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Study design:Randomized controlled trial.Objectives:To establish whether the use of mechanical insufflation/exsufflation leads to a significant improve in tracheostomy subjects with upper spinal cord injuries (C1–C7), ASIA classification grade A and bronchial hyper secretion the following parameters: forced vital capacity (FVC), forced exspiratory volume on the first second (FEV1), FEV1/FVC, peak exspiratory flow (PEF), arterious pressure of O2 (Pa O2), arterious pressure of CO2 (Pa CO2), pH, saturation of O2 (Sa O2).Setting:Spinal Cord Unit, Montecatone Rehabilitation Institute, Imola, Italy.Methods:The patients were split into two groups: the experimental group (EG) and the control group (CG). Each patient was given 10 treatments: the EG was given manual respiratory kinesitherapy associated with mechanical insufflation/exsufflation with inhale and exhale pressure between 15 cm H2O and 45 cm H2O, while the CG was only given manual kinesitherapy. The treatment sessions covered the necessary amount of time in order to achieve sufficient clearance. The study has been approved by the local ethic committee. The patients were informed before being enrolled in that study and gave their written consent.Results:At the end of the treatment associated with the mechanical insufflation/exsufflation, the EG showed a significant increase in FVC, FEV1 and PEF, although it was not possible to compare the latter with the CG. The other parameters were also subject to variations, although not statistically significant. The CG did not show signs of any significant change.Conclusion:The use of mechanical insufflation/exsufflation in subjects with the aforementioned characteristics is shown to be an effective adjunct to manual respiratory kinesitherapy, since it makes it possible to achieve adequate bronco-pulmonary clearance, even removing thick, deep secretions and making it possible to insufflate any areas affected by atelectasis.Spinal Cord (2006) 44, 614–616. doi:10.1038/sj.sc.3101870; published online 13 December 2005 [ABSTRACT FROM AUTHOR]

Sarcopenia is an age-related disease characterized by loss of muscle strength, mass and performance. Malnutrition contributes to sarcopenia pathogenesis. The aim of this systematic review is to analyze existing evidence on the efficacy of nutritional supplementation on muscle and mitochondrial health among sarcopenic or malnourished older adults. We included randomized controlled trials (RCTs) assessing the effect of branched-chain amino acid (BCAA), vitamin D and/or omega-3 polyunsaturated fatty acid (PUFA) on muscle mass, strength and performance and/or on mitochondrial activity and redox state in older sarcopenic and/or malnourished adults. The literature search was on MEDLINE, Embase and Cochrane Central, restricted to articles published in the last 10 years (2012-2022). Twelve RCTs with a total of 1337 subjects were included. BCAA with vitamin D significantly ameliorates appendicular muscle mass (4 RCTs), hand grip strength (4 RCTs), gait speed (3 RCTs), short physical performance battery (3 RCTs) or chair stand test (3 RCTs) among six out of nine RCTs. BCAA alone (2 RCTs) or PUFA (1 RCT) were not effective in improving muscle health. Mitochondrial function was significantly improved by the administration of BCAA alone (1 RCT) or in association with vitamin D (1 RCT). In conclusion, BCAA in association with vitamin D may be useful in the treatment of sarcopenia and boost mitochondrial bioenergetic and redox activity. PROSPERO CRD42022332288.

The management of endometriosis-related infertility is still a challenging issue. Women can be managed with either surgery or in vitro fertilization (IVF). The decision is tailored to the patients considering pros and cons of both approaches. Surgery might increase the chances of natural conception and relieve symptoms. IVF may be more effective, but costs are higher and unoperated women face some peculiar additional risks during the procedure and pregnancy. The unavailability of randomized trials comparing the two strategies hampers the possibility to provide precise estimates. This Randomized Controlled Trial (RCT) aims at filling this gap. This is a multicenter, non-blinded, randomized controlled trial with parallel groups and allocation 1:1. Three Italian Academic Infertility Units will be involved. Main inclusion criteria are infertility for more than one year, age less than 40 years and a sonographic diagnosis of endometriosis (ovarian endometriomas or deep peritoneal lesions). Previous IVF and previous surgery for endometriosis are exclusion criteria. Women will be randomized to either surgery and then natural pregnancy seeking or a standard program of three IVF cycles. The primary aim is the comparison of live birth rate between the two groups (IVF versus surgery) within one year of randomization. The secondary aim is the evaluation of cost-effective profile of the two interventions. The present study can influence the clinical practice of infertility treatment in women with endometriosis. From a public health perspective, information on the more cost-effective clinical management strategy would consent a wiser allocation of resources. Trial registration: NCT04743167, registered on 8 February 2021., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: - Dr. Somigliana reports grants from Ferring, grants and personal fees from Merck-Serono, grants and personal fees from Theramex, OUTSIDE the submitted work.

We have combined an anterior segment (AS) optical coherence tomography (OCT) system and a wavefront-based aberrometer with an approach that senses ocular wavefront aberrations using the OCT beam. Temporal interlacing of the OCT and aberrometer channels allows for OCT images and refractive error measurements to be acquired continuously and in real-time. The system measures refractive error with accuracy and precision comparable to that of clinical autorefractors. The proposed approach provides a compact modular design that is suitable for integrating OCT and wavefront-based autorefraction within the optical head of the ophthalmic surgical microscope for guiding cataract surgery or table-top devices for simultaneous autorefraction and ocular biometry., Competing Interests: The University of Miami and some of the authors (MR, FM, JMP and HD) stand to benefit from intellectual property in the technology used in this study., (© 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

This study investigated whether fear of falling (FOF) measured by two different instruments, the Falls Efficacy Scale-International (FES-I) and the single question on FOF and activity restriction (SQ-FAR), is associated with mortality at 6-year follow-up. Participants ( n  = 1359, 58.6% women) were community-dwelling persons enrolled in the Lausanne cohort 65 + , aged 66 to 71 years at baseline. Covariables assessed at baseline included demographic, cognitive, affective, functional and health status, while date of death was obtained from the office in charge for population registration. Unadjusted Kaplan Meyer curves were performed to show the survival probability for all-cause mortality according to the degree of FOF reported with FES-I and SQ-FAR, respectively. Bivariable and multivariable Cox regression analyses were performed to assess hazard ratios, using time-in-study as the time scale variable and adjusting for variables significantly associated in bivariable analyses. During the 6-year follow-up, 102 (7.5%) participants died. Reporting the highest level of fear at FES-I (crude HR 3.86, 95% CI 2.37-6.29, P  < .001) or "FOF with activity restriction" with SQ-FAR (crude HR 2.42, 95% CI 1.44-4.09, P  = .001) were both associated with increased hazard of death but these associations did not remain significant once adjusting for gender, cognitive, affective and functional status. As a conclusion, although high FOF and related activity restriction, assessed with FES-I and SQ-FAR, identifies young-old community-dwelling people at increased risk of 6-year mortality, this association disappears when adjusting for potential confounders. As a marker of negative health outcomes, FOF should be screened for in order to provide personalized care and reduce subsequent risks., Competing Interests: Conflicts of interestAll the authors- Giulia Belloni, Christophe Büla, Brigitte Santos-Eggimann, Yves Henchoz, Sarah Fustinoni, Laurence Seematter-Bagnoud- report no conflict of interest., (© The Author(s) 2021.)

Frailty is a clinical condition characterized by the individual's increased vulnerability to endogenous and exogenous stressors. It is determined by the reduction of homeostatic capacities of the organism and responsible for a marked risk of adverse health outcomes (including functional loss and mortality). Frailty originates from the geriatric background and may pave the way toward a model of care centered on the person, deviating from the traditional and obsolete disease-focused approach. Unfortunately, many controversies have affected the field of frailty over the years and ambiguities have been growing. In particular, the common use of frailty as condition to "exclude" from interventions is a worrisome trend. In fact, the detection of frailty should instead represent the entry point for a more in-depth analysis with the aim of identifying the causes of individual's increased vulnerability and implementing a person-tailored intervention plan. With the aim of promoting a more comprehensive and appropriate assessment of the aging population, the World Health Organization introduced the concept of intrinsic capacity (IC), defined as the composite of all physical and mental capacities that an individual can draw upon during his/her life. Frailty and IC are two constructs stemming from the same need of overcoming traditional medical paradigms that negatively impact on the correct way clinical and research practice should be conducted in older persons. In this article, we describe the similarities and differences between the two constructs, highlighting how geriatric medicine contributed to their development and will be crucial for their further integration in future healthcare models.

Background: Contrary to the most credited theories on laser therapy that see power/energy as the major factors to its effectiveness, a technique using an extremely low power/energy laser stimulation to treat musculoskeletal pain and dysfunction is proposed. The stimulus consists of a 20 s train of modulated pulses with an average power below 0.02 mW and is applied on sequences of acupuncture points selected according to the impaired segment of the patient's body. Methods : Modifications on the extracellular soft tissue matrix and on the "fascia" were sonographically demonstrated. Laboratory and clinical tests confirmed the effectiveness. Results : Responses similar to those experienced in acupuncture were observed. The device-a CE Class IIa certified medical device named Libralux-affords a clinically proven effectiveness exceeding 80% in the treatment of musculoskeletal conditions and associated motor dysfunctions. An average of just three application sessions was generally sufficient to overcome the dysfunction. Conclusions : The development of the method is supported by over 20 years of R&D activities, with a range of experiments discussed in several papers published in indexed peer-reviewed journals. A few considerations regarding the possible physiological action mechanisms involved are proposed in this paper.

The aim of the current study is to investigate the integrity of the Mirror Neurons (MN) network in normal aging, Mild Cognitive Impairment (MCI), and Alzheimer disease (AD). Although AD and MCI are considered "cognitive" diseases, there has been increasing recognition of a link between motor function and AD. More recently the embodied cognition hypothesis has also been developed: it postulates that a part of cognition results from the coupling between action and perception representations. MN represent a neuronal population which links perception, action, and cognition, therefore we decided to characterize MN functioning in neurodegenerative cognitive decline. Three matched groups of 16 subjects (normal elderly-NE, amnesic MCI with hippocampal atrophy and AD) were evaluated with a focused neuropsychological battery and an fMRI task specifically created to test MN: that comprised of an observation run, where subjects were shown movies of a right hand grasping different objects, and of a motor run, where subjects observed visual pictures of objects oriented to be grasped with the right hand. In NE subjects, the conjunction analysis (comparing fMRI activation during observation and execution), showed the activation of a bilateral fronto-parietal network in "classical" MN areas, and of the superior temporal gyrus (STG). The MCI group showed the activation of areas belonging to the same network, however, parietal areas were activated to a lesser extent and the STG was not activated, while the opposite was true for the right Broca's area. We did not observe any activation of the fronto-parietal network in AD participants. They did not perform as well as the NE subjects in all the neuropsychological tests (including tests of functions attributed to MN) whereas the MCI subjects were significantly different from the NE subjects only in episodic memory and semantic fluency. Here we show that the MN network is largely preserved in aging, while it appears involved following an anterior-posterior gradient in neurodegenerative decline. In AD, task performance decays and the MN network appears clearly deficient. The preservation of the anterior part of the MN network in MCI could possibly supplement the initial decay of the posterior part, preserving cognitive performance.

Congenital disorders of glycosylation (CDG) comprise a family of human multisystemic diseases caused by recessive mutations in genes required for protein N-glycosylation. More than 100 distinct forms of CDGs have been identified and most of them cause severe neurological impairment. The Conserved Oligomeric Golgi (COG) complex mediates tethering of vesicles carrying glycosylation enzymes across the Golgi cisternae. Mutations affecting human COG1, COG2 and COG4-COG8 cause monogenic forms of inherited, autosomal recessive CDGs. We have generated a Drosophila COG7-CDG model that closely parallels the pathological characteristics of COG7-CDG patients, including pronounced neuromotor defects associated with altered N-glycome profiles. Consistent with these alterations, larval neuromuscular junctions of Cog7 mutants exhibit a significant reduction in bouton numbers. We demonstrate that the COG complex cooperates with Rab1 and Golgi phosphoprotein 3 to regulate Golgi trafficking and that overexpression of Rab1 can rescue the cytokinesis and locomotor defects associated with loss of Cog7 . Our results suggest that the Drosophila COG7-CDG model can be used to test novel potential therapeutic strategies by modulating trafficking pathways., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2017. Published by The Company of Biologists Ltd.)

Cytokinesis requires a tight coordination between actomyosin ring constriction and new membrane addition along the ingressing cleavage furrow. However, the molecular mechanisms underlying vesicle trafficking to the equatorial site and how this process is coupled with the dynamics of the contractile apparatus are poorly defined. Here we provide evidence for the requirement of Rab1 during cleavage furrow ingression in cytokinesis. We demonstrate that the gene omelette (omt) encodes the Drosophila orthologue of human Rab1 and is required for successful cytokinesis in both mitotic and meiotic dividing cells of Drosophila melanogaster We show that Rab1 protein colocalizes with the conserved oligomeric Golgi (COG) complex Cog7 subunit and the phosphatidylinositol 4-phosphate effector GOLPH3 at the Golgi stacks. Analysis by transmission electron microscopy and 3D-SIM super-resolution microscopy reveals loss of normal Golgi architecture in omt mutant spermatocytes indicating a role for Rab1 in Golgi formation. In dividing cells, Rab1 enables stabilization and contraction of actomyosin rings. We further demonstrate that GTP-bound Rab1 directly interacts with GOLPH3 and controls its localization at the Golgi and at the cleavage site. We propose that Rab1, by associating with GOLPH3, controls membrane trafficking and contractile ring constriction during cytokinesis., (© 2017 The Authors.)