Functional Assessment Research Articles

Traffic-related ultrafine particles impair mitochondrial functions in human olfactory mucosa cells – Implications for Alzheimer's disease

Constituents of air pollution, the ultrafine particles (UFP) with a diameter of ≤0.1 μm, are considerably related to traffic emissions. Several studies link air pollution to Alzheimer's disease (AD), yet the exact relationship between the two remains poorly understood. Mitochondria are known targets of environmental toxicants, and their dysfunction is associated with neurodegenerative diseases. The olfactory mucosa (OM), located at the rooftop of the nasal cavity, is directly exposed to the environment and in contact with the brain. Mounting evidence suggests that the UFPs can impact the brain directly through the olfactory tract. By using primary human OM cultures established from nasal biopsies of cognitively healthy controls and individuals diagnosed with AD, we aimed to decipher the effects of traffic-related UFPs on mitochondria. The UFP samples were collected from the exhausts of a modern heavy-duty diesel engine (HDE) without aftertreatment systems, run with renewable diesel (A0) and petroleum diesel (A20), and from an engine of a 2019 model diesel passenger car (DI-E6d) equipped with state-of-the-art aftertreatment devices and run with renewable diesel (Euro6). OM cells were exposed to three different UFPs for 24-h and 72-h, after which cellular processes were assessed on the functional and transcriptomic levels. Our results show that UFPs impair mitochondrial functions in primary human OM cells by hampering oxidative phosphorylation (OXPHOS) and redox balance, and the responses of AD cells differ from cognitively healthy controls. RNA-Seq and IPA® revealed inhibition of OXPHOS and mitochondrial dysfunction in response to UFPs A0 and A20. Functional validation confirmed that A0 and A20 impair cellular respiration, decrease ATP levels, and disturb redox balance by altering NAD and glutathione metabolism, leading to increased ROS and oxidative stress. RNA-Seq and functional assessment revealed the presence of AD-related alterations in human OM cells and that different fuels and engine technologies elicit differential effects.

Diastolic function and dysfunction in athletes.

Abstract Cardiac remodelling is often most profound in male athletes and in athletes with the greatest volumes of endurance training and is characterized by chamber enlargement and a mild-to-modest hypertrophy. The diastolic filling of the left ventricle (LV) is a complex process including the early recoil of the contracted LV, the active relaxation of the myocardium, the compliance of the myocardium, the filling pressures, and heart rate. Echocardiography is the cornerstone for the clinical assessment of LV diastolic function. LV diastolic function is usually enhanced in elite endurance athletes characterized by improved early filling of the ventricle, while it is preserved or enhanced in other athletes associated with the type of training being performed. This allows for the high performance of any endurance athlete. Typical findings when using resting echocardiography for the assessment of LV diastolic function in endurance athletes include a dilated LV with normal or mildly reduced LV ejection fraction (EF), significantly enlarged left atrium (LA) beyond the commonly used cut-off of 34 mL/m2, and a significantly elevated E/A ratio. The early-diastolic mitral annular velocity and the E-wave peak velocity are usually normal. Importantly, interpretation of the echocardiographic indices of LV diastolic function should always consider the clinical context and other parameters of systolic and diastolic functions. In the absence of an underlying pathology, single measurements outside the expected range for similar athletes will often not represent the pathology.

Biological characteristics of tissue engineered-nerve grafts enhancing peripheral nerve regeneration

BackgroundA favorable regenerative microenvironment is essential for peripheral nerve regeneration. Neural tissue-specific extracellular matrix (ECM) is a natural material that helps direct cell behavior and promote axon regeneration. Both bone marrow-derived mesenchymal stem cells (BMSCs) and adipose-derived mesenchymal stem cells (ADSCs) transplantation are effective in repairing peripheral nerve injury (PNI). However, there is no study that characterizes the in vivo microenvironmental characteristics of these two MSCs for the early repair of PNI when combined with neural tissue-derived ECM materials, i.e., acellular nerve allograft (ANA).MethodsIn order to investigate biological characteristics, molecular mechanisms of early stage, and effectiveness of ADSCs- or BMSCs-injected into ANA for repairing PNI in vivo, a rat 10 mm long sciatic nerve defect model was used. We isolated primary BMSCs and ADSCs from bone marrow and adipose tissue, respectively. First, to investigate the in vivo response characteristics and underlying molecular mechanisms of ANA combined with BMSCs or ADSCs, eighty-four rats were randomly divided into three groups: ANA group, ANA+BMSC group, and ANA+ADSC group. We performed flow cytometry, RT-PCR, and immunofluorescence staining up to 4 weeks postoperatively. To further elucidate the underlying molecular mechanisms, changes in long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) were systematically investigated using whole transcriptome sequencing. We then constructed protein–protein interaction networks to find 10 top ranked hub genes among differentially expressed mRNAs. Second, in order to explore the effectiveness of BMSCs and ADSCs on neural tissue-derived ECM materials for repairing PNI, sixty-eight rats were randomized into four groups: ANA group, ANA+BMSC group, ANA+ADSC group, and AUTO group. In the ANA+BMSC and ANA+ADSC groups, ADSCs/BMSCs were equally injected along the long axis of the 10-mm ANA. Then, we performed histological and functional assessments up to 12 weeks postoperatively.ResultsThe results of flow cytometry and RT-PCR showed that ANA combined with BMSCs exhibited more significant immunomodulatory effects, as evidenced by the up-regulation of interleukin (IL)-10, down-regulation of IL-1β and tumor necrosis factor-alpha (TNF-α) expression, promotion of M1-type macrophage polarization to M2-type, and a significant increase in the number of regulatory T cells (Tregs). ANA combined with ADSCs exhibited more pronounced features of pro-myelination and angiogenesis, as evidenced by the up-regulation of myelin-associated protein gene (MBP and MPZ) and angiogenesis-related factors (TGF-β, VEGF). Moreover, differentially expressed genes from whole transcriptome sequencing results further indicated that ANA loaded with BMSCs exhibited notable immunomodulatory effects and ANA loaded with ADSCs was more associated with angiogenesis, axonal growth, and myelin formation. Notably, ANA infused with BMSCs or ADSCs enhanced peripheral nerve regeneration and motor function recovery with no statistically significant differences.ConclusionsThis study revealed that both ANA combined with BMSCs and ADSCs enhance peripheral nerve regeneration and motor function recovery, but their biological characteristics (mainly including immunomodulatory effects, pro-vascular regenerative effects, and pro-myelin regenerative effects) and underlying molecular mechanisms in the process of repairing PNI in vivo are different, providing new insights into MSC therapy for peripheral nerve injury and its clinical translation.

Scalable Bioreactor-based Suspension Approach to Generate Stem Cell-derived Islets From Healthy Donor-derived iPSCs.

Induced pluripotent stem cells (iPSCs) offer the potential to generate autologous iPSC-derived islets (iPSC islets), however, remain limited by scalability and product safety. Herein, we report stagewise characterization of cells generated following a bioreactor-based differentiation protocol. Cell characteristics were assessed using flow cytometry, quantitative reverse transcription polymerase chain reaction, patch clamping, functional assessment, and in vivo functional and immunohistochemistry evaluation. Protocol yield and costs are assessed to determine scalability. Differentiation was capable of generating 90.4% PDX1+/NKX6.1+ pancreatic progenitors and 100% C-peptide+/NKX6.1+ iPSC islet cells. However, 82.1%, 49.6%, and 0.9% of the cells expressed SOX9 (duct), SLC18A1 (enterochromaffin cells), and CDX2 (gut cells), respectively. Explanted grafts contained mature monohormonal islet-like cells, however, CK19+ ductal tissues persist. Using this protocol, semi-planar differentiation using 150 mm plates achieved 5.72 × 104 cells/cm2 (total 8.3 × 106 cells), whereas complete suspension differentiation within 100 mL Vertical-Wheel bioreactors significantly increased cell yield to 1.1 × 106 cells/mL (total 105.0 × 106 cells), reducing costs by 88.8%. This study offers a scalable suspension-based approach for iPSC islet differentiation within Vertical-Wheel bioreactors with thorough characterization of the ensuing product to enable future protocol comparison and evaluation of approaches for off-target cell elimination. Results suggest that bioreactor-based suspension differentiation protocols may facilitate scalability and clinical implementation of iPSC islet therapies.

Cryopreservation of human kidney organoids

Recent advances in stem cell research have led to the creation of organoids, miniature replicas of human organs, offering innovative avenues for studying diseases. Kidney organoids, with their ability to replicate complex renal structures, provide a novel platform for investigating kidney diseases and assessing drug efficacy, albeit hindered by labor-intensive generation and batch variations, highlighting the need for tailored cryopreservation methods to enable widespread utilization. Here, we evaluated cryopreservation strategies for kidney organoids by contrasting slow-freezing and vitrification methods. 118 kidney organoids were categorized into five conditions. Control organoids followed standard culture, while two slow-freezing groups used 10% DMSO (SF1) or commercial freezing media (SF2). Vitrification involved V1 (20% DMSO, 20% Ethylene Glycol with sucrose) and V2 (15% DMSO, 15% Ethylene Glycol). Assessment of viability, functionality, and structural integrity post-thawing revealed notable differences. Vitrification, particularly V1, exhibited superior viability (91% for V1, 26% for V2, 79% for SF1, and 83% for SF2 compared to 99.4% in controls). 3D imaging highlighted distinct nephron segments among groups, emphasizing V1’s efficacy in preserving both podocytes and tubules in kidney organoids. Cisplatin-induced injury revealed a significant reduction in regenerative capacities in organoids cryopreserved by flow-freezing methods, while the V1 method did not show statistical significance compared to the unfrozen controls. This study underscores vitrification, especially with high concentrations of cryoprotectants, as an effective approach for maintaining kidney organoid viability and structure during cryopreservation, offering practical approaches for kidney organoid research.

A protocol for a multidisciplinary early intervention during chemotherapy to improve dietary management behavior in breast cancer patients: a two-arm, single-center randomized controlled trial

BackgroundAdverse reactions are prone to occur in the early stage of chemotherapy and can negatively affect the dietary intake and nutritional status of breast cancer (BC) patients. Consequently, they need to participate in health self-management and lifestyle promotion programs. Early multidisciplinary interventions aim to enhance dietary management behavior and quality of life in chemotherapy-treated BC patients.MethodsThis single-blinded, single-center, randomized controlled trial will include 88 females who have not yet started the early or middle stage of the chemotherapy cycle. A random number table will be used randomly assign females to the intervention group or usual group at a 1:1 ratio. The intervention elements are based on the theoretical guidance of the Integrated Theory of Health Behavior Change (ITHBC). A multidisciplinary team (MDT) comprising oncologists, dietitians, nurses, traditional Chinese medicine (TCM) practitioners, and psychologists will provide the intervention. Intervention sessions will be conducted once a week for 8 weeks, beginning in the early or middle stage of the chemotherapy cycle and continuing through admission and a home-based interval chemotherapy period. The intervention includes face-to-face discussions, online meetings, WeChat messaging, and telephone calls. The themes target adverse reactions, dietary information and habits, self-care self-efficacy, treatment self-regulation, dietary supplement and TCM use, social support, weight management, and outcome expectations. The primary outcome is dietary management behavior measured by the Dietary Management Behavior Questionnaire (DMBQ). Secondary outcomes are self-care self-efficacy assessed by the Strategies Used by People to Promote Health (SUPPH); quality of life measured by the Functional Assessment of Cancer Therapy-Breast (FACT-B); and body mass index (BMI) measured by an electronic meter. All participants will be assessed at baseline and immediately, 1 month, 3 months, 6 months, and 12 months after the intervention.DiscussionEarly dietary intervention is needed, as diet is one of the most common health self-management behaviors influenced by chemotherapy. Early multidisciplinary interventions may provide a foundation for dietary self-management and improve nutritional status in the survival period.Trial registrationThis intervention protocol was registered with the Chinese Clinical Trials Registry (ChiCTR2300076503, October 10, 2023).

Association of combined low physical activity and low dietary diversity with mild cognitive impairment among community-dwelling Japanese older adults.

This study aimed to investigate the potential association between the combination of low physical activity and low dietary diversity with mild cognitive impairment (MCI) in older Japanese adults. Data from 600 older adults (mean age 74.1 ± 6.4 years; 62.0% women) were analyzed. We evaluated dietary variety based on the Food Frequency Score (FFS) (maximum 30 points) by assessing the one-week consumption frequencies of ten foods. An FFS of ≤ 16 indicated low dietary diversity. We assessed MCI using the National Center for Geriatrics and Gerontology (NCGG) Functional Assessment Tool. Physical activity levels was determined based on participant responses to two questions: "Do you engage in moderate levels of physical exercise or sports aimed at health?" and "Do you engage in low levels of physical exercise aimed at health?". Participants who responded "No" to both questions were classified as having low physical activity levels. We classified the participants into robust, low-dietary diversity, low-physical activity, and coexistence groups. The overall prevalence of MCI was 20.7%, with rates in the robust, low dietary diversity, low physical activity, and coexistence groups of 17.7%, 24.7%, 25.0%, and 41.9%, respectively. Multiple logistic regression analysis revealed that low dietary diversity and physical activity were associated with MCI in older adults (odds ratio [OR] 2.80, 95% confidence interval [CI] 1.22-6.28). The results of the present study demonstrated the association of the co-occurrence of low dietary diversity and low physical activity with MCI. Older adults with both risk factors may require early detection, as well as physical activity and dietary interventions.

Enzyme replacement therapy and immunotherapy lead to significant functional improvement in two children with Pompe disease: a case report

BackgroundPompe disease, a rare autosomal recessive disorder caused by acid alpha-glucosidase deficiency, results in progressive glycogen accumulation and multisystem dysfunction. Enzyme replacement therapy with recombinant human acid alpha-glucosidase is the standard of care; however, some patients develop anti-recombinant human acid alpha-glucosidase antibodies, leading to reduced efficacy. This case report presents two infants with early-onset Pompe disease who developed IgG antibodies to enzyme replacement therapy and were subsequently treated with methotrexate, highlighting the importance of monitoring antibody development and exploring alternative therapeutic approaches.Case presentationPatient 1, a 10-month-old female from Bogota, Colombia, presented with generalized hypotonia, macroglossia, hyporeflexia, and mild left ventricular hypertrophy. Diagnostic tests confirmed early-onset Pompe disease, and enzyme replacement therapy was started at 12 months. Due to a lack of improvement and high anti-recombinant human acid alpha-glucosidase IgG antibody titers (1:1800), methotrexate was started at 18 months. After 8 months of combined therapy, antibody titers were negative and significant improvement in motor function was observed using the Gross Motor Function Measure 88. Patient 2, a 7-year-old female from Bogota, Colombia, was diagnosed with early-onset Pompe disease at 12 months and initiated enzyme replacement therapy. At 5 years of age, she experienced frequent falls and grip strength alterations. Functional tests revealed motor development delay, generalized hypotonia, and positive anti-recombinant human acid alpha-glucosidase IgG antibody titers (6400). Methotrexate was initiated, leading to a reduction in falls and antibody titers (3200) after 6 months, with no adverse events or complications. Motor function improvement was assessed using the Motor Function Measurement 32.ConclusionsThe presented cases highlight the importance of monitoring patients for anti-recombinant human acid alpha-glucosidase antibody development during enzyme replacement therapy and the potential benefit of methotrexate as an immunomodulatory agent in early-onset Pompe disease. Early diagnosis and timely initiation of enzyme replacement therapy, combined with prophylactic immune tolerance induction, may improve clinical outcomes and reduce the development of anti-recombinant human acid alpha-glucosidase antibodies. The cases also highlight the importance of objective motor function assessment tools, such as Gross Motor Function Measure 88 and Motor Function Measurement 32, in assessing treatment response. Further research is needed to optimize treatment regimens, monitor long-term effects, and address the current limitations of enzyme replacement therapy in Pompe disease.

The influence of the health status and functional capacity assessment of older people with heart failure on the participation in a cardiac rehabilitation program after myocardial infarction

Abstract Background Cardiac rehabilitation (CR) after myocardial infarction (MI), conducted by a multidisciplinary team, is considered to be the most effective secondary prevention strategy. CR might be particularly beneficial in older patients, who often suffer from heart failure (HF) and other comorbidities. Low enrolment in CR programs is observed in various age groups despite the proven effectiveness of CR in the reduction of subsequent ischemic episodes, hospitalization, and mortality risk. Purpose The study aimed to analyze the impact of the health status and functional capacity assessment of elderly patients with HF using the Vulnerable Elders Survey (VES-13) scale on the willingness to participate in the CR program as part of the national Comprehensive Care Program after Myocardial Infarction. Methods The analysis of the medical records of MI patients, who were hospitalized between 2017 and 2023 and met the inclusion criteria for CR was performed. People included in the study were ≥60 years of age and had previously been diagnosed with HF. The study included 350 people who underwent VES-13 assessment during hospitalization. The median age of the studied group was 74 (IQR 68-81), with the majority of males (59.1%). Results The willingness to participate in CR was declared by 26.3% of respondents. The median VES-13 score was 3 (IQR 2-7) points and was higher in patients who did not want to participate in CR [3 (IQR 2-7) vs 2 (IQR 1-3), p <0.0001]. In the group of patients who scored <3 points in the VES-13 scale, there was a significantly higher percentage of patients declaring their willingness to participate in CR compared to the group with ≥3 points (38.8% vs 18.5%, p=0.0001). Univariate analysis showed that all parameters assessed by the VES-13 scale had a significant impact on patients' willingness to participate in CR (Figure 1). Independent factors determining patients' declaration were age, difficulties in reaching or extending arms above the shoulder level, and limitations in shopping for personal items (like toilet items or medicines) (Figure 2). Conclusion The VES-13 scale can help to identify patients with HF after MI who require additional support and motivation in the decision process to participate in coordinated care and early CR. Limitations in the everyday functioning of elderly patients with HF determine the lack of willingness to participate in CR after MI. It is necessary to carry out intensive educational and motivational activities to improve the recruitment to the CR program.

Enhancing left ventricular segmentation in echocardiography with a modified mixed attention mechanism in SegFormer architecture

Echocardiography is a key tool for the diagnosis of cardiac diseases, and accurate left ventricular (LV) segmentation in echocardiographic videos is crucial for the assessment of cardiac function. However, since semantic segmentation of video needs to take into account the temporal correlation between frames, this makes the task very challenging. This article introduces an innovative method that incorporates a modified mixed attention mechanism into the SegFormer architecture, enabling it to effectively grasp the temporal correlation present in video data. The proposed method processes each time series by encoding the image input into the encoder to obtain the current time feature map. This map, along with the historical time feature map, is then fed into a time-sensitive mixed attention mechanism type of convolution block attention module (TCBAM). Its output can serve as the historical time feature map for the subsequent sequence, and a combination of the current time feature map and historical time feature map for the current sequence. The processed feature map is then input into the Multilayer Perceptron (MLP) and subsequent networks to generate the final segmented image. Through extensive experiments conducted on two different datasets: Hamad Medical Corporation, Tampere University, and Qatar University (HMC-QU), Cardiac Acquisitions for Multi-structure Ultrasound Segmentation (CAMUS) and Sunnybrook Cardiac Data (SCD), achieving a Dice coefficient of 97.92 % on the SCD dataset and an F1 score of 0.9263 on the CAMUS dataset, outperforming all other models. This research provides a promising solution to the temporal modeling challenge in video semantic segmentation tasks using transformer-based models and points out a promising direction for future research in this field.

Relationship between frailty and executive function by age and sex in the Canadian Longitudinal Study on Aging.

Frailty reflects age-related damage to multiple physiological systems. Executive dysfunction is often a presenting symptom of diseases characterized by cognitive impairment. A decline in cardiovascular health is associated with worse executive function. We tested the hypothesis that higher frailty would be associated with executive dysfunction and that cardiovascular health would mediate this relationship. Middle- and older-aged adults at baseline (n = 29,591 [51% female]) and 3-year follow-up (n = 25,488 [49% females]) from the Canadian Longitudinal Study on Aging (comprehensive cohort) were included. Frailty was determined at baseline from a 61-item index, a cumulative cardiovascular health score was calculated from 30 variables at baseline, and participants completed a word-color Stroop task as an assessment of executive function. Multiple linear regressions and mediation analyses of cardiovascular health were conducted between frailty, Stroop interference-condition reaction time, and cardiovascular health in groups stratified by both age and sex (middle-aged males [MM], middle-aged females [MF], older-aged males [OM], older-aged females [OF]). Frailty (MM, 0.15 ± 0.05; MF, 0.16 ± 0.06; OM, 0.21 ± 0.06; OF, 0.23 ± 0.06) was negatively associated with cardiovascular health (MM, 0.12 ± 0.08; MF, 0.11 ± 0.07; OM, 0.20 ± 0.10; OF, 0.18 ± 0.09; β > 0.037, p < 0.001), as well as the Stroop reaction time at 3-year follow-up (MM, 23.7 ± 7.9; MF, 23.1 ± 7.3; OM, 32.9 ± 13.1; OF, 30.9 ± 12.0; β > 2.57, p < 0.001) across all groups when adjusted for covariates. Cardiovascular health was a partial (~ 10%) mediator between frailty and reaction time, aside from MFs. In conclusion, higher frailty levels are associated with executive dysfunction, which was partially mediated by cardiovascular health. Strategies to improve frailty and better cardiovascular health may be useful for combatting the age-related decline in executive function.

Undetected Neuromuscular Disease in Patients after Heart Transplantation.

(1) Heart transplantation (HTX) improves the overall survival and functional status of end-stage heart failure patients with cardiomyopathies (CMPs). The majority of CMPs have genetic causes, and the overlap between CMPs and inherited myopathies is well documented. However, the long-term outcome in skeletal muscle function and possibility of an undiagnosed underlying genetic cause of both a cardiac and skeletal pathology remain unknown. (2) Thirty-nine patients were assessed using open and standardized interviews on muscle function, a quality-of-life (EuroQol EQ-5D-3L) questionnaire, and a physical examination (Medical Research Council Muscle scale). Whole-exome sequencing was completed in three stages for those with skeletal muscle weakness. (3) Seven patients (17.9%) reported new-onset muscle weakness and motor limitations. Objective muscle weakness in the upper and lower extremities was seen in four patients. In three of them, exome sequencing revealed pathogenic/likely pathogenic variants in the genes encoding nexilin, myosin heavy chain, titin, and SPG7. (4) Our findings support a positive long-term outcome of skeletal muscle function in HTX patients. However, 10% of patients showed clinical signs of myopathy due to a possible genetic cause. The integration of genetic testing and standardized neurological assessment of motor function during the peri-HTX period should be considered.

Succession characteristics of phytoplankton functional groups and ecological assessment in a cold spring-type urban lake, China.

Phytoplankton functional groups have been increasingly utilized in elucidating and predicting the response of phytoplankton species to environmental conditions and seasonal succession in various aquatic systems including lakes, rivers and reservoirs. However, it is still unclear whether the trait-based functional classification can be applied to spring-type lakes. To understand the temporal and spatial characteristics of phytoplankton functional groups and their responses to environmental factors in spring-type urban lake in northern China, an investigation was conducted in Daming Lake from May 2020 to September 2021. The findings revealed the identification of 98 phytoplankton taxa belonging to 6 phyla, predominantly being Chlorophyta (39.8%), Bacillariophyta (35.7%) and Cyanophyta (15.3%). The dominant species were Microcystis sp., Merismopedia minima, Synedra acus and Scenedesmus quadricauda. These phytoplankton taxa were categorized into 21 functional groups, with 6 dominant functional groups (abbreviated as D, MP, P, J, Lo, and W1). Among them, the functional group D, primarily constituted by S. acus, exhibited absolute predominance. The seasonal succession sequence of the dominant functional groups was as follows: D/P/J/MP/ Lo →→ D/P/W1/MP/Lo/J → D/P/J → D/MP → D/P/MP. Throughout the investigation period, the trophic level index (TLI) ranged from 39.10 to 71.13, and the Q index was from 1.91 to 2.91, both indicating a medium health state for Daming Lake, which was consistent with the evaluation results of the diversity index. The results of redundancy analysis revealed that the main driving factors of phytoplankton FG biomass and composition were water temperature (WT), total nitrogen (TN), transparency (SD), TN:TP (N:P), redox potential (ORP), chemical oxygen demand (CODMn) and pH. The dominance of the functional group D positively correlated with water temperature, TN, CODMn, pH and N:P but negatively correlated with SD. It was observed that functional groups and the Q index can objectively indicate the seasonal succession of phytoplankton and the water quality status of Daming Lake. Our discoveries have significant implications for the comprehension of the effects of urbanization on phytoplankton dynamics and for enhancing lake management practices to foster sustainable urban development.

Dynamic functional network connectivity in patients with a mismatch between white matter hyperintensity and cognitive function.

White matter hyperintensity (WMH) in patients with cerebral small vessel disease (CSVD) is strongly associated with cognitive impairment. However, the severity of WMH does not coincide fully with cognitive impairment. This study aims to explore the differences in the dynamic functional network connectivity (dFNC) of WMH with cognitively matched and mismatched patients, to better understand the underlying mechanisms from a quantitative perspective. The resting-state functional magnetic resonance imaging (rs-fMRI) and cognitive function scale assessment of the patients were acquired. Preprocessing of the rs-fMRI data was performed, and this was followed by dFNC analysis to obtain the dFNC metrics. Compared the dFNC and dFNC metrics within different states between mismatch and match group, we analyzed the correlation between dFNC metrics and cognitive function. Finally, to analyze the reasons for the differences between the mismatch and match groups, the CSVD imaging features of each patient were quantified with the assistance of the uAI Discover system. The 149 CSVD patients included 20 cases of "Type I mismatch," 51 cases of Type I match, 38 cases of "Type II mismatch," and 40 cases of "Type II match." Using dFNC analysis, we found that the fraction time (FT) and mean dwell time (MDT) of State 2 differed significantly between "Type I match" and "Type I mismatch"; the FT of States 1 and 4 differed significantly between "Type II match" and "Type II mismatch." Correlation analysis revealed that dFNC metrics in CSVD patients correlated with executive function and information processing speed among the various cognitive functions. Through quantitative analysis, we found that the number of perivascular spaces and bilateral medial temporal lobe atrophy (MTA) scores differed significantly between "Type I match" and "Type I mismatch," while the left MTA score differed between "Type II match" and "Type II mismatch." Different mechanisms were implicated in these two types of mismatch: Type I affected higher-order networks, and may be related to the number of perivascular spaces and brain atrophy, whereas Type II affected the primary networks, and may be related to brain atrophy and the years of education.

Sleep apnea in schizophrenia: Estimating prevalence and impact on cognition

Undertreated medical illnesses can compound the disabling cognitive deficits of schizophrenia. Obstructive sleep apnea (OSA) impairs cognitive domains also affected by schizophrenia, is common, and is treatable. The effects of sleep apnea on cognition in schizophrenia, however, are not well understood. We estimated the prevalence of OSA in a previously characterized sample of 3942 Veterans with schizophrenia by self-report and with a predictive model to identify individuals at high risk for OSA. We then compared neuropsychological and functional capacity assessment results between those who reported OSA versus those who did not, and between those predicted to have OSA versus predicted to not have OSA. We expected that many Veterans not reporting sleep apnea would be predicted to have it, and that both reported and predicted sleep apnea would be associated with lower cognitive and functional performance. The reported prevalence of OSA in the sample was 14%, whereas 72% were predicted to be at high risk of OSA. Interestingly, participants who reported having OSA had better cognitive and functional capacity performance (p's < 0.001) compared to those who did not report OSA, particularly on speed of processing assessments (p < 0.001). Predicted OSA, by contrast, was associated with lower speed of processing, verbal learning and working memory test scores (p's < 0.001). One possible interpretation of these results is that people with higher cognitive capacity may be more likely to seek medical care, while those with cognitive impairments are at greater risk for having untreated co-occurring medical conditions that further compromise cognition.

Non-surgical management of acute proximal hamstring avulsions can produce clinically acceptable results.

To evaluate the mid-term clinical outcomes for the non-surgical and surgical management of acute proximal hamstring avulsions. Sixty physically active individuals were offered surgical or non-surgical management for their proximal hamstring avulsion injuries. Distal retraction was defined as greater than 2 cm. Primary outcome measures were the Victorian Institute of sport assessment-proximal hamstring tendons (VISA-H) and functional assessment scale for acute hamstring injuries (FASH). Secondary outcome measures included palpable gap (cm), return to sport (RTS) and the ability to perform Nordic hamstring curls. Outcome variables were adjusted in regression models for gender, age, and treatment. Thirty-one patients elected to undertake non-surgical management, and 29 chose surgery with a mean follow-up of 34.8 ± 8.7 and 34.9 ± 7.0 months, respectively. The mean VISA-H for the non-surgical and surgical groups were 87.3 ± 3.4 and 87.9 ± 4.1 (n.s.), respectively. The mean FASH for the non-surgical group was 89.3 ± 2.4 and 88 ± 3.6 for the surgical group (n.s.). This was consistent after adjusting for confounders. The mean gap for the non-surgical group was 4.5 ± 1.09and 4.9 ± 1.19 cm for the surgical group (n.s.). No significant differences were found in the abilities to perform Nordic hamstring curls (n.s.). Both groups achieved comparable RTS rates (n.s.). On average, the non-surgical group achieved RTS at 5.5 ± 1.2 months post-injury, whereas the surgical group was at 5.7 ± 0.7 months (n.s.). Physically active individuals with acute proximal hamstring avulsions and distal retraction of the tendon stump can be managed non-surgically, achieving similar functional levels and RTS compared to patients treated surgically. Level III.

Quantitative flow ratio for the functional assessment of extracranial internal carotid artery stenosis.

In asymptomatic patients presenting with significant internal carotid artery (ICA) stenoses undergoing endovascular revascularization, a selective angiography before stenting (CAS) is required. Sometimes, angiographic findings could be discordant from non-invasive assessment and a tool able to evaluate functional relevance of the stenosis could be of value. We sought to evaluate the usefulness of quantitative flow ratio (QFR) as angiography-based tool for functional assessment of ICA stenoses. We prospectively enrolled 50 asymptomatic patients undergoing CAS. Peak systolic velocity (PSV, cm/s) assessed at color Doppler echocardiography was used to identify significant stenoses (PSV >125 cm/s). At angiography, assessment of ICA stenosis was obtained visually (%DS<inf>VISUAL</inf>) and according NASCET criteria (%DS<inf>NASCET</inf>). Stenoses were considered significant if >60%. After exclusion of 20 vessels, QFR, area stenosis (AS, %) and minimal lumen area (MLA, mm2) were obtained in the remaining 80 vessels. At linear regression analysis, QFR significantly correlated with PSV (r2=0.52, P<0.001) as well as with %DS<inf>NASCET</inf> (r2=0.68, P<0.001) and %DS<inf>VISUAL</inf> (r2=0.71, P<0.001). Using PSV as reference, QFR showed good accuracy to predict functionally significant stenosis (AUC=0.98, P<0.001) with a cut-off value of 0.93. As compared with %DS<inf>NASCET</inf> and %DS<inf>VISUAL</inf>, QFR showed a significantly higher accuracy (61% vs. 73% vs. 94%, respectively; P<0.05), sensitivity (43% vs. 61% vs. 93%, respectively; P<0.05) and negative predictive value (46% vs. 51% vs. 85%, respectively; P<0.05) for detecting hemodynamically significant ICA stenoses. This study suggest the potential benefit of adopting QFR for functional assessment of extracranial ICA stenoses. These data should be validated in larger studies.

Acrylamide-targeting renal miR-21a-5p/Fibrotic and miR122-5p/ inflammatory signaling pathways and the role of a green approach for nano-zinc detected via in silico and in vivo approaches.

Introduction: Any disruption in renal function can have cascading effects on overall health. Understanding how a heat-born toxicant like acrylamide (ACR) affects kidney tissue is vital for realizing its broader implications for systemic health. Methods: This study investigated the ACR-induced renal damage mechanisms, particularly focusing on the regulating role of miR-21a-5p/fibrotic and miR-122-5p/inflammatory signaling pathways via targeting Timp-3 and TP53 proteins in an In silico preliminary study. Besides, renal function assessment, oxidative status, protein profile, and the expression of renal biomarkers (Timp-1, Keap-1, Kim-1, P53, TNF-α, Bax, and Caspase3) were assessed in a 60-day experiment. The examination was additionally extended to explore the potential protective effects of green-synthesized zinc oxide nanoparticles (ZNO-MONPs). A four-group experiment including control, ZNO-MONPs (10mg/kg b.wt.), ACR (20mg/kg b.wt.), and ZNO-MONPs + ACR was established encompassing biochemical, histological, and molecular levels. The study further investigated the protein-binding ability of ZNO and MONPs to inactivate caspase-3, Keap-1, Kim-1, and TNFRS-1A. Results: ZNO-MONPs significantly reduced ACR-induced renal tissue damage as evidenced by increased serum creatinine, uric acid, albumin, and oxidative stress markers. ACR-induced oxidative stress, apoptosis, and inflammationare revealed by biochemical tests, gene expression, and the presence of apoptotic nuclei microscopically. Also, molecular docking revealed binding affinity between ACR-BCL-2 and glutathione-synthetase, elucidating the potential mechanisms through which ACR induces renal damage. Notably, ZNO-MONPs revealed a protective potential against ACR-induced damage. Zn levels in the renal tissues of ACR-exposed rats were significantly restored in those treated with ACR + ZNO-MONPs. In conclusion, this study establishes the efficacy of ZNO-MONPs in mitigating ACR-induced disturbances in renal tissue functions, oxidative stress, inflammation, and apoptosis. The findings shed light on the potential renoprotective activity of green-synthesized nanomaterials, offering insights into novel therapeutic approaches for countering ACR-induced renal damage.

The impact of obesity on body surface area adjusted estimated glomerular filtration rate in patients with chronic kidney disease.

Assessment of kidney function is necessary for prescribing renally excreted drugs. The estimated glomerular filtration rate (eGFR) routinely reported by laboratories is indexed to a body surface area (BSA) of 1.73 m2. In obese patients, the indexed eGFR may underestimate directly measured GFR. To determine the prevalence of obesity in patients with chronic kidney disease (CKD) and examine the effect of adjusting the indexed eGFR for patient BSA (deindexing) across CKD Stages 2-5. We conducted a cross-sectional study of 575 adults with stable CKD from two general nephrology clinics over 6 months. Dialysis and kidney transplant patients were excluded. We used four equations (Mosteller, Dubois, Haycock and Schlich) to determine BSA based on actual body weight and applied Bland-Altman plots and piecewise linear regression to examine the relationship between deindexed and indexed eGFR. The median age was 68 years (58% male). The prevalence of overweight and obesity was 31% and 47% respectively. Mean body mass index was 29.7 kg/m2. The Schlich equation for BSA produced the smallest adjustment in eGFR, while the Haycock equation produced the largest adjustment. Males experienced the largest change in eGFR from deindexing because of larger BSAs. Although bias became increasingly positive with higher eGFR, the linear regression stratified by CKD stage indicated that deindexing had little impact with eGFR <45 mL/min/1.73 m2. In CKD, deindexing the Chronic Kidney Disease Epidemiology Collaboration eGFR may not be necessary when the eGFR is <45 mL/min/1.73 m2, particularly if the patient is female.

Scaffold-Forming Collagen and Motor-Endplate Expressing Muscle Cells for Porcine Laryngoplasty.

Vocal fold paralysis impairs quality of life, and no curative injectable therapy exists. We evaluated injection of a novel in situ polymerizing (scaffold-forming) collagen in the presence and absence of muscle-derived motor-endplate expressing cells (MEEs) to promote medialization and recurrent laryngeal nerve (RLN) regeneration in a porcine model of unilateral vocal fold paralysis. Twelve Yucatan minipigs underwent right RLN transection. Autologous muscle progenitor cells were isolated from muscle biopsies, differentiated, and induced to MEEs. Three weeks after RLN injury, animals received injections of collagen, collagen containing MEEs, or saline into the paralyzed right vocal fold. Stimulated laryngeal electromyography and acoustic vocalization were used for function assessments. Larynges were harvested and underwent histologic, gene expression, and further quantitative analyses. Injections were well-tolerated, with the collagen scaffold showing immunotolerance and collagen-encapsulated MEEs remaining viable. Collagen-treated paralyzed vocal folds showed increased laryngeal adductor muscle volumes relative to that of the uninjured side, with those receiving MEEs and collagen showing the highest volumes. Muscles injected with MEEs and collagen demonstrated increased expression of select neurotrophic (BDNF and NTN1), motor-endplate (DOK7, CHRNA1, and MUSK), and myogenic (MYOG and MYOD) related genes relative to saline controls. In a porcine model of unilateral vocal fold paralysis, injection of in situ polymerizing collagen in the absence and presence of MEEs enhanced laryngeal adductor muscle volume, modulated expression of neurotrophic and myogenic factors, and avoided adverse material-mediated immune responses. Further study is needed to determine long-term functional outcomes with this novel therapeutic approach. NA Laryngoscope, 2024.