Quality of life in Parkinson’s disease: Italian validation of the Parkinson’s Disease Questionnaire (PDQ-39-IT)

Translation and cross-cultural adaptation of the 39-item Parkinson’s Disease Questionnaire (PDQ-39) to the Italian culture was performed by Oxford University Innovation in 2008, but this version has never been validated. Therefore, we performed the process of validation of the Italian version of the PDQ-39 (PDQ-39-IT) following the “Consensus-Based Standards for the Selection of Health Status Measurement Instruments” checklist. The translated PDQ-39-IT was tested with 104 patients diagnosed with Parkinson’s disease (PD) who were recruited between June and October 2017. The mean age of the participants was 65.7 ± 10.2 years, and the mean duration of symptoms was 7.4 ± 5.3 years. The internal consistency of the PDQ-39-IT was assessed by Cronbach’s alpha and ranged from 0.69 to 0.92. In an assessment of test-retest reliability in 35 of the 104 patients, the infraclass correlation coefficient (ICC) ranged from 0.85 to 0.96 for the various subitems of the PDQ-39-IT (all p < 0.01). Spearman’s rank correlation coefficient for the validity of the PDQ-39-IT and the Italian version of the 36-Item Short Form (SF-36) was − 0.50 (p < 0.01). The results show that the PDQ-39-IT is a reliable and valid tool to assess the impact of PD on functioning and well-being. Thus, the PDQ-39-IT can be used in clinical and research practice to assess this construct and to evaluate the overall effect of different treatments in Italian PD patients

Tools to assess the quality of life in patients with Parkinson’s disease. A systematic review

Introduction . The clinical, social, and economic implications of Parkinson’s disease (PD) are significant; disability occurs leading to a low quality of life (QoL). Information on the QoL of patients with PD and studies on the relationship between QoL and motor and cognitive function are necessary for both research and clinical use to make informed decisions in healthcare and rehabilitation. The aim of this study was to determine which scales are most used to assess QoL in patients with PD. Area covered . A literature search was conducted in MEDLINE, Scopus, CINAHL, PsycINFO, and Web of Science. Two authors independently identified eligible studies based on predefined inclusion criteria and extracted the data. Study quality and the risk of bias were assessed using the COSMIN checklist. Expert opinion . 116 suitable studies were included, and 42 different instruments were identified. The most frequently used scales were the 39-items and 8-items Parkinson’s Disease Questionnaire (PDQ-39) (PDQ-8). These findings suggest further investigation of existing PD outcome measures would benefit patients, researchers, and clinicians. Validated, universal outcome measures are required to allow comparisons across practice; therefore, we recommend that future researchers use a common set of outcome assessments based on the results of this review

In Vitro and in vivo anti-tumoral effects of the flavonoid apigenin in malignant mesothelioma

Malignant mesothelioma (MM) is a tumor arising from mesothelium. MM patients' survival is poor. The polyphenol 4',5,7,-trihydroxyflavone Apigenin (API) is a "multifunctional drug". Several studies have demonstrated API anti-tumoral effects. However, little is known on the in vitro and in vivo anti-tumoral effects of API in MM. Thus, we analyzed the in vitro effects of API on cell proliferation, cell cycle regulation, pro-survival signaling pathways, apoptosis, and autophagy of human and mouse MM cells. We evaluated the in vivo anti-tumor activities of API in mice transplanted with MM #40a cells forming ascites. API inhibited in vitro MM cells survival, increased reactive oxygen species intracellular production and induced DNA damage. API activated apoptosis but not autophagy. API-induced apoptosis was sustained by the increase of Bax/Bcl-2 ratio, increase of p53 expression, activation of both caspase 9 and caspase 8, cleavage of PARP-1, and increase of the percentage of cells in subG1 phase. API treatment affected the phosphorylation of ERK1/2, JNK and p38 MAPKs in a cell-type specific manner, inhibited AKT phosphorylation, decreased c-Jun expression and phosphorylation, and inhibited NF-κB nuclear translocation. Intraperitoneal administration of API increased the median survival of C57BL/6 mice intraperitoneally transplanted with #40a cells and reduced the risk of tumor growth. Our findings may have important implications for the design of MM treatment using API

Focal Stroke in the Developing Rat Motor Cortex Induces Age- and Experience-Dependent Maladaptive Plasticity of Corticospinal System

Motor system development is characterized by an activity-dependent competition between ipsilateral and contralateral corticospinal tracts (CST). Clinical evidence suggests that age is crucial for developmental stroke outcome, with early lesions inducing a "maladaptive" strengthening of ipsilateral projections from the healthy hemisphere and worse motor impairment. Here, we investigated in developing rats the relation between lesion timing, motor outcome and CST remodeling pattern. We induced a focal ischemia into forelimb motor cortex (fM1) at two distinct pre-weaning ages: P14 and P21. We compared long-term motor outcome with changes in axonal sprouting of contralesional CST at red nucleus and spinal cord level using anterograde tracing. We found that P14 stroke caused a more severe long-term motor impairment than at P21, and induced a strong and aberrant contralesional CST sprouting onto denervated spinal cord and red nucleus. The mistargeted sprouting of CST, and the worse motor outcome of the P14 stroke rats were reversed by an early skilled motor training, underscoring the potential of early activity-dependent plasticity in modulating lesion outcome. Thus, changes in the mechanisms controlling CST plasticity occurring during the third postnatal week are associated with age-dependent regulation of the motor outcome after stroke

Overall Survival Following Anastomotic Leakage After Surgery for Carcinoma of the Esophagus and Gastroesophageal Junction: A Systematic Review

The effect of anastomotic leakage, in patients who underwent surgery for carcinoma of the esophagus and gastroesophageal junction, on overall survival (OS) is a debated and controversial topic. The aim of this systematic review was to clarify the impact of anastomotic leakage on long-term survival of patients with esophageal cancer undergoing esophagectomy. A systematic literature review was carried out from 2000 to 2022. We chose articles reporting data from patients who underwent surgery for carcinoma of the esophagus and gastroesophageal junction. Data regarding 1-, 3- and 5-year OS were analyzed. Twenty studies met the inclusion criteria, yielding a total of 9,279 patients. Analyzing data from selected studies, anastomotic leakage was found to be associated with decreased OS in 5,456 cases while in the remaining 3,823 it had no impact on long term survival (p&lt;0.05). However, this result did not emerge from the other studies considered in the systematic review. Anastomotic leakage is a severe postoperative complication, which seems to have an impact on overall survival. However, the topic remains debated and not supported by all case series included in this systematic review

Focal Stroke in the Developing Rat Motor Cortex Induces Age- and Experience-Dependent Maladaptive Plasticity of Corticospinal System

Motor system development is characterized by an activity-dependent competition between ipsilateral and contralateral corticospinal tracts (CST). Clinical evidence suggests that age is crucial for developmental stroke outcome, with early lesions inducing a “maladaptive” strengthening of ipsilateral projections from the healthy hemisphere and worse motor impairment. Here, we investigated in developing rats the relation between lesion timing, motor outcome and CST remodeling pattern. We induced a focal ischemia into forelimb motor cortex (fM1) at two distinct pre-weaning ages: P14 and P21. We compared long-term motor outcome with changes in axonal sprouting of contralesional CST at red nucleus and spinal cord level using anterograde tracing. We found that P14 stroke caused a more severe long-term motor impairment than at P21, and induced a strong and aberrant contralesional CST sprouting onto denervated spinal cord and red nucleus. The mistargeted sprouting of CST, and the worse motor outcome of the P14 stroke rats were reversed by an early skilled motor training, underscoring the potential of early activity-dependent plasticity in modulating lesion outcome. Thus, changes in the mechanisms controlling CST plasticity occurring during the third postnatal week are associated with age-dependent regulation of the motor outcome after stroke

Massage accelerates brain development and the maturation of visual function

Environmental enrichment (EE) was shown recently to accelerate brain development in rodents. Increased levels of maternal care, and particularly tactile stimulation through licking and grooming, may represent a key component in the early phases of EE. We hypothesized that enriching the environment in terms of body massage may thus accelerate brain development in infants. We explored the effects of body massage in preterm infants and found that massage accelerates the maturation of electroencephalographic activity and of visual function, in particular visual acuity. In massaged infants, we found higher levels of blood IGF-1. Massage accelerated the maturation of visual function also in rat pups and increased the level of IGF-1 in the cortex. Antagonizing IGF-1 action by means of systemic injections of the IGF-1 antagonist JB1 blocked the effects of massage in rat pups. These results demonstrate that massage has an influence on brain development and in particular on visual development and suggest that its effects are mediated by specific endogenous factors such as IGF-1

Prognostic and Predictive Role of Body Composition in Metastatic Neuroendocrine Tumor Patients Treated with Everolimus: A Real-World Data Analysis

Neuroendocrine tumors (NETs) are rare neoplasms frequently characterized by an up- regulation of the mammalian rapamycin targeting (mTOR) pathway resulting in uncontrolled cell proliferation. The mTOR pathway is also involved in skeletal muscle protein synthesis and in adipose tissue metabolism. Everolimus inhibits the mTOR pathway, resulting in blockade of cell growth and tumor progression. The aim of this study is to investigate the role of body composition in- dexes in patients with metastatic NETs treated with everolimus. The study population included 30 patients with well-differentiated (G1-G2), metastatic NETs treated with everolimus at the IRCCS Romagnolo Institute for the Study of Tumors (IRST) “Dino Amadori”, Meldola (FC), Italy. The body composition indexes (skeletal muscle index [SMI] and adipose tissue indexes) were assessed by measuring on a computed tomography (CT) scan the cross-sectional area at L3 at baseline and at the first radiological assessment after the start of treatment. The body mass index (BMI) was assessed at baseline. The median progression-free survival (PFS) was 8.9 months (95% confidence interval [CI]: 3.4–13.7 months). The PFS stratified by tertiles was 3.2 months (95% CI: 0.9–10.1 months) in patients with low SMI (tertile 1), 14.2 months (95% CI: 2.3 months-not estimable [NE]) in patients with intermediate SMI (tertile 2), and 9.1 months (95% CI: 2.7 months-NE) in patients with high SMI (tertile 3) (p = 0.039). Similarly, the other body composition indexes also showed a statistically significant difference in the three groups on the basis of tertiles. The median PFS was 3.2 months (95% CI: 0.9–6.7 months) in underweight patients (BMI 18.49 kg/m2) and 10.1 months (95% CI: 3.7–28.4 months) in normal-weight patients (p = 0.011). There were no significant differences in terms of overall survival. The study showed a correlation between PFS and the body composition indexes in patients with NETs treated with everolimus, underlining the role of adipose and muscle tissue in these patients

Hematopoietic progenitor cell liabilities and alarmins S100A8/A9-related inflammaging associate with frailty and predict poor cardiovascular outcomes in older adults

Frailty affects the physical, cognitive, and social domains exposing older adults to an increased risk of cardiovascular disease and death. The mechanisms linking frailty and cardiovascular outcomes are mostly unknown. Here, we studied the association of abundance (flow cytometry) and gene expression profile (RNAseq) of stem/progenitor cells (HSPCs) and molecular markers of inflammaging (ELISA) with the cardiorespiratory phenotype and prospective adverse events of individuals classified according to levels of frailty. Two cohorts of older adults were enrolled in the study. In a cohort of pre‐frail 35 individuals (average age: 75 years), a physical frailty score above the median identified subjects with initial alterations in cardiorespiratory function. RNA sequencing revealed S100A8/A9 upregulation in HSPCs from the bone marrow (>10‐fold) and peripheral blood (>200‐fold) of individuals with greater physical frailty. Moreover higher frailty was associated with increased alarmins S100A8/A9 and inflammatory cytokines in peripheral blood. We then studied a cohort of 104 more frail individuals (average age: 81 years) with multidomain health deficits. Reduced levels of circulating HSPCs and increased S100A8/A9 concentrations were independently associated with the frailty index. Remarkably, low HSPCs and high S100A8/A9 simultaneously predicted major adverse cardiovascular events at 1‐year follow‐up after adjustment for age and frailty index. In conclusion, inflammaging characterized by alarmin and pro‐inflammatory cytokines in pre‐frail individuals is mirrored by the pauperization of HSPCs in frail older people with comorbidities. S100A8/A9 is upregulated within HSPCs, identifying a phenotype that associates with poor cardiovascular outcomes