At the highest dose tested (100 mg/kg, twice daily), ACT-1004-1239 delayed disease onset and significantly reduced immune cell infiltrates into the CNS and plasma neurofilament light chain concentration. Treatment with ACT-1004-1239 dose-dependently increased plasma CXCL12 concentration, which correlated with a reduction of the cumulative disease score. Furthermore, in the cuprizone model, ACT-1004-1239 treatment significantly increased the number of mature myelinating oligodendrocytes and enhanced myelination in vivo. In vitro, ACT-1004-1239 promoted the maturation of OPCs into myelinating oligodendrocytes. These results provide evidence that ACT-1004-1239 both reduces neuroinflammation and enhances myelin repair substantiating the rationale to explore its therapeutic potential in a clinical setting.

What is the central question of this study? Can two non-drug therapies, carvacrol and aerobic physical training, together have additive effects on the reduction of cardiovascular risks and control of arterial hypertension? What is the main finding and its importance? The oral use of carvacrol (20mg/kg/day) can control sustained hypertension in spontaneously hypertensive rats, and when this use is associated with aerobic physical training, there is a more pronounced effect on the reduction of blood pressure values, making these therapies an adjunct option in the drug treatment of hypertension.

Systemic arterial hypertension is considered the foremost cardiovascular risk factor, and it is important to examine different therapies that help prevent and treat it, especially when associated with other cardiovascular risk factors. In this context, it is known that both carvacrol and aerobic physical training benefit the cardiovascular system. This study investigated the effects of treatment with carvacrol combinrienced reductions in atherogenic indices and improvement in all analysed lipid parameters, with no differences observed in the Exer group. The findings indicated that the interaction between aerobic exercise and carvacrol offers a greater BP reduction. Exercise is particularly effective for controlling biochemical parameters of cardiovascular risk, regardless of carvacrol use.Piper nigrum is extensively utilized because of its antioxidation, antiallergic, antitumor, antiinflammatory, antidiarrhea, and gastrointestinal protection. We attempted to indicate whether the Piper nigrum extract (PNE) could alleviate ovalbumin (OVA)-induced food allergy, and to explore its potential mechanism. An OVA-induced food allergy mouse model was established, and different concentrations of PNE were administrated. Symptoms of food allergy, levels of immunoglobulin E (IgE), mucosal mast cell protease-1 (mMCP-1), and intestine pathological changes were assessed. Additionally, the expressions of T helper (Th) 2, Th17 and regulatory T (Treg)-associated cytokines and the proportion of Th17 and Treg cells in CD4+ T cells were measured. We found PNE attenuated symptoms of food allergy and decreased the levels of IgE and mMCP-1. In PNE group, the infiltration degree of inflammatory cells was ameliorated and the villi of small intestine were more complete. Moreover, the expressions of Th2 and Th17 cell-associated cytokines were down-regulated by PNE pretreatment, while the levels of Treg cell-associated cytokines were up-regulated. PNE decreased the number of Th17 cells, while increased the Tregs cells. Chk2 Inhibitor II ic50 PNE treatment dose-dependently improved the Th17/Treg balance. PNE plays a protective role in OVA-induced food allergy through inhibiting Th2 cell response and regulating the Th17/Treg balance.

To compare the prevalence of middle ear abnormalities in pugs and in French bulldogs and evaluate the influence of nasopharyngeal dimensions on middle ear effusion.

Retrospective study.

Thirty pugs and 30 French bulldogs with brachycephalic airway syndrome and no known history of ear disease.

Computed tomographic (CT) studies were reviewed for middle ear effusion, mucosal contrast enhancement, signs of osteitis, and tympanic wall thickness. Soft palate thickness and cross-sectional areas of the nasopharynx at the opening of the auditory tube were measured and normalized to each individual’s skull index before statistical comparison between breeds. Statistical dependence of middle ear abnormalities and nasopharyngeal dimensions was assessed by using Spearman’s rank correlation tests.

Middle ear effusion was observed in 17 of 30 (56.7%) French bulldogs and five of 30 (16.7%) pugs. Contrast enhancement of the tympanic bulla was noted in 25 of 60 (41.6%) French bulldog ears and three of 60 (5.0%) pug ears. The cross-sectional airway dimensions (difference [Δ] = 0.31 cm

, P < .0001) and soft palate thickness (Δ = 0.44 cm, P < .0001) were reduced in pugs compared with in French bulldogs. Weak correlations were detected between soft palate thickness and nasopharyngeal dimensions and presence of tympanic bulla effusion (r = 0.324 and r = 0.198, respectively) or contrast enhancement (r = 0.270 and r = 0.199, respectively).

Middle ear effusion and inflammation were more common in French bulldogs than in pugs and did not seem related to nasopharyngeal dimensions.

French bulldogs with brachycephalic airway syndrome seem predisposed to middle ear effusion and inflammation.

French bulldogs with brachycephalic airway syndrome seem predisposed to middle ear effusion and inflammation.

Knee joint bleedings are responsible for quadriceps atrophy and strength deficit in patients with severe haemophilia. Little is known about patients with moderate haemophilia (PWMH).

To evaluate isokinetic quadriceps and hamstrings strength in PWMH and to assess correlation with radiological and clinical parameter.

18 PWMH aged 37.1±11.4 and 18 healthy age-, weight- and height-matched controls performed a knee isokinetic test at 180°/s to assess quadriceps and hamstrings strength. In the PWMH group, knee Pettersson’s score was pursued and Haemophilia Joint Health Score 2.1 (HJHS) was performed to determine unaffected knees (knee HJHS=0) and affected ones (knee HJHS >0).

Affected knees had a decrease of quadriceps strength compared to controls, 1.26±0.47 vs 1.64±0.27Nm/kg and a decrease of hamstring strength, 0.60±0.29 vs 1.03±0.21Nm/kg, (P<0.001). Unaffected knees also had a decrease of quadriceps strength compared to controls, 1.36±0.31 vs 1.64±0.27Nm/kg and a decrease of hamstring strength, 0.