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Frailty in aging marks a state of decreased reserves resulting in increased vulnerability to adverse outcomes when exposed to stressors. This Perspective synthesizes the evidence on the aging-related pathophysiology underpinning the clinical presentation of physical frailty as a phenotype of a clinical syndrome that is distinct from the cumulative-deficit-based frailty index. We focus on integrating the converging evidence on the conceptualization of physical frailty as a state, largely independent of chronic diseases, that emerges when the dysregulation of multiple interconnected physiological and biological systems crosses a threshold to critical dysfunction, severely compromising homeostasis. Our exegesis posits that the physiology underlying frailty is a critically dysregulated complex dynamical system. This conceptual framework implies that interventions such as physical activity that have multisystem effects are more promising to remedy frailty than interventions targeted at replenishing single systems. We then consider how this framework can drive future research to further understanding, prevention and treatment of frailty, which will likely preserve health and resilience in aging populations. Linda Fried and colleagues argue that physical frailty reflects the dysregulation of a complex dynamical system underpinning health and resilience, and discuss the implications for new prevention and treatment approaches.

Recently the LHCb collaboration reported a new exotic state Tcc+ which possesses ccu¯d¯ flavor structure. Since its mass is very close to the threshold of D0D∗+ (or D∗0D+) and its width is very narrow, it is inclined to conjecture that Tcc+ is a molecular state of D0D∗+ (or D∗0D+). In this paper we study the possible molecular structures of D(∗)D(∗) and B(∗)B(∗) within the Bethe–Salpeter (B–S) framework. We employ one boson exchange model to stand the interaction kernels in the B–S equations. With reasonable input parameters we find the isospin eigenstate 12(D0D∗+-D∗0D+) (JP=1+) constitutes a solution, which supports the ansatz of Tcc+ being a molecular state of D0D∗+ (or D∗0D+). With the same parameters we also find that the isospin-1 state 12(D∗0D∗++D∗0D∗+) (JP=0+) can exist. Moreover, we also study the systems of B(∗)B(∗) and their counterparts exist as possible molecular states. Consistency of theoretical computations based on such states with the data of the future experiments may consolidate the molecular structure of the exotic state Tcc+.

Independent of Ma et al.’s finding, evidence in support of this theory is mounting that disability, comorbidity, and age separately or in combination do not fully explain substantial differences in health outcomes across patient populations (e.g., geriatric vs. disease-specific populations) and clinical settings (e.g., primary care vs. elective surgery) [3]. [...]the concept of frailty provides a new window into latent vulnerability that is both integrative and systemic rather than system- or organ-specific. [...]treatment decisions should be made to minimize the invasiveness of medical procedures prescribed for frail patients. [...]less invasive treatment options such as continuous positive airway pressure should be considered. The radical transformation of the health care system in response to the pandemic, e.g., the replacement of in-person visit with telemedicine in order to preserve critical care capacity, has already affected our ability to maintain high-quality care for vulnerable patient populations [9].

INTRODUCTION Physical frailty is reversible, but little is known about the sustainability of frailty remission and its impact on dementia. METHODS Data were derived from the National Health and Aging Trends Study (NHATS) (2011 to 2021). Physical frailty was assessed using the Fried frailty phenotype, and frailty transition patterns across three waves were defined. The relationship of sustained frailty remission with incident dementia was examined using Cox proportional regression, stratified by age and gender. RESULTS Among 1931 participants, 348 (18.0%) were capable of sustained frailty remission. During the 8‐year follow‐up, 279 participants developed dementia. In a fully adjusted model, sustained remission was associated with a lower risk of dementia (hazard ratio = 0.66, 95% confidence interval = 0.47 to 0.93). The association was more pronounced among younger‐old and male participants but not observed among their counterparts. DISCUSSION Sustained frailty remission was associated with a reduced risk of developing dementia. Physical frailty could be an essential forewarning of dementia and a target for interventions. Highlights We provided new insights into the natural progression of frailty and its impact on dementia risk using a nationally representative sample Sustained frailty remission reduced risk of incident dementia. Age and gender played a role in the frailty‐dementia link, and thus individualized dementia risk screening is necessary. Physical frailty could be an essential forewarning of cognitive decline and an ideal target for interventions to prevent dementia.

Based on the fact that the long expected pentaquark which possesses the exotic quantum numbers of B = 1 and S = 1 was not experimentally found, although exotic states of X Y Z have been observed recently, we conjecture that the heavy flavors may play an important role in stabilizing the hadronic structures beyond the traditional q q ¯ and q q q composites.

In this work we study the weak decays of Ξ cc → Ξ c and Ξ cc → Ξ c ′ in the light-front quark model. Generally, a naive, but reasonable conjecture suggests that the cc subsystem in Ξ cc ( us pair in Ξ c ( ′ ) ) stands as a diquark with definite spin and color assignments. During the concerned processes, the diquark of the initial state is not a spectator, namely must be broken. A Racah transformation would decompose the original ( cc ) q into a combination of c ( cq ) components. Thus we may deal with the decaying c quark alone while keeping the ( cq ) subsystem as a spectator. With the re-arrangement of the inner structure we calculate the form factors numerically and then obtain the rates of semi-leptonic decays and non-leptonic decays, which will be measured in the future.

Decline in neuromuscular function with aging is known to be a major determinant of disability and all‐cause mortality in late life. Despite the importance of the problem, the neurobiology of age‐associated muscle weakness is poorly understood. In a previous report, we performed untargeted metabolomics on frail older adults and discovered prominent alteration in the kynurenine pathway, the major route of dietary tryptophan degradation that produces neurotoxic intermediate metabolites. We also showed that neurotoxic kynurenine pathway metabolites are correlated with increased frailty score. For the present study, we sought to further examine the neurobiology of these neurotoxic intermediates by utilizing a mouse model that has a deletion of the quinolinate phosphoribosyltransferase (QPRT) gene, a rate‐limiting step of the kynurenine pathway. QPRT−/− mice have elevated neurotoxic quinolinic acid level in the nervous system throughout their lifespan. We found that QPRT−/− mice have accelerated declines in neuromuscular function in an age‐ and sex‐specific manner compared to control strains. In addition, the QPRT−/− mice show premature signs of frailty and body composition changes that are typical for metabolic syndrome. Our findings suggest that the kynurenine pathway may play an important role in frailty and age‐associated muscle weakness. The kynurenine pathway is a major route of dietary tryptophan degradation that produces neurotoxic intermediate metabolites. In the present study, we utilized a mouse model that has elevated neurotoxic quinolinic acid level throughout their lifespan. We found that these mice have accelerated declines in neuromuscular function and premature signs of frailty, in an age‐ and sex‐specific manner compared to control strains. Our findings suggest that the kynurenine pathway is associated with increased frailty and age‐associated muscle weakness. Image created with BioRender.com.

The WIMPs are considered to belong to the favorable dark matter (DM) candidates, but the upper bounds on the interactions between DM and standard model (SM) particles obtained by the upgraded facilities of DM direct detection get lower and lower. Researchers turn their attention to the search for less massive DM candidates, i.e. light dark matter of the MeV scale. The recently measured anomalous transition in [Formula omitted]Be suggests that there exists a vectorial boson which may mediate the interaction between DM and SM particles. Based on this scenario, we combine the relevant cosmological data to constrain the mass range of DM, and we have found that there exists a model parameter space where the requirements are satisfied, a range of [Formula omitted] 16.7 MeV for scalar DM, and [Formula omitted] MeV for vectorial DM is demanded. Then a possibility of directly detecting such light DM particles via DM-electron scattering is briefly studied in this framework.

Evidence of its deleterious impact on health has been consistent, including a two-fold increase in risks of falls and fractures, physical impairment, loss of independence in activities of daily living, hospitalization, and death [15]. [...]longitudinal studies revealed exponential trajectory of frailty progression with aging in both sexes and in both frailty models [13], and in the case of physical frailty, a recent study concluded that meeting all five PF criteria signifies “a critical transition toward a point of no return beyond which the process becomes irreversible and death becomes imminent” [16]. [...]there remains an urgent need to balance between the continuing quests for development of therapeutics targeting frailty in its own right, and improving the quality of life of frail individuals by modernizing healthcare delivery systems. [...]the increasing use of omics-based technologies in frailty research represents a new frontier in a quest to identify novel biological molecules and mechanisms responsible for the generalized physiological dysregulation associated with frailty [25]. [...]heterogeneity in frailty assessment and causes of frailty (e.g., secondary vs. primary frailty) impairs our ability to discern signal amidst noise (or different signals depending on the cause of frailty) and conduct cross-study comparisons. [...]omics studies built on specific hypothesis may be a more fruitful approach.

INTRODUCTION Associations between television/computer use and dementia in socially inactive older adults remain unclear, and optimal limits are unknown. METHODS We followed 89,671 dementia‐free, socially inactive adults aged ≥55 from UK Biobank for a mean of 12.2 years. Adjusted Cox models assessed associations with incident all‐cause dementia and subtypes. RESULTS Computer use ≤2.4 h/day was associated with lower all‐cause dementia risk (hazard ratio [HR] 0.88; 95% confidence interval [CI] 0.82–0.94), whereas higher use increased risk (HR 1.19, 95% CI 1.05–1.34); patterns were similar for Alzheimer's and vascular dementia. Television viewing showed no association below 2.06 h/day but higher risk thereafter (HR 1.17; 95% CI 1.03–1.32), with a roughly linear increase for vascular dementia. Heavy computer use in apolipoprotein E (APOE) ‐ε4 homozygotes and higher television viewing in adults < 65 were more harmful. DISCUSSION In socially inactive older adults, moderate computer use may be protective, whereas higher computer use and television viewing are linked to increased dementia risk. Highlights Among socially inactive older adults, computer use showed a J‐shaped association with all‐cause dementia: up to about 2.4 h/day was associated with lower risk, whereas higher use was associated with increased risk. The J‐shaped pattern extended to Alzheimer's disease with an inflection near 2.4 h/day and to vascular dementia with an inflection near 2.2 h/day, while no association was observed for frontotemporal dementia. Television viewing below about 2.1 h/day was not associated with higher all‐cause dementia risk, but risk increased at higher viewing times. Television viewing showed a roughly linear increase in vascular dementia risk and an apparent reduction in Alzheimer's disease risk that is likely spurious and should be interpreted with caution. Risk varied by subgroup: heavy computer use was particularly harmful among apolipoprotein E (APOE) ‐ε4 homozygotes, and higher television time was more detrimental in adults younger than 65 years.