Cell shape sensing licenses dendritic cells for homeostatic migration to lymph nodes.

Immune cells experience large cell shape changes during environmental patrolling because of the physical constraints that they encounter while migrating through tissues. These cells can adapt to such deformation events using dedicated shape-sensing pathways. However, how shape sensing affects immune cell function is mostly unknown. Here, we identify a shape-sensing mechanism that increases the expression of the chemokine receptor CCR7 and guides dendritic cell migration from peripheral tissues to lymph nodes at steady state. This mechanism relies on the lipid metabolism enzyme cPLA2, requires nuclear envelope tensioning and is finely tuned by the ARP2/3 actin nucleation complex. We also show that this shape-sensing axis reprograms dendritic cell transcription by activating an IKKß-NF-κB-dependent pathway known to control their tolerogenic potential. These results indicate that cell shape changes experienced by immune cells can define their migratory behavior and immunoregulatory properties and reveal a contribution of the physical properties of tissues to adaptive immunity.

The Neurorehabilitation of Neurological Movement Disorders Requires Rigorous and Sustained Research.

Movement disorders that stem from neurological conditions such as stroke, cerebral palsy, multiple sclerosis (MS), Parkinson's disease (PD), and spinocerebellar degeneration (SCD) can significantly impair a person's activities of daily living (ADL) [...].

Theoretical proposal for restoration of hand motor function based on plasticity of motor-cortical interhemispheric interaction and its developmental rule.

After stroke, the poorer recovery of motor function of upper extremities compared to other body parts is a longstanding problem. Based on our recent functional MRI evidence on healthy volunteers, this perspective paper proposes systematic hand motor rehabilitation utilizing the plasticity of interhemispheric interaction between motor cortices and following its developmental rule. We first discuss the effectiveness of proprioceptive intervention on the paralyzed (immobile) hand synchronized with voluntary movement of the intact hand to induce muscle activity in the paretic hand. In healthy participants, we show that this bilateral proprioceptive-motor coupling intervention activates the bilateral motor cortices (= bilaterally active mode), facilitates interhemispheric motor-cortical functional connectivity, and augments muscle activity of the passively-moved hand. Next, we propose training both hands to perform different movements, which would be effective for stroke patients who becomes able to manage to move the paretic hand. This bilaterally different movement training may guide the motor cortices into left-right independent mode to improve interhemispheric inhibition and hand dexterity, because we have shown in healthy older adults that this training reactivates motor-cortical interhemispheric inhibition (= left-right independent mode) declined with age, and can improve hand dexterity. Transition of both motor cortices from the bilaterally active mode to the left-right independent mode is a developmental rule of hand motor function and a common feature of motor function recovery after stroke. Hence, incorporating the brain's inherent capacity for spontaneous recovery and adhering to developmental principles may be crucial considerations in designing effective rehabilitation strategies.

Central Sensitization-Related Symptoms and Influencing Factors on Health-Related Quality of Life among Frail Older Adults in Senior Day Care Centers: A Cross-Sectional Study.

The recent increase in the number of frail older adults has led to increased attention being paid to care services in communities such as senior day care centers. Maintaining health-related quality of life (HRQOL) in frail older adults is important for managing long-term care. The purpose of this study was to comprehensively explore the impact of physical, mental, and cognitive factors, particularly central sensitization-related symptoms (CSSs), on the HRQOL among frail older adults in senior day care centers. HRQOL, physical, mental, and cognitive factors, and severity of CSSs were comprehensively measured using validated methods. Correlation and multiple regression analyses were used to examine factors affecting HRQOL among frail older adults in senior day care centers. The results showed that the timed up and go test significantly affected the HRQOL among frail older adults at senior day care centers. Additionally, knee extension muscle strength, number of pain sites, depressive tendencies, and CSS severity showed a significant negative correlation with HRQOL but were not significant influencing factors. This suggests that functional mobility assessments and approaches are important for maintaining and improving the HRQOL in frail older adults at senior day care centers.

Association between Subjective Cognitive Complaints and Sleep Disturbance among Community-Dwelling Elderly Individuals in Japan.

Subjective cognitive complaints (SCCs) are a crucial modifiable risk factor for dementia. There is increasing interest in the association between SCC and sleep disturbance; however, the effects of sleep disturbance on SCC development among community-dwelling elderly individuals in Japan remain unclear. We aimed to cross-sectionally investigate the association between SCC and sleep disturbance, with adjustment for multiple factors related to cognitive decline, among 241 community-dwelling elderly persons without cognitive impairment. The measures were SCCs (Kihon Checklist-Cognitive Function, KCL-CF), sleep disturbance (Japanese version of the Athens Insomnia Scale, AIS-J), general cognitive function (Mini-Mental State Examination), and depressive symptoms (five-item version of the Geriatric Depression Scale [GDS-5]). The following data were collected: sex, age, educational history, whether the participants had visited a medical institution for diseases (hypertension, diabetes, hyperlipidemia, heart disease), and the presence/absence of established risk factors (hearing loss, history of head injury, drinking habits, smoking habits, social isolation, and physical inactivity and activity). Based on the KCL-CF, 96 and 145 participants were considered to have and lack SCCs, respectively. On logistic regression analysis, the AIS-J score and smoking history were significantly associated with SCCs. Our findings suggest that sleep disturbance is associated with SCC development among community-dwelling elderly people in Japan. Evaluating and managing sleep disturbances can be important in preventing SCCs and dementia.

Relationship between Subjective Grip Strength and Physical Functioning among Community-Dwelling Older Women.

This study investigated the relationship between subjective grip strength and physical function in community-dwelling older women. Subjective grip strength was assessed using a questionnaire, and physical function and body composition were compared between groups with strong and weak subjective grip strength. Additionally, the two groups were compared in those with mild cognitive impairment (MCI) and those with normal cognitive function, respectively. The results showed significant differences in grip strength (p < 0.001), 30 s chair-stand (CS-30) test (p = 0.039), timed up-and-go (TUG) test (p = 0.027), maximal gait speed (p = 0.029), and skeletal muscle mass (p < 0.001). Older adults with normal cognitive function showed significant differences in grip strength (p < 0.001), quadriceps muscle strength (p < 0.009), one-leg standing time (p = 0.041), CS-30 (p = 0.002), TUG (p = 0.014), gait speed (p = 0.006), and skeletal muscle mass (p = 0.003). Older adults with low subjective grip strength had lower physical function and skeletal muscle mass. However, no items showed significant differences between groups among older adults with MCI. Thus, subjective grip strength is an indicator of an overall decline in physical function and a reduction in skeletal muscle mass in older adults, and cognitive function should be considered when assessing subjective grip strength in older adults.

Dominance of attentional focus: a comparative study on its impact on standing postural control in healthy younger and older adults.

Introduction: Attentional focus is a phenomenon in which shifting the focus of attention alters performance of standing postural control. It can be categorized as internal focus (IF), which directs attention to the body parts, or external focus (EF), which directs attention to the external environment. Although attentional focus that improves standing postural control in younger people exhibits individual dominance, the dominance of attentional focus in standing postural control in older adults remains ambiguous. Therefore, this study aimed to compare the dominance of attentional focus in standing postural control between healthy younger and older adults, a crucial step for understanding the aging process. Methods: The participants performed a standing postural control task under the IF and EF conditions. Based on the condition during which they exhibited superior performance, the participants were divided into two groups: IF-dominant and EF-dominant. The standing postural control performance in each group under the IF and EF conditions was subsequently compared. Results: The results showed that the participants, encompassing both younger and older adults, were divided into the IF-dominant and EF-dominant groups, confirming the dominance of attentional focus. The performance under the EF condition in older adults was also influenced by the dominance of attentional focus. Conclusion: These results highlight the potential importance of intervention methods based on the dominance of attentional focus, providing valuable insights into future research and clinical practice.

The Influence of Physical, Mental, and Cognitive Factors on Health-Related Quality of Life among Community-Dwelling Older Adults: A Focus on Central Sensitization-Related Symptoms.

Most older adults wish to maintain independence in their familiar communities. However, many experience pain and pain-related disabilities which reduce their health-related quality of life (HRQOL), leading to increased hospitalizations and mortality. This study aimed to determine the impact of physical, mental, and cognitive factors, particularly central sensitization-related symptoms (CSS), on the HRQOL of community-dwelling older adults. A total of 206 participants were included in the analysis, which measured HRQOL, basic attributes, physical functions and body pain, mental factors, cognitive factors, and CSS severity using validated tools. A correlation analysis was used to examine the association between HRQOL and each measure. Furthermore, multiple regression analysis (forced entry method) was performed to identify the factors influencing the HRQOL. The study found that pain intensity and CSS severity significantly influenced the HRQOL among community-dwelling older adults. The higher the pain intensity and CSS severity, the lower their HRQOL. The participants had mild pain and CSS, demonstrating the need to monitor, address, and treat even non-severe issues in community-dwelling older adults. This association, revealed for the first time in this study, suggests that approaches to reduce pain and CSS are important for maintaining and improving the HRQOL of community-dwelling older adults.

GM-CSF-dependent CD301b+ lung dendritic cells confer tolerance to inhaled allergens.

The severity of allergic asthma is driven by the balance between allergen-specific T regulatory (Treg) and T helper (Th)2 cells. However, it is unclear whether specific subsets of conventional dendritic cells (cDCs) promote the differentiation of these two T cell lineaeges. We have identified a subset of lung resident type 2 cDCs (cDC2s) that display high levels of CD301b and have potent Treg-inducing activity ex vivo. Single cell RNA sequencing and adoptive transfer experiments show that during allergic sensitization, many CD301b+ cDC2s transition in a stepwise manner to CD200+ cDC2s that selectively promote Th2 differentiation. GM-CSF augments the development and maintenance of CD301b+ cDC2s in vivo, and also selectively expands Treg-inducing CD301b+ cDC2s derived from bone marrow. Upon their adoptive transfer to recipient mice, lung-derived CD301b+ cDC2s confer immunological tolerance to inhaled allergens. Thus, GM-CSF maintains lung homeostasis by increasing numbers of Treg-inducing CD301b+ cDC2s.

Olanzapine Plus Triple Antiemetic Therapy for the Prevention of Carboplatin-Induced Nausea and Vomiting: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial.

PURPOSE: We evaluated the efficacy and safety of antiemetic therapy with olanzapine, a neurokinin-1 receptor antagonist (RA), a 5-hydroxytryptamine-3 (5-HT3) RA, and dexamethasone for preventing chemotherapy-induced nausea and vomiting in patients receiving carboplatin-containing chemotherapy. PATIENTS AND METHODS: Chemotherapy-naïve patients scheduled to receive carboplatin (AUC ≥5) were randomly assigned to receive either olanzapine 5 mg once daily (olanzapine group) or placebo (placebo group) in combination with aprepitant, a 5-HT3 RA, and dexamethasone. The primary end point was the complete response (CR; no vomiting and no rescue therapy) rate in the overall phase (0-120 hours). Secondary end points included the proportion of patients free of nausea and safety. RESULTS: In total, 355 patients (78.6% male, median age 72 years, 100% thoracic cancer), including 175 and 180 patients in the olanzapine and placebo groups, respectively, were evaluated. The overall CR rate was 86.9% in the olanzapine group versus 80.6% in the placebo group. The intergroup difference in the overall CR rate was 6.3% (95% CI, -1.3 to 13.9). The proportions of patients free of chemotherapy-induced nausea in the overall (88.6% in the olanzapine group v 75.0% in the placebo group) and delayed (89.7% v 75.6%, respectively) phases were significantly higher in the olanzapine group than in the placebo group (both P < .001). Somnolence was observed in 43 (24.6%) and 41 (22.9%) patients in the olanzapine and placebo groups, respectively, and no events were grade ≥3 in severity. CONCLUSION: The addition of olanzapine was not associated with a significant increase in the overall CR rate. Regarding the prevention of nausea, adding olanzapine provided better control in patients receiving carboplatin-containing chemotherapy, which needs further exploration.

Doença arterial obstrutiva periférica: um estudo comparativo entre revascularizações abertas e endovasculares realizadas em caráter de urgência no sistema público de saúde do Brasil entre 2010 e 2020 / Peripheral artery disease: a comparison of urgent open and endovascular revascularizations on the public health system in Brazil, from 2010 to 2020

RESUMO Contexto A doença arterial obstrutiva periférica apresenta alta prevalência, sendo associada a elevado risco de eventos cardiovasculares. A intervenção cirúrgica ou endovascular faz-se necessária na isquemia crítica do membro. Objetivos Avaliar a distribuição de realização de revascularizações abertas e endovasculares nas diferentes regiões do Brasil, analisando os custos para o sistema de saúde e a mortalidade relacionada a esses procedimentos. Métodos Foi realizado um estudo epidemiológico observacional transversal descritivo para avaliar as cirurgias abertas e endovasculares realizadas no sistema público de saúde do Brasil entre 2010 e 2020. Os dados foram coletados através do Departamento de Informática do SUS (Datasus). Resultados No período analisado, foram registradas 83.218 internações para realização de cirurgias abertas e endovasculares, com um custo total de R$ 333.989.523,17. Houve predominância das internações para os procedimentos percutâneos (56.132) em relação aos cirúrgicos convencionais (27.086). As Regiões Sudeste e Sul concentraram a maior parte do total de procedimentos realizados no país (83%), enquanto a Região Norte foi a que apresentou a menor taxa de internação. Observou-se uma tendência decrescente para os procedimentos abertos, e uma tendência crescente para os endovasculares. A média de permanência hospitalar foi menor nos procedimentos endovasculares (5,3 dias) em relação aos abertos (10,2 dias). Além disso, notou-se uma maior taxa de mortalidade hospitalar relacionada à revascularização aberta em relação à endovascular (5,24% versus 1,56%). Conclusões As técnicas endovasculares consistiram em uma abordagem dominante no tratamento cirúrgico da isquemia crítica, apresentando menor taxa de mortalidade hospitalar e menor tempo de internação quando comparada às cirurgias abertas.

ABSTRACT Background Peripheral artery disease (PAD) has high prevalence and is associated with high risk of cardiovascular events. Surgical or endovascular intervention is necessary in chronic limb-threatening ischemia. Objectives To evaluate the distribution of open and endovascular revascularizations in different regions of Brazil, analyzing the health system costs and mortality related to these procedures. Methods A descriptive, cross-sectional, observational, epidemiological study was carried out to evaluate open and endovascular surgeries performed on the SUS public healthcare system in Brazil, from 2010 to 2020. Data were collected from the SUS Department of Informatics (Datasus). Results Over the period analyzed, 83,218 admissions for open and endovascular surgeries were registered, with a total cost of R$ 333,989,523.17. There were more hospital admissions for percutaneous procedures (56,132) than for conventional surgery (27,086). Most of the procedures (83%) were performed in the country's Southeast and South regions, while the North region had the lowest number of procedures. Over the period evaluated, there was a decreasing trend for open procedures and an increasing trend for endovascular procedures. The average hospital stay was shorter for endovascular procedures (5.3 days) than for open surgery (10.2 days). The analysis of mortality related to these procedures revealed a higher rate of in-hospital mortality associated with open revascularization than with endovascular (5.24% vs. 1.56%). Conclusions Endovascular techniques constituted the primary approach for revascularization treatment in critical limb-threatening ischemia, with a lower in-hospital mortality rate and shorter hospital stay when compared to open surgeries.

Efeito residual da deltametrina (k-othrine flow sc 50) no controle de Triatomíneos em Pirenópolis, Goiás / Residual effect of Deltamenthrin (k-Othrine flow sc 50) in the control of Triatominae bugs in the district of \"Pirenópolis,Goiás\",Brazil

Estudou-se o efeito da deltametrina (K-Othrine Flow SC 50) em 34 unidades habitacionais, domicílio e anexos, em Goianópolis, localizada no município de Pirenópolis, Goiás, Brasil. Estas habitaçÆes estavam infestadas por triatomíneos. As espécies encontradas foram Panstrongylus geniculatos, Rhodnius neglectus, Triatoma pseudomaculata e T. sordida infestando domicílio e/ou anexos. A deltrametrina foi rociada na dose de 25mg/m2, no ambiente domiciliar, nas 34 unidades e locais infestados por triatomíneos mantendo-as livres destes insetos por um período de um ano. Os levantamentos e as buscas de triatomíneos nas unidades habitacionas foram feitos nos 3§, 6§, 9§ e 12§ meses após o tratamento. Deste trabalho pode-se concluir que o efeito residual da deltrametrina persistiu durante um ano e foi letal para as espécies consideradas de pequeno porte, e que R. neglectus e T. sordida foram as espécies que evidenciaram o maior poder de invasåo domiciliar pela dispersåo ativa