PAR Group Research Articles

Improvement of the immunological and antioxidant capacity of rainbow trout (Oncorhynchus mykiss) by using the paraprobiotic Bacillus subtilis subsp. spizizenii

The aim of this study was to produce Bacillus subtilis subsp. spizizenii as a paraprobiotic for the nutrition of rainbow trout (Oncorhynchus mykiss). Fifty-four trout (74.51 ± 3.15 g) were transferred to nine 300-liter tanks and fed PRO (live freeze-dried form), PAR (irradiated freeze-dried form) and control feed (n=3) for 8 weeks. Growth, hematological, immunological and enzymatic liver functions, as well as antioxidant capacity were then analyzed. Kidney, liver, and intestinal tissue as well as the expression of cytokines (TNF-1, TNF-2, IL-1β1, and IL-1β2) in spleen, and kidney were analyzed. The growth indices, white, and red blood cells, neutrophils, monocytes and granulocytes, total protein and globulin improved in the PAR and PRO groups compared to the control group (p<0.05). The results showed that the PAR and PRO groups resulted in modulation of ALT, AST and ALP compared to the control group (p<0.05). Antioxidant indices were highest in the PAR group compared to the PRO and control groups (p<0.05). Intestinal histology results showed that the height of intestinal folds and goblet cells increased in fish fed PRO and PAR compared to the control group (p<0.05). Although melatonin increased in the PAR and PRO groups, it decreased in the liver of PAR compared to PRO (p<0.05). Immunological indices improved in the PAR and PRO groups compared to the control group (p<0.05), with no differences between PAR and PRO (p<0.05). The results of this study show that the paraprobiotic produced in this study is effective under culture conditions and can therefore be used as a supplement in trout farming.

Attenuating Atherosclerosis through Inhibition of the NF-κB/NLRP3/IL-1β Pathway-Mediated Pyroptosis in Vascular Smooth Muscle Cells (VSMCs)

Objective. We investigated the effects of resveratrol (Res) and MCC950 on the pyroptosis of vascular smooth muscle cells (VSMCs) and the potential pathway. Methods and Results. Compared with the control (Con) group, the atherosclerosis (AS) group showed calcified nodules, which suggested that the calcification medium induced the calcification of VSMCs. VSMCs showed proliferative activity and significantly attenuated calcification under treatment with 10 μmol/L Res. The calcium salt was detected by alizarin red S staining. Res and MCC950 downregulated the calcification, inflammatory, pyroptosis, and transcription factor-related indicators all decreased by RT-qPCR with Western blot and immunofluorescence. The results showed that Res and MCC950 refrained the calcification of VSMCs and that Res has a better effect than MCC950. Plaques and calcium salt deposits were present in the carotid region in the control group. More calcium salt deposits were evident in the plaques of the Par group by HE staining and alizarin red S staining. The calcification indexes BMP2, Runx2, and related indexes declined by immunofluorescence, which showed parthenolide-inhibited AS. The related protein expressions were consistent with the expression of the cell experiments. Conclusion. Our data demonstrated that inflammatory response and pyroptosis exacerbate AS and unravel the link between VSMCs and the progression of AS lesions. Res and MCC950 inhibited the calcification of VSMCs by regulating NF-κB/NLRP3/IL-1β signaling axis. P53 can exacerbate the AS lesions by acting on NLRP3 inflammasome and pyroptosis. Our findings supported the clinical applications of Res and MCC950 in VSMCs individuals to counteract pyroptosis and AS, and P53 inhibitors also can be a potential treatment for AS.

Possible role of lncRNAs in amelioration of Parkinson’s disease symptoms by transplantation of dopaminergic cells

Long non-coding RNAs (lncRNAs) are biomarkers for diagnosis and treatment of Parkinson’s disease (PD). Since dopaminergic cell transplantation is a clinical method to treat PD, this study investigated the effects of dopaminergic cell therapy on the expression of some lncRNAs and genes related to PD. In this study, Twenty-eight rats were randomly assigned to four experimental groups. The control group (Sal group) received saline injections. The Par group was a PD rat model with 6-hydroxydopamine (6-OHDA) injection in right striatum (ST). PD animals were transplanted by undifferentiated P19 stem cells (Par-E group), and P19-derived dopaminergic cells (Par-N group). Cell transplant effects were evaluated using behavioral tests (cylinder, open field, and rotarod tests), and histological methods (H&E and Nissl staining, and immunohistochemistry). Moreover, the expression of lncRNAs MALAT1, MEG3, and SNHG1, alongside specific neuronal (synaptophysin) and dopaminergic (tyrosine hydroxylase) markers was evaluated by qRT-PCR. Behavioral and histopathological examinations revealed that cell transplantation partially compensated dopaminergic cell degeneration in ST and substantia nigra (SN) of PD rats. The expression of MALAT1, SNHG1, and MEG3 was decreased in the ST of the Par group, while MEG3 and SNHG1 gene expression was increased in PBMC relative to the Sal group. In PBMC of the Par-N group, all three lncRNAs showed a reduction in their expression. Conversely, MALAT1 and SNHG1 expression was increased in ST tissue, while MEG3 gene expression was decreased compared to the Sal group. In conclusion, dopaminergic cell transplantation could change the lncRNAs expression. Furthermore, it partially improves symptoms in PD rats.

Parthenolide targets NF-κB (P50) to inhibit HIF-1α-mediated metabolic reprogramming of HCC.

We focus on investigating the role of Parthenolide (Par), a small sesquiterpenoid molecule, in hepatocellular carcinoma (HCC) and its effective target.Highly-metastatic HCC cells, MHCC97-H, were divided into the DMSO and the Par groups, of which the Par group was intervened at 5 and 10 mg/L doses. Cell viability was assessed by CCK-8 assay. Transwell chamber assay was performed to examine the metastatic and invasive abilities, while plate clone formation assay was conducted to detect the clone formation ability. For analysis of glucose uptake, glycolytic ability and lactate level, the glycolysis assay was employed. Brdu staining was performed to evaluate the cell proliferative potential. The P50 and HIF-1α levels were measured by immunofluorescence, while the expressions of p-P50 and HIF-1α were determined by Western-Blot. Small molecule-protein docking and Pull-down experiments were conducted to validate the Par-P50 binding model. After establishing the tumor-bearing mouse model, Par was administered by gavage to measure the tissue levels of P50 and HIF-1α, followed by plotting of tumor growth curves.Par could inhibit the metastatic, invasive and clone formation abilities of MHCC97-H cells, reduce the cell proliferative potential, and suppress the glycolysis, as manifested by down-regulated level of lactate and reduced oxygen consumption. Meanwhile, Par inhibited the HIF-1α expression. We found that after silencing P50, the HIF-1α was down-regulated, the glycolytic ability decreased drastically, and the cellular metastatic and invasive abilities were suppressed. After P50 knockout, the effect of Par intervention on the MHCC97-H cells was reduced. In HCC-bearing mice, Par also exhibited an excellent anti-tumor effect, decreasing the tissue levels of P50 and HIF-1α.This study discovers that Par can inhibit the HIF-1α-mediated glycolysis of HCC cells by targeting P50, thereby exerting an anti-tumor effect. P50 is a major effective target of Par.

Effect of Different Exercise Training Modalities on Fasting Levels of Oxylipins and Endocannabinoids in Middle-Aged Sedentary Adults: A Randomized Controlled Trial

This study aimed to investigate the effects of different exercise training programs on fasting plasma levels of oxylipins, endocannabinoids (eCBs), and eCBs-like molecules in middle-aged sedentary adults. A 12-week randomized controlled trial was conducted using a parallel group design. Sixty-five middle-aged adults (40-65years old) were randomly assigned to: (a)no exercise (control group), (b)concurrent training based on international physical activity recommendations (PAR group), (c)high-intensity interval training (HIIT group), and (d)HIIT together with whole-body electromyostimulation (HIIT + EMS group). Plasma levels of oxylipins, eCBs, and eCBs-like molecules were determined in plasma samples before and after the intervention using targeted lipidomics. Body composition was assessed through dual-energy X-ray absorptiometry, and dietary intake through a food frequency questionnaire and three nonconsecutive 24-hr recalls. The physical activity recommendations, HIIT, and HIIT-EMS groups showed decreased plasma levels of omega-6 and omega-3-derived oxylipins, and eCBs and eCBs-like molecules after 12weeks (all Δ ≤ -0.12; all p < .05). Importantly, after Bonferroni post hoc corrections, the differences in plasma levels of omega-6 and omega-3 oxylipins were not statistically significant compared with the control group (all p > .05). However, after post hoc corrections, plasma levels of anandamide and oleoylethanolamide were increased in the physical activity recommendations group compared with the control group (anandamide: Δ = 0.05 vs. -0.09; oleoylethanolamide: Δ = -0.12 vs. 0.013, all p ≤ .049). In conclusion, this study reports that a 12-week exercise training intervention, independent of the modality applied, does not modify fasting plasma levels of omega-6 and omega-3 oxylipins, eCBs, and eCBs-like molecules in middle-aged sedentary adults.

Outcomes of Percutaneous Achilles Repair Compared With Endoscopic Flexor Hallucis Longus Tendon Transfer to Treat Achilles Tendon Ruptures.

Both percutaneous and endoscopically assisted methods are reported to produce good results in the surgical management of acute Achilles tendon ruptures. The aim of this retrospective study was to compare between a percutaneous method and a recently described isolated endoscopically assisted flexor hallucis longus (FHL) transfer method as surgical means of management in patients with acute Achilles tendon ruptures. One hundred seventeen patients were included in the current study and divided into 2 groups: 59 patients who underwent percutaneous Achilles repair (PAR Group) and 58 patients who underwent isolated endoscopic FHL transfer (FHL Group) were compared. Patients were clinically evaluated using American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, Achilles tendon Total Rupture Score (ATRS), and Achilles tendon resting angle (ATRA) measures. In addition, ankle plantarflexion power, FHL dynamometry, Tegner activity levels, and return to previous levels of activity were also documented for all patients. Nine months after surgery, patients in the FHL transfer group were more likely to be able to return to normal activities (91% vs 73%, P < .01). Thirty months after surgical treatment, we found no difference in ATRS, AOFAS, ATRA, ankle plantarflexion strength, or Tegner activity scores between study groups. Overall complications were reported in 6 patients in the FHL group (10.3%) and in 8 patients in the PAR group (13.6%). No major neurovascular or skin complications were encountered. The current study demonstrated satisfactory and comparable results and complications when comparing isolated endoscopic FHL tendon transfer or percutaneous Achilles tendon repairs in the surgical management of acute Achilles tendon ruptures. Level III, retrospective controlled trial.

The expression analysis of IL-6, IL-18, IL-21, IL-23, and TGF-β mRNA in the nasal mucosa of patients with Allergic rhinitis.

The profile of inflammatory and suppressing cytokines is important to contribute to the disruption of TH1/TH2 balance in Allergic rhinitis (AR). This study aimed to assess the expression levels of IL-6, IL-18, IL-21, IL-23, and TGF-β in nasal biopsies in AR patients and evaluate its correlation with the severity of AR. The study included 30 patients with mild persistent allergic rhinitis (MPAR), patients with moderate-to-severe (M/S) PAR, and 30 healthy individuals. The biopsies of nasal inferior turbinate mucosa were collected from each participant. The expression of IL-6, IL-18, IL-21, IL-23, and TGF-β was evaluated by the quantitative real-time polymerase chain reaction. The degree of eosinophil infiltration into the nasal mucosa, blood eosinophils, and total serum IgE level were also measured. The expression of IL-6, IL-18, and IL-23 in patients with AR significantly increased compared to the control group. Conversely, the gene expression of the TGF-β declined in the M/S PAR group rather than the AR- group. The data did not show a significant difference in the expression of the IL-21 gene between AR+ and AR- groups. We suggested that inflammatory cytokines including IL-6, IL-18, and IL-23 may be involved in the severity of AR and associated with markers of inflammation.

Valsalva-derived Measures and Phenylephrine Test in Patients With Heart Failure With Reduced Ejection Fraction Receiving Comprehensive Neurohormonal Blockade Drug Therapy: A 5-year Event-free Survival Analysis

BackgroundTo assess the relationships between Valsalva- and phenylephrine test-derived measures and outcome in patients with heart failure with reduced ejection fraction (HFrEF) receiving comprehensive neurohormonal blockade pharmacotherapy. Methods and ResultsData from 56 patients with HFrEF (mean left ventricle ejection fraction of 32 ± 6%) subjected to Valsalva and phenylephrine tests were analyzed retrospectively. Baroreflex-related (Valsalva-ratio and blood pressure–RR interval slope from phase IV) and non–baroreflex-related measures (systolic blood pressure rise in phase IV [ΔSBPPHASE_IV], and pulse amplitude ratio [PAR]) were calculated from Valsalva. Short-term outcomes (HF-related hospitalization, implantable cardioverter-defibrillator shock or all-cause death within 24 months from examination) and long-term outcomes (implantable cardioverter-defibrillator shock or all-cause death within 60 months) were analyzed. The end point occurred in 16 and 18 patients, for the short- and long-term outcomes, respectively. A low ΔSBPPHASE_IV identified patients at risk in the long term, as evidenced by a low vs high ΔSBPPHASE_IV comparison (square-wave response patients assigned to low ΔSBPPHASE_IV group, P = .002), and Cox model (hazard ratio 0.91, 95% confidence interval 0.86–0.96, P < .001), and tended to identify patients at risk in the short term outcome (hazard ratio 0.95, 95% confidence interval 0.91–1.00, P = .055). There was a tendency toward a higher event-free survival in the low PAR group (low vs high PAR; hazard ratio 0.44, 95% CI 0.17–1.18, P = .104). ConclusionsNon–baroreflex-related measures obtained from Valsalva—namely, ΔSBPPHASE_IV and PAR—might carry prognostic value in patients with HFrEF receiving neurohormonal blockade pharmacotherapy.

Effect of Exercise Training on 1,25(OH)2D Levels: The FIT-AGEING Randomized Controlled Trial.

Vitamin D deficiency is currently endemic worldwide and is considered as an important factor in the development of several chronic conditions. Physical exercise has been postulated as an auspicious strategy to counteract age-related disorders preventing premature mortality. However, the effects of chronic exercise training on 1,25-dihydroxyvitamin D [1,25(OH)2D] is unclear. This 12-week randomized controlled trial aimed to investigate the effects of different training modalities on 1,25(OH)2D in healthy sedentary adults. Exercise training will increase 1,25(OH)2D in the study cohort. Randomized controlled clinical trial. Level 1. A total of 89 healthy sedentary adults (53% women; 53.5 ± 4.9 years old) were enrolled in the FIT-AGEING study. The participants were randomized to (1) a control group (no exercise), (2) physical activity recommendation from the World Health Organization (PAR group), (3) high-intensity interval training (HIIT group), and (4) HIIT adding whole-body electromyostimulation training (HIIT + EMS). 1,25(OH)2D plasma levels were measured using a DiaSorin Liaison immunochemiluminometric analyzer. Compared with the control group, 1,25(OH)2D increased in PAR (Δ = 10.99 ± 3.44 pg/mL; P = 0.01), HIIT (Δ = 11.63 ± 3.51 pg/mL; P = 0.009), and HIIT + EMS groups (Δ = 14.01 ± 3.59 pg/mL; P = 0.001) without statistical differences between them (all Ps > 0.1). In summary, the results show that a 12-week exercise intervention produced an increment of 1,25(OH)2D independently of age, sex, and exercise modality in healthy sedentary adults. The implementation of physical exercise could be considered a strategy not only aiming to reverse the seasonal decrease of 1,25(OH)2D in winter explained by low sunlight exposure but also for obtaining subsequent increases of this hormone even in these a priori adverse conditions.

Parecoxib improves atherosclerotic plaque stability by suppressing inflammation and inhibiting matrix metalloproteinases production

With the aging population, coronary syndrome is one of the leading causes of mortality. Atherosclerosis is the pathophysiological basis of coronary syndrome, which is caused by plaque rupture and predisposed or aggravated by many perioperative complications. Parecoxib is one of the most widely used nonsteroidal anti-inflammatory perioperative drugs. This study aims to evaluate the potential benefits of parecoxib on atherosclerosis progression. Apolipoprotein E-deficient (Apo E-/-) mice were intraperitoneally injected by parecoxib (par group) or saline (control group) and, meanwhile, were given a western diet for 12 weeks. The aorta and aortic root were examined by oil red O (ORO) staining for atherosclerotic lesions. The expression level of matrix metalloproteinases (MMPs), was investigated using immunofluorescence and western blot. Macrophage inflammation was investigated by Q-PCR. Parecoxib treatment increased the number of vascular smooth muscle cells (VSMC) and amount of collagen, while and decreased the number of macrophages in murine aortic walls. The expression of MMP1, 2, 9, and 13 as well as IL- 1β and IL-6 were also decreased in the par group. However, there was no statistical difference in lipid infiltration between the two groups. Parecoxib could improve plaque stability by suppressing inflammation and inhibiting MMPs production.

Low serum 25-hydroxyvitamin D levels are associated with perennial allergic rhinitis but not disease severity.

BackgroundVitamin D deficiency plays an essential role in allergic rhinitis(AR), but the role of vitamin D deficiency in perennial allergic rhinitis (pAR) remains unclear. Therefore, our study explored 25(OH)D levels in patients with pAR and healthy individuals in a single center in China for three years.MethodsA total of 655 patients with pAR and 682 healthy controls were enrolled in this study from 2015 to 2017. Patients' clinical history and symptoms were recorded. sIgE tests were performed using the allergen detection system (UniCAP), and the ADVIA centaur XP system (SIEMENS) was used to measure serum 25(OH)D levels.ResultsSerum 25(OH)D levels were significantly different between the pAR group and control group over the three‐year study period(all P < .05). Specifically, 25(OH)D levels were decreased in the pAR groups over three years. Serum25(OH)D deficiency, insufficiency, and sufficiency were noted in 66.9% ~71.9%, 22.5% ~29.4%, and 2.5%~5.6%, respectively, of patients in the pAR group and 53.2%~60.7%, 31.4%~36.6%, and 7.9% ~11.4%, respectively, of participants in the control group. We did not identify significant associations between serum 25(OH)D levels and clinical characteristics of patients with pAR over the three‐year period (all P > .05) after adjusting for sex, age, duration of disease, total nasal symptom score (TNSS), sIgE levels, number of positive allergens, and family history.ConclusionpAR patients exhibited lower serum 25(OH)D levels compared with healthy people with a high prevalence of 25(OH)D deficiency or insufficiency. We did not identify a significant correlation between 25(OH)D and pAR associated factors.

Metabolic rate in sedentary adults, following different exercise training interventions: The FIT-AGEING randomized controlled trial

This study compares the influence of different exercise training programs on basal metabolic rate (BMR) and fat oxidation, in basal conditions (BFox) and during exercise (MFO), in sedentary, middle-aged adults. The study subjects of this 12 week-long, randomised controlled trial, were 71 middle-aged adults (age 53.5±4.9 years; 52% women). Subjects were randomly assigned to one of the following groups: (1) no exercise, (2) concurrent training based on international physical activity recommendations (PAR group), (3) high intensity interval training (HIIT group), and (4) high intensity interval training plus whole-body electromyostimulation (HIIT+EMS group). Subject BMR, BFox and MFO were determined by indirect calorimetry before and after the intervention. The HIIT+EMS subjects showed significant increases in BFox following the intervention compared with the control group (all P=0.043); no such differences were seen in the PAR and HIIT compared with the control group (all P≥0.1). A significant increase in post-intervention MFO was noted for the HIIT and HIIT+EMS group compared to the non-exercise control group (P<0.05); no such difference was seen in the PAR group compared to the control group (all P≥0.05). Twelve weeks of high intensity interval training plus whole-body electromyostimulation may increase the BFox and MFO of middle-aged sedentary adults. These findings have important clinical implications; a well-designed high-intensity interval training program plus whole-body electromyostimulation might be followed to help combat the appearance of chronic metabolic diseases characterized by metabolic inflexibility in middle-aged sedentary adults, though it will be necessary to determine how long the effects last.

Exercise Training as a Treatment for Cardiometabolic Risk in Sedentary Adults: Are Physical Activity Guidelines the Best Way to Improve Cardiometabolic Health? The FIT-AGEING Randomized Controlled Trial.

This 12-week randomized controlled trial investigates the effects of different training modalities on cardiometabolic risk in sedentary, middle-aged adults, and examines whether alterations in cardiometabolic risk are associated with changes in those health-related variables that are modifiable by exercise training. The study subjects were 71 middle-aged adults (~54 years old; ~50% women) who were randomly assigned to one of the following treatment groups: (1) no exercise (control group), (2) concurrent training based on international physical activity recommendations (PAR group), (3) high intensity interval training (HIIT) group, or (4) HIIT plus whole-body electromyostimulation (HIIT+EMS group). A cardiometabolic risk score was calculated based on the International Diabetes Federation’s clinical criteria. A significant reduction in cardiometabolic risk was observed for all exercise training groups compared to the control group (all p < 0.05), which persisted after adjusting potential confounders (all p < 0.05). However, the HIIT+EMS group experienced the most significant reduction (p < 0.001). A significant inverse relationship was detected between the change in lean mass and the change in cardiometabolic risk (p = 0.045). A 12-week exercise training programs-especially the HIIT+EMS program-significantly reduced cardiometabolic risk in sedentary, middle-aged adults independent of sex, age, and cardiorespiratory fitness.

Advances in Understanding Parosmia: An fMRI Study

Introduction: A number of patients with a diminished sense of smell also can suffer from parosmia. These patients with such a qualitative smell disorder are often more severely affected than patients exhibiting only a quantitative smell disorder. Qualitative smell disorders have heretofore been poorly investigated. The focus of the present study was, using functional MRI, to compare the central processing of olfactory stimulation in patients with qualitative smell disorders. Material and Methods: A total of 23 patients were investigated, 12 hyposmic patients without parosmia (HYP group) and 11 hyposmic patients with parosmia (PAR group). Both groups were matched with regard to sex and age. The olfactory smells used were peach and coffee odors. Results: The two groups exhibited different patterns of activation. In HYP patients a stronger activation was observed in the medial orbitofrontal cortex, anterior cingulate cortex, and parahippocampal gyrus, whereas in the PAR group stronger activation in the thalamus and putamen was seen. Discussion: These results are consistent with the hypothesis that there are specific patterns in the central processing of olfactory stimuli which differ in hyposmic patients with and without parosmia.

Changes in Physical Fitness After 12 Weeks of Structured Concurrent Exercise Training, High Intensity Interval Training, or Whole-Body Electromyostimulation Training in Sedentary Middle-Aged Adults: A Randomized Controlled Trial.

This study aimed to investigate the influence of different exercise training modalities [(i) a concurrent training based on physical activity recommendation from the World Health Organization group (PAR group), (ii) a high intensity interval training group (HIIT group), and (iii) a high intensity interval training adding whole-body electromyostimulation group (WB-EMS group)] on physical fitness in sedentary middle-aged adults. A total of 89 (52.7% women) middle-aged sedentary adults (53.7 ± 5.1 years old) were enrolled in the FIT-AGING study. Cardiorespiratory fitness was determined by a maximum treadmill test using indirect calorimetry. Lower, upper, and core body muscular strength were assessed by an isokinetic strength test, by the handgrip strength test, and by several core strength endurance tests, respectively. All the exercise types induced similar increases on cardiorespiratory fitness (Δ VO2max ≥ 11%, Δ maximal heart rate ≥ 8%, and Δ total test duration ≥ 14%; all P ≤ 0.034), as well as on muscular strength (Δ extension and flexion peak torque ≥ 10%, Δ total hand grip ≥ 3%, Δ core strength endurance tests ≥ 20%; all P ≤ 0.050) compared with a control group. In conclusion, our results suggest that a 12-week structured exercise intervention improves physical fitness regardless of the training program in sedentary middle-aged adults. Despite slightly greater improvements in some physical fitness variables, the changes observed in the WB-EMS group were not superior to the other exercise programs.

Effects of different exercise training programs on body composition: A randomized control trial.

We aimed to investigate the effects of different exercise training programs on body composition parameters in sedentary middle-aged adults. A total of 89 middle-aged adults (53.5±4.9years old; ~53% women) participated in the FIT-AGEING study. A 12-week randomized controlled trial was performed with a parallel group design. The participants were randomly assigned to (a) a concurrent training based on physical activity recommendation from the World Health Organization group (PAR group), (b) a high-intensity interval training group (HIIT group), and (c) a high-intensity interval training group adding whole-body electromyostimulation group (WB-EMS group). A significant decrease of fat body mass, fat body mass index, and visceral adipose tissue was observed in all training modalities compared to the control group (all P≤0.001). There was a significant increase in lean body mass in the HIIT group as well as in the WB-EMS group compared to the control group and the PAR group (all P≤0.044), whereas an increment of lean body mass index was only observed in the WB-EMS group compared to the control group and the PAR group (all P≤0.042). A significant increase of bone mineral content was observed in the WB-EMS group compared to the control group (P=0.015), while no changes were found in the PAR group and in the HIIT group compared to the control group (all P≥0.2). Our findings suggest that PAR, HIIT, and WB-EMS can be used as a strategy to improve body composition parameters, obtaining slightly better results with the application of WB-EMS.

Tumour volume reduction after neoadjuvant chemotherapy impacts outcome in localised embryonal rhabdomyosarcoma.

Response (tumour volume reduction) to induction chemotherapy has been used to stratify secondary local and systemic treatment of Intergroup Rhabdomyosarcoma Study Group III (IRSG-III) embryonal rhabdomyosarcoma (RME) in consecutive CWS-trials. To evaluate its actual impact we studied response-related treatment and outcomes. Patients with IRSG-III RME <21 years and non-response (NR, <33% volume reduction) in five consecutive CWS-trials were analysed and compared with partial responders (PAR, ≥ 33% reduction). The NR was reviewed and sub-classified as Objective Response (OR, <0%-33% reduction) or Stable/Progressive Disease (SPD). Fifty-nine of 529 patients had NR (n = 34 OR, n = 25 SPD). Primary risk-factors including age, tumour size, and TN-classification did not differ between NR and PAR groups but NR had more patients with unfavourable sites comparatively (P = 0.04). There were no differences in primary risk-factors between OR and SPD. Significant factors associated with poor outcome in multivariate analysis were NR, TN-classification, age >10 years, tumour size >5 cm and therapy in older trials. After response assessment n = 24 NR continued to receive induction chemotherapy, n = 32 received other combinations and n = 3 no further chemotherapy. Forty-two non-responders were irradiated, and the tumours were completely resected in n = 20. After a median follow-up of 8 years, 34 NR are alive. Seventeen of 21 failures leading to disease-related deaths were locoregional. The five-year overall survival rate (OS) was 76 ± 4% for PAR, 79 ± 14% for OR, but only 40 ± 19% for SPD (P < 0.001). Response to induction chemotherapy appears to be an important surrogate marker of poor outcome in patients with SPD largely due to ineffective local control.

Evaluation of the effectiveness of the implementation of the A PAR parental intervention programme in Portugal. Child development and parenting support

ABSTRACTThis cross-sectional study attempts to investigate the effects of the Aprender em Parceria (A PAR) programme, an intervention in early childhood education and parenting support in the suburbs of Great Lisbon which aims to increase the educational achievement of disadvantaged children from birth to six-years-old. A quasi-experimental design was used in which children and their families participating in the intervention programme were compared to a comparison group of children who were not participating. The sample consisted of 103 children and their families in the first year (2008), 142 in the second year (2009) and 187 in the third year (2010). Results showed that families and children in the A PAR groups made significantly greater gains in the following areas: social support, pleasure in parenting activities, parent–child joint activities, capacity to interact with their children, able to observe their daily progress, recognise the most important moments of interaction. Children made significant progress in their cognitive and social development.

Local expression of interleukin-17a is correlated with nasal eosinophilia and clinical severity in allergic rhinitis.

Interleukin (IL)-17A is a major cytokine produced by Th17 cells, which are associated with chronic inflammations. The local expression of IL-17A in allergic rhinitis (AR) remains to be characterized. We sought to determine the role of IL-17A expression in human inferior turbinate mucosa in the pathophysiology of AR. Inferior turbinate mucosa was sampled from medical treatment–resistant, surgery-required patients with perennial AR (PAR, n = 21), nonallergic rhinitis with eosinophilia syndrome (NARES, n = 7), and nonallergic hypertrophic rhinitis (HR, n = 13). IL-17A expression was determined with immunohistochemical staining. The mean number of IL-17A+ cells and eosinophils per field were counted. Total serum immunoglobulin E (IgE) levels, blood eosinophil count, and forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio were also examined in each patient. IL-17A was primarily expressed in infiltrating inflammatory cells. The number of IL-17A+ cells in nasal mucosa was significantly higher in the PAR group compared with HR (p = 0.002) and NARES (p = 0.021) groups. There was a significant and positive correlation between the number of IL-17A+ cells and total nasal symptom score (rho = 0.403; p = 0.011), especially sneezing score (rho = 0.471; p = 0.003). The number of IL-17A+ cells was significantly and positively correlated with the degree of eosinophil infiltration (rho = 0.623; p < 0.001), but not with total serum IgE levels (rho = 0.284; p = 0.098), blood eosinophil counts (rho = 0.302; p = 0.056), or FEV1/FVC ratio (rho = 0.092; p = 0.569). The present study provides evidence that IL-17A expression in the nasal mucosa is associated with the pathophysiology of AR, including disease severity and nasal eosinophilia.

Over Diagnosis of Persistent Allergic Rhinitis in Perennial Allergic Rhinitis Patients: A Nationwide Study in Mexico

Allergic rhinitis (AR) symptom phenotypes have been described, and two different classifications exist. The former classification, seasonal versus perennial AR (SAR-PAR), and the Allergic Rhinitis and Its Impact on Asthma (ARIA) classifications, intermittent (INT) versus persistent (PER; ≥4 days/wk and ≥4 consecutive weeks) and mild versus moderate/severe. ARIA cataloging of INT-PER is based on the patient's description of the frequency of symptoms. This study was designed to (1) describe the epidemiology of these two AR classifications and relate them to one another and to a visual analog severity scale (VAS) and (2) describe how the cataloging of these classifications differs between patients and allergists. Skin-prick test-positive AR patients seen nationwide by Mexican allergists completed a validated questionnaire cataloging AR. They recorded demographic data and AR severity on a VAS. The patients' physicians were also asked to classify the AR phenotypes. Of the patients, 56.5% had INT and 82.2% had PAR and moderate-severe (84.7%) AR. However, 57% of the INT-PAR patients were misdiagnosed as PER-PAR by their physicians. PER patients had more severe disease with a longer clinical history, more PAR, nose and eye symptoms, and a higher VAS score, and only 7% had mild symptoms. VAS values ≥7.45 relate to PER (sensitivity, 68%; specificity, 65%). VAS ≤6.2 indicated mild and ≥6.4 indicated moderate-severe AR. Similar to the adults, in the 2- to 11 year and 12- to 17-year age groups perennial, INT, and moderate-severe AR was the most frequent finding, but the children had more INT (p < 0.01) and mild (p < 0.03) symptoms, less SAR (p = 0.03), and more physician-diagnosed asthma (p < 0.05). Public health care (PHC) patients had more INT (p = 0.016). In the PAR group, the physicians' classification of INT-PER often goes astray. PER overdiagnoses might affect treatment decisions because PER is a more severe phenotype. VAS is useful to evaluate severity. In Mexican AR patients, rhinitis symptom phenotypes differ according to age and between private and PHC system patients.