Level Of Impairment Research Articles

Efficiency and safety of Vortioxetine in the treatment of depressive disorders in cardiac patients

Importance of the problem. Diseases of the cardiovascular system are in the first place among the causes of death and disability in most industrialized countries, which is undoubtedly an urgent medical and social problem and causes significant economic damage. The prevalence of depressive disorders in modern society, according to WHO estimates, is quite high, and the causes of depressive disorders and methods for their correction in patients with various somatic diseases have been the subject of study by specialists around the world for many decades. The comorbidity of depressive disorders with cardiac pathology is beyond doubt, and the bidirectional relationship of these disorders significantly aggravates the condition of patients, worsens their quality of life and reduces adherence to treatment. The most important conditions for the use of antidepressants in cardiology practice are good tolerability, absence of toxic effect, minimal interaction with other drugs, and relative safety in case of overdose. Vortioxetine, being a modern multimodal antidepressant, demonstrates not only a sufficiently high antidepressant and anti-anxiety activity, but also has a procognitive effect, as well as minimal side effects and undesirable cross-interactions with other drugs, which is confirmed by international randomized placebo-controlled trials. The aim of this work was to evaluate the efficacy and safety of Vortioxetine in the treatment of concomitant depressive disorders in patients with coronary heart disease (CHD), angina pectoris 2-3 functional class (FC) (I 20.8 according to ICD-10), receiving complex therapy for the main (cardiological) diseases at the inpatient and outpatient stages of therapy. Materials and methods. The study included patients with a diagnosis of coronary artery disease, angina pectoris FC 2-3, hypertension 2-3, aged 45 to 66 years (mean age 57.1±1.1 years), receiving complex therapy for the underlying cardiac disease and Vortioxetine at a dose of 10-15 mg/day. within 8 weeks. Anxiety and depressive manifestations were assessed on the HADS scale, the level of cognitive impairment on the PDQ questionnaire, social functioning on the SF-36 questionnaire, the general clinical impression on the CGI-C scale, and the main indicators of the functioning of the cardiovascular system upon admission to the hospital, after 4 weeks of hospitalization. treatment and another 4 weeks after discharge during the period of outpatient observation.The result of the combined therapy of patients with cardiac pathology and concomitant depressive disorder (basic therapy for CVD and Vortioxetine) was not only an improvement in the cardiovascular system (decrease in heart rate, blood pressure, the frequency of anginal pain, an increase in exercise tolerance), but also the relief of depressive manifestations, which contributed to an increase in the adherence of cardiological patients to the implementation of medical recommendations, and, in turn, led to a decrease in the level of end points—mortality, hospitalization rates, progression of chronic heart failure and disability. Conclusions. Appointment of Vortioxetine to cardiac patients with concomitant depressive disorder of moderate severity is quite effective not only in terms of relief of painful manifestations of the CVS, but also leads to a reduction in anxiety-depressive disorders and an improvement in cognitive and social functioning. The good tolerability of the drug makes it possible to recommend it for the treatment of depressive disorders in cardiological patients in a hospital setting and in outpatient practice.

Reading and lexical–semantic retrieval tasks outperforms single task speech analysis in the screening of mild cognitive impairment and Alzheimer's disease

Age-related cognitive impairment have increased dramatically in recent years, which has risen the interes in developing screening tools for mild cognitive impairment and Alzheimer's disease. Speech analysis allows to exploit the behavioral consequences of cognitive deficits on the patient's vocal performance so that it is possible to identify pathologies affecting speech production such as dementia. Previous studies have further shown that the speech task used determines how the speech parameters are altered. We aim to combine the impairments in several speech production tasks in order to improve the accuracy of screening through speech analysis. The sample consists of 72 participants divided into three equal groups of healthy older adults, people with mild cognitive impairment, or Alzheimer's disease, matched by age and education. A complete neuropsychological assessment and two voice recordings were performed. The tasks required the participants to read a text, and complete a sentence with semantic information. A stepwise linear discriminant analysis was performed to select speech parameters with discriminative power. The discriminative functions obtained an accuracy of 83.3% in simultaneous classifications of several levels of cognitive impairment. It would therefore be a promising screening tool for dementia.

Speech-in-noise perception in autistic adolescents with and without early language delay.

Speech-in-noise perception seems aberrant in individuals with autism spectrum disorder (ASD). Potential aggravating factors are the level of linguistic skills and impairments in auditory temporal processing. Here, we investigated autistic adolescents with and without language delay as compared to non-autistic peers, and we assessed speech perception in steady-state noise, temporally modulated noise, and concurrent speech. We found that autistic adolescents with intact language capabilities and not those with language delay performed worse than NT peers on words-in-stationary-noise perception. For the perception of sentences in stationary noise, we did not observe significant group differences, although autistic adolescents with language delay tend to perform worse in comparison to their TD peers. We also found evidence for a robust deficit in speech-in-concurrent-speech processing in ASD independent of language ability, as well as an association between early language delay in ASD and inadequate temporal speech processing. We propose that reduced voice stream segregation and inadequate social attentional orienting in ASD result in disproportional informational masking of the speech signal. These findings indicate a speech-in-speech processing deficit in autistic adolescents with broad implications for the quality of social communication.

Enhancing Cognition in Older Adults with Mild Cognitive Impairment through High-Intensity Functional Training: A Single-Blind Randomized Controlled Trial.

Physical exercise is a very promising non-pharmacological approach to prevent or reduce the cognitive decline that occurs in people aged 60 years or older. The objective of this study was to determine the effect of a high-intensity intervallic functional training (HIFT) program on cognitive functions in an elderly Colombian population with mild cognitive impairment. A controlled clinical trial was developed with a sample of 132 men and women aged >65 years, linked to geriatric care institutions, which were systematically blind randomized. The intervention group (IG) received a 3-month HIFT program (n = 64) and the control group (CG) (n = 68) received general physical activity recommendations and practiced manual activities. The outcome variables addressed cognition (MoCA), attention (TMTA), executive functions (TMTB), verbal fluency (VFAT test), processing speed (Digit Symbol Substitution Test-DSST), selective attention and concentration (d2 test). After the analysis, improvement was found in the IG with significant differences with respect to the CG in the level of cognitive impairment (MoCA), attention (TMTA), verbal fluency and concentration (p < 0.001). Executive functions (TMTB) showed differences in both groups, being slightly higher in the IG (p = 0.037). However, no statistically significant results were found for selective attention (p = 0.55) or processing speed (p = 0.24). The multiple analysis of covariance (MANCOVA) showed the influence of the education level on all cognition assessments (p = 0.026); when adjusting for sociodemographic variables, the influence of the intervention remained significant (p < 0.001). This study empirically validates that the implementation of a HIFT program has a positive effect on cognitive functions in elderly people with mild cognitive impairment. Therefore, professionals specialized in the care of this population could consider including functional training programs as an essential part of their therapeutic approaches. The distinctive features of this program, such as its emphasis on functional training and high intensity, appear to be relevant for stimulating cognitive health in the geriatric population.

Association between cognitive diagnosis and a range of significant life events in an elderly essential tremor cohort: a longitudinal, prospective analysis.

Although essential tremor (ET) patients have greater odds of mild cognitive impairment (MCI) and dementia than age-matched controls, the functional consequences of these enhanced odds are unknown. We examined associations between cognitive diagnosis and the occurrence of near falls, falls, use of a walking aid or a home health aide, non-independent living, or hospitalizations within a prospective, longitudinal study of ET patients. A total of 131 ET patients (mean baseline age = 76.4 ± 9.4 years) completed a battery of neuropsychological tests and questions about life events and were assigned diagnoses of normal cognition (NC), MCI, or dementia at the baseline and at 18-, 36-, and 54-month follow-ups. Kruskall-Wallis, chi-square, and Mantel-Haenszel tests assessed whether the diagnosis was associated with the occurrence of these life events. Patients with final diagnoses of dementia were more often reported as living non-independently than NC or MCI patients and more often used walking aids than NC patients, with a p-value of <0.05. Patients with a final MCI or dementia diagnosis more often employed a home health aide than NC patients, with a p-value of <0.05. Moreover, Mantel-Haenzsel tests revealed linear associations between the occurrence of these outcomes and the level of cognitive impairment, with a p-value of <0.001 (i.e., dementia > MCI > NC). Cognitive diagnosis was associated with reported life events of ET patients, including the use of a mobility aid, employment of a home health aide, and removal from an independent living situation. These data provide rare insights into the important role cognitive decline plays in the experiences of ET patients.

Comparable Response Following Exposure to Biodiesel and Diesel Exhaust Particles in Advanced Multicellular Human Lung Models.

Biodiesel is considered to be a sustainable alternative for fossil fuels such as petroleum-based diesel. However, we still lack knowledge about the impact of biodiesel emissions on humans, as airways and lungs are the primary target organs of inhaled toxicants. This study investigated the effect of exhaust particles from well-characterized rapeseed methyl ester (RME) biodiesel exhaust particles (BDEP) and petro-diesel exhaust particles (DEP) on primary bronchial epithelial cells (PBEC) and macrophages (MQ). The advanced multicellular physiologically relevant bronchial mucosa models were developed using human primary bronchial epithelial cells (PBEC) cultured at air-liquid interface (ALI) in the presence or absence of THP-1 cell-derived macrophages (MQ). The experimental set-up used for BDEP and DEP exposures (18 µg/cm2 and 36 µg/cm2) as well as the corresponding control exposures were PBEC-ALI, MQ-ALI, and PBEC co-cultured with MQ (PBEC-ALI/MQ). Following exposure to both BDEP and DEP, reactive oxygen species as well as the stress protein heat shock protein 60 were upregulated in PBEC-ALI and MQ-ALI. Expression of both pro-inflammatory (M1: CD86) and repair (M2: CD206) macrophage polarization markers was increased in MQ-ALI after both BDEP and DEP exposures. Phagocytosis activity of MQ and the phagocytosis receptors CD35 and CD64 were downregulated, whereas CD36 was upregulated in MQ-ALI. Increased transcript and secreted protein levels of CXCL8, as well as IL-6 and TNF-α, were detected following both BDEP and DEP exposure at both doses in PBEC-ALI. Furthermore, the cyclooxygenase-2 (COX-2) pathway, COX-2-mediated histone phosphorylation and DNA damage were all increased in PBEC-ALI following exposure to both doses of BDEP and DEP. Valdecoxib, a COX-2 inhibitor, reduced the level of prostaglandin E2, histone phosphorylation, and DNA damage in PBEC-ALI following exposure to both concentrations of BDEP and DEP. Using physiologically relevant multicellular human lung mucosa models with human primary bronchial epithelial cells and macrophages, we found BDEP and DEP to induce comparable levels of oxidative stress, inflammatory response, and impairment of phagocytosis. The use of a renewable carbon-neutral biodiesel fuel does not appear to be more favorable than conventional petroleum-based alternative, as regards of its potential for adverse health effects.

#5302 REVISITING THE PATHOGENIC ROLE OF THE SLC8A1 GENE IN A FAMILY WITH A NOVEL TERMINAL GROSS DELETION IN THE UMOD GENE

Abstract Background and Aims Autosomal dominant tubulointerstitial kidney disease (ADTKD) - the third most common genetic disorder in adults with CKD - comprises a heterogeneous group of rare, hereditary kidney diseases characterized by family history of progressive chronic kidney disease (CKD) with bland urine sediment, absence of significant proteinuria and normal or small-sized kidneys. Biopsy findings are nonspecific and the gold standard for definitive diagnosis is identification of a pathogenic variant in the genes UMOD, MUC1, HNF1β, REN or SEC61A1. Method Case report. Results The proband was a 27-year-old white male referred for CKD, KDIGO stage 3a. His medical history was relevant for nocturnal enuresis until age 10; arterial hypertension diagnosed at age 19; and asymptomatic hyperuricemia, disproportional to the level of renal function impairment. Urinalysis was negative for protein, red blood cells or leucocytes and magnetic resonance imaging showed normal sized kidneys with bilateral cysts in the medulla and the corticomedullary junction. The family pedigree (Figure 1) illustrates that hyperuricemic nephropathy and CKD segregated in this family with an autosomal dominant pattern of inheritance. A custom NGS-based gene panel allowed to identify in the proband (IV-2) and his affected brother (IV-1): (i) a previously unreported large deletion in the UMOD gene, encompassing the entire exon 11, classified as “likely pathogenic”; ii) an ultra-rare nonsense SLC8A1 allele — c.16C&amp;gt;T p.(Arg6*), classified as “variant of uncertain clinical significance (VUS)”; (iii) an ultra-rare missense variant in the gene encoding polycystin-1 (PKD1) — c.9170T&amp;gt;C p.(Val3057Ala), classified as VUS. Since the latter was inherited from their healthy mother (III-1) it was considered a benign variation, similar to the more common p.Val3057Met variant affecting the same codon. Other affected family member (III-5) was heterozygous for the UMOD exon 11 deletion, which was excluded in two healthy relatives (III-1, III-4), establishing the primary diagnosis of ADTKD-UMOD. It is noteworthy that the only two gross UMOD deletions associated with ADTKD affected evolutionarily conserved residues in exon 4 [1]. The presence of the SLC8A1 p.(Arg6*) allele in patients IV-1 and IV-2, who had early clinical presentations, together with its absence in patient III-5, who had a significantly later clinical onset than her older brother (III-2), suggests that it exerted a pathogenic or disease modifier role in this family, in accordance with the predicted protein truncating effect. Indeed, genome-wide linkage analysis in 5 multiplex families with ADTKD identified involvement of chromosome 2p22.1-p21; SLC8A1 was the most likely gene but no pathogenic variants could be identified; copy number variants might have been missed [2]. Unfortunately, in our family study, we could not identify any subject segregating only the SLC8A1 p.(Arg6*) allele, which would have been indispensable to demonstrate its pathogenicity. Conclusion Herein, we report a family with hyperuricemic nephropathy where genetic testing identified a novel, likely pathogenic UMOD variant. The mechanisms underlying the pathogenicity of exon 11 deletion require further study. Additionally, the co-segregation of an ultra-rare nonsense SLC8A1 variant in some individuals was associated with earlier onset and faster progression of CKD, suggesting once again a role for SLC8A1 in the pathogenesis of ADTKD.

Quality of life and depression in patients with amyotrophic lateral sclerosis – does the country of origin matter?

BackgroundGiven the inevitable relentless progressing nature of amyotrophic lateral sclerosis (ALS), it is essential to identify factors influencing patients’ wellbeing. The study aimed to prospectively assess factors influencing the quality of life (QoL) and depression in ALS patients compared to healthy controls (HCs) from Poland, Germany and Sweden and their relationship to socio-demographic and clinical factors.Methods314 ALS patients (120 from Poland, 140 from Germany, 54 from Sweden) and 311 age-, sex- and education-level-matched HCs underwent standardized interviews for quality of life, depression, functional status and pain.ResultsPatients from all three countries showed similar levels of functional impairment (ALSFRS-R). Overall, ALS patients assessed their quality of life as lower compared to HCs (p < 0.001 for the anamnestic comparative self-assessment (ACSA), p = 0.002 for the Schedule for the evaluation of the subjective quality of life - SEIQoL- direct weighting (SEIQoL-DW). Also, the German and Swedish patients, but not the Polish, reported higher depression levels than the corresponding HCs (p < 0.001). Analysis of ALS groups revealed that functional impairment was related to a lower quality of life (ACSA) and higher depression levels among German ALS patients. Longer time since diagnosis predicted lower depression and (in male subjects) higher quality of life.ConclusionsALS patients assess their quality of life and mood lower than healthy individuals within the studied countries. The relationships between clinical and demographic factors are moderated by country of provenance, which bears implications for the design and interpretation of scientific and clinical studies, which should reflect the complexity and heterogeneity of mechanisms determining QoL.

High levels of intracellular endotrophin in adipocytes mediate COPII vesicle supplies to autophagosome to impair autophagic flux and contribute to systemic insulin resistance in obesity

Background and aimsExtracellular matrix (ECM) homeostasis plays a crucial role in metabolic plasticity and endocrine function of adipose tissue. High levels of intracellular endotrophin, a cleavage peptide of type VI collagen alpha 3 chain (Col6a3), have been frequently observed in adipocyte in obesity and diabetes. However, how endotrophin intracellularly traffics and influences metabolic homeostasis in adipocyte remains unknown. Therefore, we aimed to investigate the trafficking of endotrophin and its metabolic effects in adipocytes depending on lean or obese condition. MethodsWe used doxycycline-inducible adipocyte-specific endotrophin overexpressed mice for a gain-of-function study and CRISPR-Cas9 system-based Col6a3-deficient mice for a loss-of-function study. Various molecular and biochemical techniques were employed to examine the effects of endotrophin on metabolic parameters. ResultsIn adipocytes during obesity, the majority of endosomal endotrophin escapes lysosomal degradation and is released into the cytosol to mediate direct interactions between SEC13, a major component of coat protein complex II (COPII) vesicles, and autophagy-related 7 (ATG7), leading to the increased formation of autophagosomes. Autophagosome accumulation disrupts the balance of autophagic flux, resulting in adipocyte death, inflammation, and insulin resistance. These adverse metabolic effects were ameliorated by either suppressing ATG7 with siRNA ex vivo or neutralizing endotrophin with monoclonal antibodies in vivo. ConclusionsHigh levels of intracellular endotrophin-mediated autophagic flux impairment in adipocyte contribute to metabolic dysfunction such as apoptosis, inflammation, and insulin resistance in obesity.

Combination of Paper and Electronic Trail Making Tests for Automatic Analysis of Cognitive Impairment: Development and Validation Study.

Computer-aided detection, used in the screening and diagnosing of cognitive impairment, provides an objective, valid, and convenient assessment. Particularly, digital sensor technology is a promising detection method. This study aimed to develop and validate a novel Trail Making Test (TMT) using a combination of paper and electronic devices. This study included community-dwelling older adult individuals (n=297), who were classified into (1) cognitively healthy controls (HC; n=100 participants), (2) participants diagnosed with mild cognitive impairment (MCI; n=98 participants), and (3) participants with Alzheimer disease (AD; n=99 participants). An electromagnetic tablet was used to record each participant's hand-drawn stroke. A sheet of A4 paper was placed on top of the tablet to maintain the traditional interaction style for participants who were not familiar or comfortable with electronic devices (such as touchscreens). In this way, all participants were instructed to perform the TMT-square and circle. Furthermore, we developed an efficient and interpretable cognitive impairment-screening model to automatically analyze cognitive impairment levels that were dependent on demographic characteristics and time-, pressure-, jerk-, and template-related features. Among these features, novel template-based features were based on a vector quantization algorithm. First, the model identified a candidate trajectory as the standard answer (template) from the HC group. The distance between the recorded trajectories and reference was computed as an important evaluation index. To verify the effectiveness of our method, we compared the performance of a well-trained machine learning model using the extracted evaluation index with conventional demographic characteristics and time-related features. The well-trained model was validated using follow-up data (HC group: n=38; MCI group: n=32; and AD group: n=22). We compared 5 candidate machine learning methods and selected random forest as the ideal model with the best performance (accuracy: 0.726 for HC vs MCI, 0.929 for HC vs AD, and 0.815 for AD vs MCI). Meanwhile, the well-trained classifier achieved better performance than the conventional assessment method, with high stability and accuracy of the follow-up data. The study demonstrated that a model combining both paper and electronic TMTs increases the accuracy of evaluating participants' cognitive impairment compared to conventional paper-based feature assessment.

Exploring the Experience of Breathlessness with the Common-Sense Model of Self-Regulation (CSM).

Chronic breathlessness is a multidimensional, unpleasant symptom common to many health conditions. The Common-Sense Model of Self-Regulation (CSM) was developed to help understand how individuals make sense of their illness. This model has been underused in the study of breathlessness, especially in considering how information sources are integrated within an individual's cognitive and emotional representations of breathlessness. This descriptive qualitative study explored breathlessness beliefs, expectations, and language preferences of people experiencing chronic breathlessness using the CSM. Twenty-one community-dwelling individuals living with varying levels of breathlessness-related impairment were purposively recruited. Semi-structured interviews were conducted with questions reflecting components of the CSM. Interview transcripts were synthesized using deductive and inductive content analysis. Nineteen analytical categories emerged describing a range of cognitive and emotional breathlessness representations. Representations were developed through participants' personal experience and information from external sources including health professionals and the internet. Specific words and phrases about breathlessness with helpful or nonhelpful connotations were identified as contributors to breathlessness representations. The CSM aligns with current multidimensional models of breathlessness and provides health professionals with a robust theoretical framework for exploring breathlessness beliefs and expectations.

DrunkChain: Blockchain-Based IoT System for Preventing Drunk Driving-Related Traffic Accidents

Traffic accidents present significant risks to human life, leading to a high number of fatalities and injuries. According to the World Health Organization’s 2022 worldwide status report on road safety, there were 27,582 deaths linked to traffic-related events, including 4448 fatalities at the collision scenes. Drunk driving is one of the leading causes contributing to the rising count of deadly accidents. Current methods to assess driver alcohol consumption are vulnerable to network risks, such as data corruption, identity theft, and man-in-the-middle attacks. In addition, these systems are subject to security restrictions that have been largely overlooked in earlier research focused on driver information. This study intends to develop a platform that combines the Internet of Things (IoT) with blockchain technology in order to address these concerns and improve the security of user data. In this work, we present a device- and blockchain-based dashboard solution for a centralized police monitoring account. The equipment is responsible for determining the driver’s impairment level by monitoring the driver’s blood alcohol concentration (BAC) and the stability of the vehicle. At predetermined times, integrated blockchain transactions are executed, transmitting data straight to the central police account. This eliminates the need for a central server, ensuring the immutability of data and the existence of blockchain transactions that are independent of any central authority. Our system delivers scalability, compatibility, and faster execution times by adopting this approach. Through comparative research, we have identified a significant increase in the need for security measures in relevant scenarios, highlighting the importance of our suggested model.

Omentin-1 ameliorates experimental inflammatory bowel disease via Nrf2 activation and redox regulation

AimsOmentin-1 production is decreased in patients with IBD. However, the specific role of Omentin-1 in IBD has not been fully elucidated. This study aimed to investigate the expression and role of Omentin-1 in IBD and the potential mechanisms. Main methodsWe collected human serum and colon biopsy samples at the Wuhan Union Hospital. Omentin-1 recombinant protein was injected intraperitoneally in a DSS-induced experimental IBD mouse model. Omentin-1 levels were measured in IBD patients, colitis mice, and LPS-induced HT-29 cells. Omentin-1 and/or a Nrf2 specific inhibitor (ML385) were administered to DSS mice and LPS-induced HT-29 cells. The effects of Omentin-1 on inflammation, intestinal barrier function, Nrf2 pathway, oxidative stress, and NF-κB signaling were detected in vivo and in vitro. Key findingsSerum Omentin-1 levels were significantly reduced in UC and CD patients compared with controls (173.7 (IQR, 120.1–221.2) ng/ml, 80.8 (43.8–151.8) ng/ml, and 270.7 (220.7–306.5) ng/ml, respectively). The levels of Omentin-1 were also significantly lower in colitis mice and LPS-induced HT-29 cells. Omentin-1 treatment effectively ameliorated inflammation and impaired intestinal barrier, decreased ROS and MDA levels, and increased GSH and SOD production in the DSS-induced colitis mice and LPS-induced HT-29 cells. Mechanically, Omentin-1 repaired the intestinal barrier by activating Nrf2, then improving oxidative stress and inhibiting NF-κB signaling. Furthermore, the interaction between Omentin-1 and Nrf2 was identified. SignificanceOmentin-1 activates the Nrf2 pathway to regulate redox balance, ultimately protecting intestinal barrier function and reducing intestinal inflammation. In general, Omentin-1 can be used as a promising therapeutic target for IBD.

Survival status and predictors of mortality from severe community-acquired pneumonia among under-five children admitted at Debre Tabor comprehensive specialized hospital: a prospective cohort study.

Globally, Pneumonia continues to be the leading cause of mortality among under-five children. Ethiopia ranks fourth out of 15 countries worldwide in terms of the highest death rate of under-five children due to severe community-acquired pneumonia (SCAP). However, to date, there is no recent study that shows survival status and predictors of mortality from SCAP. Therefore, this study aimed to determine survival status and predictors of mortality from this dangerous disease among under-five children. A facility-based prospective cohort study was conducted from 1 November 2021 to 31 October 2022 at Debre Tabor comprehensive specialized hospital. All under-five children with SCAP admitted during the study period were included. Participants were selected using a systematic sampling technique. The collected data were coded, edited, and entered into epi-data version 4.2 and then exported to STATA version 17 for further analysis. The Kaplan Meier failure estimate with log-rank test was employed to determine the survival estimates. A cox-proportional hazard regression model was fitted to identify significant variables. The overall incidence density rate of mortality was 5.7 /1000 children with a median hospital stay of 8.2 days. Heart disease (AHR: 4.37; 95%CI: 1.68-11.32), previous admission of SCAP (AHR: 3.87; 95% CI: 1.31-11.43), WFL < -3Z score (AHR: 3.57; 95% CI: 1.02-12.42), impaired consciousness level at admission 3.41(1.14-10.19), and pleural effusion (AHR: 3.42; 95%CI: 1.18-9.93) were significant predictors of mortality. In this study, the survival probability of children with SCAP was low. Children with heart disease, previous admission of SCAP, WFL < -3Z score, impaired consciousness level at admission, and pleural effusion had low survival. Therefore, much emphasis is needed on children with SCAP, particularly those with identified predictors.

Effects of T cell leptin signaling on systemic glucose tolerance and T cell responses in obesity.

Leptin is an adipokine secreted in proportion to adipocyte mass and is therefore increased in obesity. Leptin signaling has been shown to directly promote inflammatory T helper 1 (Th1) and T helper 17 (Th17) cell number and function. Since T cells have a critical role in driving inflammation and systemic glucose intolerance in obesity, we sought to determine the role of leptin signaling in this context. Male and female T cell-specific leptin receptor knockout mice and littermate controls were placed on low-fat diet or high-fat diet to induce obesity for 18 weeks. Weight gain, serum glucose levels, systemic glucose tolerance, T cell metabolism, and T cell differentiation and cytokine production were examined. In both male and female mice, T cell-specific leptin receptor deficiency did not reverse impaired glucose tolerance in obesity, although it did prevent impaired fasting glucose levels in obese mice compared to littermate controls, in a sex dependent manner. Despite these minimal effects on systemic metabolism, T cell-specific leptin signaling was required for changes in T cell metabolism, differentiation, and cytokine production observed in mice fed high-fat diet compared to low-fat diet. Specifically, we observed increased T cell oxidative metabolism, increased CD4+ T cell IFN-γ expression, and increased proportion of T regulatory (Treg) cells in control mice fed high-fat diet compared to low-fat diet, which were not observed in the leptin receptor conditional knockout mice, suggesting that leptin receptor signaling is required for some of the inflammatory changes observed in T cells in obesity. T cell-specific deficiency of leptin signaling alters T cell metabolism and function in obesity but has minimal effects on obesity-associated systemic metabolism. These results suggest a redundancy in cytokine receptor signaling pathways in response to inflammatory signals in obesity.

Medium and long-term prognosis in hospitalised older adults with multimorbidity. A prospective cohort study.

Data about long-term prognosis after hospitalisation of elderly multimorbid patients remains scarce. Evaluate medium and long-term prognosis in hospitalised patients older than 75 years of age with multimorbidity. Explore the impact of gender, age, frailty, physical dependence, and chronic diseases on mortality over a seven-year period. We included prospectively all patients hospitalised for medical reasons over 75 years of age with two or more chronic illnesses in a specialised ward. Data on chronic diseases were collected using the Charlson comorbidity index and a questionnaire for disorders not included in this index. Demographic characteristics, Clinical Frailty Scale, Barthel index, and complications during hospitalisation were collected. 514 patients (46% males) with a mean age of 85 (± 5) years were included. The median follow-up was 755 days (interquartile range 25-75%: 76-1,342). Mortality ranged from 44% to 68%, 82% and 91% at one, three, five, and seven years. At inclusion, men were slightly younger and with lower levels of physical impairment. Nevertheless, in the multivariate analysis, men had higher mortality (p<0.001; H.R.:1.43; 95% C.I.95%:1.16-1.75). Age, Clinical Frailty Scale, Barthel, and Charlson indexes were significant predictors in the univariate and multivariate analysis (all p<0.001). Dementia and neoplastic diseases were statistically significant in the unadjusted but not the adjusted model. In a cluster analysis, three patterns of patients were identified, with increasing significant mortality differences between them (p<0.001; H.R.:1.67; 95% CI: 1.49-1.88). In our cohort, individual diseases had a limited predictive prognostic capacity, while the combination of chronic illness, frailty, and physical dependence were independent predictors of survival.

The impact of depressive symptomology, rumination and objective memory performance on subjective cognitive complaints

IntroductionCognitive impairment in depression can present as subjective or objective, but the intensity of the former is higher and is not correlated with the deficits measured in neuropsychological tests. We hypothesised that rumination would be associated with subjective cognitive impairment. MethodsThe study was performed through the online PsyToolkit platform. It included 168 healthy people and 93 people with depression. To examine memory, a recognition-type task was used with emotionally charged words as the stimulus. Depression symptoms were measured using the Beck Depression Inventory-II, subjective cognitive impairment with the Perceived Deficits Questionnaire-20, and intensity of rumination with the Polish Questionnaire of Rumination. ResultsMDD patients had significantly higher levels of depression symptoms, rumination, and subjective cognitive deficits than the control group. In the memory task, the MDD group had a higher error rate than the control group. In hierarchical regression analysis, depression and rumination were found to be significant predictors of subjective cognitive impairment, whereas objective memory performance was not. Exploratory analyses revealed that rumination mediates the association between depression and subjective cognitive complaints. ConclusionCognitive problems are common in depression and affect the quality of life. The results suggest that patients with depression have higher levels of rumination and subjective memory impairment, and that there is no direct link between subjective and objective cognitive decline. The findings may have implications for the development of effective treatment strategies for depression and cognitive impairment.

Association between amyloid, tau and cerebral small vessel disease

AbstractBackgroundControversy exists with respect to the etiological role of cerebral small vessel disease (CSVD) in Alzheimer’s disease (AD). We thus evaluated the association between white matter hyperintensity (WMH), an MRI marker of CSVD, with brain amyloid β (Aβ) and tau burden and their plasma markers among subjects with varying severity levels of cognitive impairment.MethodsWe recruited 84 subjects from the CU‐SEEDS (The Chinese University of Hong Kong‐Screening for Early AlzhEimer’s DiseaSe) study who were stroke‐free and had varying severity levels of cognitive impairment: 10 healthy controls [HC], 32 with subjective cognitive decline [SCD], 26 with mild cognitive impairment [MCI] and 16 with dementia. All subjects underwent structural MRI, 11C‐ PIB, and 18F‐T807 positron emission tomography (PET), to measure WMH volume, and pathological Aβ deposition (A+) and tau burden (T+), respectively. WMH volume was quantified by automatic segmentation using AccuBrain® IV 1.1. Plasma levels of Aβ40, Aβ42, total tau (t‐tau), phosphorylated tau at 181 (p‐tau181) and neurofilament light chain (NfL) were measured by Single Molecule Array (SiMoA) assays among 71 subjects.ResultsThe mean age of the subjects was 67.5. 34 (40.8%) were male. No significant associations were found between WMH volume and global 11C‐PIB or 18F‐T807 standardized uptake value ratio (SUVR) on PET. Interestingly, we found that increasing WMH volume significantly correlated with higher plasma p‐tau181 level (β = 0.10; 95% C.I.: 0.012 – 0.188; P = 0.03). There were no associations between WMH volume and plasma Aβ40, Aβ42, t‐tau or NfL levels.ConclusionBrain WMH volume was associated with plasma p‐tau181 level but not with PET tau positivity in the brain. Our results suggest that CSVD burden may contribute to elevated plasma phosphorylated tau in AD, and such change may precede PET‐detectable elevated tau burden in the brain.

Prediction of cognitive status and 5‐year survival for elderly with diabetes by using the Neurocognitive Frailty Index (NFI)

AbstractBackgroundType 2 diabetes mellitus has been shown to be associated to cognitive decline and an increased risk of mild cognitive impairment and dementia in elderly persons (Biessels et al., 2014). The aim of this research was to determine whether the Neurocognitive Frailty Index (NFI, Pakzad et al., 2017) could help to predict cognitive changes in elderly people with diabetes.MethodParticipants in this study were drawn from waves 1 (1991 to 1992) and 2 (1996 to 1997) of the Canadian Study of Health and Aging (CSHA) for prediction of 5‐year cognitive changes in those who received a consensus diagnosis of no cognitive impairment (NCI) or cognitive impairment but not dementia (CIND) in wave 1 (n = 997). The CIND category was contained to individuals whose level of cognitive impairment was measured to be greater than the NCI group but less than the dementia group. NFI was defined as a combined score of 41 physical and mental components (in 8 cognitive domains) as they were available in the dataset (NFI has 42 components but we withdraw diabetes). Cognitive score (measured by 3MS) at follow‐up, and mortality were outcome.ResultMean NFI and standard deviation was 9.7±6.22 in people without diabetes, 11.71±5.42 in people with diabetes and 9.36±5.30 in people with diabetes but are using treatment. Multiple linear regression indicated that NFI score is significantly associated to cognitive status (3MS at follow‐up, p&lt;0.05), however, diabetes did not show any significant association to predict this outcome. CHAID decision tree analysis stratified NFI scores into five categories, while proportional hazards analysis adjusted for age, gender and education indicated that NFI was more correlated to survival than age and had a dose‐response effect in relation to survival. Those with diabetes had a higher probability of death compared to those without (p&lt;0.05).ConclusionNFI was significantly associated with cognitive changes for the elderly in those with and without diabetes. Given that the NFI is proving to be a valuable tool to assess the risk of developing dementia, further investigation is needed to clarify which modifiable risk factors may help reduce the risk of cognitive decline.

Association of Telomere Length with Cognitive Impairment.

Telomere attrition is attributed to Alzheimer's disease (AD), major depressive disorder, stress levels, physical inactivity, short sleep duration, and reduced educational abilities. In this article, we tried to assess the association between the telomere length in peripheral blood leukocytes and level of cognitive impairment and its dependence on age and sex.Healthy subjects and patients with amnestic mild cognitive impairment (aMCI) and different AD stages were recruited in the study. All patients were assessed by the same standard diagnostic procedure, including neurological examination-Mini-Mental State Examination (MMSE). Blood samples from 66 subjects (18 men and 48 women, mean age 71.2 ± 0.56years) were collected for DNA extraction from peripheral mononuclear cells (PBMC). Relative telomere length (RTL) was measured by monochrome multiplex polymerase chain reaction.The data obtained in the study indicate that RTL in PBMCs has a statistically significant association with MMSE score (p < 0.02). Moreover, the sex-specific difference was observed for the association between telomere length and various parameters of MMSE. Also, it has been found that a decrease in RTL by one unit is associated with an increase in the odds to get AD at a ratio of 2.54 (95% CI, 1.25 to 5.17).The results obtained in this research are in coherence with other studies that telomere length may be a valuable biomarker of cognitive decline. However, the potential need for longitudinal studies of telomere length, in order to estimate the influence of hereditary and environmental factors, remains.