Abstract-The metabolic syndrome represents a constellation of cardiovascular risk factors that promote the development of cardiovascular disease. Oxidative stress is a mediator of endothelial dysfunction and vascular remodeling. We investigated vascular dysfunction in the metabolic syndrome and the oxidant mechanisms involved. New Zealand obese (NZO) mice with metabolic syndrome and New Zealand black control mice were studied. NZO mice showed insulin resistance and increased visceral fat and blood pressure compared with New Zealand black mice. Mesenteric resistance arteries from NZO mice exhibited increased media:lumen ratio and media cross-sectional area, demonstrating hypertrophic vascular remodeling. Endothelium-dependent relaxation to acetylcholine, assessed by pressurized myography, was impaired in NZO mice, not affected by N G -nitro-L-arginine methyl ester, inhibitor of endothelial NO synthase, and improved by the antioxidant Tempol, suggesting reduced NO bioavailability and increased oxidative stress. Dimer:monomer ratio of endothelial NO synthase was decreased in NZO mice compared with New Zealand black mice, suggesting endothelial NO synthase uncoupling. Furthermore, vascular superoxide and peroxynitrite production was increased, as well as adhesion molecule expression. Perivascular adipose tissue of NZO mice showed increased superoxide production and NADPH oxidase activity, as well as adipocyte hypertrophy, associated with inflammatory Mac-3-positive cell infiltration. Vasoconstriction to norepinephrine decreased in the presence of perivascular adipose tissue in New Zealand black mice but was unaffected by perivascular adipose tissue in NZO mice, suggesting loss of perivascular adipose tissue anticontractile properties. Our data suggest that this rodent model of metabolic syndrome is associated with perivascular adipose inflammation and oxidative stress, hypertrophic resistance artery remodeling, and endothelial dysfunction, the latter a result of decreased NO and enhanced superoxide generated by uncoupled endothelial NO synthase. Key Words: obesity Ⅲ hypertension Ⅲ NO Ⅲ eNOS Ⅲ superoxide Ⅲ NADPH T he metabolic syndrome represents a constellation of cardiovascular risk factors of metabolic origin that promote the development of cardiovascular disease and type 2 diabetes mellitus. 1 In the past few years, to identify patients with metabolic syndrome, several clinical and biochemical criteria have been established, such as visceral obesity, increased plasma glucose, atherogenic dyslipidemia, and increased blood pressure (BP). 2,3 Among them, visceral obesity is widely accepted as a diagnostic prerequisite, and it is believed to be involved in the pathogenesis of the metabolic disarray itself by inducing insulin resistance.Although the clinical association of metabolic risk factors and BP increase is well established, the underlying mechanisms are still a matter of debate. Vascular dysfunction of resistance arteries plays a key role in the development of hypertension and is mediated, at least in part, b...

Lemarié CA, Shbat L, Marchesi C, Angulo OJ, Deschênes ME, Blostein MD, Paradis P, Schiffrin EL. Mthfr deficiency induces endothelial progenitor cell senescence via uncoupling of eNOS and downregulation of SIRT1.

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Objective To establish the therapeutic action of a nicotinic cholinergic agonist agent  (CA) composition in the symptoms in a group of human patients infected with SARS-CoV-2 vs. control group. Methods Basic Odds Ratio study (95% confidence interval) in 20 patients for intervention group and 15 patients for the control group. The evaluation in the groups was carried out during 15 days assessing the improvement or worsening of each symptom daily. Results: Cough, (OR = 0.5), Dyspnea (OR = 0.38), Muscle fatigue (OR = 0.69), Ageusia (OR = 0.27), Anosmia (OR = 0.21) General malaise (OR = 0.62), are less than 1 converting the use of the cholinergic agent in a protective and therapeutic factor showing therefore improvement of these symptoms, after its use, compared to the control group. Conclusions: The positive results obtained on the symptoms caused by COVID-19 using cholinergic agonists molecules by delivering a cholinergic agent (CA) composition with special oral and nasal route of administration and specific pharmacological design against COVID-19 in humans infected by SARS-CoV-2 versus the control group, endorse preliminary the nicotinic hypothesis on SARS-CoV-2 and the therapeutic potential of the use of these molecules. Larger multicentrical trials in humans are encouraged.

Case series Patients: 3 women • 3 men Final Diagnosis: Athlete 5, who received the Atlasprofilax procedure, showed the most favorable results in the balance assessments compared with the 5 other athletes who did not receive the intervention Symptoms: Balance problems Clinical Procedure: AtlasProfilax Specialty: Orthopedics and Traumatology • Rehabilitation Objective: Unusual clinical course Background: High-performance athletes, such as archers, require optimal proprioception and balance. Subclinical or underestimated metabolic and pathomechanic alterations in the suboccipital myofascia could lead to loss of performance in balance and proprioception. Therapeutic optimization of myofascia and its complex structures through noninvasive stimulation by mechanotransductive vibropressure could be a preliminary key factor in high-performance athletes for high-performance sport. Case Reports: This study was conducted with 6 athletes from the Brazilian Olympic archery team to evaluate the impact of the Atlasprofilax intervention on body balance. The results were measured using a standardized medical stabilometric platform, which assessed static balance and proprioception capacity. One athlete underwent the intervention before the entire team was tested for balance and reflexes in their archery performance. The study found that the intervened athlete showed improved balance and reflexes, as indicated by superior scores in the risk of fall assessment and fall index. The results suggest the potential for the Atlasprofilax intervention to improve body balance and proprioception in high-performance athletes. Conclusions: A single intervention using the Atlasprofilax method in 1 of 6 Olympic archers resulted in significant improvement in balance and proprioception when compared with that of the non-intervened athletes. This preliminary evidence suggests that the Atlasprofilax intervention on the suboccipital myofascia may have a positive impact on enhancing balance and performance in elite athletes by improving proprioception.

Patient: Male, 42-year-old Final Diagnosis: The disc extrusion at L4–L5 was totally resorbed and improvement in the L3–L4 and L4–L5 disc bulges Symptoms: Bilateral trapezius pain • right brachialgia • constant chronic lumbalgia • right sciatica • gait claudication • paresthesia and dysesthesias in the lower limbs with associated pain and numbness in the calves Medication: — Clinical Procedure: AtlasProfilax Specialty: Rehabilitation Objective: Unusual clinical course Background: The intervertebral disc extrusion resorption has been described in the literature by various authors. It occurs in up to 75% of patients with symptomatic extruded lumbar discs. The Atlasprofilax method favors osteo-musculo-articular rehabilitation processes, mainly impacting on 2 levels: the first is the bone anatomy of the atlanto-occipital joint, and the second is the fasciae located in the cervical region. Case Report: A 42-year-old male patient diagnosed by MRI with dehydration of L2–L3 to L5–S1 intervertebral discs, disc bulging at L2–L3 and L3–L4, and disc extrusion at L4–L5, received a one-time neuromuscular treatment, called the Atlasprofilax method, to the suboccipital region. In a repeat MRI 6 months later, the disc extrusion at L4–L5 was totally resorbed and improvement in the L3–L4 and L4–L5 disc bulges was seen. The patient’s symptoms prior to the Atlasprofilax treatment included bilateral trapezius pain, right brachialgia, constant chronic low back pain, right sciatica, gait claudication, and paresthesia and dysesthesias in the lower limbs with associated pain and numbness in the calves. These symptoms were ameliorated after the treatment. The sciatica disappeared 1 week after the treatment and did not recur. In a follow-up 5 years later, the remaining symptoms had improved even further. Conclusions: We propose that alterations of the cervical musculature and deep fascia could predispose to the development of lumbar disc abnormalities. We therefore also propose that improvements in this patient, both in symptoms and in imaging findings, are due to a reduction of the asymmetric distribution of forces and elastic loading as a result of the Atlasprofilax treatment.

Background:  Since the SARS-CoV-2 pandemic emerged in December 2019, it has triggered 4.4 million deaths and strained health systems across the world. Yet more than a year and a half since the pandemic emerged, therapeutic drugs to treat COVID-19 disease are limited. Objective To investigate the therapeutic potential of a nicotinic Cholinergic Agonists Mixture (CAM), delivered daily as oral drops and as nasal spray, in alleviating ten common COVID-19 related symptoms in 80 symptomatic human adults with confirmed SARS-CoV-2.  Methods This randomized open-label pilot trial recruited 80 symptomatic adults with confirmed SARS-CoV-2 infection after RT-PCR test less than five days. Participants were recruited from databases of several Colombian hospitals and were randomly assigned to the control group, which received the Standard of Care (SOC) treatment (outpatient treatment), or the intervention group, which received SOC combined with the Cholinergic Agent Mixture (CAM SOC). Both groups received their treatment for a total of 14 days. The duration of symptoms was compared across the 14-day period. Results: This study found statistically significant reductions in symptom duration for 5 out of 10 symptoms, including dyspnea (reduction of 4.43 days [95% CI: 2.70 ; 6.15], p <0.0001), cough (reduction of 3.18 days [95% CI: 1.29 ; 5.06],  p=0.0089), cephalea (reduction of 3.13 days [95% CI: 1.53 ; 4.72], p= 0.0019), muscle fatigue (reduction of 4.18 days [95% CI: 2.03 ; 6.32], p=0.0019) and general malaise (reduction of 5.98 days [95% CI: 4.20 ; 7.76],  p <0.0001).The study found no significant reductions in the duration of the following symptoms: fever, ageusia, anosmia, chest tightness, and nasal congestion. Conclusion:  In comparison to the control group, the intervention group witnessed statistically significant and clinically relevant reductions in the duration of 5 out of 10 common COVID-19 disease symptoms within two weeks.  This includes a reduction of approximately 4.4 days in the duration of dyspnea, a symptom that appears to be strongly correlated to severe COVID-19 disease and admission to Intensive Care Units. Further studies are needed to confirm these preliminary findings and to evaluate whether this specific nicotinic cholinergic agonists mixture could have implications for public health.