A Higher Kick Frequency Swimming Training Program Optimizes Swim-to-Cycle Transition in Triathlon.

ABSTRACT: Ambrosini, L, Presta, V, Vitale, M, Menegatti, E, Guarnieri, A, Bianchi, V, De Munari, I, Condello, G, and Gobbi, G. A higher kick frequency swimming training program optimizes swim-to-cycle transition in triathlon. J Strength Cond Res 38(5): 976-984, 2024-The purpose of this study was to evaluate the effect of an 8-week swimming training program on biomechanical and physiological responses during a swim-to-cycle simulation. Fifteen triathletes were randomly allocated to 3 groups: a 6-beat-kick group (K6), a 4-beat-kick group (K4), and a control group (CG). Biomechanical and physiological parameters were evaluated during a 400-m swim and a 10-minute cycle segment before (Pretraining) and after (Posttraining) the program. A lower stroke frequency ( p = 0.004) and a higher stroke length ( p = 0.002) was found in K6 compared with CG at Posttraining. A reduction in the K6 emerged between Pretraining and Posttraining during cycling for heart rate ( p = 0.005), V̇O 2 ( p = 0.014), and energy expenditure ( p = 0.008). A positive association emerged between swim kick index and cycling cadence in the K6 group. The improvement in stroke frequency and length observed in the K6 group could be explained as an improvement in swimming technique. Similarly, the reduction in energy expenditure during cycling at Posttraining for the K6 group suggests an improvement in the working economy. Triathlon coaches and athletes should consider the inclusion of high swim kick into their training programs to enhance swim and cycling performance, which can ultimately lead to an improvement in the swim-to-cycle transition and the overall triathlon performance.

The Effect of Active Stretching Training in Patients with Chronic Venous Insufficiency Monitored by Raster-Stereography.

(1) Background: Musculoskeletal disorders can be associated with advanced clinical stages of chronic venous insufficiency (CVI). The aim of the study is to investigate the effect of active stretching (AS) training on lower limb venous function and quality of life in patients affected by CVI. (2) Methods: A prospective two-armed pilot randomized controlled was conducted. Twenty (20) CVI patients were randomly assigned to an AS training or to a control group (C) who did not receive any exercise indication. At baseline and after three months all the participants were tested for leg volumetry (LV), air plethysmography (APG), and quality of life (QoL) measured by a disease specific validated questionnaire (VVSymQ), ankle range of motion (ROM), and postural deformities using an optoelectronic body posture machine. (3) Results: At the end of the training in the AS group a significant leg volume reduction was detected (from 2340 ± 239 mL to 2239 ± 237 mL (4.3%); p < 0.0001), whereas in the C group no significant volume changes were found. The ejection fraction rate (EF%) increased significantly from 49.3 ± 9.3 to 61.1 ± 14.5, p < 0.005. A moderate-strong linear correlation with EF% and ankle ROM variation was found (R2 = 0.6790; p < 0.0034). Several postural outcomes such as pelvic tilt, pelvic torsion, and lordotic angle significantly improved in the AS group (p < 0.01, p < 0.04, p < 0.01 respectively). (4) Conclusion: The AS training impacts on the APG parameters related to the musculoskeletal pump efficiency, opening a further possibility in the management of CVI patients by means of an appropriate adapted physical exercise program.

Maintenance of Exercise Habit and Its Impact on Cardiovascular Risk Factors in Previously Sedentary People: A 7-Year Follow-Up.

The aim of the study was to assess whether the level of physical activity in daily life in previously sedentary adults had been sustained 7 years beyond a 1-year supervised walking program. One hundred ten participants (63 females, 57.5 ± 8.4 years; 47 males, 66.4 ± 7.9 years) were recalled and assessed for physical activity in daily life, weight, body mass index, blood pressure, and walking speed. Fifty-nine percentage of the participants measured met and exceeded the World Health Organization physical activity guidelines (Group 1), while 41% did not (Group 2). In both groups, we observed a significant decrease of weight (72.0 ± 14.0 kg vs. 69.7 ± 14.0 kg in Group 1; 77.4 ± 19.5 kg vs. 75.4 ± 18.6 kg in Group 2) and body mass index (25.9 ± 3.7 vs. 25.1 ± 3.9 in Group 1; 27.9 ± 5.6 vs. 27.2 ± 5.4 in Group 2). Group 1 showed a significant increase in walking speed (5.8 ± 0.7 km/hr vs. 6.2 ± 0.8 km/hr), while systolic pressure did not change from the baseline. In Group 2, systolic pressure significantly increased (131.3 ± 13.5 mmHg vs. 138.0 ± 15.5 mmHg), while walking speed did not change. A guided walking program seems to have been effective in educating sedentary people to remain physically active over time.

Combination of Genomic and Transcriptomic Approaches Highlights Vascular and Circadian Clock Components in Multiple Sclerosis.

Aiming at exploring vascular components in multiple sclerosis (MS) with brain outflow disturbance, we combined transcriptome analysis in MS internal jugular vein (IJV) wall with WES in MS families with vertical transmission of disease. Main results were the differential expression in IJV wall of 16 MS-GWAS genes and of seven genes (GRIN2A, GRIN2B, IL20RB, IL26, PER3, PITX2, and PPARGC1A) not previously indicated by GWAS but encoding for proteins functionally interacting with MS candidate gene products. Strikingly, 22/23 genes have been previously associated with vascular or neuronal traits/diseases, nine encoded for transcriptional factors/regulators and six (CAMK2G, GRIN2A, GRIN2B, N1RD1, PER3, PPARGC1A) for circadian entrainment/rhythm components. Among the WES low-frequency (MAF ≤ 0.04) SNPs (n = 7) filtered in the 16 genes, the NR1D1 rs17616365 showed significantly different MAF in the Network for Italian Genomes affected cohort than in the 1000 Genome Project Tuscany samples. This pattern was also detected in five nonintronic variants (GRIN2B rs1805482, PER3 rs2640909, PPARGC1A rs2970847, rs8192678, and rs3755863) in genes coding for functional partners. Overall, the study proposes specific markers and low-frequency variants that might help (i) to understand perturbed biological processes in vascular tissues contributing to MS disease, and (ii) to characterize MS susceptibility genes for functional association with disease-pathways.

The eagle jugular syndrome.

BACKGROUND: The elongation of the styloid process is historically associated with two variants of the Eagle syndrome. The classic one, mainly characterized by pain and dysphagia, and the carotid variant characterized by pain and sometimes by cerebral ischemia. We observed a further variant characterized by a styloid elongation coursing adjacent to the transverse process of C1, causing significant compression of the internal jugular vein. METHODS: We reviewed all the cases of Eagle syndrome, including the jugular variant, admitted in our Hospital in the last six years. We compared symptomatology, associated comorbidities and imaging. Data were statistically analyzed. RESULTS: Overall 23 patients were admitted to the Hospital for symptomatic elongation of the styloid process, 11 male and 12 females. The jugular variant of the Eagle syndrome is clinically delineated by significant differences, as compared to the classic variant and carotid variants. Headache was the more prominent symptom (p < .009) as well as a documented peri-mesencephalic hemorrhage was the more significant comorbidity (p < .0003). The group classic-carotid variant was characterized by ipsilateral pain respect to the jugular variant (p < .0003). CT angiography with venous phase extended to the neck veins and imaging reconstruction is highly recommended as imaging technique, complemented by color-Doppler ultrasound. CONCLUSIONS: The elongation of the styloid process may have different paths which creates compression on the surrounding anatomical structures. There may be a possible association of jugular impingement by an elongated styloid process with symptoms. TRIAL REGISTRATION: Protocol n°45-2013.

JEDI (jugular entrapment, dilated ventricles, intracranial hypertension) syndrome: a new clinical entity? A case report.

Patients with idiopathic intracranial hypertension are frequently obese women with normal/slit ventricles. Patients with high-pressure hydrocephalus, instead, present enlarged ventricles. We describe a 63-year-old woman with signs and symptoms of intracranial hypertension. Brain MRI revealed hydrocephalus. Venous Doppler ultrasound showed external compression of the omohyoid muscles on the internal jugular veins. During jugular vein decompression, intracranial pressure dropped from 18 to 6 mmHg. Patient is asymptomatic at 2-year follow-up, with decreased brain ventricles. These findings could represent a novel form of high-pressure hydrocephalus that can be successfully treated without a CSF shunt. We called this syndrome JEDI (jugular entrapment dilated ventricles intracranial hypertension).

A near-infrared spectroscopy-assisted test discriminates patients with peripheral arterial disease and venous insufficiency with changes of foot oxygenation following light elastic compression therapy.

Background: Elastic compression therapy (CT) in patients with peripheral artery disease (PAD) and chronic venous insufficiency (CVI) may compromise arterial perfusion. We evaluated the feasibility of a toe-flexion test, which quantifies dynamic foot perfusion by near-infrared spectroscopy (NIRS), for the assessment of hemodynamic sustainability of CT in PAD patients with CVI. Patients and methods: In this prospective observational study, PAD patients aged 50-85 with combined CVI at CEAP stages II-IV were studied. The ankle-brachial index (ABI) was measured, and foot perfusion was determined after 10 consecutive toe-flexion movements with NIRS sensors placed on the dorsum of each foot. Knee-high open-toe compression stockings were applied, and the degree of compression was measured. Toflex-area was determined by calculating the area under the curve of the oxygenated hemoglobin track recorded by NIRS. A toflex-area reduction > 20 % following CT was arbitrarily defined to identify limbs of patients with improved foot perfusion. These subjects received CT to be worn and a diary to report adherence and symptoms. Results: Forty-seven PAD patients (74 ± 9 years; ABI 0.67 ± 0.24) with CVI were enrolled. For all legs, superimposable toflex-areas were observed for the first two attempts (ICC 0.92). Following application of CT (17 ± 2 mmHg), the toflex-area improved (from -162 ± 110 a.u. to -112 ± 104 a.u.; p < .001). Sixty-two limbs (n = 32 patients) exhibited improved foot perfusion after CT, with a mean variation of 80 ± 47 a.u., while 32 limbs (n = 23 patients) showed stable or worsened values. In a regression model, favorable variations in toflex-area after CT were linked to a worse baseline toflex-area (R2 = 0.18; p < 0.001; rpartial = -0.42) while the percentage improvement directly correlated with CEAP class (p = 0.033). Conclusions: The NIRS-assisted test, which is feasible in a laboratory context, objectively discriminates the hemodynamic tolerability of the treatment and identifies subjects with combined PAD and CVI with improved perfusion after CT, in spite of the presence of PAD.

Changes in expression profiles of internal jugular vein wall and plasma protein levels in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory, demyelinating and degenerative disorder of the central nervous system (CNS). Several observations support interactions between vascular and neurodegenerative mechanisms in multiple sclerosis (MS). To investigate the contribution of the extracranial venous compartment, we analysed expression profiles of internal jugular vein (IJV), which drains blood from CNS, and related plasma protein levels. METHODS: We studied a group of MS patients (n = 19), screened by echo-color Doppler and magnetic resonance venography, who underwent surgical reconstruction of IJV for chronic cerebrospinal venous insufficiency (CCSVI). Microarray-based transcriptome analysis was conducted on specimens of IJV wall from MS patients and from subjects undergoing carotid endarterectomy, as controls. Protein levels were determined by multiplex assay in: i) jugular and peripheral plasma from 17 MS/CCSVI patients; ii) peripheral plasma from 60 progressive MS patients, after repeated sampling and iii) healthy individuals. RESULTS: Of the differentially expressed genes (≥ 2 fold-change, multiple testing correction, P < 0.05), the immune-related CD86 (8.5 fold-change, P = 0.002) emerged among the up regulated genes (N = 409). Several genes encoding HOX transcription factors and histones potentially regulated by blood flow, were overexpressed. Smooth muscle contraction and cell adhesion processes emerged among down regulated genes (N = 515), including the neuronal cell adhesion L1CAM as top scorer (5 fold-change, P = 5 × 10- 4). Repeated measurements in jugular/peripheral plasma and overtime in peripheral plasma showed conserved individual plasma patterns for immune-inflammatory (CCL13, CCL18) and adhesion (NCAM1, VAP1, SELL) proteins, despite significant variations overtime (SELL P < 0.0001). Both age and MS disease phenotypes were determinants of VAP1 plasma levels. Data supported cerebral related-mechanisms regulating ANGPT1 levels, which were remarkably lower in jugular plasma and correlated in repeated assays but not between jugular/peripheral compartments. CONCLUSIONS: This study provides for the first time expression patterns of the IJV wall, suggesting signatures of altered vascular mRNA profiles in MS disease also independently from CCSVI. The combined transcriptome-protein analysis provides intriguing links between IJV wall transcript alteration and plasma protein expression, thus highlighting proteins of interest for MS pathophysiology.

Comparison Between Duplex Ultrasound and Multigate Quality Doppler Profile Software in the Assessment of Lower Limb Perforating Vein Direction.

OBJECTIVES: The aim was to assess more accurately the net flow of the lower limb perforating veins (PVs). MATERIAL AND METHODS: This was an observational prospective study. Two hundred and twenty one limbs with chronic venous disease (C1-6EpAs,pPr) of 193 patients underwent a duplex ultrasound (DUS). All identified PVs were scanned also by means of quality Doppler profile (QDP) multigate analysis in order to determine their net inward and outward flow direction. A comparison between the traditional pulsed wave Doppler analysis and QDP was performed to detect potential discrepancy between the traditional definition of PV incompetence and a net outward flow. RESULTS: The DUS investigation identified 774 PVs. Only 7.7% of the PVs showed an outward flow lasting more than 500 ms. Among the PVs showing a longer than 500 ms outward flow, QDP assessment revealed net outward flow in only 84% of the PVs along the thigh and in 28.6% along the lower leg. Among the PVs showing a shorter than 500 ms outward flow, QDP assessment reported a net outward flow in 2.4% of the PVs along the thigh and in 47.3% of those along the lower leg. The sensitivity of an outward flow lasting more than 500 ms in detecting an actual net outward flow was 13.9% (9-20.1%). The specificity of an outward flow lasting less than 500 ms in detecting a net inward flow was 96.4% (93.2-98.3%). CONCLUSIONS: A lack of overlap exists between the finding of a PV outward flow lasting more than 500 ms and the net outward flow of the same vessel. The traditional definition of PV incompetence is challenged by the reported data and further investigations are required to identify a gold standard assessment.

Oscillatory flow suppression improves inflammation in chronic venous disease.

BACKGROUND: To assess if suppression of the oscillatory component of reflux may improve the inflammatory phenotype in chronic venous disease (CVD). MATERIALS AND METHODS: From 193 CVD patients, we selected 54 (13 males, 41 females, CEAP C2-4EpAsPr) for a blinded, case-control prospective investigation. All of them underwent echo-color-Doppler assessment of reflux parameters. In the same patients a blood systemic assessment of 19 inflammatory cytokines was obtained. Follow-up lasted 6 months. The control group (C) was constituted by 21 homogenous CVD patients, unselected and not operated. RESULTS: Thirty-one of 54 patients were excluded from post-operative evaluation in consequence of reported new other inflammatory episodes. Twenty-three (23) completed the follow up, showing the suppression of the oscillatory component of venous reflux; 4 of the 19 cytokines decreased significantly after the procedure: Tumor Necrosis Factor-α (TNFα), Granulocyte Colony Stimulating Factor (G-CSF), Interferon gamma-induced Protein 10 (IP-10), Interleukin-15 (IL-15). Particularly, TNFα and IP-10 even returned inside a physiological range: 5.3 ± 2.7 to 4.2 ± 2.2 pg/mL (P < 0.003) and from 303.7 ± 168.4 to 254.0 ± 151.6 pg/mL (P < 0.024), respectively. Both cytokines showed a weak but significant correlation with parameters of oscillatory flow correction. Finally, three cytokines implicated in repair and remodeling of tissue, Epidermal Growth Factor, Monocyte Chemoattractant Protein-1 and Platelet Derived Growth Factor-BB (PDGF-BB), significantly increased. Our findings are further reinforced by the significant changes of the same cytokines when compared to C group. CONCLUSIONS: The surgical suppression of the oscillatory component of reflux modulates the inflammatory phenotype, suggesting a pivotal role of flow among factors concurring to inflammation in CVD.

Attenuation of the increase of heart rate and oxygen consumption during progressive exercise in professional rugby players.

BACKGROUND: The response of oxygen uptake (VO2) and heart rate (HR) to continuous progressive large muscle mass exercise is not always linear. This study aimed to compare the patterns of the Speed/VO2 (S/VO2) and speed/HR (S/HR) relationships during an incremental treadmill-running test in professional rugby players. METHODS: Fourteen professional rugby athletes performed a maximal incremental treadmill-running test, following the Conconi test protocol. Speed, heart rate, and gas exchange parameters were recorded. The slope of the S/VO2 and S/HR relationships were mathematically determined. RESULTS: The S/VO2 and S/HR relationships were linear up to a submaximal speed and curvilinear thereafter. The speed of locomotion at which the slope of the S/VO2 and S/HR relationships start to attenuate (VO2att and HRatt) were coincident (12.3±1.0 and 12.4±0.9 km/h), strongly correlated and in good agreement. VO2 values at VO2att (44.9±8.7 mL/kg/min) were significantly correlated with VO2 values at the ventilatory threshold (43.3±6.0 mL/kg/min) (R2=0.83, P=0.001) and in good agreement. The running speed/VO2 ratio (ΔS/ΔVO2) up to VO2att was significantly lower than that beyond VO2att (2.98±1.1 vs. 5.16±2.31); P<0,001). CONCLUSIONS: The speed/oxygen uptake and S/HR relationships during progressive exercise start to attenuate at a coincident exercise intensity, and at oxygen uptake values strongly correlated with the ventilatory threshold. These findings further support the usefulness of the attenuation of the S/HR relationship as a practical tool for exercise testing and training purposes in professional rugby players.

Change in Peak Oxygen Uptake Predicted by the Moderate 1-km Treadmill Walking Test After Walking Training in Outpatients With Cardiovascular Disease.

PURPOSE: The purpose of this study was to determine the ability of the moderate 1-km treadmill walking test (1km-TWT) to predict changes in peak oxygen uptake (V˙O 2peak ) in patients with stable cardiovascular disease (CVD) during an exercise-based secondary prevention program. METHODS: Sixty-four male outpatients with stable CVD (age 64 [41-85] yr) performed the 1km-TWT before and after an 8-wk walking training program. Patient V˙O 2peak was estimated using a sex-specific equation including age, body mass index, 1km-TWT performance time, and heart rate (V˙O 2peakEST ). Forty-one patients completed a maximal cardiopulmonary treadmill test (CPX) for direct V˙O 2peak determination (V˙O 2peakMEAS ). The training prescription consisted of moderate-to-high intensity supervised walking for 30-40 min/session, and an additional 2-4 times/wk of unsupervised home moderate walking sessions between 20-60 min at the end of the program. The walking intensity was based on the results of the 1km-TWT. RESULTS: Patients participated in an average of 14 of the 16 supervised sessions. An overall significant improvement in V˙O 2peakMEAS and weekly recreational physical activity levels were observed. No differences were observed between V˙O 2peakMEAS and V˙O 2peakEST . Compared with CPX results, the 1km-TWT underestimated the V˙O 2peak increase after the exercise intervention (mean difference -0.3 mL/kg/min, P > .05). CONCLUSIONS: The 1km-TWT provides a reasonably accurate and simple tool to predict changes in V˙O 2peak due to moderate walking training in male outpatients with CVD. These findings contribute to the growing body of evidence supporting the use of the 1km-TWT for exercise testing and training purposes in the context of cardiac rehabilitation/secondary prevention programs.

Endothelial PDGF-BB produced ex vivo correlates with relevant hemodynamic parameters in patients affected by chronic venous disease.

Surgical specimens of vein were obtained from the tertiary venous network and/or saphenous vein from patients (n=20) affected by chronic venous disease (CVD). Into the venous segments, which subsequently were surgically ablated, the following hemodynamic parameters were assessed by echo-color-doppler (ECD): peak systolic velocity, end diastolic velocity, whose combination allowed the calculation of the resistance index (RI) and the reflux time (RT). Highly purified venous endothelial cell (VEC) cultures derived from venous segments of these CVD patients were then characterized for the profile of cytokines and chemokines released in the culture supernatants. Among the 27 cytokines and chemokines examined, we found a positive and significant correlation (R=0.5; p=0.03) only between the spontaneous release of PDGF-BB by VEC cultures and the RT values of the patients from which the VEC were isolates. In addition, the release of PDGF-BB in the VEC culture supernatants was significantly (p<0.01) increased upon in vitro treatment with recombinant TNF-α. By using pharmacological inhibitors, specific for the main pathways, NF-kB, ERK1/2 and p38 MAPK, activated by exposure of endothelial cells to TNF-α, we found that only NF-kB appeared to be significantly involved in mediating the PDGF-BB induction by TNF-α. Of interest, the release of PDGF-BB in response to the in vitro inflammatory stimulation, maintained a positive and significant correlation with RT (R=0.6; p=0.01), while showing a negative correlation with RI (R=-0.5; p=0.03). The potential implications of our findings for the pathophysiology of CVD are discussed.

Changes of cine cerebrospinal fluid dynamics in patients with multiple sclerosis treated with percutaneous transluminal angioplasty: a case-control study.

PURPOSE: To investigate characteristics of cine phase contrast-calculated cerebrospinal fluid (CSF) flow and velocity measures in patients with relapsing-remitting (RR) multiple sclerosis (MS) receiving standard medical treatment who had been diagnosed with chronic cerebrospinal venous insufficiency (CCSVI) and underwent percutaneous transluminal angioplasty (PTA). MATERIALS AND METHODS: This case-controlled, magnetic resonance (MR) imaging-blinded study included 15 patients with RR MS who presented with significant stenoses (≥50% lumen reduction on catheter venography) in the azygous or internal jugular veins. Eight patients underwent PTA in addition to medical therapy immediately following baseline assessments (case group) and seven had delayed PTA after 6 months of medical therapy alone (control group). CSF flow and velocity measures were quantified over 32 phases of the cardiac cycle by a semiautomated method. Outcomes were compared between groups at baseline and at 6 and 12 months of the study by mixed-effect model analysis. RESULTS: At baseline, no significant differences in CSF flow or velocity measures were detected between groups. At month 6, significant improvement in flow (P<.001) and velocity (P = .013) outcomes were detected in the immediate versus the delayed group, and persisted to month 12 (P = .001 and P = .021, respectively). Within-group flow comparisons from baseline to follow-up showed a significant increase in the immediate group (P = .033) but a decrease in the delayed group (P = .024). Altered CSF flow and velocity measures were associated with worsening of clinical and MR outcomes in the delayed group. CONCLUSIONS: PTA in patients with MS with CCSVI increased CSF flow and decreased CSF velocity, which are indicative of improved venous parenchyma drainage.

An ultrasound model to calculate the brain blood outflow through collateral vessels: a pilot study.

BACKGROUND: The quantification of the flow returning from the head through the cervical veins and the collaterals of the internal jugular vein (IJV), is becoming of prominent interest in clinical practice. We developed a novel model to calculate the cerebral venous return, normalized to the arterial inflow, in the different segments of the IJV. METHODS: We assessed, by established Echo Colour Doppler (ECD) methodology, the head inflow (HBinF) defined as the sum of common carotids and vertebral arteries, as well as the cerebral flow (CBF) defined as the sum of internal carotid and vertebral arteries. We also assessed the head outflow (HBoutF) defined as the sum of the measurements at the junction of the IJV and the vertebral veins. In addition, we also calculated the collateral flow index (CFI) by estimating the flow which re-enters directly into the superior vena cava as the amount of blood extrapolated by the difference between the HBinF and the HBoutF. We preliminarily tested the model by comparing ten healthy controls (HC) with ten patients affected by chronic cerebral spinal venous insufficiency (CCSVI), a condition characterized by some blockages in the IJV which are bypassed by collateral circulation. RESULTS: In HC the HBinF was 956+-105ml/min, whereas the HBoutF was > 90% of the HBinF, leading to a final CFI value of 1%. The last result shows that a very small amount of blood is drained by the collaterals. In upright we confirmed a reduction of the outflow through the IJV which increased CFI to 9%. When we applied the model to CCSVI, the HBinF was not significantly different from controls. In supine, the flow of CCSVI patients in the IJV junction was significantly lower (p < 0.001) while the correspondent CFI value significantly increased (61%, p < 0.0002). CONCLUSIONS: Our preliminary application of the novel model in the clinical setting suggests the pivotal role of the collateral network in draining the blood into the superior vena cava under CCSVI condition.

Inhibitory effect of natural anti-inflammatory compounds on cytokines released by chronic venous disease patient-derived endothelial cells.

Large vein endothelium plays important roles in clinical diseases such as chronic venous disease (CVD) and thrombosis; thus to characterize CVD vein endothelial cells (VEC) has a strategic role in identifying specific therapeutic targets. On these bases we evaluated the effect of the natural anti-inflammatory compounds α-Lipoic acid and Ginkgoselect phytosome on cytokines/chemokines released by CVD patient-derived VEC. For this purpose, we characterized the levels of a panel of cytokines/chemokines (n = 31) in CVD patients' plasma compared to healthy controls and their release by VEC purified from the same patients, in unstimulated and TNF-α stimulated conditions. Among the cytokines/chemokines released by VEC, which recapitulated the systemic profile (IL-8, TNF-α, GM-CSF, INF- α2, G-CSF, MIP-1ß, VEGF, EGF, Eotaxin, MCP-1, CXCL10, PDGF, and RANTES), we identified those targeted by ex vivo treatment with α-Lipoic acid and/or Ginkgoselect phytosome (GM-CSF, G-CSF, CXCL10, PDGF, and RANTES). Finally, by investigating the intracellular pathways involved in promoting the VEC release of cytokines/chemokines, which are targeted by natural anti-inflammatory compounds, we documented that αLipoic acid significantly counteracted TNF-α-induced NF-κB and p38/MAPK activation while the effects of Ginkgo biloba appeared to be predominantly mediated by Akt. Our data provide new insights into the molecular mechanisms of CVD pathogenesis, highlighting new potential therapeutic targets.

GM-CSF exhibits anti-inflammatory activity on endothelial cells derived from chronic venous disease patients.

Twenty patients affected by chronic venous disease (CVD) in tertiary venous network and/or saphenous vein were analyzed before surgical ablation by echo-color-doppler for the hemodynamic parameters reflux time (RT) and resistance index (RI), a negative and a positive prognostic factor, respectively. RT and RI were next correlated with relevant in vitro parameters of venous endothelial cells (VEC) obtained from surgical specimens, such as cell migration in response to serum gradient, proliferation index, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 expression, as well as cytokines release. Of interest, ICAM-1 expression in patient-derived VEC cultures correlated positively with RT and negatively with RI. Moreover, RT showed a positive correlation with the baseline osteoprotegerin (OPG) expression by VEC and an inverse correlation with VEC proliferation index. On the other hand, RI correlated positively with TNF-related apoptosis inducing ligand (TRAIL) expression. Among the cytokines released by VEC, GM-CSF showed a positive correlation with VEC proliferation and TRAIL expression and a negative correlation with OPG, ICAM-1 and VCAM-1 expression. Since in vitro recombinant GM-CSF induced VEC proliferation and counteracted the induction of ICAM-1, VCAM-1 and OPG upon exposure to TNF-α, our data suggest an anti-inflammatory activity of GM-CSF on venous endothelial cells.

Water-based exercise for upper and lower limb lymphedema treatment.

BACKGROUND: Lymphedema is a debilitating illness caused by insufficient lymph drainage, which can have serious physical and psychological consequences. Although water-based exercise can be useful, at present, little evidence is available regarding the outcomes of aquatic treatment for patients with lymphedema. Therefore, the aim of the present scoping review was to evaluate, from reported studies, the effects of water-based exercise on pain, limb motor function, quality of life (QoL), and limb volume among patients affected by primary and secondary upper and lower limb lymphedema. METHODS: We performed a scoping review to examine clinical studies and randomized controlled trials reported in English from 2000 to 2021 by screening the MEDLINE (PubMed) and PEDro databases. RESULTS: The search produced a total of 88 studies. Eight randomized controlled trials and one clinical study of patients with primary or secondary lymphedema of upper or lower limbs who had undergone water-based treatment were included in the present study. Most trials had focused on breast cancer-related lymphedema. The shoulder range of flexion, external rotation, and abduction have been shown to improve after performing a water-based exercise protocol. Some evidence has also demonstrated that the lymphedematous limb strength can improve. Moreover, water-based exercise seemed to improve pain perception and QoL for patients with upper or lower limb lymphedema. In contrast, in the control groups, the QoL showed a tendency to worsen over time. Although some studies had not reported beneficial effects on the lymphedematous limb volume, most of the studies examined had reported a reduction in volume, especially in the short term. No adverse events were reported in the included studies. CONCLUSIONS: The findings from the present review have shown the potential for aquatic exercise in lymphedema management. However, at the same time, the findings underline the multiple limitations resulting from the heterogeneity in the study populations and related physical activity protocols. The role of aquatic exercise in the conservative treatment of lymphedema requires further investigation in the future to define specific protocols of application.

Randomized controlled trial on occupational graduated compression clinical and cost-effectiveness.

BACKGROUND: Subjects exposed to occupational standing are at risk of developing chronic venous disease. Graduated compression stockings (GCS) counteract venous hypertension. Aim of the present investigation was to assess GCS clinical and cost effectiveness in prolonged standing up workers. METHODS: Randomized controlled trial involving 75 healthy healthcare professionals working in 6 hours standing up shifts without or with GCS (group A and B, respectively). Outcome measures were performed before and after the shift, at baseline (T0), at 1 (T1), 6 (T6) and 12 (T12) months and included lower limb volume, air plethysmography (APG), quality of life, and dedicated cost-effectiveness questionnaires. RESULTS: Seventy-two subjects completed the data collection. Leg volume increased in group A and decreased in B at all assessment points (T0, 1, 6, 12) (P<0.0001). Venous filling index did not change within the 12 months, but, after every shift, its value was lower in B compared to A (P<0.0001). At 12 months, VVSymQ worsened in A and improved in B (P<0.0001) and CIVIQ significantly worsened in A (P<0.0001), while in B it significantly improved (P<0.0001). Perceived disability was higher in A at 12 months (P<0.001) and the cost calculation revealed a saving of 1510 euro per year in B. CONCLUSIONS: GCS counteracted occupational oedema and positively influenced venous filling index, while improving vein specific quality of life measurements in addition to cost savings.

Treating Binge Eating Disorder With Physical Exercise: A Systematic Review and Meta-analysis.

OBJECTIVE: This review aimed to collect evidence about the effectiveness of exercise programs for managing binge eating disorder (BED) (recurrent binge eating episodes). METHODS: Meta-analysis was developed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Articles were searched in PubMed, Scopus, Web of Science, and Cochrane Library. Randomized controlled trials were eligible for inclusion if they reported the effect of an exercise-based program on BED symptoms in adults. Outcomes were changes in binge eating symptom severity, measured through validated assessment instruments, after an exercise-based intervention. Study results were pooled using the Bayesian model averaging for random and fixed effects meta-analysis. RESULTS: Of 2,757 studies, 5 trials were included, with 264 participants. The mean age was 44.7 ± 8.1 years for the intervention group and 46.6 ± 8.5 years for the control group. All participants were female. A significant improvement was observed between groups (standardized mean difference, 0.94; 95% credibility interval, -1.46 to -0.31). Patients obtained significant improvements either following supervised exercise programs or home-based exercise prescriptions. IMPLICATIONS FOR RESEARCH AND PRACTICE: These findings suggest that physical exercise, within a multidisciplinary clinical and psychotherapeutic approach, may be an effective intervention for managing BED symptoms. Further comparative studies are needed to clarify which exercise modality is associated with greater clinical benefits.