Upregulation of cholesterol synthesis by lysosomal defects requires a functional mitochondrial respiratory chain.

Mitochondria and lysosomes are two organelles that carry out both signaling and metabolic roles in cells. Recent evidence has shown that mitochondria and lysosomes are dependent on one another, as primary defects in one cause secondary defects in the other. Although there are functional impairments in both cases, the signaling consequences of primary mitochondrial dysfunction and lysosomal defects are dissimilar. Here, we used RNA sequencing to obtain transcriptomes from cells with primary mitochondrial or lysosomal defects to identify the global cellular consequences associated with mitochondrial or lysosomal dysfunction. We used these data to determine the pathways affected by defects in both organelles, which revealed a prominent role for the cholesterol synthesis pathway. We observed a transcriptional upregulation of this pathway in cellular and murine models of lysosomal defects, while it is transcriptionally downregulated in cellular and murine models of mitochondrial defects. We identified a role for the posttranscriptional regulation of transcription factor SREBF1, a master regulator of cholesterol and lipid biosynthesis, in models of mitochondrial respiratory chain deficiency. Furthermore, we found that retention of Ca2+ in lysosomes of cells with mitochondrial respiratory chain defects contributes to the differential regulation of the cholesterol synthesis pathway in the mitochondrial and lysosomal defects tested. Finally, we verified in vivo, using a model of mitochondria-associated disease in Caenorhabditis elegans that normalization of lysosomal Ca2+ levels results in partial rescue of the developmental delay induced by the respiratory chain deficiency.

UVB-Aged Microplastics and Cellular Damage: An in Vitro Study.

Plastics are synthetic organic compounds whose widespread use generates enormous waste. Different processes, such as mechanical abrasion, microbiological activity, and UVB irradiation, can fragment the plastic material and generate microplastics (MPs). MPs are ubiquitous, and various organisms, including humans, can ingest or inhale them, with potential adverse health effects. The differences between UV-aged and virgin particles were studied to evaluate the genotoxic damage and oxidative stress induced by polystyrene MPs with 1 and 5 µm sizes on the monocyte-like cell line (THP-1). Fourier transform infrared spectroscopy and Ζ-potential measurements were used to characterise MP particles after UVB exposure. Cells exposed to MPs show a widespread change in the cellular environment with the generation of reactive oxidative species (ROS), as indicated by the increased malondialdehyde level. The occurrence of genotoxic damage is correlated to the smaller size and ageing state of the MPs. The biochemical and genomic alterations observed in this in vitro study suggest that MPs, ubiquitous pollutants, following natural degradation and oxidation processes can cause various adverse effects on the health of the exposed population, making it necessary to carry out further studies to better define the real risk.

DJ-1 promotes energy balance by regulating both mitochondrial and autophagic homeostasis.

The protein DJ-1 is mutated in rare familial forms of recessive Parkinson's disease and in parkinsonism accompanied by amyotrophic lateral sclerosis symptoms and dementia. DJ-1 is considered a multitasking protein able to confer protection under various conditions of stress. However, the precise cellular function still remains elusive. In the present work, we evaluated fruit flies lacking the expression of the DJ-1 homolog dj-1ß as compared to control aged-matched individuals. Behavioral evaluations included lifespan, locomotion in an open field arena, sensitivity to oxidative insults, and resistance to starvation. Molecular analyses were carried out by analyzing the mitochondrial morphology and functionality, and the autophagic response. We demonstrated that dj-1ß null mutant flies are hypoactive and display higher sensitivity to oxidative insults and food deprivation. Analysis of mitochondrial homeostasis revealed that loss of dj-1ß leads to larger and more circular mitochondria, characterized by impaired complex-I-linked respiration while preserving ATP production capacity. Additionally, dj-1ß null mutant flies present an impaired autophagic response, which is suppressed by treatment with the antioxidant molecule N-Acetyl-L-Cysteine. Overall, our data point to a mechanism whereby DJ-1 plays a critical role in the maintenance of energy homeostasis, by sustaining mitochondrial homeostasis and affecting the autophagic flux through the maintenance of the cellular redox state. In light of the involvement of DJ-1 in neurodegenerative diseases and considering that neurons are highly energy-demanding cells, particularly sensitive to redox stress, our study sheds light on a key role of DJ-1 in the maintenance of cellular homeostasis.

Hyaluronic acid injections for pain relief and functional improvement in patients with temporomandibular disorders: An umbrella review of systematic reviews.

BACKGROUND: Temporomandibular disorders (TMD) are the main cause of chronic facial pain, and intra-articular (IA) injections of hyaluronic acid (HA) are commonly performed. OBJECTIVES: This umbrella review of systematic reviews aimed at analysing the effectiveness of HA injections on pain and functional outcomes in patients affected by TMD. METHODS: PubMed, Cochrane Library and PEDro were systematically searched from inception until 17 January 2023 to identify systematic reviews evaluating the effects on pain and functional outcomes of HA IA injections. PROSPERO registration number: CRD42022382586. RESULTS: Out of 316 papers suitable for title/abstract screening, 18 articles were included in the umbrella review. Thirteen studies included only randomized controlled clinical trials (RCTs). The included systematic reviews reported no statistically significant differences between HA and corticosteroids, whereas platelet derivates seem to have good results in pain relief. The literature did not show severe adverse events, except for mild pain in the site of injection. Concerning the quality assessment of the 18 systematic reviews, 2 (11.11%) had a high quality, 3 (16.67%) a moderate quality, 7 (38.89%) a low quality and 6 (33.33%) a critically low quality. CONCLUSIONS: Taken together, findings of this umbrella review showed intriguing effects of IA HA injections in terms of reduction of pain intensity and improvement of functioning in patients affected by TMD. Furthermore, there is no agreement on the effectiveness of a combination of arthrocentesis or arthroscopy with IA HA injections. Although the literature showed these positive results after IA HA injections, the overlapping of primary studies in the systematic reviews included might have affect our results, such as the very low quality of the papers. Thus, further RCTs are needed to confirm the efficacy of IA injections of HA on pain relief in patients with TMD.

Efficacy of orofacial myofunctional therapy combined with myofascial release in patients with mild obstructive sleep apnoea: a randomized controlled trial.

BACKGROUND: Obstructive sleep apnoea (OSA) is characterized by repetitive narrowing and collapse of pharyngeal airway during sleep, leading to apnoea or hypopnoea. In this context, myofunctional therapy and myofascial release might be effective, despite the literature on the combination of these approaches is still scarce. OBJECTIVES: This randomized controlled trial aimed to assess the efficacy of oro-facial myofunctional therapy combined with myofascial release in terms of functioning in patients with mild OSA. METHODS: Patients aged from 40 to 80 years with diagnosis of mild OSA were randomly allocated into intervention group (oro-facial myofunctional therapy plus myofascial release) and control group (only oro-facial myofunctional therapy). At the baseline (T0), after 4 weeks (T1), and after 8 weeks (T2), the following outcomes were assessed: apnoea/hypopnoea index (AHI), average oxygen saturation (SpO2 ), sleep time spent with oxygen saturation < 90% (T90), snoring index, and Pittsburgh Sleep Quality Index (PSQI). RESULTS: Out of the 60 patients enrolled, 28 (aged 61.46 ± 8.74 years) complete the treatment in the intervention group and 24 (aged 60.42 ± 6.61 years) in the control group. There were no significant differences in AHI between groups. A significant difference was reported for ΔT0-T1 SpO2 (p = .01), T90 (p = .030), ΔT0-T1 and ΔT0-T2 snoring index (p = .026 and <.001 respectively), and ΔT0-T1 and ΔT0-T2 Pittsburgh Sleep Quality Index (p = .003 and <.001 respectively). CONCLUSION: Taken together, a combination of oro-facial myofunctional therapy and myofascial release showed a potential treatment for sleep quality in patients with mild OSA. Future studies are necessary to better investigate the role of these interventions in OSA patients.

Postural Analysis Using Rasterstereography and Inertial Measurement Units in Volleyball Players: Different Roles as Indicators of Injury Predisposition.

Background and Objectives: Acute and chronic injuries are frequent in volleyball. Biomechanics of sport-specific tasks can influence the risk of injury, which is also related to specific court positions. We investigated posture at raster-stereography, balance, and dynamic tasks using inertial motion units to find differences between roles, which can be predictive of a higher risk of injury. Materials and Methods: We cross-sectionally evaluated amateur volleyball athletes. Participants were divided into roles as outside hitters, setters, middle blockers, and opposite hitters. We excluded the "libero" position from our analysis. Results: Sixteen players were included in the analysis. A statistically significant difference was found in left lower limb stiffness among the outside hitter and setter groups. Conclusions: Differences in stiffness might be related to the different training and the different abilities among the two groups. Raster-stereography is extending its indications and should be implemented for non-invasive postural analysis. The use of inertial motion units provides objective measurements of variables that could go unrecognized within a clinical evaluation; its use should be considered in injury preventive programs.

Oxygen-Ozone Therapy for Reducing Pro-Inflammatory Cytokines Serum Levels in Musculoskeletal and Temporomandibular Disorders: A Comprehensive Review.

To date, the application of oxygen-ozone (O2O3) therapy has significantly increased in the common clinical practice in several pathological conditions. However, beyond the favorable clinical effects, the biochemical effects of O2O3 are still far from being understood. This comprehensive review aimed at investigating the state of the art about the effects of O2O3 therapy on pro-inflammatory cytokines serum levels as a modulator of oxidative stress in patients with musculoskeletal and temporomandibular disorders (TMD). The efficacy of O2O3 therapy could be related to the moderate oxidative stress modulation produced by the interaction of ozone with biological components. More in detail, O2O3 therapy is widely used as an adjuvant therapeutic option in several pathological conditions characterized by chronic inflammatory processes and immune overactivation. In this context, most musculoskeletal and temporomandibular disorders (TMD) share these two pathophysiological processes. Despite the paucity of in vivo studies, this comprehensive review suggests that O2O3 therapy might reduce serum levels of interleukin 6 in patients with TMD, low back pain, knee osteoarthritis and rheumatic diseases with a concrete and measurable interaction with the inflammatory pathway. However, to date, further studies are needed to clarify the effects of this promising therapy on inflammatory mediators and their clinical implications.

Information Survey on the Use of Complementary and Alternative Medicine.

Background and Objectives: Complementary and alternative medicines (CAMs) are generally considered non-scientific and poor effective therapies. Nevertheless, CAMs are extensively used in common clinical practice in Western countries. We decided to promote a Delphi consensus to intercept the opinion of Italian physicians on CAM use in clinical practice. Materials and Methods: We run a Delphi-based consensus, interviewing anonymously 97 physicians. Of these, only 78 participate to the questionnaire. Results: Consensus about agreement and disagreement have been reached in several topics, including indication, as well as safety issues concerning CAMs. Conclusions: The use of CAMs in clinical practice still lacks evidence. Experts agree about the possibility to safely use CAMs in combination with conventional medicines to treat non-critical medical conditions.

Tailored patient self-management and supervised, home-based, pulmonary rehabilitation for mild and moderate chronic obstructive pulmonary disease.

[Purpose] Our study aimed to estimate the effects of a supervised, intensive, home-based-pulmonary-rehabilitation (HBPR) program for mild and moderate chronic-obstructive-pulmonary-disease (COPD) patients. [Participants and Methods] A retrospective, case-control study. Forty-three (N=43) patients were observed, divided into Treatment-Group (TG) and Control-Group (CG). The TG (N=23) underwent a 4-week training program, consisting of endurance and strength training sessions, performed 4-times per week. In addition, inspiration muscle training was performed, with a threshold device. The primary outcome was dyspnea improvements, measured by the modified-Borg-scale (mBS), and the secondary outcome was the determination of diaphragm excursion and function, using ultrasound (US) assessment to measure clinical parameters. [Results] The results suggested significantly improved mBS scores, measured for the ΔT0-T1 and ΔT0-T2 time points; improved diaphragm-excursion (Dia-Ex) at ΔT0-T1 and ΔT0-T2; and improved maximum Dia-Ex at ΔT0-T1 and ΔT1-T2 in the TG compared with the CG. Moreover, the results showed improvements over time for all parameters in the TG versus CG, suggesting a constant improvement in respiratory pathology. [Conclusion] A supervised HBPR plan was effective in reducing dyspnea by the mBS, and improving diaphragmatic function, as determined by US evaluation, and lastly improving quality of life in patients with mild-to-moderate COPD.

Micronuclei in Fish Erythrocytes as Genotoxic Biomarkers of Water Pollution: An Overview.

Freshwater and marine water bodies receive chemical contaminants from industrial, agricultural, urban, and domestic wastes. Eco-genotoxicity assays are useful tools to assess the cumulative genotoxicity of these pollutants. Fish are suitable indicators for biomonitoring of mutagenic and carcinogenic pollution.In this review, we present a complete overview of the studies performed so far using the micronucleus test in peripheral erythrocytes of fish exposed to polluted water. We have listed all the species of fish used and the geographical distribution of the investigations. We have analyzed and discussed all technical aspects of using this test in fish, as well as the advantages and disadvantages of the different experimental protocols. We have reported the results of all studies. This assay has become, for years, one of the simplest, fastest, and most cost-effective for assessing genotoxic risk in aquatic environments. However, there are still several factors influencing the variability of the results. Therefore, we have given indications and suggestions to achieve a standardization of experimental procedures and ensure uniformity of future investigations.

The sequelae of mastectomy and quadrantectomy with respect to the reaching movement in breast cancer survivors: evidence for an integrated rehabilitation protocol during oncological care.

BACKGROUND: Breast cancer (BC) is the most common cancer among women in developed countries. Several types of surgical interventions are commonly used in BC, such as mastectomy and quadrantectomy, followed by radiation or not. Today, BC rehabilitation can help survivors obtain and maintain the highest physical, social, psychological, and vocational functioning possible, within the limits that are created by cancer and its treatments. OBJECTIVE: To verify, before and after a specific rehabilitation protocol treatment, the recovery of the fluidity of the reaching movement. METHODS: Patients after BC surgery were enrolled and assigned by cluster randomization into 2 groups through a block randomization list: mastectomy (Mas) and quadrantectomy (Quad). Evaluation scales (DASH and VAS) were administered, and biomechanical evaluations were performed for each group before treatment (T0 = baseline), at the end of the rehabilitative treatment (T1 = 12 sessions, 2/week), and after 3 months of follow-up (T2). RESULTS: Fifty-nine (Mas group = 29; Quad group = 30) after BC surgery were enrolled. VAS scores improved along the evaluation times at T0-T1 and T0-T2 (p < 0.001), without a statistically significant difference between groups. With regard to the normalized jerk, there was no significant interaction between time group (F = 2.029; p = 0.136). There was a significant decrease between T0-T1 and T1-T2 (F = 60.189; p < 0.001). Velocity improved significantly between T0-T1 and T1-T2 (F = 10.322; p < 0.001). There was a significant interaction for the elbow angle at the end of movement between time and group at T2 (F = 5.022; p = 0.029). CONCLUSION: The integrated, low-intensity, rehabilitative intervention is effective, even if it is not performed in the first period after BC surgery, without any difference between mastectomy and quadrantectomy.

Robotic rehabilitation for end-effector device and botulinum toxin in upper limb rehabilitation in chronic post-stroke patients: an integrated rehabilitative approach.

BACKGROUND: Determine the effects of an integrated rehabilitation protocol, including botulinum toxin and conventional rehabilitation exercise plus end-effector (EE) robotic training for functional recovery of the upper limb (UL) compared to training with the robot alone in post-chronic stroke patients with mild to severe spasticity, compared to training with the robot alone. METHODS: In this prospective, observational case-control study, stroke patients were allocated into 2 groups: robot group (RG, patients who underwent robotic treatment with EE) and robot-toxin group (RTG, patients who in addition have carried out the injection of botulinum toxin for UL recovery). All patients were assessed by Fugl-Meyer Assessment (FMA), Motricity Index (MI), modified Ashworth scale (MAS), numeric rating scale (NRS), Box and Block Test (BBT), Frenchay Arm Test (FAT), and Barthel Index (BI) at baseline (T0), T1 (end of treatment), and T2 (3 months of follow-up). RESULTS: Forty-four patients were included and analyzed (21RG; 23RTG). From the analysis between groups, the results suggested how there was a statistically significant difference in favor of RTG, specifically ΔT0-T1 and ΔT0-T2 for B&B p = 0.009 and p = 0.035; ΔT0-T1 and ΔT0-T2 for FAT with p = 0.016 and p = 0.031; ΔT0-T1 for MAS shoulder p = 0.016; ΔT0-T1 and ΔT0-T2 with p = 0.010 and p = 0.005 for MAS elbow; and ΔT0-T1 and ΔT0-T2 with p = 0.001 and p = 0.013 for MAS wrist. CONCLUSION: Our results suggest, in line with the literature, a good efficacy in the reduction of spasticity and in the improvement of the function of the UL, with the reduction of pain, adopting a rehabilitation protocol integrated with BoTN, robot-assisted training, and traditional physiotherapy.

Heart valve calcification and cardiac hemodynamics.

PURPOSE: Heart valve calcification (VC) is associated with increased cardiovascular risk, but the hemodynamic and functional profile of patients affected by VC has not been fully explored. METHODS: The study population was formed by consecutive unselected patients included in seven echocardiographic laboratories in a 2-week period. A comprehensive echocardiographic examination was performed. VC was defined by the presence of calcification on at least one valve. RESULTS: Population was formed of 1098 patients (mean age 65 ± 15 years; 47% female). VC was present in 31% of the overall population. Compared with subjects without VC, VC patients were older (60 ± 14 vs 75 ± 9; P < .0001), had more hypertension (40% vs 57%; P = .0005), diabetes (11% vs 18%; P = .002), coronary artery disease (22% vs 38%; P = .04), and chronic kidney disease (4% vs 8%; P = .007). Furthermore, VC patients had lower ejection fraction (55 ± 14 vs 53 ± 25; P < .0001), worse diastolic function (E/e' 8.5 ± 4.6 vs 13.0 ± 7.1; P < .0001) and higher pulmonary artery pressure (29 ± 9 vs 37 ± 12; P < .0001). The association between VC and EF was not independent of etiology (p for VC 0.13), whereas the association with E/e' and PASP was independent in a full multivariate model (P < .0001 and P = .0002, respectively). CONCLUSION: Heart valve calcification patients were characterized by a worse functional and hemodynamic profile compared to patients with normal valve. The association between VC and diastolic function and PASP were independent in comprehensive multivariate models.

Metformin Repurposing for Parkinson Disease Therapy: Opportunities and Challenges.

Parkinson disease (PD) is a severe neurodegenerative disorder that affects around 2% of the population over 65 years old. It is characterized by the progressive loss of nigrostriatal dopaminergic neurons, resulting in motor disabilities of the patients. At present, only symptomatic cures are available, without suppressing disease progression. In this frame, the anti-diabetic drug metformin has been investigated as a potential disease modifier for PD, being a low-cost and generally well-tolerated medication, which has been successfully used for decades in the treatment of type 2 diabetes mellitus. Despite the precise mechanisms of action of metformin being not fully elucidated, the drug has been known to influence many cellular pathways that are associated with PD pathology. In this review, we present the evidence in the literature supporting the neuroprotective role of metformin, i.e., autophagy upregulation, degradation of pathological α-synuclein species, and regulation of mitochondrial functions. The epidemiological studies conducted in diabetic patients under metformin therapy aimed at evaluating the correlation between long-term metformin consumption and the risk of developing PD are also discussed. Finally, we provide an interpretation for the controversial results obtained both in experimental models and in clinical studies, thus providing a possible rationale for future investigations for the repositioning of metformin for PD therapy.

In Ovarian Cancer Multicellular Spheroids, Platelet Releasate Promotes Growth, Expansion of ALDH+ and CD133+ Cancer Stem Cells, and Protection against the Cytotoxic Effects of Cisplatin, Carboplatin and Paclitaxel.

A high platelet count is associated with a poor prognosis in ovarian cancer (OvCa). Despite good clinical responses with platinating agents in combination with taxanes, numerous OvCa patients relapse due to chemotherapy resistance. Here, we report that treatment of OvCa cells A2780, OVCAR5 and MDAH with releasate from activated platelets (PR) promoted multicellular tumor spheroid (MCTS) formation. These OvCa-MCTSs had increased percentages of CD133+ and aldehyde dehydrogenase (ALDH)+ cells, bona fide markers of OvCa cancer stem cells (CSCs). PR increased OVCAR5- and MDAH-MCTS viability and decreased the cytotoxic and pro-apoptotic effects of paclitaxel, cisplatin and carboplatin. PR increased the volume of spontaneously formed OVCAR8-MCTSs and counteracted their size reduction due to cisplatin, carboplatin and paclitaxel treatment. PR promoted the survival of ALDH+ and CD133+ OvCa cells during cisplatin, carboplatin and paclitaxel treatment. In conclusion, molecules and growth factors released by activated platelets (EGF, PDGF, TGF-ß, IGF and CCL5) may protect tumor cells from chemotherapy by promoting the expansion of ALDH+ and CD133+ OvCa-CSCs, favoring drug resistance and tumor relapse.

Rehabilitation in an Italian thermal setting: a new therapeutic strategy for patients with musculoskeletal disability-the results of an Italian survey.

Traditionally, in the past, patients with musculoskeletal diseases visit the spa centers (Salus per aquam) for traditional treatments, including mud therapy, or for holiday. Spas have begun to offer, as the only means of treatment, rehabilitation therapy for patients with musculoskeletal disabilities alone or in association with other traditional thermal therapies. The purpose of this paper is to describe the results of a recent survey on Italian thermal centers conducted by a section of "Rehabilitation in the Thermal Environment" of the Italian Society of Physical Medicine and Rehabilitation. The study investigated the current diffusion, type, and overall quality of rehabilitation treatments performed at the Italian spas. The survey requested information from 174 centers, but only 132 responded by returning the completed questionnaire. Eighty-nine percent of the centers offered rehabilitation therapy for orthopedic-rheumatological diseases, including post-operative conditions (after hip or knee replacement), 37% offered rehabilitation therapy for neurological diseases and 10% rehabilitation for lymph-vascular conditions. Seventy-one percent employed a multidisciplinary team (which included a physiatrist, a physiotherapist, and other figures such as a hydrologist or rheumatologist). The rehabilitative approach generally included therapeutic exercises (land or aquatic therapies), instrumental physical therapies (ultrasounds, electrotherapy, LASER-therapy, and others), and, less frequently, health education and preventive measures. The survey did not investigate respiratory or nasopharyngeal diseases. In conclusion, the results of this survey suggest that rehabilitation, performed in the thermal environment, could be a new opportunity to treat many musculoskeletal disabilities.

Spa therapy and rehabilitation of musculoskeletal pathologies: a proposal for best practice in Italy.

Spa therapy is a heterogeneous collection of treatments and methods based on natural resources. It is often considered as an option in the common therapeutic approach to many musculoskeletal disorders, as well as respiratory, vascular, and dermatological disorders. The objective of this paper is to highlight possible interactions between rehabilitation and spa medicine in the field of musculoskeletal disorders, through an analysis of the scientific literature, in order to give the practitioner the ability to integrate good clinical practice in the field of rehabilitation through practical application involving spa therapies. The literature search was conducted using Medline, PEDro, Cochrane Database, and Google Scholar. Only studies published in English and works concerning the implementation of spa thermal treatment in neuro-musculoskeletal diseases were included. Specifically, the publications analyzed dealt with the treatment of diseases such as arthritis, rheumatic arthritis, ankylosing spondylitis, and low back pain through the use of thermal spa therapies. In conjunction with its widespread use in clinical practice, many studies in the literature suggest the effectiveness of crenobalneotherapy for a number of musculoskeletal disorders, generally those which are chronic and debilitating, finding significant clinical improvement both in terms of pain and functional limitations. Some of the guidelines formulated by national and international bodies on the treatment of specific diseases, such as the Italian Rheumatology Society (SIR) and the Osteoarthritis Research Society International (OARSI) guidelines, recognize the value of thermal medicine as a complement, but not a replacement, for conventional therapy (pharmacological or not).

Peroneus Brevis flap in Achilles tendon reconstruction. Clinical, radiological and functional analysis.

BACKGROUND: We would like to describe our experience with Peroneus Brevis flap in complicated Achilles tendon re-ruptures with fringed stumps. METHODS: Eight patients with monolateral re-rupture of Achilles tendon were selected as eligible for surgical repair with Peroneus Brevis flap. Patients' outcome was evaluated clinically (ATRS and ROM), functionally (Gait analysis) and MRI was performed before and after surgery. RESULTS: Effective coverage of tissue defect was reached in all patients. Functional assessment evaluation results were registered in a follow-up time that ranged from 12 to 18 months. ATRS and ROM tests' results showed good functional recovery without functional limitations or subjective reports pain. Post-operative MRI showed no signs of inflammation or tissue gaps. Gait analysis showed a partial reduction of performance in the affected side that did not affect patients' quality of life. CONCLUSIONS: In the presence of fringed stumps in Achilles tendon re-rupture, tendon flaps have the benefits of autologous tissues transfers and present less risks of failure than free flaps. Among them, Peroneus Brevis flap is easy to perform and leads to donor site's low morbidity. Our preliminary experience provides support for this technique to be potentially validated in larger more controlled trial.

Refined 4-group classification of left ventricular hypertrophy based on ventricular concentricity and volume dilatation outlines distinct noninvasive hemodynamic profiles in a large contemporary echocardiographic population.

BACKGROUND: Left ventricular hypertrophy (LVH) may reflect a wide variety of physiologic and pathologic conditions. Thus, it can be misleading to consider all LVH to be homogenous or similar. Refined 4-group classification of LVH based on ventricular concentricity and dilatation may be identified. To determine whether the 4-group classification of LVH identified distinct phenotypes, we compared their association with various noninvasive markers of cardiac stress. METHODS: Cohort of unselected adult outpatients referred to a seven tertiary care echocardiographic laboratory for any indication in a 2-week period. We evaluated the LV geometric patterns using validated echocardiographic indexation methods and partition values. RESULTS: Standard echocardiography was performed in 1137 consecutive subjects, and LVH was found in 42%. The newly proposed 4-group classification of LVH was applicable in 88% of patients. The most common pattern resulted in concentric LVH (19%). The worst functional and hemodynamic profile was associated with eccentric LVH and those with mixed LVH had a higher prevalence of reduced EF than those with concentric LVH (P < .001 for all). CONCLUSIONS: The new 4-group classification of LVH system showed distinct differences in cardiac function and noninvasive hemodynamics allowing clinicians to distinguish different LV hemodynamic stress adaptations in patients with LVH.

Standardization of platelet releasate products for clinical applications in cell therapy: a mathematical approach.

BACKGROUND: Standardized animal-free components are required for manufacturing cell-based medicinal products. Human platelet concentrates are sources of growth factors for cell expansion but such products are characterized by undesired variability. Pooling together single-donor products improves consistency, but the minimal pool sample size was never determined. METHODS: Supernatant rich in growth factors (SRGF) derived from n = 44 single-donor platelet-apheresis was obtained by CaCl2 addition. n = 10 growth factor concentrations were measured. The data matrix was analyzed by a novel statistical algorithm programmed to create 500 groups of random data from single-donor SRGF and to repeat this task increasing group statistical sample size from n = 2 to n = 20. Thereafter, in created groups (n = 9500), the software calculated means for each growth factor and, matching groups with the same sample size, the software retrieved the percent coefficient of variation (CV) between calculated means. A 20% CV was defined as threshold. For validation, we assessed the CV of concentrations measured in n = 10 pools manufactured according to algorithm results. Finally, we compared growth rate and differentiation potential of adipose-derived stromal/stem cells (ASC) expanded by separate SRGF pools. RESULTS: Growth factor concentrations in single-donor SRGF were characterized by high variability (mean (pg/ml)-CV); VEGF: 950-81.4; FGF-b: 27-74.6; PDGF-AA: 7883-28.8; PDGF-AB: 107834-32.5; PDGF-BB: 11142-48.4; Endostatin: 305034-16.2; Angiostatin: 197284-32.9; TGF-ß1: 68382-53.7; IGF-I: 70876-38.3; EGF: 2411-30.2). In silico performed analysis suggested that pooling n = 16 single-donor SRGF reduced CV below 20%. Concentrations measured in 10 pools of n = 16 single SRGF were not different from mean values measured in single SRGF, but the CV was reduced to or below the threshold. Separate SRGF pools failed to differently affect ASC growth rate (slope pool A = 0.6; R2 = 0.99; slope pool B = 0.7; R2 0.99) or differentiation potential. DISCUSSION: Results deriving from our algorithm and from validation utilizing real SRGF pools demonstrated that pooling n = 16 single-donor SRGF products can ameliorate variability of final growth factor concentrations. Different pools of n = 16 single donor SRGF displayed consitent capability to modulate growth and differentiation potential of expanded ASC. Increasing the pool size should not further improve product composition.