Cognitive impairment is associated with gait variability and fall risk in amyotrophic lateral sclerosis.

BACKGROUND: In amyotrophic lateral sclerosis (ALS), gait abnormalities contribute to poor mobility and represent a relevant risk for falls. To date, gait studies in ALS patients have focused on the motor dimension of the disease, underestimating the cognitive aspects. METHODS: Using a wearable gait analysis device, we compared gait patterns in ambulatory ALS patients with mild cognitive impairment (ALS MCI+; n = 18), and without MCI (ALS MCI-; n = 24), and healthy subjects (HS; n = 16) under two conditions: (1) normal gait (single task) and (2) walking while counting backward (dual task). Finally, we examined if the occurrence and number of falls in the 3 months following the baseline test were related to cognition. RESULTS: In the single task condition, ALS patients, regardless of cognition, displayed higher gait variability than HS, especially for stance and swing time (p < 0.001). The dual task condition revealed additional differences in gait variability parameters between ALS MCI+ and ALS MCI- for cadence (p = 0.005), stance time (p = 0.04), swing time (p = 0.04) and stability index (p = 0.02). Moreover, ALS MCI+ showed a higher occurrence (p = 0.001) and number of falls (p < 0.001) at the follow-up. Regression analyses demonstrated that MCI condition predicted the occurrence of future falls (ß = 3.649; p = 0.01) and, together with executive dysfunction, was associated with the number of falls (cognitive impairment: ß = 0.63; p < 0.001; executive dysfunction: ß = 0.39; p = 0.03), regardless of motor impairment at clinical examination. CONCLUSION: In ALS, MCI is associated with exaggerated gait variability and predicts the occurrence and number of short-term falls.

The Role of High-Flow Nasal Cannula Oxygen Therapy in Exercise Testing and Pulmonary Rehabilitation: A Review of the Current Literature.

High-flow nasal cannula (HFNC) has recently emerged as a crucial therapeutic strategy for hypoxemic patients both in acute and chronic settings. Indeed, HFNC therapy is able to deliver higher fractions of inspired oxygen (FiO2) with a heated and humidified gas flow ranging from 20 up to 60 L per minute, in a more comfortable way for the patient in comparison with Conventional Oxygen Therapy (COT). In fact, the flow keeps the epithelium of the airways adequately moisturized, thus positively affecting the mucus clearance. Finally, the flow is able to wash out the carbon dioxide in the dead space of the airways; this is also enhanced by a modest positive end-expiratory pressure (PEEP) effect. Recent evidence has shown applications of HFNC in exercise training and chronic settings with promising results. In this narrative review, we explored how HFNC might contribute to enhancing outcomes of exercise training and pulmonary rehabilitation among patients dealing with chronic obstructive pulmonary disease, interstitial lung diseases, and lung cancer.

Lifestyle and Risk Factors in Hemorrhoidal Disease.

Constipation, a low fiber diet, a high Body Mass Index, pregnancy, and a sedentary lifestyle are often assumed to increase the risk of hemorrhoidal disease (HD). However, evidence regarding these factors is controversial. This mini-review aims to examine and critically analyze the association between main risk factors and the prevalence of HD, focusing both on the patient's clinical history and on a tailored treatment. Moreover, some practical suggestions about lifestyle and conservative approaches are given to help clinicians in the management of patients with HD and to obtain the best results from therapy.

Brain hemodynamic response in Examiner-Examinee dyads during spatial short-term memory task: an fNIRS study.

The Corsi Block-Tapping test (CBT) is a measure of spatial working memory (WM) in clinical practice, requiring an examinee to reproduce sequences of cubes tapped by an examiner. CBT implies complementary behaviors in the examiners and the examinees, as they have to attend a precise turn taking. Previous studies demonstrated that the Prefrontal Cortex (PFC) is activated during CBT, but scarce evidence is available on the neural correlates of CBT in the real setting. We assessed PFC activity in dyads of examiner-examinee participants while completing the real version of CBT, during conditions of increasing and exceeding workload. This procedure allowed to investigate whether brain activity in the dyads is coordinated. Results in the examinees showed that PFC activity was higher when the workload approached or reached participants' spatial WM span, and lower during workload conditions that were largely below or above their span. Interestingly, findings in the examiners paralleled the ones in the examinees, as examiners' brain activity increased and decreased in a similar way as the examinees' one. In the examiners, higher left-hemisphere activity was observed suggesting the likely activation of non-spatial WM processes. Data support a bell-shaped relationship between cognitive load and brain activity, and provide original insights on the cognitive processes activated in the examiner during CBT.

Probiotic Cell-Free Supernatants Exhibited Anti-Inflammatory and Antioxidant Activity on Human Gut Epithelial Cells and Macrophages Stimulated with LPS.

The incidence of inflammatory bowel disease is increasing all over the world, especially in industrialized countries. The aim of the present work was to verify the anti-inflammatory activity of metabolites. In particular, cell-free supernatants of Lactobacillus acidophilus, Lactobacillus casei, Lactococcus lactis, Lactobacillus reuteri, and Saccharomyces boulardii have been investigated. Metabolites produced by these probiotics were able to downregulate the expression of PGE-2 and IL-8 in human colon epithelial HT-29 cells. Moreover, probiotic supernatants can differently modulate IL-1ß, IL-6, TNF-α, and IL-10 production by human macrophages, suggesting a peculiar anti-inflammatory activity. Furthermore, supernatants showed a significant dose-dependent radical scavenging activity. This study suggests one of the mechanisms by which probiotics exert their anti-inflammatory activity affecting directly the intestinal epithelial cells and the underlying macrophages. This study provides a further evidence to support the possible use of probiotic metabolites in preventing and downregulating intestinal inflammation as adjuvant in anti-inflammatory therapy.

Anti-inflammatory effect of multistrain probiotic formulation (L. rhamnosus, B. lactis, and B. longum).

OBJECTIVE: In recent years, a great number of studies have been directed toward the evaluation of gastrointestinal microbiota modulation through the introduction of beneficial microorganisms, also known as probiotics. Many studies have highlighted how this category of bacteria is very important for the good development, functioning, and maintenance of our immune system. There is a delicate balance between the immune system, located under the gut epithelial barrier, and the microbiota, but many factors can induce a disequilibrium that leads to an inflammatory state and dysbiosis. The aim of this work is to verify the anti-inflammatory effects of a probiotic formulation of Lactobacillus rhamnosus, Bifidobacterium lactis, and Bifidobacterium longum (Serobioma). METHODS: To mimic the natural host compartmentalization between probiotics and immune cells through the intestinal epithelial barrier in vitro, the transwell model was used. We focused on a particular subset of immune cells that play a key role in the mucosal immune system. The immunomodulatory effects of probiotic formulation were investigated in the human macrophage cell line THP1 and macrophages derived from ex vivo human peripheral blood mononuclear cells. RESULTS: Probiotic formulation induced a significant increase in anti-inflammatory cytokine interleukin-10 (IL-10) production and was able to decrease the secretion of the major proinflammatory cytokines IL-1ß and IL-6 by 70% and 80%, respectively. Finally, for the first time, the ability of probiotic formulation to favor the macrophage M2 phenotype has been identified. CONCLUSION: The transwell model is an intriguing toll approach to studying the human epithelial barrier.

Antibiofilm and Antioxidant Activity of Propolis and Bud Poplar Resins versus Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a common biofilm-forming bacterial pathogen implicated in lung, skin, and systemic infections. Biofilms are majorly associated with chronic lung infection, which is the most severe complication in cystic fibrosis patients characterized by drug-resistant biofilms in the bronchial mucus with zones, where reactive oxygen species concentration is increased mainly due to neutrophil activity. Aim of this work is to verify the anti-Pseudomonas property of propolis or bud poplar resins extracts. The antimicrobial activity of propolis and bud poplar resins extracts was determined by MIC and biofilm quantification. Moreover, we tested the antioxidant activity by DPPH and neutrophil oxidative burst assays. In the end, both propolis and bud poplar resins extracts were able to inhibit P. aeruginosa biofilm formation and to influence both swimming and swarming motility. Moreover, the extracts could inhibit proinflammatory cytokine production by human PBMC and showed both direct and indirect antioxidant activity. This work is the first to demonstrate that propolis and bud poplar resins extracts can influence biofilm formation of P. aeruginosa contrasting the inflammation and the oxidation state typical of chronic infection suggesting that propolis or bud poplar resins can be used along with antibiotic as adjuvant in the therapy against P. aeruginosa infections related to biofilm.

Montmorillonite-chitosan-chlorhexidine composite films with antibiofilm activity and improved cytotoxicity for wound dressing.

HYPOTHESIS: Chlorhexidine (CLX) is a good antimicrobial agent, but its use in treatment of wounds is limited because of its cytotoxicity towards human fibroblasts. A delivery system, able to release CLX in a localized and prolonged manner, could guarantee antimicrobial activity with reduced cytotoxic. Thus in this work the preparation and characterization of chitosan/montmorillonite composite films containing CLX, able to offer a prolonged CLX release, is described. The antimicrobial and antibiofilm activities and cytotoxicity of films were investigated. EXPERIMENTAL: CLX was intercalated between the layers of montmorillonite (MONT-Na), and the intercalated product (MONT-CLX) was characterized by X-ray powder diffraction (XRPD), thermogravimetric analysis (TGA) and FT-IR spectroscopy. Then chitosan/MONT-CLX films were prepared and characterized. For comparison, films loaded with neat CLX and MONT-Na/CLX were prepared. All prepared films were tested for their antimicrobial and antibiofilm activities. Cytotoxicity towards human skin keratinocytes and human fibroblasts HuDe was evaluated as well. FINDINGS: All prepared films showed good antimicrobial and antibiofilm activities. As concerns cytotoxicity the film containing MONT-CLX at 1% CLX concentration resulted no cytotoxic. These results confirm the potential use of chitosan films containing MONT-CLX as a potential wound dressing material to prevent microbial colonization in wounds.

Diphenyl diselenide derivatives inhibit microbial biofilm formation involved in wound infection.

BACKGROUND: Organoselenium compounds have antimicrobial activity against some bacteria and fungi; furthermore, the antioxidant activity of diselenides has been demonstrated. The aim of the present work was to examine the in vitro minimal inhibitory concentration of a panel of differently substituted diselenides and their effectiveness in inhibiting biofilm formation and dispersing preformed microbial biofilm of Staphylococcus epidermidis, Staphylococcus aureus, Streptococcus pyogenes and Pseudomonas aeruginosa and the yeast Candida albicans, all involved in wound infections. Moreover, the cytotoxicity of the compounds was determined in human dermal fibroblast and keratinocytes. In closing, we tested their direct antioxidant activity. RESULTS: Diselenides showed different antimicrobial activity, depending on the microorganism. All diselenides demonstrated a good antibiofilm activity against S. aureus and S. epidermidis, the compounds camphor diselenide, bis[ethyl-N-(2'-selenobenzoyl) glycinate] and bis[2'-seleno-N-(1-methyl-2-phenylethyl) benzamide] were active against S. pyogenes and C. albicans biofilm while only diselenides 2,2'-diselenidyldibenzoic acid and bis[ethyl-N-(2'-selenobenzoyl) glycinate] were effective against P. aeruginosa. Moreover, the compounds bis[ethyl-N-(2'-selenobenzoyl) glycinate] and bis[2'-seleno-N-(1-methyl-2-phenylethyl) benzamide] showed an antioxidant activity at concentrations lower than the 50 % of cytotoxic concentration. CONCLUSIONS: Because microbial biofilms are implicated in chronic infection of wounds and treatment failure, the combination of antimicrobial activity and potential radical scavenging effects may contribute to the improvement of wound healing. Therefore, this study suggests that bis[ethylN-(2'-selenobenzoyl) glycinate] and bis[2'-seleno-N-(1-methyl-2-phenylethyl) benzamide] are promising compounds to be used in preventing and treating microbial wound infections.

Growth Hormone Deficiency in Prepubertal Children: Predictive Markers of Cardiovascular Disease.

BACKGROUND: Cardiovascular (CV) risk factors have been identified in adults with untreated growth hormone deficiency (GHD). Existing evidence suggests that the development of the atheromatous plaque begins early in childhood. Previous reports have shown that GHD children are prone to increased CV risks including impaired cardiac function, dyslipidemia and abnormalities in body composition. Recent studies in epigenetics and metabolomics have defined specific fingerprints that might be associated with an increased risk of CV disease. AIM: The aim of this review is to point out the most significant biochemical and clinical predictive markers of CV disease in prepubertal children and to evaluate the effect of recombinant human growth hormone therapy on most of these alterations. The novel findings in epigenetics and metabolomics are also reviewed, with a particular focus on translating them into clinical practice.

A straightforward method to determine flavouring substances in food by GC-MS.

A straightforward GC-MS method was developed to determine the occurrence of fourteen flavouring compounds in food. It was successfully validated for four generic types of food (liquids, semi-solids, dry solids and fatty solids) in terms of limit of quantification, linearity, selectivity, matrix effects, recovery (53-120%) and repeatability (3-22%). The method was applied to a survey of 61 Dutch food products. The survey was designed to cover all the food commodities for which the EU Regulation 1334/2008 set maximum permitted levels. All samples were compliant with EU legislation. However, the levels of coumarin (0.6-63 mg/kg) may result in an exposure that, in case of children, would exceed the tolerable daily intake (TDI) of 0.1mg/kg bw/day. In addition to coumarin, estragole, methyl-eugenol, (R)-(+)-pulegone and thujone were EU-regulated substances detected in thirty-one of the products. The non-EU regulated alkenylbenzenes, trans-anethole and myristicin, were commonly present in beverages and in herbs-containing products.

Array-CGH characterization of a de novo t(X;Y)(p22;q11) in a female with short stature and mental retardation.

We report the clinical and molecular investigations in a girl with 46,X,-X,+der(X)t(X;Y)(p22;q11) de novo karyotype who presented an intricate phenotype characterized by mental retardation and facial dysmorphisms in combination with short stature. The structure of the derivative X chromosome was studied using BAC array-CGH which disclosed the Xp22 breakpoint between the STS and the VCX3A gene and the presence of the Yq11.1qter chromosome. It is common that females with Xp;Yq translocations present only short stature and are normal in every other aspect. Thus, this would be the first case in which a girl with Xp;Yq translocation presents an unusual phenotype with intermediate male clinical features with Xp;Yq translocations. The risk of developing gonadoblastoma in females with Y chromosome material is also discussed and, to this effect, different explanations related to this apparent variation are also presented.

Serum levels of receptors for advanced glycation end products in normal-weight and obese children born small and large for gestational age.

OBJECTIVE: To assess potential alterations in soluble and endogenous secretory receptors for advanced glycation end products (sRAGE and esRAGE) in normal-weight (NW) and obese (Ob) children born small (SGA) and large (LGA) compared with appropriate for gestational age (AGA) subjects and to explore if birth weight (BW), insulin resistance (IR), and obesity represent independent risk factors. RESEARCH DESIGN AND METHODS: We categorized 130 prepubertal children into six groups according to BW and obesity and evaluated sRAGE, esRAGE, and homeostasis model assessment of IR. RESULTS: sRAGE and esRAGE were lower in Ob SGA and LGA children than Ob AGA subjects (all P < 0.05), and in NW SGA and LGA children than NW AGA subjects (all P < 0.05). Interestingly, BW and IR were significantly and independently related to RAGE. CONCLUSIONS: sRAGE and esRAGE are decreased in SGA and LGA children, and BW and IR seem to play an important role in the reduction of RAGE.

Unbalanced oxidant-antioxidant status and its effects in pediatric diseases.

Oxidative stress results from a disparity between the generation of reactive oxygen species and the antioxidant ability of the organism. The alteration of the oxidant-antioxidant system brings in adults an effective state of imbalance, which may influence the pathogenesis of many diseases. Oxidative stress also plays a pivotal role in the progression of various pathologies in childhood, through a manipulation of regulatory proteins. In fact, several studies have demonstrated that an unbalanced oxidant-antioxidant status is able to determine toxic effects even during infancy. Therefore, the aim of this review was to summarize current knowledge about the dynamic relationship between oxidative stress and systemic diseases during childhood. In order to better understand these complex mechanisms, a comprehensive review of the literature was done, focusing mainly on pre-pubertal children. In fact, this age-group offers a unique opportunity to exclude confounding factors, especially those related to the metabolic effects induced by puberty. Early identification of these very young patients should be aimed at minimizing the degree of oxidative damage. Only by achieving early diagnosis, will it be possible to identify those children who could benefit from specific therapeutic approaches targeting oxidative stress.