Search

Accumulation of amyloid-β plaques and tau contribute to the pathogenesis of Alzheimers disease (AD), but it is unclear whether targeting tau pathology by antioxidants independently of amyloid-β causes beneficial effects on memory and neuropsychiatric symptoms. Selenium, an essential antioxidant element reduced in the aging brain, prevents development of neuropathology in AD transgenic mice at early disease stages. The therapeutic potential of selenium for ameliorating or reversing neuropsychiatric and cognitive behavioral symptoms at late AD stages is largely unknown. Here, we evaluated the effects of chronic dietary sodium selenate supplementation for 4 months in female 3xTg-AD mice at 12-14 months of age. Chronic sodium selenate treatment efficiently reversed hippocampal-dependent learning and memory impairments, and behavior- and neuropsychiatric-like symptoms in old female 3xTg-AD mice. Selenium significantly decreased the number of aggregated tau-positive neurons and astrogliosis, without globally affecting amyloid plaques, in the hippocampus of 3xTg-AD mice. These results indicate that selenium treatment reverses AD-like memory and neuropsychiatric symptoms by a mechanism involving reduction of aggregated tau and/or reactive astrocytes but not amyloid pathology. These results suggest that sodium selenate could be part of a combined therapeutic approach for the treatment of memory and neuropsychiatric symptoms in advanced AD stages.

Droughts and climate-change-driven warming are leading to more frequent and intense wildfires.sup.1-3, arguably contributing to the severe 2019-2020 Australian wildfires.sup.4. The environmental and ecological impacts of the fires include loss of habitats and the emission of substantial amounts of atmospheric aerosols.sup.5-7. Aerosol emissions from wildfires can lead to the atmospheric transport of macronutrients and bio-essential trace metals such as nitrogen and iron, respectively.sup.8-10. It has been suggested that the oceanic deposition of wildfire aerosols can relieve nutrient limitations and, consequently, enhance marine productivity.sup.11,12, but direct observations are lacking. Here we use satellite and autonomous biogeochemical Argo float data to evaluate the effect of 2019-2020 Australian wildfire aerosol deposition on phytoplankton productivity. We find anomalously widespread phytoplankton blooms from December 2019 to March 2020 in the Southern Ocean downwind of Australia. Aerosol samples originating from the Australian wildfires contained a high iron content and atmospheric trajectories show that these aerosols were likely to be transported to the bloom regions, suggesting that the blooms resulted from the fertilization of the iron-limited waters of the Southern Ocean. Climate models project more frequent and severe wildfires in many regions.sup.1-3. A greater appreciation of the links between wildfires, pyrogenic aerosols.sup.13, nutrient cycling and marine photosynthesis could improve our understanding of the contemporary and glacial-interglacial cycling of atmospheric CO.sub.2 and the global climate system. Oceanic deposition of wildfire aerosols can enhance marine productivity, as supported here by satellite and in situ profiling floats data showing that emissions from the 2019-2020 Australian wildfires fuelled phytoplankton blooms in the Southern Ocean., Author(s): Weiyi Tang [sup.1] [sup.11] , Joan Llort [sup.2] [sup.3] , Jakob Weis [sup.2] [sup.4] , Morgane M. G. Perron [sup.2] , Sara Basart [sup.3] , Zuchuan Li [sup.1] [sup.5] [...]

Coping with emotional stressors strongly impacts older people due to their age-related impaired neuroendocrine and immune systems. Elevated cortisol levels seem to be associated with an increased risk of cognitive decline and dementia. In Alzheimer’s disease (AD), alterations in the innate immune system result in crosstalk between immune mediators and neuronal and endocrine functions. Besides, neuropsychiatric symptoms such as depression, anxiety, or agitation are observed in most patients. Here, we studied the psychophysiological response to intrinsic (AD-phenotype) and extrinsic (anxiogenic tests) stress factors and their relation to liver, kidneys, heart, and spleen oxidative status in 18-months-old female gold-standard C57BL/6 mice and 3xTg-AD mice model for AD. The emotional, cognitive, and motor phenotypes were assessed under three different anxiogenic conditions. Survival, frailty index, and immunoendocrine status (corticosterone levels and oxidative stress of peripheral organs) were evaluated. Genotype differences in neuropsychiatric-like profiles and cognitive disfunction in 3xTg-AD females that survived beyond advanced stages of the disease persisted despite losing other behavioral and hypothalamic–pituitary–adrenal (HPA) physiological differences. A secondary analysis studied the impact of social isolation, naturally occurring in 3xTg-AD mice due to the death of cage mates. One month of isolation modified hyperactivity and neophobia patterns and disrupt the obsessive-compulsive disorder-like digging ethogram. Frailty index correlated with spleen organometrics in all groups, whereas two AD-specific salient functional correlations were identified: (1) Levels of corticosterone with worse performance in the T-maze, (2) and with a lower splenic GPx antioxidant enzymatic activity, which may suppose a potent risk of morbidity and mortality in AD.

Research on Alzheimer’s disease (AD) has classically focused on alterations that occur in the brain and their intra- and extracellular neuropathological hallmarks. However, the oxi-inflammation hypothesis of aging may also play a role in neuroimmunoendocrine dysregulation and the disease’s pathophysiology, where the liver emerges as a target organ due to its implication in regulating metabolism and supporting the immune system. In the present work, we demonstrate organ (hepatomegaly), tissue (histopathological amyloidosis), and cellular oxidative stress (decreased glutathione peroxidase and increased glutathione reductase enzymatic activities) and inflammation (increased IL-6 and TNF𝛼) as hallmarks of hepatic dysfunction in 16-month-old male and female 3xTg-AD mice at advanced stages of the disease, and as compared to age- and sex-matched non-transgenic (NTg) counterparts. Moreover, liver–brain axis alterations were found through behavioral (increased neophobia) and HPA axis correlations that were enhanced under forced isolation. In all cases, sex (male) and isolation (naturalistic and forced) were determinants of worse hepatomegaly, oxidative stress, and inflammation progression. In addition, obesity in old male NTg mice was translated into a worse steatosis grade. Further research is underway determine whether these alterations could correlate with a worse disease prognosis and to establish potential integrative system targets for AD research.

A sample of 351 adults (women/men 4:1) aged 18 to 60 participated in an online survey administered during the first two waves (15 March–25 April and 10 October–25 November 2020) of the COVID-19 pandemic in Ukraine. The user ethnography profile was Generation Z (born in the 1990s), female (81.2%), Instagrammer (60.3%), unmarried (56.9%) and student (42.9%). An increased time spent on social media (3.18 h/day), searching for COVID-19-related information (1.01 h/day) after the first COVID-19 case and the observation of fake news that went viral (58.8%) decreased in the second wave. Alterations (increase or reduction) in sleep patterns (46.7%) and changes (increase or loss) in appetite (32.7%) affected participants’ well-being, but only sleep ameliorated in the second wave. Mental health reports unveiled moderate perceived stress (PSS-10: 20.61 ± 1.13) and mild anxiety (GAD-7: 14.17 ± 0.22), which improved in the second wave. A higher prevalence of severe anxiety (8.5%) was found among individuals in the first survey (8.5%) than those in the second (3.3%). Social media counteracted physical distance policies and played as an immediate source of (mis)information for users, but also anticipated the impact of the most uncertain times of this COVID-19 physical health crisis on well-being and mental health.

The phenotypic transformation of astrocytes in Alzheimer's disease (AD) is still not well understood. Recent analyses based on single-nucleus RNA sequencing of postmortem Alzheimer's disease (AD) samples are limited by the low number of sequenced astrocytes, small cohort sizes, and low number of differentially expressed genes detected. To optimize the detection of astrocytic genes, we employed a novel strategy consisting of the localization of pre-determined astrocyte and neuronal gene clusters in publicly available whole-brain transcriptomes. Specifically, we used cortical transcriptomes from 766 individuals, including cognitively normal subjects (Controls), and people diagnosed with mild cognitive impairment (MCI) or dementia due to AD. Samples came from three independent cohorts organized by the Mount Sinai Hospital, the Mayo Clinic, and the Religious Order Study/Memory and Aging Project (ROSMAP). Astrocyte- and neuron-specific gene clusters were generated from human brain cell-type specific RNAseq data using hierarchical clustering and cell-type enrichment scoring. Genes from each cluster were manually annotated according to cell-type specific functional Categories. Gene Set Variation Analysis (GSVA) and Principal Component Analysis (PCA) were used to establish changes in these functional categories among clinical cohorts. We highlight three novel findings of the study. First, individuals with the same clinical diagnosis were molecularly heterogeneous. Particularly in the Mayo Clinic and ROSMAP cohorts, over 50% of Controls presented down-regulation of genes encoding synaptic proteins typical of AD, whereas 30% of patients diagnosed with dementia due to AD presented Control-like transcriptomic profiles. Second, down-regulation of neuronal genes related to synaptic proteins coincided, in astrocytes, with up-regulation of genes related to perisynaptic astrocytic processes (PAP) and down-regulation of genes encoding endolysosomal and mitochondrial proteins. Third, down-regulation of astrocytic mitochondrial genes inversely correlated with the disease stages defined by Braak and CERAD scoring. Finally, we interpreted these changes as maladaptive or adaptive from the point of view of astrocyte biology in a model of the phenotypical transformation of astrocytes in AD. The main prediction is that early malfunction of the astrocytic endolysosomal system, associated with progressive mitochondrial dysfunction, contribute to Alzheimer's disease. If this prediction is correct, therapies preventing organelle dysfunction in astrocytes may be beneficial in preclinical and clinical AD.

Imidazoline receptors (IR) are classified into three receptor subtypes (I1R, I2R, and I3R) and previous studies showed that regulation of I2R signaling has neuroprotective potential. In order to know if I2R has a role in modulating vascular tone in health and disease, we evaluated the putative vasoactive effects of two recently synthesized I2R ligands, diethyl (1RS,3aSR,6aSR)-5-(3-chloro-4-fluorophenyl)-4,6-dioxo-1-phenyl-1,3a,4,5,6,6a-hexahydropyrrolo[3,4-c]pyrrole -1-phosphonate (B06) and diethyl [(1-(3-chloro-4-fluorobenzyl)-5,5-dimethyl-4-phenyl-4,5-dihydro-1H-imidazol-4-yl]phosphonate] (MCR5). Thoracic aortas from Oncins France 1 (3- to 4-months-old) and C57BL/6 (3- to 4- and 16- to 17-months-old mice) were mounted in tissue baths to measure isometric tension. In young mice of both strains, MCR5 induced greater relaxations than either B06 or the high-affinity I2R selective ligand 2-(2-benzofuranyl)-2-imidazoline (2-BFI), which evoked marginal responses. MCR5 relaxations were independent of I2R, as IR ligands did not significantly affect them, involved activation of smooth muscle KATP channels and inhibition of L-type voltage-gated Ca2+ channels, and were only slightly modulated by endothelium-derived nitric oxide (negatively) and prostacyclin (positively). Notably, despite the presence of endothelial dysfunction in old mice, MCR5 relaxations were preserved. In conclusion, the present study provides evidence against a functional contribution of I2R in the modulation of vascular tone in the mouse aorta. Moreover, the I2R ligand MCR5 is an endothelium-independent vasodilator that acts largely via I2R-independent pathways and is resistant to aging. We propose MCR5 as a candidate drug for the management of vascular disease in the elderly.

Framtidsfortellinger er tilknyttet epistemologiske, strukturelle og institusjonelle rammer. Disse rammene setter grenser for hvordan vi kan se for oss drømmene våre for framtiden og hvem som har anledning til framtidsdrømming. Denne rundebordssamtalen analyserer rammene gjennom en dialogisk tilnærming fra et interseksjonelt perspektiv for å undersøke dynamikkene som betinger framtidsfortellinger i vestlige samfunn.

Despite its robust proteopathic nature, the spatiotemporal signature of disrupted protein modules in sporadic Alzheimer’s disease (AD) brains remains poorly understood. This considered oxidative stress contributes to AD progression and early intervention with coenzyme Q10 or its reduced form, ubiquinol, delays the progression of the disease. Using MALDI–MSI and functional bioinformatic analysis, we have developed a protocol to express how deregulated protein modules arise from hippocampus and cortex in the AD mice model 3xTG-AD in an age-dependent manner. This strategy allowed us to identify which modules can be efficiently restored to a non-pathological condition by early intervention with ubiquinol. Indeed, an early deregulation of proteostasis-related protein modules, oxidative stress and metabolism has been observed in the hippocampus of 6-month mice (early AD) and the mirrored in cortical regions of 12-month mice (middle/late AD). This observation has been validated by IHC using mouse and human brain sections, suggesting that these protein modules are also affected in humans. The emergence of disrupted protein modules with AD signature can be prevented by early dietary intervention with ubiquinol in the 3xTG-AD mice model.

The perception of body and social odours (SOP) is crucial for interpersonal chemosensory signalling and mate choice, yet little is known about the role of the SOP on the quality of partnerships and the attachment style. The aim of this study was to investigate the role of the SOP in women’s stress responses by considering the role of biopsychosocial variables in the quality of interpersonal relationships (also considering intimate partner violence). In total, 253 women filled out an online survey that included a series of questionnaires to investigate self-perceived stress (PSS), emotional regulation (ERQ), olfactory social assessment (SOS), quality of partnership (RRQ), attachment style (RQ), and the Conflict Tactile Scale 2 (CTS-2). The main results highlight that a high awareness of social odours correlates with a good quality of relationship and with an emotional regulation capacity; the PSS correlates negatively with the ERQ (i.e., as the PSS increases, the ERQ decreases). The level of IPV predicts an interpersonal style characterized by a low desire to develop meaningful relationships but with a tendency to depend on and trust another. The idea of being hurt by the other is not central in women who experience this type of relationship. The study’s main conclusion is that social odour perception is important for emotional regulation and in partner relationships.

The continuously expanding field of Alzheimer's disease (AD) research is now beginning to defocus the brain to take a more systemic approach to the disease, as alterations in the peripheral organs could be related to disease progression. One emerging hypothesis is organ involvement in the process of Aβ clearance. In the present work, we aimed to examine the status and involvement of the kidney as a key organ for waste elimination and the spleen, which is in charge of filtering the blood and producing lymphocytes, and their influence on AD. The results showed morphological and structural changes due to acute amyloidosis in the kidney (glomeruli area) and spleen (red pulp area and red/white pulp ratio) together with reduced antioxidant defense activity (GPx) in 16-month-old male and female 3xTg-AD mice when compared to their age- and sex-matched non-transgenic (NTg) counterparts. All these alterations correlated with the anxious-like behavioral phenotype of this mouse model. In addition, forced isolation, a cause of psychological stress, had a negative effect by intensifying genotype differences and causing differences to appear in NTg animals. This study further supports the relevance of a more integrative view of the complex interplay between systems in aging, especially at advanced stages of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Non-invasive and precise methods are critical for monitoring paediatric brain cancers. Here the authors show that the molecular alterations and heterogeneity of paediatric medulloblastomas can be reliably detected in circulating tumour DNA from the cerebrospinal fluid – a routinely collected sample.

Introduction There is urgent need to investigate type 2 diabetes and dementia crosstalk in sub‐Saharan African countries with special attention to women who have higher vulnerability. Nigeria which has the highest number of diabetics on the African continent is a good location for the investigation. Methods Biophysical parameters, occupation, education, burden of diabetes mellitus, cardiovascular health, and cognition were evaluated in 102 type 2 diabetics and 99 controls. Results Short physical stature and lower level of education were hallmarks of diabetes in females. Two dementia scales (Mini–Mental State Examination and six‐item Cognitive Impairment Test) showed cognitive impairment status, with the six‐item Cognitive Impairment Test scale being more specific and sensitive. Both scales showed correlations with age, education, weight, height, and disease onset, whereas fasten blood glucose was negatively correlated with height and their blood pressure was normal. Discussion Height, an easy‐to‐measure parameter in Nigeria, may reveal increased risk of dementia in poorly educated female Nigerian diabetics, thus helping to improve preventive and therapeutic interventions.

The temporal course and the severity of the involution of sensory systems through aging can be critical since they ensure the ability to perceive and recognize the world. In older people, sensory impairments significantly increase their risk of biological, psychological, and social impoverishment. Besides this, olfactory loss is considered an early biomarker in Alzheimer’s disease (AD) neurodegenerative process. Here we studied olfactory ethograms in middle-aged male and female gold-standard C57BL/6 mice and 3xTg-AD mice, a genetic model of AD that presents cognitive dysfunction and a conspicuous neuropsychiatric-like phenotype. A paradigm involving 1-day food deprivation was used to investigate the ethological patterns shown in the olfactory inspection of a new cage and the sniffing, finding, and eating of hidden food pellets. The sniffing–find–eat temporal patterns were independent of the loss of weight and unveiled (fast) olfactory signatures in Alzheimer’s disease, differing from those (slow progressive) in normal aging. Male 3xTg-AD mice exhibited an early signature than female mice, opposite to animals with normal aging. The sequence of actions was correlated in male and female 3xTg-AD mice in contrast to control mice. Social isolation, naturally occurring in male 3xTg-AD due to the death of cage mates, emphasized their olfactory patterns and disrupted the behavioral correlates. The paradigm provided distinct contextual, sex, and genotype olfactory ethogram signatures useful to investigate olfactory function in normal and AD-pathological aging. Isolation had an impact on enhancing the changes in the olfactory signature here described, for the first time, in the 3xTg-AD model of Alzheimer’s disease.

The issue of monitoring the structural condition of bridges is becoming a top priority worldwide. As is well known, any infrastructure undergoes a progressive deterioration of its structural conditions due to aging by normal service loads and environmental conditions. At the same time, it may suffer serious damages or collapse due to natural phenomena such as earthquakes or strong winds. For this reason, it is essential to rely on efficient and widespread monitoring techniques applied throughout the entire road network. This paper aims to introduce an integrated procedure for structural and material monitoring. With regard to structural monitoring, an innovative approach for monitoring based on Vehicle by Bridge Interaction (VBI) will be proposed. Furthermore, with regard to material monitoring, to evaluate concrete degradation, a non-invasive method based on the continuous monitoring of the pH, as well as chloride and sulfate ions concentration in the concrete, is presented.

Bizarre behaviors (BB) are elicited in animals during stressful conditions and represent behavioral markers of disease/sickness relevant to animal welfare. These behaviors are disregarded in most experimental screenings due to their low incidence and short duration, despite their translational value mimicking disruptive behaviors associated with neurological/psychiatric diseases. However, we previously reported experimental conditions with conspicuous BB incidence: (1) 3xTg-AD mice for Alzheimer’s disease vs. wild-types; (2) the open-field test (OF) vs. other tests; (3) +6 months of age; (4) female sex; (5) older age (+13 months) male 3xTg-AD mice also exhibit more circling behavior (BB-CB) than control mice; (6) early neonatal handling reduces BB; whereas (7) BB are enhanced by d-galactose-induced accelerated aging. In the present work, we studied the BB patterns elicited in the OF using a longitudinal design with sixty-six 13-month-old male/female mice with normal/AD-pathological aging under social/isolated housing conditions, and aimed to explore the effects of intrinsic (genotype, sex) and extrinsic (environment) factors (n = 7–8/group). BB were recorded in 39% of animals. Sex, re-testing at an older age, and genotype factors differentiated two BB patterns: higher circling behavior (BB-CB, n = 12) in wild-types and males, but higher backward movements (BB-BM, n = 14) in 3xTg-AD, female, and older age mice. Isolation increased the incidence of freezing, mostly in 3xTg-AD mice, and exerted a modulatory role in BB, but interaction effects with other factors led to a residual significance. The results point to BB-BM as the most pervasive BB pattern in this animal model, which is also sensitive to the progress of aging/disease.

The severity of sensory involution during aging is critical for perceiving and recognizing the world. In addition, sensory deficits significantly increase the risk of older adults’ biological, mental, and social decline. Conversely, the loss of smell is an early biomarker of neurodegeneration in Alzheimer’s (AD) and Parkinson’s diseases. The worsening of these neurodegenerative diseases also involves physical deterioration, social deficits, and isolation. In the present translational work, a new food finding test (FFT) olfactory paradigm without food deprivation was used to investigate olfaction in old animals. The effects of social isolation in 12-months-old female 3xTg-AD mice, a genetic model of AD, and their age-matched wild-type counterparts, the gold-standard C57BL/6 mice, were also studied. The animals were placed in a test cage and were observed until reaching the criteria for three goal-directed behaviors, ‘Sniffing’, ‘Finding’ and ‘Eating’, towards the hidden food. Video recordings were analyzed blind to the genotype and social condition in order to determine the behaviors’ ethogram and functional correlations. The results showed that the FFT paradigm without food deprivation elicited longer ethograms than previously reported with the standard overnight food deprivation protocol. However, it identified the genotype-dependent olfactory signatures in normal and AD-pathological aging. Social isolation slightly increased the latencies, but the olfactory signatures were preserved. However, a functional derangement was detected since the internal correlation among the three goal-directed behaviors was lost under isolation. In conclusion, the new paradigm without overnight deprivation was sensitive to genotype and isolation changes in the ethogram and function and can be used to study old animals.

Alzheimer’s disease (AD) patients suffer from circadian rhythm alterations affecting their daily physical activity patterns with less willingness to perform a voluntary exercise. In preclinical studies, there is no clarity on whether animal models of AD can replicate these impairments. Here, we provide a proof of concept of the performance and behavioral effects of four weeks of voluntary wheel running (VWR) in a group of 14-month-old male and female 3xTg-AD mice at advanced stages of AD and the daily variance (behavioral circadian rhythmicity) of VWR associated with sex and their neuropsychiatric-like phenotype. Higher levels of horizontal exploration in the open field (OF) test were found in mice submitted to exercise. A linear mixed effect model showed significant sex-dependent differences in the VWR activity performed on the first night of follow-up, with high-NIBI males running less than high-NIBI females. Thus, an influence of NPS-like symptoms on the circadian patterns of VWR may account for such differences. In addition, males remained more active than females during diurnal periods. We hypothesize that this increment in energy expenditure during resting periods may be related to hyperactive behavior, similar to that observed in humans’ exacerbated agitation or sundowning behavior. These findings support the usage of the 3xTg-AD mouse as a reliable model for studying circadian rhythm alterations in AD and, at the translational level, the importance of tailored and individualized physical activity programs in clinical settings.

In Western societies, death is a social and educational taboo. Poor education about death and mourning processes and overprotective family and social attitudes move children away from death to avoid “unnecessary suffering.” The COVID-19 outbreak highlighted these shortcomings and the difficult management of grief's complexity under sudden and unexpected scenarios. The need for immediate and constant updates related to COVID-19 benefited from social media coverage's immediacy. The use of YouTube as a digital platform to disseminate/search for knowledge exploded, raising the need to conduct ethnographic studies to describe this community's people and culture and improve the booming social media's educational capacity and quality. The present virtual ethnography studied 255,862 YouTube views/users and their behavior related to “Vuela Mariposa, Vuela,” a children's story available online since 2009 (not monetized) about the cycle of life, death, and disenfranchised grief (not acknowledged by society) that went viral (+>999%) on May. To our knowledge, this case study is the first original research that explores the ethnography of (i) a viral video, (ii) on death and grief taboo topics, (iii) for prescholars, and (iv) before and during the COVID pandemic. The quantitative and qualitative analyses identified a change in the users' profiles, engagement, and feedback. During the previous 11 years, the users were 35–44 years old Mexican and Spanish women. Those in grief used narrative comments to explain their vital crisis and express their sorrow. In the pandemic, the analysis pointed to Ecuador as the virality geographical niche in a moment when the tragic scenarios in its streets were yet unknown. The timeline match with the official records confirmed the severity of their pandemic scenario. The viral video reached a broad population, with normal distribution for age, and including male gender. Engagement by non-subscribers, direct search (traffic sources), and mean visualization times suggested educational purposes as confirmed by the users' feedback with critical thinking referring to the cycle of life's meaning and societal mourning. For the youngest users, the video was part of academic assignments. The ethnography pointed at YouTube as a flexible education resource, immediately reaching diverse users, and being highly sensitive to critical events.

The increase of the aging population, where quite chronic comorbid conditions are associated with pain, draws growing interest across its investigation and the underlying nociceptive mechanisms. Burn injuries associated problems might be of relevance in the older adult’s daily life, but in people with dementia, exposure to high temperatures and heat sources poses a significantly increased risk of burns. In this brief report, the hind paws and tail pain withdrawal reflexes and the emotional responses to thermal nociception in 3xTg-AD mice were characterized for the first time in the plantar test and compared to their non-transgenic (NTg) counterparts. We studied a cohort of male and female 3xTg-AD mice at asymptomatic (2 months), early (6 months), middle (9 months), and advanced (12 and 15 months) stages of the disease and as compared to sex- and age-matched NTg control mice with normal aging. At 20 and 40W intensities, the sensorial-discriminative thresholds eliciting the withdrawal responses were preserved from asymptomatic to advanced stages of the disease compared to NTg counterparts. Moreover, 3xTg-AD females consistently showed a greater sensory-discriminative sensitivity already at premorbid ages, whereas increased emotionality was shown in males. False-negative results were found in “blind to sex and age” analysis, warning about the need to study sexes independently. The current results and previous report in cold thermal stimulation provide two paradigms unveiling sex-specific early AD-phenotype nociceptive biomarkers to study the mechanistic underpinnings of sex-, age- and AD-disease-dependent thermal pain sensitivity.

Depression, stress, anxiety disorders, and PTSD are some of the mental health problems that are prevalent among immigrant populations despite being underdiagnosed. Stigma, difficulties in adapting, cultural barriers, and reduced access to mental health support can seriously hamper their ability to build resilience and recover. Other limitations include assuming that therapies can be universally applied, the lack of sufficient evidence on mental health issues of this population, and the use of therapeutic models developed on Caucasian populations. Here, professional guidance to find the meaning of life through interventions such as logotherapy could help them in this process. The present work systematically reviewed studies investigating the effectiveness of logotherapy in diverse populations and its relevance to a Muslim immigrant population in Europe. Following PRISMA guidelines and the keywords ‘logotherapy, mental health problems, immigrant, and treatment’, the search identified 16 relevant studies conducted since 2005. The studies revealed that logotherapy could be implemented through paradoxical intention, de-reflection, Socratic dialogue, and attitude modification. All these techniques have the potential to help the client to realize long-term relief for underlying stressors associated with migration and settling in a new location. Though data on logotherapy are still scarce, it is evident that it deserves more research so that a structured, evidence-based, and effective therapy for Muslim immigrants in Europe can be developed and tested. In this regard, we propose that the four logotherapy techniques have huge potential in helping psychiatrists develop an effective therapy for mental health problems among these immigrant populations confronting adversity.

The crosstalk between obesity, diabetes, steatohepatitis, and dementia creates a controversial scenario when also studied using animal models. In the present work, this crosstalk was investigated in male and female 3xTg-AD mice for Alzheimer’s disease (AD) at different ages/stages and compared to sex- and age-matched counterparts with normal aging. The relevance of the genetic background and classical intrinsic factors (AD genotype and sex) were determined using a retrospective analysis of population data and an experimental design. Age/stage of disease was considered a source of stochastic and non-stochastic factors. Data from two different colonies of 3xTg-AD mice with distinct genetic backgrounds were analyzed to verify the functional interplay between the studied factors. Data from asymptomatic/prodromal to early/advanced stages of the disease were screened. Then, all factors’ relationships were studied in an experimental design using the same set of animals. The population data unveiled that the genetic background and sex effects were confirmed with regards to the variable body weight, with changes during disease development and progress. Sexual dimorphism was found as an important factor in glucose metabolism. Statistically significant differences in glucose tolerance and behavioral assessment (exploration, anxiety, and cognition in a two-days open-field paradigm) were found when all the factors were analyzed. In summary, the present study shows that all the studied factors should always be considered when assessing the outcome of the research interventions in the field because they have a distinct functional interplay through the process of normal and AD-pathological aging and from a gendered perspective.