Neurological phenotype of Potocki–Lupski syndrome

Potocki–Lupski syndrome is a condition mainly characterized by infantile hypotonia, developmental delay/intellectual disability (DD/ID), and congenital anomalies, caused by duplications of the 17p11.2 region, encompassing RAI1 gene. Its clinical presentation is extremely variable, especially for what concerns the cognitive level and the behavioral phenotype. Such aspects, as well as the dysmorphic/malformative ones, have been covered by previous studies; otherwise neurological features have never been systematically described. In order to delineate the neurological phenotype of Potocki–Lupski Syndrome, we collect an 8‐patients cohort. Developmental milestones are delayed and a mild to moderate cognitive impairment is present in all patients, variably associated with features of autism spectrum disorder, behavioral disturb, and sleep disturb. Hypotonia appears a less frequent finding than what previously reported, while motor clumsiness/coordination impairment is frequent. EGG registration demonstrated a common pattern with excess of diffuse rhythmic activity in sleep phases or while the patient is falling asleep. Brain MRI did not reveal common anomalies, although unspecific white matter changes may be present. We discuss such findings and compare them to literature data, offering an overview on the neurological and cognitive‐behavioral presentation of the syndrome.     

Chronic low frequency/low volume resistance training reduces pro-inflammatory cytokine protein levels and TLR4 mRNA in rat skeletal muscle

Skeletal muscle is the source of pro- and anti-inflammatory cytokines, and recently, it has been recognized as an important source of interleukin 6 (IL-6), a cytokine that exerts inhibitory effects on several pro-inflammatory cytokines. Although dynamic chronic resistance training has been shown to produce the known “repeated bout effect”, which abolishes the acute muscle damage, performing of high-intensity resistance training has been regarded highly advisable, at least from the hypertrophy perspective. On the other hand, a more therapeutic, “non-damaging” resistance training program, mainly composed of concentric forces, low frequency/low volume of training, and the same exercise, could theoretically benefit the muscle when the main issue is to avoid muscle inflammation (as in the treatment of several “low-grade” inflammatory diseases) because the acute effect of each resistance exercise session could be diminished/avoided, at the same time that the muscle is still being overloaded in a concentric manner. However, the benefits of such “less demanding” resistance training schedule on the muscle inflammatory profile have never been investigated. Therefore, we assessed the protein expression of IL-6, TNF-α, IL-10, IL-10/TNF-α ratio, and HSP70 levels and mRNA expression of SCF^β-TrCP, IL-15, and TLR-4 in the skeletal muscle of rats submitted to resistance training. Briefly, animals were randomly assigned to either a control group (S, n = 8) or a resistance-trained group (T, n = 7). Trained rats were exercised over a duration of 12 weeks (two times per day, two times per week). Detection of IL-6, TNF-α, IL-10, and HSP70 protein expression was carried out by western blotting and SCF^β-TrCP (SKP Cullin F-Box Protein Ligases), a class of enzymes involved in the ubiquitination of protein substrates to proteasomal degradation, IL-15, and TLR-4 by RT-PCR. Our results show a decreased expression of TNF-α and TLR4 mRNA (40 and 60%, respectively; p < 0.05) in the plantar muscle from trained, when compared with control rats. In conclusion, exercise training induced decreased TNF-α and TLR-4 expressions, resulting in a modified IL-10/TNF-α ratio in the skeletal muscle. These data show that, in healthy rats, 12-week resistance training, predominantly composed of concentric stimuli and low frequency/low volume schedule, down regulates skeletal muscle production of cytokines involved in the onset, maintenance, and regulation of inflammation.     

Cigarette smoking increases gastric luminal prostaglandin F2 alpha and thromboxane B2 in healthy smokers

Pentagastrin-stimulated gastric luminal prostaglandin E2 (PGE2), 6-keto-PGF1 alpha, PGF2 alpha and thromboxane B2 (TxB2) were measured using a second antibody solid-phase enzyme immunoassay before, during and after cigarette smoking in healthy smokers. Smoking significantly increased PGF2 alpha and TxB2 concentration and output; in contrast no significant changes were found for PGE2 and 6-keto-PGF1 alpha levels. In addition, cigarette smoking caused a significant reduction in gastric juice volume and acid output but did not alter intragastric acidity. These findings may suggest a possible role of prostanoids in the response of the stomach to cigarette smoking.     

Value of diffusion-weighted images in diagnosis of locoregionally recurrent rectal tumors

IntroductionTo assess the value of referring to Diffusion-weighted images in evaluation of T2-weighted images of patients clinically suspicious of locoregional rectal cancer recurrence.MethodsAfter ethics committee approval and informed consent were obtained, 37 consecutive patients (male/female of 22/15; mean age 56 ± 13.5 SD) clinically suspicious of recurrent rectal tumor were prospectively included in the study over a two-year period. T2-weighted images of the patients were reviewed and the results were recorded. Right after that, the corresponding DWI images were provided for the radiologist and new ratings were given to the patients after taking into account the DWI findings. Finally, the patients underwent tissue biopsy. Receiver Operating Characteristic (ROC) analysis was performed, and Area Under the Curve (AUC) of the “T2-weighted alone” and “T2-weighted + DWI” methods were calculated and compared.Results“T2-weighted alone” and “T2-weighted + DWI” methods had an AUC of 0.64 (95% CI 0.47 to 0.79) and 0.75 (95% CI 0.58 to 0.88), respectively. The Difference between the two AUCs was 0.11 (P = 0.16). In the subgroup of patients having equivocal ratings in T2-weighted images, DWI images correctly identified 81% (13/16) of patients with true tumor recurrence and 66% (8/12) of patients without recurrence.ConclusionOur results suggest that referring to DWI does not significantly change the overall diagnostic performance of T2-weighted images. However, DWI is of great value in evaluation of the subgroup of patients with equivocal findings in T2-weighted images. Studies with larger sample sizes are needed to confirm these findings.Implications for practiceWhen T2-weighted images are equivocal, DWI images may be helpful in evaluation of patients with suspected locoregional recurrence of rectal tumor.     

The institution of a Multi‐disciplinary Italian Breast Unit: Reflections of the first psychosocial research study results on distress and quality of life

Breast cancer affects patients both emotionally and physically. It is time to consider distress as the sixth vital sign in breast cancer patients in Europe. Between 2012 and 2015, our EUSOMA‐certified multi‐disciplinary group conducted a study on emotional distress and quality‐of‐life in breast cancer patients at diagnosis, and observed their trend over the first 8 months of treatment. One hundred and forty‐nine patients concluded the program. The psycho‐oncologist and the breast nurses gave out SF36, Hospital Anxiety and Depression Scale and Distress Thermometer. Our Italian data go along with the reported literature on distress and quality‐of‐life. Despite modern advances, experiencing breast cancer impacts on overall quality‐of‐life.     

Effect of antioxidant supplementation on the auditory threshold in sensorineural hearing loss: a meta-analysis

Introduction

Hearing loss is conceptualized as any impairment of the ability to hear and/or detect speech or environment sounds, regardless of cause, type, or degree. It may occur at different stages of life; during pregnancy or childbirth, in childhood, adulthood or old age. It should be noted that aging is the most common cause of sensorineural hearing loss followed by noise-induced hearing loss, and both are closely related to the formation of reactive oxygen species. Dietary antioxidant supplementation has been employed as a therapeutic strategy to prevent and/or delay the risks of major human diseases.

A multicenter,observational, prospective study of self- and parent-reported quality of life in adolescent multiple sclerosis patients self-administering interferon-β1a using RebiSmart™—the FUTURE study

Besides the impact of disease per se, the use of immunomodulatory therapies in adolescents with relapsing-remitting multiple sclerosis (RRMS) may have an effect on quality of life (QL). The FUTURE (Quality of liFe in adolescent sUbjecTs affected by mUltiple sclerosis treated with immunomodulatoRy agEnt using self-injecting device) study was designed to evaluate the changes in QL of Italian adolescents with RRMS receiving treatment with IFN-β1a (Rebif; 22 μg), administered subcutaneously three times weekly using the RebiSmart? electronic autoinjection device over a 52-week period. Fifty adolescents with RRMS were enrolled and 40 completed the study. Changes from baseline to end of treatment (EoT) in adolescent self-reported and parent-reported QL were assessed using the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL), which has been validated for use in pediatric MS and for which an Italian version is available. The adolescent self-reported total PedsQL4.0 score and all of its subscales tended to increase from baseline to EoT, the only exception being “Emotional functioning.” In parent-reported measures, the total PedsQL4.0 score increased significantly from baseline to EoT (+ 5.27 points, p = 0.041). Significant increases were also evident for parent-reported “Psychosocial health summary score” (+ 5.90 points; p = 0.015) and “School functioning” (+ 7.84 points; p = 0.029). Our results indicate that adolescents with RRMS using the electronic injection device RebiSmart? for self-administration of Rebif® can experience long-term improvements in QL.