A longitudinal MRI analysis reveals altered brain connectivity and microstructural changes in a transgenic mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is characterized by progressive cognitive decline and neuropathological changes, yet the underlying neurobiological mechanisms remain elusive. Here, we employed a multimodal longitudinal neuroimaging approach, using anatomical and functional sequences on a high field magnetic resonance imaging (MRI) preclinical scanner, to investigate alterations in brain connectivity and white matter microstructure in a transgenic mouse model of AD (J20) when compared to wild-type (WT) littermates. Functional connectivity analysis revealed distinct network disruptions in J20 mice, primarily involving connections between posterior and anterior brain regions; importantly, a significant interaction between group and age highlighted an exacerbation of these connectivity changes with advancing age in J20 mice. In addition, significant reductions in fractional anisotropy (FA) were observed in the corpus callosum of J20 mice compared to WT, indicative of microstructural alterations consistent with white matter pathology. The observed alterations in brain connectivity and microstructure provide valuable insights into the spatiotemporal processes underlying AD-related decline and underscore the utility of multimodal neuroimaging in elucidating the neurobiological substrates of AD pathology in animal models.

Exploring the relationship between Total Athleticism score and CrossFit® Open Performance in amateur athletes: single measure involving body fat percentage, aerobic capacity, muscle power and local muscle endurance.

There has been an increasing interest among CrossFit® coaches and practitioners in identifying indicators of sport performance. This study aimed to examine the correlation between anthropometric measures, cardiorespiratory capacity, power, local muscle endurance, and total athleticism score, with performance in the CrossFit® Open 2021. Fourteen male volunteers (aged 30.3 ± 5.8 years) participated in the study and underwent a series of tests on separate weeks. These tests included assessments of body fat percentage (subcutaneous adipose thickness measured at seven sites), maximal oxygen consumption (2 km test in rowing ergometer), muscle power (one repetition maximum in power clean), and muscle endurance (Tibana test, which included the conclusion of four distinct rounds of work). These results were used to calculate the total score of athleticism, which was then compared to the participants performance during the CrossFit® Open 2021. The athletes presented an average of body fat (8.6 ± 2.0%), maximal oxygen consumption (53.3 ± 2.4 mL. (kg.min)-1), 2km row time (07:00 ± 00:21 mm:ss), 1-Repetition maximum in power clean (125.2 ± 21.2 kg) and Tibana test performance (281.0 ± 35.9 repetitions). Interestingly, the top five athletes with the highest scores also achieved the highest z-scores in the CrossFit® Open 2021. Conversely, the four athletes with the lowest TSA score had the lowest z-scores in the CrossFit® Open. Moreover, almost perfect correlation (r = 0.91; p<0.01) was found between the total athleticism score and z-scores in the CrossFit® Open 2021. The total score may be a single measure and holistic indication of athleticism level in CrossFit®. Furthermore, coaches can potentially apply this useful tool for monitoring athletic performance and designing training sessions that address specific areas of CrossFit® performance.

Development and optical characterisation of agarose-based phantoms mimicking biological tissues for studies of light penetration in the brain.

Searching for materials that accurately mimic the optical properties of biological tissues is essential, particularly for transcranial photobiomodulation (PBM) research, where it is necessary to comprehend how light propagates through the head tissues. In this research, we characterised, in the 500-1200 nm range, the transmittance spectra of porcine tissues (skin, muscle, cranium, brain, and cerebellum) and different agarose-based phantoms. These phantoms were developed using different combinations of titanium dioxide (TiO2), India ink, organometallic compounds, and laser-ablated gold and zinc oxide nanoparticles. The surface and mechanical properties of these phantoms were also characterized. The results showed that an increased TiO2 concentration decreased the optical transmittance of the phantoms. However, when TiO2 was added to the India ink and laser-ablated nanoparticles' phantoms, not only did it reduce transmittance amplitude, but it also flattened its spectra. Comparing the phantoms and biological tissues' results, the spectral profiles of TiO2 samples appeared similar to those of muscle, skin, and brain/cerebellum; organometallic compounds replicated the skin and muscle curves; India ink emulated skin and cranium; and the laser-ablated nanoparticles mimicked the muscle. Although it was possible to establish qualitative similarities between the phantoms and the biological tissues' optical transmittance spectra, there is a need for further studies with different components' combinations to ascertain curves that more closely mimic the biological tissues.

Unveiling the molecular landscape of cognitive aging: insights from polygenic risk scores, DNA methylation, and gene expression.

BACKGROUND: Aging represents a significant risk factor for the occurrence of cerebral small vessel disease, associated with white matter (WM) lesions, and to age-related cognitive alterations, though the precise mechanisms remain largely unknown. This study aimed to investigate the impact of polygenic risk scores (PRS) for WM integrity, together with age-related DNA methylation, and gene expression alterations, on cognitive aging in a cross-sectional healthy aging cohort. The PRSs were calculated using genome-wide association study (GWAS) summary statistics for magnetic resonance imaging (MRI) markers of WM integrity, including WM hyperintensities, fractional anisotropy (FA), and mean diffusivity (MD). These scores were utilized to predict age-related cognitive changes and evaluate their correlation with structural brain changes, which distinguish individuals with higher and lower cognitive scores. To reduce the dimensionality of the data and identify age-related DNA methylation and transcriptomic alterations, Sparse Partial Least Squares-Discriminant Analysis (sPLS-DA) was used. Subsequently, a canonical correlation algorithm was used to integrate the three types of omics data (PRS, DNA methylation, and gene expression data) and identify an individual "omics" signature that distinguishes subjects with varying cognitive profiles. RESULTS: We found a positive association between MD-PRS and long-term memory, as well as a correlation between MD-PRS and structural brain changes, effectively discriminating between individuals with lower and higher memory scores. Furthermore, we observed an enrichment of polygenic signals in genes related to both vascular and non-vascular factors. Age-related alterations in DNA methylation and gene expression indicated dysregulation of critical molecular features and signaling pathways involved in aging and lifespan regulation. The integration of multi-omics data underscored the involvement of synaptic dysfunction, axonal degeneration, microtubule organization, and glycosylation in the process of cognitive aging. CONCLUSIONS: These findings provide valuable insights into the biological mechanisms underlying the association between WM coherence and cognitive aging. Additionally, they highlight how age-associated DNA methylation and gene expression changes contribute to cognitive aging.

Detection of active SARS-CoV-2 in cough aerosols from COVID-19 patients.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an airborne pathogen, but detection of infectious SARS-CoV-2 in air and in particular the introduction of the virus into the environment by different human expiratory manoeuvres is not well studied. OBJECTIVES: The aim of this study was to investigate the presence of SARS-CoV-2 in cough from coronavirus disease of 2019 (COVID-19) in-patients and to study contamination of the virus in the patient's environment. METHODS: Detection of SARS-CoV-2 in cough was analyzed by PCR, culture and imaging. Detection in cough was compared to presence of the virus in air and on surfaces from patient rooms. RESULTS: Twenty-five patients in 21 rooms were included in the study. SARS-CoV-2 RNA was found in cough aerosols from 16 out of 22 patients that produced voluntary cough. As demonstrated by plaque-forming unit assays, active virus was isolated from 11 of these 16 patients. Using mainly molecular detection, the virus was also found in air, on high-contact surfaces, and no-touch surfaces from the room of the COVID-19 patients. CONCLUSIONS: These results show that infectious SARS-CoV-2 circulating in air can originate from patient cough and should be considered against the risk of acquiring COVID-19 through inhalation.

Nurses' Role in the Control and Treatment of Asthma in Adults: A Systematic Literature Review.

Bronchial asthma is a chronic pathology and a global public health problem. However, asthma can be controlled and treated for the most part by patients, so the Portuguese General Directorate of Health recommends shared medical appointments in primary health care (PHC). The present study aims to identify the role of PHC nurses in the control and treatment of asthma in adults. Using the MeSH platform, the following descriptors were validated: asthma, nurses, adults. An individual search was carried out in the following databases: CINAHL (ESBSCO host), MEDLINE (Pubmed host), Web of Science, and Scopus. Out of a total of 280 publications, 79 of which were duplicates and 185 publications which did not meet the inclusion criteria, 16 publications remained readable. Of the eligible articles, there were 13 specialist reports, one mixed study, one quasi-experimental study, and one randomized trial. Education was the intervention most identified in the scientific evidence analyzed, and patient assessment, application of an asthma control questionnaire, verification and training of inhalation technique, empowerment for self-management of the disease, support, promotion of seasonal influenza vaccination, and use of written action plans were also identified. The results reveal that, although the scientific evidence on the intervention of these professionals is poorly developed, nurses play a crucial role in the control and treatment of asthma. The scientific evidence analyzed allowed the identification of interventions that can help the organization of a nursing health appointment, providing nurses with a crucial role in the control and treatment of asthma in adults in the context of PHC.

Physiological and behavioral contagion/buffering effects of chronic unpredictable stress in a socially enriched environment: A preliminary study.

Rodents are sensitive to the emotional state of conspecifics. While the presence of affiliative social partners mitigates the physiological response to stressors (buffering), the partners of stressed individuals show behavioral and endocrine changes indicating that stress parameters can be transmitted across the group members (contagion). In this study, we investigated the social contagion/buffering phenomena in behavior and neuroendocrine mechanisms after exposure to chronic stress, in groups of rats living in the PhenoWorld (PhW). Three groups were tested (8 stressed rats, 8 unstressed rats, and a mixed group with 4 and 4) and these were analyzed under 4 conditions: stressed (pure stress group, n = 8), unstressed (naive control group, n = 8), stressed from mixed group (stressed companion group, n = 8), unstressed from mixed group (unstressed companion group, n = 8. While naive control animals remained undisturbed, pure stress group animals were all exposed to stress. Half of the animals under the mixed-treatment condition were exposed to stress (stressed companion group) and cohabitated with their unstressed partners (unstressed companion group). We confirmed the well-established chronic unpredictable stress (CUS) effects in physiological, behavioral, and neuroendocrine endpoints; body weight gain, open arm entries and time in EPM, and oxytocin receptor expression levels in the amygdala decreased by stress exposure, whereas adrenal weight was increased by stress. Furthermore, we found that playing, rearing and solitary resting behaviors decreased, whereas huddling behavior increased by CUS. In addition, we detected significant increases (stress-buffering) in body weight gain and huddling behaviors between pure stress and stress companion animals, and significant stress contagion effects in emotional behavior and oxytocin receptor expression levels between naive control and control companion groups. Hence, we demonstrate buffering and contagion effects were evident in physiological parameters, emotional behaviors, and social home-cage behaviors of rats and we suggest a possible mediation of these effects by oxytocin neurotransmission. In conclusion, the results herein suggest that the stress status of animals living in the same housing environment influences the behavior of the group.

Devices used for photobiomodulation of the brain-a comprehensive and systematic review.

A systematic review was conducted to determine the trends in devices and parameters used for brain photobiomodulation (PBM). The revised studies included clinical and cadaveric approaches, in which light stimuli were applied to the head and/or neck. PubMed, Scopus, Web of Science and Google Scholar databases were used for the systematic search. A total of 2133 records were screened, from which 97 were included in this review. The parameters that were extracted and analysed in each article were the device design, actuation area, actuation site, wavelength, mode of operation, power density, energy density, power output, energy per session and treatment time. To organize device information, 11 categories of devices were defined, according to their characteristics. The most used category of devices was laser handpieces, which relate to 21% of all devices, while 28% of the devices were not described. Studies for cognitive function and physiological characterisation are the most well defined ones and with more tangible results. There is a lack of consistency when reporting PBM studies, with several articles under defining the stimulation protocol, and a wide variety of parameters used for the same health conditions (e.g., Alzheimer's or Parkinson's disease) resulting in positive outcomes. Standardization for the report of these studies is warranted, as well as sham-controlled comparative studies to determine which parameters have the greatest effect on PBM treatments for different neurological conditions.

Nucleus accumbens neurons dynamically respond to appetitive and aversive associative learning.

To survive, individuals must learn to associate cues in the environment with emotionally relevant outcomes. This association is partially mediated by the nucleus accumbens (NAc), a key brain region of the reward circuit that is mainly composed by GABAergic medium spiny neurons (MSNs), that express either dopamine receptor D1 or D2. Recent studies showed that both populations can drive reward and aversion, however, the activity of these neurons during appetitive and aversive Pavlovian conditioning remains to be determined. Here, we investigated the relevance of D1- and D2-neurons in associative learning, by measuring calcium transients with fiber photometry during appetitive and aversive Pavlovian tasks in mice. Sucrose was used as a positive valence unconditioned stimulus (US) and foot shock was used as a negative valence US. We show that during appetitive Pavlovian conditioning, D1- and D2-neurons exhibit a general increase in activity in response to the conditioned stimuli (CS). Interestingly, D1- and D2-neurons present distinct changes in activity after sucrose consumption that dynamically evolve throughout learning. During the aversive Pavlovian conditioning, D1- and D2-neurons present an increase in the activity in response to the CS and to the US (shock). Our data support a model in which D1- and D2-neurons are concurrently activated during appetitive and aversive conditioning.

Negative associations between maternal prenatal hair cortisol and child socioemotional problems.

Maternal prenatal distress can participate in the programming of offspring development, in which exposure to altered maternal long-term cortisol levels as measured by hair cortisol concentrations (HCC) may contribute. Yet, studies investigating whether and how maternal prenatal HCC associates with problems in child socioemotional development are scarce. Furthermore, questions remain regarding the timing and potential sex-specificity of fetal exposure to altered cortisol levels and whether there are interactions with maternal prenatal distress, such as depressive symptoms. The subjects were drawn from those FinnBrain Birth Cohort families that had maternal reports of child socioemotional problems (the Brief Infant-Toddler Social and Emotional Assessment [BITSEA] at 2 years and/or the Strengths and Difficulties Questionnaire [SDQ] at 5 years) as follows: HCC1 population: maternal mid-pregnancy HCC measured at gestational week 24 with 5 cm segments to depict cortisol levels from the previous five months (n = 321); and HCC2 population: end-of-pregnancy HCC measured 1-3 days after childbirth (5 cm segment; n = 121). Stepwise regression models were utilized in the main analyses and a sensitivity analysis was performed to detect potential biases. Negative associations were observed between maternal HCC2 and child BITSEA Total Problems at 2 years but not with SDQ Total difficulties at 5 years, and neither problem score was associated with HCC1. In descriptive analyses, HCC2 was negatively associated with Internalizing problems at 2 years and SDQ Emotional problems at 5 years. A negative association was observed among 5-year-old girls between maternal HCC1 and SDQ Total Difficulties and the subscales of Conduct and Hyperactivity/inattentive problems. When interactions were also considered, inverse associations between HCC2 and BITSEA Internalizing and Dysregulation Problems were observed in subjects with elevated prenatal depressive symptoms. It was somewhat surprising that only negative associations were observed between maternal HCC and child socioemotional problems. However, there are previous observations of elevated end-of-pregnancy cortisol levels associating with better developmental outcomes. The magnitudes of the observed associations were, as expected, mainly modest. Future studies with a focus on the individual changes of maternal cortisol levels throughout pregnancy as well as studies assessing both maternal and child HPA axis functioning together with child socioemotional development are indicated.

A Cardiopulmonary Exercise Testing for Prescribing High-Intensity Interval Training Sessions with Elastic Resistance.

This study aims to analyze the agreement of cardiopulmonary variables between a cardiopulmonary exercise test with elastic resistance (CPxEL) and high-intensity interval exercise with elastic resistance (EL-HIIE). METHODS: Twenty-two physically independent participants were recruited. Visit one consisted of conducting a health survey and anthropometric assessment. On visit two, the participants performed CPxEL. After seven days, on visit three, the participants performed EL-HIIE. The CPxEL was carried out on a rubber mat demarcated by lines representing eight stages. The test consisted of alternating back and forth steps against elastic resistance. The increments were performed at a rate of one stage per minute, following a cadence controlled by a metronome calibrated by beats per minute (bpm). The EL-HIIE was performed at the stage corresponding to an intensity of ~85% VO2max, as determined by CPxEL. The EL-HIIE consisted of 10 × 1 min (work):1 min (passive rest), with a cadence of 200 bpm. Cardiopulmonary parameters, heart rate (HR), and oxygen consumption (VO2) were measured during exercise. Bland-Altman was applied to analyze the agreement between the HR and VO2 found in EL-HIIE and the values prescribed by CPxEL (~85-90% VO2max). RESULTS: The HRpeak and VO2peak in the EL-HIIE showed good agreement with the VO2CPxEL and HRCPxEL values, showing an average difference of (-1.7 mL·kg-1·min-1) and (0.3 bpm). CONCLUSIONS: The results of the present study demonstrate the agreement of cardiopulmonary variables between the CPxEL and the EL-HIIE. Therefore, for a more specific prescription of EL-HIIE intensity, CPxEL can be used.

Omission of axillary lymph node dissection in breast cancer patients with micrometastasis or isolated tumor cells in sentinel lymph nodes: a 12-year experience in a tertiary breast unit.

INTRODUCTION: After the IBCSG 23-01 trial, our breast center no longer performed axillary lymph node dissection (ALND) after detection of isolated tumor cells (ITC) or micrometastasis in the sentinel lymph nodes (SLN). A recent study suggested that up to half of the patients with micrometastasis in the SLN could benefit from ALND in terms of disease-free survival (DFS) and overall survival (OS). METHODS: This retrospective, unicentric, study analyzed 261 consecutive cT1-3 cN0 breast cancer patients with ITC or micrometastasis in their SLN. Primary objective was comparison of ALND vs. SLN biopsy (SLNB) with regard to DFS and OS. Secondary objectives included analysis of factors associated with an increased rate of locoregional recurrence (LRR), distant metastasis (DM) and metachronous contralateral breast cancer (MCBC). RESULTS: DFS events occurred in 19 patients (7.3%) and 14 patients died (5.4%). Median follow-up time was 78 months. 251 patients (96.2%) had micrometastasis in their SLN. There was no difference in the OS or DFS of ALND vs. SLNB patients. History of previous contralateral breast cancer and WBI were associated with an increased and decreased rate of LRR, respectively. Larger tumor size was associated with an increased rate of DM. Non-ductal histological types were associated with an increased rate of MCBC. DISCUSSION: Avoiding ALND may be safe in pN1mi/pN0(i+) patients. Besides, we strongly encourage clinicians to develop their own follow-up protocols based on the best available evidence, to rapidly identify and treat breast cancer recurrence.

A hitchhikers' guide to the terminology of accreditation processes for health professionals and institutions.

Accreditation processes for health care professions are designed to ensure that individuals and programs in these fields meet established standards of quality and effectiveness. The accelerating pace of globalization in the health care professions has increased the need for a shared understanding of the vocabulary of evaluation, assessment, and accreditation. The psychometric principles of valid and reliable assessment are commonly accepted, but the terminology is confusing. We believe that all stakeholders - evaluators, faculty, students but also the community - will benefit from a shared language and common set of definitions. We recognize that not all readers will agree with the definitions we propose, but we hope that this guide will help to ensure clarity, consistency, transparency, and fairness, and that it will promote through the stimulation of a debate greater collaboration across national and international boundaries.

Astrocytes Undergo Metabolic Reprogramming in the Multiple Sclerosis Animal Model.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that presents a largely unknown etiopathology. The presence of reactive astrocytes in MS lesions has been described for a long time; however, the role that these cells play in the pathophysiology of MS is still not fully understood. Recently, we used an MS animal model to perform high-throughput sequencing of astrocytes' transcriptome during disease progression. Our data show that astrocytes isolated from the cerebellum (a brain region typically affected in MS) showed a strong alteration in the genes that encode for proteins related to several metabolic pathways. Specifically, we found a significant increase in glycogen degradation, glycolytic, and TCA cycle enzymes. Together with these alterations, we detected an upregulation of genes that characterize "astrocyte reactivity". Additionally, at each disease time point we also reconstructed the morphology of cerebellum astrocytes in non-induced controls and in EAE animals, near lesion regions and in the normal-appearing white mater (NAWM). We found that near lesions, astrocytes presented increased length and complexity compared to control astrocytes, while no significant alterations were observed in the NAWM. How these metabolic alterations are linked with disease progression is yet to be uncovered. Herein, we bring to the literature the hypothesis of performing metabolic reprogramming as a novel therapeutic approach in MS.

Larotrectinib efficacy and safety in adult patients with tropomyosin receptor kinase fusion sarcomas.

BACKGROUND: Larotrectinib, a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor, has demonstrated efficacy in adult and pediatric patients with various solid tumors harboring NTRK gene fusions. This subset analysis focuses on the efficacy and safety of larotrectinib in an expanded cohort of adult patients with TRK fusion sarcomas. METHODS: Patients (≥18 years old) with sarcomas harboring NTRK gene fusions were identified from three clinical trials. Patients received larotrectinib 100 mg orally twice daily. Response was investigator-assessed per RECIST v1.1. Data cutoff was July 20, 2021. RESULTS: At the data cutoff, 36 adult patients with TRK fusion sarcomas had initiated larotrectinib therapy: two (6%) patients had bone sarcomas, four (11%) had gastrointestinal stromal tumors, and 30 (83%) had soft tissue sarcomas. All patients were evaluable for response and demonstrated an objective response rate of 58% (95% confidence interval, 41-74). Patients responded well to larotrectinib regardless of number of prior lines of therapy. Adverse events (AEs) were mostly grade 1/2. Grade 3 treatment-emergent AEs (TEAEs) occurred in 15 (42%) patients. There were no grade 4 TEAEs. Two grade 5 TEAEs were reported, neither of which were considered related to larotrectinib. Four (11%) patients permanently discontinued treatment due to TEAEs. CONCLUSIONS: Larotrectinib demonstrated robust and durable responses, extended survival benefit, and a favorable safety profile in adult patients with TRK fusion sarcomas with longer follow-up. These results continue to demonstrate that testing for NTRK gene fusions should be incorporated into the clinical management of adult patients with various types of sarcomas. PLAIN LANGUAGE SUMMARY: Tropomyosin receptor kinase (TRK) fusion proteins result from translocations involving the NTRK gene and cause cancer in a range of tumor types. Larotrectinib is an agent that specifically targets TRK fusion proteins and is approved for the treatment of patients with TRK fusion cancer. This study looked at how well larotrectinib worked in adult patients with sarcomas caused by TRK fusion proteins. Over half of patients had a durable response to larotrectinib, with no unexpected side effects. These results show that larotrectinib is safe and effective in adult patients with TRK fusion sarcomas.

The Shank3-InsG3680(+/+) mouse model of autism spectrum disorder displays auditory avoidance in a novel behavioral test.

Introduction: Autism spectrum disorder (ASD) is characterized by deficits in communication and social interaction, restricted interests, repetitive behaviors, and sensory alterations, with auditory hypersensitivity being one of the most commonly reported sensory-perceptual abnormalities. Several candidate genes for involvement in this disorder have emerged from patient studies, including SHANK3, a gene that encodes a protein (SHANK3) in the postsynaptic density of excitatory synapses. Previous work has shown that mutant mice carrying a human ASD mutation in the Shank3 gene (InsG3680) exhibit repetitive behaviors and social interaction deficits, indicating important construct and face validity for this genotype as an animal model of ASD. Methods: To further address whether these mice also present auditory sensory-perceptual alterations, we developed a novel behavioral test in which mice can choose between different soundscapes. Results: Our results reveal that, in comparison to wild-type mice, Shank3 mutants display a strong behavioral preference toward silent regions of the arena. Discussion: These data suggest that Shank3- mutant mice might express an auditory hypersensitivity phenotype, further adding to the face validity of this genotype as an animal model of ASD.

Pattern recognition of hematological profiles of tumors of the digestive tract: an exploratory study.

Aims: In this study, we aimed to apply laboratory blood analysis to identify the hematological (based on hemoglobin concentration, erythrocytes, hematocrit, and RDW count) profiles associated with the most prevalent forms of digestive tract malignancies. Furthermore, we aimed to evaluate how these profiles contributed to distinguishing these tumors at diagnosis. Methods: We collected data from the date of ICD-10 diagnostic coding for C15 esophagus, C16 stomach, C18 colon, and C19 rectum tumors of 184 individuals. The statistical analysis and data visualization approaches, notably the heat map and principal component analysis (PCA), allowed for creating a summary hematological profile and identifying the most associated parameters for each pathologic state. Univariate and multivariate data modeling and ROC analysis were performed in both SPSS and Python. Results: Our data reveal unique patterns based on tumor development anatomical location, clustering the C18 colon and C19 rectum from the C15 esophagus and C16 stomach. We found a significant difference between C16 stomach carcinoma and the other tumors, which substantially correlated with raised RDW in conjunction with low hemoglobin concentration, erythrocytes, and hematocrit counts. In contrast, C18 colon carcinoma had the higher red blood cell count, allowing for the best classification metrics in the test set of the binary logistic regression (LR) model, accounting for an AUC of 0.77 with 94% sensitivity and 52% specificity. Conclusion: This study emphasizes the significance of adding hematological patterns in diagnosing these malignancies, which could path further investigations regarding profiling and monitoring at the point of care.

Involvement of nucleus accumbens D2-medium spiny neurons projecting to the ventral pallidum in anxiety-like behaviour.

BACKGROUND: The nucleus accumbens (NAcc) is a crucial brain region for emotionally relevant behaviours. The NAcc is mainly composed of medium spiny neurons (MSNs) expressing either dopamine receptor D1 (D1-MSNs) or D2 (D2-MSNs). The D1-MSNs project to the ventral tegmental area (VTA) and the ventral pallidum (VP), whereas the D2-MSNs project only to the VP. The D1- and D2-MSNs have been associated with depression-like behaviours, but their contribution to anxiety remains to be determined. METHODS: We used optogenetic tools to selectively manipulate D1-MSN projections from the NAcc core to the VP or VTA and D2-MSN projections to the VP during validated anxiety-producing behavioural procedures in naive mice. In addition, we assessed the effects of optical stimulation on neuronal activity using in vivo electrophysiologic recordings in anesthetized animals. RESULTS: Optogenetic activation of D1-MSN projections to the VTA or VP did not trigger anxiety-like behaviour. However, optical activation of D2-MSN projections to the VP significantly increased anxiety-like behaviour. This phenotype was associated with a decrease in the neuronal activity of putative GABAergic neurons in the VP. Importantly, pretreating D2-MSN-VP animals with the γ-aminobutyric acid modulator diazepam prevented the optically triggered anxiety-like behaviour. LIMITATIONS: The exclusive use of males in the behavioural tests limits broader interpretation of the findings. Although we used optogenetic conditions that trigger quasi-physiologic changes, there are caveats associated with the artificial manipulation of neuronal activity. CONCLUSION: The D2-MSN-VP projections contributed to the development of anxiety-like behaviour, through modulation of GABAergic activity in the VP.

Chronic Stress, Depression, and Alzheimer's Disease: The Triangle of Oblivion.

Chronic stress and high levels of the main stress hormones, and glucocorticoids (GC), are implicated in susceptibility to brain pathologies such as depression and Alzheimer's disease (AD), as they promote neural plasticity damage and glial reactivity, which can lead to dendritic/synaptic loss, reduced neurogenesis, mood deficits, and impaired cognition. Moreover, depression is implicated in the development of AD with chronic stress being a potential link between both disorders via common neurobiological underpinnings. Hereby, we summarize and discuss the clinical and preclinical evidence related to the detrimental effect of chronic stress as a precipitator of AD through the activation of pathological mechanisms leading to the accumulation of amyloid ß (Aß) and Tau protein. Given that the modern lifestyle increasingly exposes individuals to high stress loads, it is clear that understanding the mechanistic link(s) between chronic stress, depression, and AD pathogenesis may facilitate the treatment of AD and other stress-related disorders.