Age-Related Variations of Muscle Mass,Strength, and Physical Performance in Community-Dwellers: Results From the Milan EXPO Survey

Objectives

Declining muscle mass and function are hallmarks of the aging process. The preservation of muscle trophism may protect against various negative health outcomes. Age- and sex-specific curves of muscle mass, strength, and function, using data from a large sample of community-dwelling people, are necessary.

Use of Medications of Questionable Benefit During the Last Year of Life of Older Adults With Dementia

Objectives

To investigate the prevalence and factors associated with the use of medications of questionable benefit throughout the final year of life of older adults who died with dementia.

Searching for bridges between psychopathology and real-world functioning in first-episode psychosis: A network analysis from the OPTiMiSE trial

BackgroundNetwork analysis has been used to explore the interplay between psychopathology and functioning in psychosis, but no study has used dedicated statistical techniques to focus on the bridge symptoms connecting these domains. The current study aims to estimate the network of depressive, negative, and positive symptoms, general psychopathology, and real-world functioning in people with first-episode schizophrenia or schizophreniform disorder, focusing on bridge nodes.MethodsBaseline data from the OPTiMiSE trial were analyzed. The sample included 446 participants (age 40.0 ± 10.9 years, 70% males). The network was estimated with a Gaussian graphical model, using scores on individual items of the positive and negative syndrome scale (PANSS), the Calgary depression scale for schizophrenia, and the personal and social performance scale. Stability, strength centrality, expected influence (EI), predictability, and bridge centrality statistics were computed. The top 20% scoring nodes on bridge strength were selected as bridge nodes.ResultsNodes from different rating scales assessing similar psychopathological and functioning constructs tended to cluster together in the estimated network. The most central nodes (EI) were Delusions, Emotional Withdrawal, Depression, and Depressed Mood. Bridge nodes included Depression, Conceptual Disorganization, Active Social Avoidance, Delusions, Stereotyped Thinking, Poor Impulse Control, Guilty Feelings, Unusual Thought Content, and Hostility. Most of the bridge nodes belonged to the general psychopathology subscale of the PANSS. Depression (G6) was the bridge node with the highest value.ConclusionsThe current study provides novel insights for understanding the complex phenotype of psychotic disorders and the mechanisms underlying the development and maintenance of comorbidity and functional impairment after psychosis onset.     

Dual IGF1R/IR inhibitors in combination with GD2-CAR T-cells display a potent anti-tumor activity in diffuse midline glioma H3K27M-mutant

BackgroundDiffuse midline gliomas (DMG) H3K27M-mutant, including diffuse intrinsic pontine glioma (DIPG), are pediatric brain tumors associated with grim prognosis. Although GD2-CAR T-cells demonstrated significant anti-tumor activity against DMG H3K27M-mutant in vivo, a multimodal approach may be needed to more effectively treat patients. We investigated GD2 expression in DMG/DIPG and other pediatric high-grade gliomas (pHGG) and sought to identify chemical compounds that would enhance GD2-CAR T-cell anti-tumor efficacy.MethodsImmunohistochemistry in tumor tissue samples and immunofluorescence in primary patient-derived cell lines were performed to study GD2 expression. We developed a high-throughput cell-based assay to screen 42 kinase inhibitors in combination with GD2-CAR T-cells. Cell viability, western blots, flow-cytometry, real time PCR experiments, DIPG 3D culture models, and orthotopic xenograft model were applied to investigate the effect of selected compounds on DIPG cell death and CAR T-cell function.ResultsGD2 was heterogeneously, but widely, expressed in the tissue tested, while its expression was homogeneous and restricted to DMG/DIPG H3K27M-mutant cell lines. We identified dual IGF1R/IR antagonists, BMS-754807 and linsitinib, able to inhibit tumor cell viability at concentrations that do not affect CAR T-cells. Linsitinib, but not BMS-754807, decreases activation/exhaustion of GD2-CAR T-cells and increases their central memory profile. The enhanced anti-tumor activity of linsitinib/GD2-CAR T-cell combination was confirmed in DIPG models in vitro, ex vivo, and in vivo.ConclusionOur study supports the development of IGF1R/IR inhibitors to be used in combination with GD2-CAR T-cells for treating patients affected by DMG/DIPG and, potentially, by pHGG.     

Multimodal study of pelvic splenosis: a rare cause of abdominal pain

We present a rare case of pelvic splenosis, in a 46-year-old man, with a previous history of partial splenectomy, complaining of nonspecific pain in the lower abdominal quadrants. Splenosis is a benign acquired condition, defined as a heterotopic autotransplantation of splenic tissue in other compartments of the body, caused by rupture of the splenic capsule following trauma or splenectomy. Splenosis is often asymptomatic and incidentally found and does not require treatment. Surgery is indicated only in patients presenting with symptoms or complications. In our case, the multimodal imaging study (ultrasound, MRI, CT, and scintigraphy) allowed a correct differential diagnosis without resorting to invasive procedures, susceptible to complications     

Coactivation of the elbow antagonist muscles is not affected by the speed of movement in isokinetic exercise

Since muscle coactivation increases the stiffness and stability of a joint, greater coactivation is likely during faster than slower movements. Very few studies, though, have been conducted to verify this hypothesis. Moreover, a large number of studies have examined coactivation of muscles surrounding the knee joint whereas there are few reports on the elbow joint. The aim of this study was therefore to compare the antagonist activation of the elbow flexors and extensors during isokinetic concentric exercises and to investigate the influence of angular velocity on their activation. Twelve men participated in the study. The surface electromyographic signals (sEMG) were recorded from the biceps brachii (BB) and triceps brachii (TB) muscles during three maximal voluntary isometric contractions (MVC) of elbow flexors and extensors and a set of three maximal elbow flexions and extensions each at 15 degrees, 30 degrees , 60 degrees, 120 degrees, 180 degrees, and 240 degrees.s(-1). Normalized root mean square (RMS) of sEMG was calculated during the isokinetic phase of movement as an index of sEMG amplitude. During elbow flexion, the antagonist activation of BB averaged 16.2% lower than TB, and this difference was statistically significant at all angular velocities. The normalized RMS values ranged from 26.0% +/- 19.0 at MVC to 37.8% +/- 13.9 at 240 degrees.s(-1) for antagonist TB activation, and from 5.7% +/- 5.2 at MVC to 18.9% +/- 8.6 at 240 degrees.s(-1) for antagonist BB activation. No influence of angular velocity on agonist and antagonist activity was found. Moreover, flexion and extension torques were both strongly affected by the amount of antagonist activation. The functional specialization of the two muscle groups could be responsible for the different levels of antagonist activation. The frequent use of BB, which is not assisted by gravity during daily activities, could lead to reduced coactivation due to a better functioning of the control system based upon reciprocal innervation. These findings may have significant implications in the design of rehabilitation programs directed to the elbow joint.