevant information for reducing mortality in captive capercaillies and improving both living conditions in captivity and the adaptation of these animals to the wild.