Sustained increase in physical fitness independently predicts improvements in cardiometabolic risk profile in type 2 diabetes.

AIMS: To investigate the relationship between changes in physical fitness and cardiovascular risk factors and scores in patients with type 2 diabetes receiving either a behavioural counselling intervention to increase moderate-to-vigorous-intensity physical activity (MVPA) and decrease sedentary-time (SED-time) or standard care. MATERIALS AND METHODS: This is a pre-specified ancillary analysis of the Italian Diabetes and Exercise Study_2, a 3-year randomized clinical trial in which 300 physically inactive and sedentary patients were randomized 1:1 to receive either a one-month theoretical and practical counselling each year or standard care. Mean changes from baseline throughout the 3-year period in MVPA, SED-time, cardiorespiratory fitness (VO2max ), muscle strength, flexibility, cardiovascular risk factors and scores were calculated for study completers (n = 267) and considered irrespective of study arm. RESULTS: Haemoglobin (Hb) A1c and coronary heart disease (CHD) risk scores decreased with quartiles of VO2max and lower body muscle strength changes. Multivariable linear regression analysis showed that increases in VO2max independently predicted decreases in HbA1c , blood glucose, diastolic blood pressure (BP), CHD and total stroke 10-year risk and increases in HDL cholesterol, whereas increases in lower body muscle strength independently predicted decreases in body mass index (BMI), waist circumference, triglycerides, systolic BP, CHD and fatal stroke 10-year risk. These associations remained after including changes in BMI, waist circumference, fat mass and fat-free mass, or MVPA and SED-time as covariates. CONCLUSIONS: Improvement in physical fitness predicts favourable changes in cardiometabolic risk profile, independent of changes not only in (central) adiposity or body composition but also in MVPA and SED-time. TRIAL REGISTRATION: ClinicalTrials.gov; NCT01600937; URL https://clinicaltrials.gov/ct2/show/NCT01600937.

Influence of cardiopulmonary bypass set-up and management on clinical outcomes after minimally invasive aortic valve surgery.

INTRODUCTION: Minimally invasive aortic valve replacement (MIAVR) requires changes in cannulation strategy and cardiopulmonary bypass (CPB) management when compared to the conventional approach (CAVR). We aimed at evaluating if these differences could influence perfusion-related quality parameters and impair postoperative outcomes. METHODS: Overall, 339 consecutive patients underwent MIAVR or CAVR between 2014 and 2020 and were analyzed retrospectively. To account for baseline differences, a propensity-matching analysis was performed, obtaining two groups of 97 patients each. RESULTS: MIAVR group had longer CPB time [107 (95-120) vs 95 (86-105) min, p = .003] than CAVR group. Of note, average pump flow rate index [2.4 (2.2-2.5) vs 2.7 (2.4-2.8) l/min/m2, p = .004] was lower in the MIAVR group. Mean arterial pressure was 73 = 9 mmHg vs 62 = 11 mmHg for the MIAVR and CAVR group, respectively (p < .001). Cell-salvaged blood was most commonly used in the MIAVR group (25.8% vs 11.3%, p = .02). Finally, CPB temperature was 32.8°C (32.1-34.8) for MIAVR group vs 34.9°C (33.2-36.1) for the CAVR group (p = .02). Postoperative complications were similar between groups. CONCLUSIONS: In conclusion, despite differences in CPB parameters in patients undergoing CAVR and MIAVR, the incidences of adverse outcomes were similar. However, compared to CAVR, MIAVR was associated with shorter durations of mechanical ventilation and hospital stay as well as less transfusion of blood products.

Mutations in INPP5K Cause a Form of Congenital Muscular Dystrophy Overlapping Marinesco-Sjögren Syndrome and Dystroglycanopathy.

Congenital muscular dystrophies display a wide phenotypic and genetic heterogeneity. The combination of clinical, biochemical, and molecular genetic findings must be considered to obtain the precise diagnosis and provide appropriate genetic counselling. Here we report five individuals from four families presenting with variable clinical features including muscular dystrophy with a reduction in dystroglycan glycosylation, short stature, intellectual disability, and cataracts, overlapping both the dystroglycanopathies and Marinesco-Sjögren syndrome. Whole-exome sequencing revealed homozygous missense and compound heterozygous mutations in INPP5K in the affected members of each family. INPP5K encodes the inositol polyphosphate-5-phosphatase K, also known as SKIP (skeletal muscle and kidney enriched inositol phosphatase), which is highly expressed in the brain and muscle. INPP5K localizes to both the endoplasmic reticulum and to actin ruffles in the cytoplasm. It has been shown to regulate myoblast differentiation and has also been implicated in protein processing through its interaction with the ER chaperone HSPA5/BiP. We show that morpholino-mediated inpp5k loss of function in the zebrafish results in shortened body axis, microphthalmia with disorganized lens, microcephaly, reduced touch-evoked motility, and highly disorganized myofibers. Altogether these data demonstrate that mutations in INPP5K cause a congenital muscular dystrophy syndrome with short stature, cataracts, and intellectual disability.

PULP-NN: accelerating quantized neural networks on parallel ultra-low-power RISC-V processors.

We present PULP-NN, an optimized computing library for a parallel ultra-low-power tightly coupled cluster of RISC-V processors. The key innovation in PULP-NN is a set of kernels for quantized neural network inference, targeting byte and sub-byte data types, down to INT-1, tuned for the recent trend toward aggressive quantization in deep neural network inference. The proposed library exploits both the digital signal processing extensions available in the PULP RISC-V processors and the cluster's parallelism, achieving up to 15.5 MACs/cycle on INT-8 and improving performance by up to 63 × with respect to a sequential implementation on a single RISC-V core implementing the baseline RV32IMC ISA. Using PULP-NN, a CIFAR-10 network on an octa-core cluster runs in 30 × and 19.6 × less clock cycles than the current state-of-the-art ARM CMSIS-NN library, running on STM32L4 and STM32H7 MCUs, respectively. The proposed library, when running on a GAP-8 processor, outperforms by 36.8 × and by 7.45 × the execution on energy efficient MCUs such as STM32L4 and high-end MCUs such as STM32H7 respectively, when operating at the maximum frequency. The energy efficiency on GAP-8 is 14.1 × higher than STM32L4 and 39.5 × higher than STM32H7, at the maximum efficiency operating point. This article is part of the theme issue 'Harmonizing energy-autonomous computing and intelligence'.

Multiple roles of integrin-α3 at the neuromuscular junction.

The neuromuscular junction (NMJ) is the synapse between motoneurons and skeletal muscle, and is responsible for eliciting muscle contraction. Neurotransmission at synapses depends on the release of synaptic vesicles at sites called active zones (AZs). Various proteins of the extracellular matrix are crucial for NMJ development; however, little is known about the identity and functions of the receptors that mediate their effects. Using genetically modified mice, we find that integrin-α3 (encoded by Itga3), an adhesion receptor at the presynaptic membrane, is involved in the localisation of AZ components and efficient synaptic vesicle release. Integrin-α3 also regulates integrity of the synapse - mutant NMJs present with progressive structural changes and upregulated autophagy, features commonly observed during ageing and in models of neurodegeneration. Unexpectedly, we find instances of nerve terminal detachment from the muscle fibre; to our knowledge, this is the first report of a receptor that is required for the physical anchorage of pre- and postsynaptic elements at the NMJ. These results demonstrate multiple roles of integrin-α3 at the NMJ, and suggest that alterations in its function could underlie defects that occur in neurodegeneration or ageing.

Effect of a Behavioral Intervention Strategy on Sustained Change in Physical Activity and Sedentary Behavior in Patients With Type 2 Diabetes: The IDES_2 Randomized Clinical Trial.

Importance: There is no definitive evidence that changes in physical activity/sedentary behavior can be maintained long term in individuals with type 2 diabetes. Objective: To investigate whether a behavioral intervention strategy can produce a sustained increase in physical activity and reduction in sedentary time among individuals with type 2 diabetes. Design, Setting, and Participants: The Italian Diabetes and Exercise Study 2 was an open-label, assessor-blinded, randomized clinical superiority trial, with recruitment from October 2012 to February 2014 and follow-up until February 2017. In 3 outpatient diabetes clinics in Rome, 300 physically inactive and sedentary patients with type 2 diabetes were randomized 1:1 (stratified by center, age, and diabetes treatment) to receive a behavioral intervention or standard care for 3 years. Interventions: All participants received usual care targeted to meet American Diabetes Association guideline recommendations. Participants in the behavioral intervention group (n = 150) received 1 individual theoretical counseling session and 8 individual biweekly theoretical and practical counseling sessions each year. Participants in the standard care group (n = 150) received only general physician recommendations. Main Outcomes and Measures: Co-primary end points were sustained change in physical activity volume, time spent in light-intensity and moderate- to vigorous-intensity physical activity, and sedentary time, measured by an accelerometer. Results: Of the 300 randomized participants (mean [SD] age, 61.6 [8.5] years; 116 women [38.7%]), 267 completed the study (133 in the behavioral intervention group and 134 in the standard care group). Median follow-up was 3.0 years. Participants in the behavioral intervention and standard care groups accumulated, respectively, 13.8 vs 10.5 metabolic equivalent-h/wk of physical activity volume (difference, 3.3 [95% CI, 2.2-4.4]; P < .001), 18.9 vs 12.5 min/dof moderate- to vigorous-intensity physical activity (difference, 6.4 [95% CI, 5.0-7.8]; P < .001), 4.6 vs 3.8 h/d of light-intensity physical activity (difference, 0.8 [95% CI, 0.5-1.1]; P < .001), and 10.9 vs 11.7 h/d of sedentary time (difference, -0.8 [95% CI, -1.0 to -0.5]; P < .001). Significant between-group differences were maintained throughout the study, but the between-group difference in moderate- to vigorous-intensity physical activity decreased during the third year from 6.5 to 3.6 min/d. There were 41 adverse events in the behavioral intervention group and 59 in the standard care group outside of the sessions; participants in the behavioral intervention group experienced 30 adverse events during the sessions (most commonly musculoskeletal injury/discomfort and mild hypoglycemia). Conclusions and Relevance: Among patients with type 2 diabetes at 3 diabetes clinics in Rome who were followed up for 3 years, a behavioral intervention strategy compared with standard care resulted in a sustained increase in physical activity and decrease in sedentary time. Further research is needed to assess the generalizability of these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT01600937.

Hypophosphatasia: clinical manifestation and burden of disease in adult patients.

Hypophosphatasia (HPP) is a rare inherited disease with a heterogeneous clinical expression. The adult form of HPP is often difficult to be recognized with a delayed diagnosis and inappropriate treatments. Though severity of HPP decreases with age at onset, important complications could occur at any age and the burden of HPP among adult patients is found to be significant. Adult patients with HPP suffer of chronic pain, recurrent fractures and other orthopedics problems, with severe disability that have a serious negative impact on all aspects of their life. The aim of this paper is to summarize the main aspects of HPP in adult patients reviewing the literature and focusing on its burden for patients suffering from this condition.

Short fasting test as a reliable and effective tool to diagnose insulinoma.

PURPOSE: The diagnosis of insulinoma can be challenging, requiring documentation of hypoglycaemia associated with non-suppressed insulin and C-peptide, often achieved during a prolonged 72 h fast performed in inpatient setting. Our goal is to predict weather a shorter outpatient fasting test initiated overnight and prolonged up until 24 h could be a sensitive method for diagnosing insulinoma. METHODS: We conducted a retrospective monocentric study on subjects admitted to our Unit of Endocrinology from 2019 to 2022 for clinical suspicion of insulinoma and underwent the short fasting test. A comparison between the short test group and the group of subjects who underwent the standard prolonged fasting test (from 2003 to 2018) has also been performed. The short fasting test was initiated by the patient overnight at home and proceeded the following day in outpatient setting (Day Hospital). As in the standard protocol, symptoms and capillary blood glucose (CBG) were strictly monitored. Venous blood was drawn for glycaemia, insulin and C-peptide at admission and at established intervals, in case of symptoms of hypoglycaemia or if CBG ≤ 45 mg/dl, when the fast would be suspended. RESULTS: The final sample consisted of 37 patients, with mean age of 44.5 ± 12.6 years (17-74). Short and standard tests were performed in 15 and 22 subjects, respectively. Diagnostic values for insulinoma were observed in 12 patients: in 5/15 who underwent the short fasting test, in 6/22 who underwent the prolonged test and in 1 patient who was initially negative on the short test and subsequently showed diagnostic values during the prolonged test. The diagnosis of insulinoma was achieved in 11/12 cases within 24 h of the beginning of the fast (91.7%). CONCLUSIONS: A short fasting test could be a valid, sensitive and reliable first-line workup in diagnosing insulinoma.

Raman spectroscopy and topological machine learning for cancer grading.

In the last decade, Raman Spectroscopy is establishing itself as a highly promising technique for the classification of tumour tissues as it allows to obtain the biochemical maps of the tissues under investigation, making it possible to observe changes among different tissues in terms of biochemical constituents (proteins, lipid structures, DNA, vitamins, and so on). In this paper, we aim to show that techniques emerging from the cross-fertilization of persistent homology and machine learning can support the classification of Raman spectra extracted from cancerous tissues for tumour grading. In more detail, topological features of Raman spectra and machine learning classifiers are trained in combination as an automatic classification pipeline in order to select the best-performing pair. The case study is the grading of chondrosarcoma in four classes: cross and leave-one-patient-out validations have been used to assess the classification accuracy of the method. The binary classification achieves a validation accuracy of 81% and a test accuracy of 90%. Moreover, the test dataset has been collected at a different time and with different equipment. Such results are achieved by a support vector classifier trained with the Betti Curve representation of the topological features extracted from the Raman spectra, and are excellent compared with the existing literature. The added value of such results is that the model for the prediction of the chondrosarcoma grading could easily be implemented in clinical practice, possibly integrated into the acquisition system.

Clinical and molecular description of the first Italian cohort of 33 subjects with hypophosphatasia.

Introduction: Hypophosphatasia (HPP) is a rare genetic disease caused by inactivating variants of the ALPL gene. Few data are available on the clinical presentation in Italy and/or on Italian HPP surveys. Methods: There were 30 suspected HPP patients recruited from different Italian tertiary cares. Biological samples and related clinical, biochemical, and anamnestic data were collected and the ALPL gene sequenced. Search for large genomic deletions at the ALPL locus (1p36) was done. Phylogenetic conservation and modeling were applied to infer the effect of the variants on the protein structure. Results: There were 21 ALPL variants and one large genomic deletion found in 20 out of 30 patients. Unexpectedly, NGS-driven differential diagnosis allowed uncovering three hidden additional HPP cases, for a total of 33 HPP subjects. Eight out of 24 coding variants were novel and classified as "pathogenic", "likely pathogenic", and "variants of uncertain significance". Bioinformatic analysis confirmed that all the variants strongly destabilize the homodimer structure. There were 10 cases with low ALP and high VitB6 that resulted negative to genetic testing, whereas two positive cases have an unexpected normal ALP value. No association was evident with other biochemical/clinical parameters. Discussion: We present the survey of HPP Italian patients with the highest ALPL mutation rate so far reported and confirm the complexity of a prompt recognition of the syndrome, mostly for HPP in adults. Low ALP and high VitB6 values are mandatory for the genetic screening, this latter remaining the gold standard not only to confirm the clinical diagnosis but also to make differential diagnosis, to identify carriers, to avoid likely dangerous therapy in unrecognized cases.

Mice carrying a complete deletion of the talin2 coding sequence are viable and fertile.

Mice homozygous for several Tln2 gene targeted alleles are viable and fertile. Here we show that although the expression of talin2 protein is drastically reduced in muscle from these mice, other tissues continue to express talin2 albeit at reduced levels. We therefore generated a Tln2 allele lacking the entire coding sequence (Tln2(cd)). Tln2(cd/cd) mice were viable and fertile, and the genotypes of Tln2(cd/+) intercrosses were at the expected Mendelian ratio. Tln2(cd/cd) mice showed no major difference in body mass or the weight of the major organs compared to wild-type, although they displayed a mildly dystrophic phenotype. Moreover, Tln2(cd/cd) mouse embryo fibroblasts showed no obvious defects in cell adhesion, migration or proliferation. However, the number of Tln2(cd/cd) pups surviving to adulthood was variable suggesting that such mice have an underlying defect.

Talin 1 and 2 are required for myoblast fusion, sarcomere assembly and the maintenance of myotendinous junctions.

Talin 1 and 2 connect integrins to the actin cytoskeleton and regulate the affinity of integrins for ligands. In skeletal muscle, talin 1 regulates the stability of myotendinous junctions (MTJs), but the function of talin 2 in skeletal muscle is not known. Here we show that MTJ integrity is affected in talin 2-deficient mice. Concomitant ablation of talin 1 and 2 leads to defects in myoblast fusion and sarcomere assembly, resembling defects in muscle lacking beta1 integrins. Talin 1/2-deficient myoblasts express functionally active beta1 integrins, suggesting that defects in muscle development are not primarily caused by defects in ligand binding, but rather by disruptions of the interaction of integrins with the cytoskeleton. Consistent with this finding, assembly of integrin adhesion complexes is perturbed in the remaining muscle fibers of talin 1/2-deficient mice. We conclude that talin 1 and 2 are crucial for skeletal muscle development, where they regulate myoblast fusion, sarcomere assembly and the maintenance of MTJs.

Adherence to Calcium and Vitamin D supplementations: results from the ADVICE Survey.

OBJECTIVE: The ADVICE (ADherence in VItamin-D and Calcium Embedded or not) survey was aimed to evaluate the effect of a patient-focused motivation strategy on the adherence to calcium and vitamin D supplementation. The survey also intended to identify possible factors being able to influence the compliance (i.e. the existence of individual preferences towards different dosages or regimens of supplementation). METHODS: We planned to involve consecutive patients visited between 2010 and 2011 at 35 centres specialized in diagnosis and treatment of osteoporosis in different Italian regions. Each patient has been requested to declare if he/she was already assuming any supplementation with calcium and vitamin D (naïve or not naïve). All patients underwent a first visit (T0) and two follow up visits at 6 and 12 months (T6 e T12). The assessment of the adherence was measured through the Morinsky Medication Adherence Scale, a score based on 8 different questions, specifically validated to determine therapeutical compliance (0-5: not acceptable; 6-7: acceptable; 8: ideal). RESULTS: 732 women (mean age: 66.9; average BMI: 25.3) and 30 men (mean age: 71.9; average BMI: 24.5) were enrolled; 34% of female patients (n=245) and 66% of males (n=20) reported previous fractures. Not naïve patients were 385 (54%). A total of 309 patients (43%) were concurrently assuming an antifracture drug; 229 subjects were osteoporotic (45%), while 224 were osteopenic (44%). The mean Morinsky score in not naïve patients was 5.72, 6.19 and 6.18 at T0, T6, and T12, respectively. Thus, no differences in the Morinsky score were observed between T6 and T12. Naïve patients showed an average Morinsky score of 5.78 at T6 and 6.39 at T12. Older age was not significantly associated with the observed changes in the scores. The onset of AEs related to the supplementation with calcium and vitamin D was able to negatively influence the adherence at the subsequent control point. Bone mineral density, previous fractures, and concurrent assumption of any antifracture drug did not significantly influence the adherence, as well as the differences in the dosages or regimens of calcium and vitamin D administration. CONCLUSION: Activities aimed to strengthen motivation of the patients improved the adherence to calcium and vitamin D supplementations after only 6 months.

On the Construction of Group Equivariant Non-Expansive Operators via Permutants and Symmetric Functions.

Group Equivariant Operators (GEOs) are a fundamental tool in the research on neural networks, since they make available a new kind of geometric knowledge engineering for deep learning, which can exploit symmetries in artificial intelligence and reduce the number of parameters required in the learning process. In this paper we introduce a new method to build non-linear GEOs and non-linear Group Equivariant Non-Expansive Operators (GENEOs), based on the concepts of symmetric function and permutant. This method is particularly interesting because of the good theoretical properties of GENEOs and the ease of use of permutants to build equivariant operators, compared to the direct use of the equivariance groups we are interested in. In our paper, we prove that the technique we propose works for any symmetric function, and benefits from the approximability of continuous symmetric functions by symmetric polynomials. A possible use in Topological Data Analysis of the GENEOs obtained by this new method is illustrated.

Transiently expressed CRISPR/Cas9 induces wild-type dystrophin in vitro in DMD patient myoblasts carrying duplications.

Among the mutations arising in the DMD gene and causing Duchenne Muscular Dystrophy (DMD), 10-15% are multi-exon duplications. There are no current therapeutic approaches with the ability to excise large multi-exon duplications, leaving this patient cohort without mutation-specific treatment. Using CRISPR/Cas9 could provide a valid alternative to achieve targeted excision of genomic duplications of any size. Here we show that the expression of a single CRISPR/Cas9 nuclease targeting a genomic region within a DMD duplication can restore the production of wild-type dystrophin in vitro. We assessed the extent of dystrophin repair following both constitutive and transient nuclease expression by either transducing DMD patient-derived myoblasts with integrating lentiviral vectors or electroporating them with CRISPR/Cas9 expressing plasmids. Comparing genomic, transcript and protein data, we observed that both continuous and transient nuclease expression resulted in approximately 50% dystrophin protein restoration in treated myoblasts. Our data demonstrate that a high transient expression profile of Cas9 circumvents its requirement of continuous expression within the cell for targeting DMD duplications. This proof-of-concept study therefore helps progress towards a clinically relevant gene editing strategy for in vivo dystrophin restoration, by highlighting important considerations for optimizing future therapeutic approaches.

Sustained decreases in sedentary time and increases in physical activity are associated with preservation of estimated ß-cell function in individuals with type 2 diabetes.

AIMS: In the Italian Diabetes and Exercise Study_2, a counselling intervention produced modest but sustained increments in moderate-to vigorous-intensity physical activity (MVPA), with reallocation of sedentary-time (SED-time) to light-intensity physical activity (LPA). This post hoc analysis evaluated the impact of intervention on estimated ß-cell function and insulin sensitivity. METHODS: Patients with type 2 diabetes were randomized to one-month counselling once-a-year or standard care for 3 years. The HOmeostatic Model Assessment-2 (HOMA-2) method was used for estimating indices of ß-cell function (HOMA-B%), insulin sensitivity (HOMA-S%), and insulin resistance (HOMA-IR); the disposition index (DI) was estimated as HOMA-ß%/HOMA-IR; MVPA, LPA, and SED-time were objectively measured by accelerometer. RESULTS: HOMA-B% and DI decreased in control group, whereas HOMA-B% remained stable and DI increased in intervention group. Between-group differences were significant for almost all insulin secretion and sensitivity indices. Changes in HOMA-B% and DI correlated with SED-time, MVPA and LPA. Changes in HOMA-B%, DI, and all indices were independently predicted by changes in SED-time (or LPA), MVPA, and BMI (or waist circumference), respectively. CONCLUSIONS: In individuals with type 2 diabetes, increasing MVPA, even without achieving the recommended target, is effective in maintaining estimated ß-cell function if sufficient amounts of SED-time are reallocated to LPA.

Effect of a Behavioural Intervention for Adoption and Maintenance of a Physically Active Lifestyle on Psychological Well-Being and Quality of Life in Patients with Type 2 Diabetes: The IDES_2 Randomized Clinical Trial.

BACKGROUND: Psychological well-being and quality of life (QoL) are important outcomes of lifestyle interventions, as a positive impact may favour long-term maintenance of behaviour change. OBJECTIVE: This study investigated the effect of a behavioural intervention for adopting and maintaining an active lifestyle on psychological well-being and health-related QoL in individuals with type 2 diabetes. METHODS: Three hundred physically inactive and sedentary patients were randomized 1:1 to receive 1 month's theoretical and practical counselling once a year (intervention group, INT) or standard care (control group, CON) for 3 years. Psychological well-being and QoL, assessed using the World Health Organization (WHO)-5 and the 36-Item Short Form (SF-36) questionnaire, respectively, were pre-specified secondary endpoints. The primary endpoint was sustained behaviour change, as assessed by accelerometer-based measurement of physical activity (PA) and sedentary time. RESULTS: WHO-5 and SF-36 physical and mental component summary (PCS and MCS) scores increased progressively in the INT group and decreased in the CON group, resulting in significant between-group differences (WHO-5: mean difference 7.35 (95% confidence interval (CI) 3.15-11.55), P = 0.0007; PCS 4.20 (95% CI 2.25-6.15), P < 0.0001; MCS 3.04 (95% CI 1.09-4.99), P = 0.0025). Percentage of participants with likely depression decreased in the INT group and increased in the CON group. PA volume changes were independently associated with WHO-5 changes, which were significantly higher in participants who accumulated > 150 min·wk-1 of moderate-to-vigorous intensity PA versus those who did not (13.06 (95% CI 7.51-18.61), P < 0.0001), whereas no relationship was detected for QoL. CONCLUSION: A counselling intervention that was effective in promoting a sustained change in PA and sedentary behaviour significantly improved psychological well-being and QoL. TRIAL REGISTRATION: ClinicalTrials.gov; NCT01600937; 10 October 2012.

Relationships of Changes in Physical Activity and Sedentary Behavior With Changes in Physical Fitness and Cardiometabolic Risk Profile in Individuals With Type 2 Diabetes: The Italian Diabetes and Exercise Study 2 (IDES_2).

OBJECTIVE: In the Italian Diabetes and Exercise Study_2 (IDES_2), behavioral counseling promoted a sustained increase in physical activity (PA) volume (+3.3 MET h ⋅ week-1), moderate- to vigorous-intensity PA (MVPA) (+6.4 min ⋅ day-1), and light-intensity PA (LPA) (+0.8 h ⋅ day-1) and decrease in sedentary time (SED-time) (-0.8 h ⋅ day-1). Here, we investigated the relationships of changes in PA/SED-time with changes in physical fitness and cardiometabolic risk profile in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: In this 3-year randomized clinical trial, 300 physically inactive and sedentary patients were randomized 1:1 to receive 1-month theoretical and practical counseling once a year or standard care. Changes in physical fitness and cardiovascular risk factors/scores according to quartiles of accelerometer-measured changes in PA/SED-time were assessed, together with univariate and multivariable associations between these parameters, in the whole cohort and by study arm. RESULTS: Physical fitness increased and HbA1c and coronary heart disease 10-year risk scores decreased with quartiles of MVPA and SED-time change. In quartile IV of MVPA increase and SED-time decrease, cardiorespiratory fitness increased by 5.23 and 4.49 mL ⋅ min-1 ⋅ kg-1 and HbA1c decreased by 0.73 and 0.85%, respectively. Univariate correlations confirmed these relationships, and mean changes in both MPVA and SED-time predicted changes in physical fitness and cardiovascular risk factors/scores independently of one another and of other confounders. Similar findings were observed with LPA and PA volume and in each group separately. CONCLUSIONS: Even modest increments in MVPA may have a clinically meaningful impact, and reallocating SED-time to LPA may also contribute to improved outcomes, possibly by increasing total energy expenditure.

alpha3beta1 integrin-controlled Smad7 regulates reepithelialization during wound healing in mice.

Effective reepithelialization after injury is essential for correct wound healing. The upregulation of keratinocyte alpha3beta1 integrin during reepithelialization suggests that this adhesion molecule is involved in wound healing; however, its precise role in this process is unknown. We have shown here that retarded reepithelialization in Itga3(-/-) mouse skin wounds is due predominantly to repressed TGF-beta1-mediated responses. Specifically, expression of the inhibitor of TGF-beta1-signaling Smad7 was elevated in Itga3(-/-) keratinocytes. Indeed, in vivo blockade of Smad7 increased the rate of reepithelialization in Itga3(-/-) and WT wounds to similar levels. Our data therefore indicate that the function of alpha3beta1 integrin as a mediator of keratinocyte migration is not essential for reepithelialization but suggest instead that alpha3beta1 integrin has a major new in vivo role as an inhibitor of Smad7 during wound healing. Moreover, our study may identify a previously undocumented function for Smad7 as a regulator of reepithelialization in vivo and implicates Smad7 as a potential novel target for the treatment of cutaneous wounds.

Robust Real-Time Embedded EMG Recognition Framework Using Temporal Convolutional Networks on a Multicore IoT Processor.

Hand movement classification via surface electromyographic (sEMG) signal is a well-established approach for advanced Human-Computer Interaction. However, sEMG movement recognition has to deal with the long-term reliability of sEMG-based control, limited by the variability affecting the sEMG signal. Embedded solutions are affected by a recognition accuracy drop over time that makes them unsuitable for reliable gesture controller design. In this paper, we present a complete wearable-class embedded system for robust sEMG-based gesture recognition, based on Temporal Convolutional Networks (TCNs). Firstly, we developed a novel TCN topology (TEMPONet), and we tested our solution on a benchmark dataset (Ninapro), achieving 49.6% average accuracy, 7.8%, better than current State-Of-the-Art (SoA). Moreover, we designed an energy-efficient embedded platform based on GAP8, a novel 8-core IoT processor. Using our embedded platform, we collected a second 20-sessions dataset to validate the system on a setup which is representative of the final deployment. We obtain 93.7% average accuracy with the TCN, comparable with a SoA SVM approach (91.1%). Finally, we profiled the performance of the network implemented on GAP8 by using an 8-bit quantization strategy to fit the memory constraint of the processor. We reach a 4× lower memory footprint (460 kB) with a performance degradation of only 3% accuracy. We detailed the execution on the GAP8 platform, showing that the quantized network executes a single classification in 12.84 ms with a power envelope of 0.9 mJ, making it suitable for a long-lifetime wearable deployment.