Dietary Interventions to Modulate the Gut Microbiome-How Far Away Are We From Precision Medicine

The importance of the gut microbiome in human health and disease is fully acknowledged. A perturbation in the equilibrium among the different microbial populations living in the gut (dysbiosis) has been associated with the development of several types of diseases. Modulation of the gut microbiome through dietary intervention is an emerging therapeutic and preventive strategy for many conditions. Nevertheless, interpersonal differences in response to therapeutic treatments or dietary regimens are often observed during clinical trials, and recent research has suggested that subject-specific features of the gut microbiota may be responsible. In this review, we summarize recent findings in personalized nutrition, highlighting how individualized characterization of the microbiome may assist in designing ad hoc tailored dietary intervention for disease treatment and prevention. Moreover, we discuss the limitations and challenges encountered in integrating patient-specific microbial data into clinical practice

Analysis of Catania Flash Flood Case Study by Using Combined Microwave and Infrared Technique

Abstract In this paper, the analysis of an extreme convective event atypical for the winter season, which occurred on 21 February 2013 on the east coast of Sicily and caused a flash flood over Catania, is presented. In just 1 h, more than 50 mm of precipitation was recorded, but it was not forecast by numerical weather prediction (NWP) models and, consequently, no severe weather warnings were sent to the population. The case study proposed is first examined with respect to the synoptic situation and then analyzed by means of two algorithms based on satellite observations: the Cloud Mask Coupling of Statistical and Physical Methods (MACSP) and the Precipitation Evolving Technique (PET), developed at the National Research Council of Italy. Both of the algorithms show their ability in the near-real-time monitoring of convective cell formation and their rapid evolution. As quantitative precipitation forecasts by NWP could fail, especially for atypical convective events like in Catania, tools like MACSP and PET shall be adopted by civil protection centers to monitor the real-time evolution of deep convection events in aid to the severe weather warning service

Metabolomics of COPD Pulmonary Rehabilitation Outcomes via Exhaled Breath Condensate

: Chronic obstructive pulmonary disease (COPD) is characterized by different phenotypes and clinical presentations. Therefore, a single strategy of pulmonary rehabilitation (PR) does not always yield the expected clinical outcomes as some individuals respond excellently, others discreetly, or do not respond at all. Fifty consecutive COPD patients were enrolled. Of them, 35 starting a 5-week PR program were sampled at admission (T0), after 2 (T2W) and 5 (T5W) weeks, while 15 controls not yet on PR were tested at T0 and T5W. Nuclear magnetic resonance (NMR) profiling of exhaled breath condensate (EBC) and multivariate statistical analysis were applied to investigate the relationship between biomarkers and clinical parameters. The model including the three classes correctly located T2W between T0 and T5W, but 38.71% of samples partially overlapped with T0 and 32.26% with T5W, suggesting that for some patients PR is already beneficial at T2W (32.26% overlapping with T5W), while for others (38.71% overlapping with T0) more time is required. Rehabilitated patients presented several altered biomarkers. In particular, methanol from T0 to T5W decreased in parallel with dyspnea and fatigue, while the walk distance increased. Methanol could be ascribed to lung inflammation. We demonstrated that the metabolic COPD phenotype clearly evolves during PR, with a strict relationship between clinical and molecular parameters. Methanol, correlating with clinical parameters, represents a useful biomarker for monitoring personalized outcomes and establishing more targeted protocols

Centrality of Striatal Cholinergic Transmission in Basal Ganglia Function

Work over the past two decades revealed a previously unexpected role for striatal cholinergic interneurons in the context of basal ganglia function. The recognition that these interneurons are essential in synaptic plasticity and motor learning represents a significant step ahead in deciphering how the striatum processes cortical inputs, and why pathological circumstances cause motor dysfunction. Loss of the reciprocal modulation between dopaminergic inputs and the intrinsic cholinergic innervation within the striatum appears to be the trigger for pathophysiological changes occurring in basal ganglia disorders. Accordingly, there is now compelling evidence showing profound changes in cholinergic markers in these disorders, in particular Parkinson's disease and dystonia. Based on converging experimental and clinical evidence, we provide an overview of the role of striatal cholinergic transmission in physiological and pathological conditions, in the context of the pathogenesis of movement disorders

Models and methods for conditioning the ischemic brain

Abstract Background In the last decades the need to find new neuroprotective targets has addressed the researchers to investigate the endogenous molecular mechanisms that brain activates when exposed to a conditioning stimulus. Indeed, conditioning is an adaptive biological process activated by those interventions able to confer resistance to a deleterious brain event through the exposure to a sub-threshold insult. Specifically, preconditioning and postconditioning are realized when the conditioning stimulus is applied before or after, respectively, the harmul ischemia. Aims and Results The present review will describe the most common methods to induce brain conditioning, with particular regards to surgical, physical exercise, temperature-induced and pharmacological approaches. It has been well recognized that when the subliminal stimulus is delivered after the ischemic insult, the achieved neuroprotection is comparable to that observed in models of ischemic preconditioning. In addition, subjecting the brain to both preconditioning as well as postconditioning did not cause greater protection than each treatment alone. Conclusions The last decades have provided fascinating insights into the mechanisms and potential application of strategies to induce brain conditioning. Since the identification of intrinsic cell‐survival pathways should provide more direct opportunities for translational neuroprotection trials, an accurate examination of the different models of preconditioning and postconditioning is mandatory before starting any new project

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Ionic homeostasis in brain conditioning

Most of the current focus on developing neuroprotective therapies is aimed at preventing neuronal death. However, these approaches have not been successful despite many years of clinical trials mainly because the numerous side effects observed in humans and absent in animals used at preclinical level. Recently, the research in this field aims to overcome this problem by developing strategies which induce, mimic, or boost endogenous protective responses and thus do not interfere with physiological neurotransmission. Preconditioning is a protective strategy in which a subliminal stimulus is applied before a subsequent harmful stimulus, thus inducing a state of tolerance in which the injury inflicted by the challenge is mitigated. Tolerance may be observed in ischemia, seizure, and infection. Since it requires protein synthesis, it confers delayed and temporary neuroprotection, taking hours to develop, with a pick at 1-3 days. A new promising approach for neuroprotection derives from post-conditioning, in which neuroprotection is achieved by a modified reperfusion subsequent to a prolonged ischemic episode. Many pathways have been proposed as plausible mechanisms to explain the neuroprotection offered by preconditioning and post-conditioning. Although the mechanisms through which these two endogenous protective strategies exert their effects are not yet fully understood, recent evidence highlights that the maintenance of ionic homeostasis plays a key role in propagating these neuroprotective phenomena. The present article will review the role of protein transporters and ionic channels involved in the control of ionic homeostasis in the neuroprotective effect of ischemic preconditioning and post-conditioning in adult brain, with particular regards to the Na(+)/Ca2(+) exchangers (NCX), the plasma membrane Ca2(+)-ATPase (PMCA), the Na(+)/H(+) exchange (NHE), the Na(+)/K(+)/2Cl(-) cotransport (NKCC) and the acid-sensing cation channels (ASIC). Ischemic stroke is the third leading cause of death and disability. Up until now, all clinical trials testing potential stroke neuroprotectants failed. For this reason attention of researchers has been focusing on the identification of brain endogenous neuroprotective mechanisms activated after cerebral ischemia. In this context, ischemic preconditioning and ischemic post-conditioning represent two neuroprotecive strategies to investigate in order to identify new molecular target to reduce the ischemic damage

Validation of satellite OPEMW precipitation product with ground-based weather radar and rain gauge networks

Abstract. The Precipitation Estimation at Microwave Frequencies (PEMW) algorithm was developed at the Institute of Methodologies for Environmental Analysis of the National Research Council of Italy (IMAA-CNR) for inferring surface rain intensity (sri) from satellite passive microwave observations in the range from 89 to 190 GHz. The operational version of PEMW (OPEMW) has been running continuously at IMAA-CNR for two years. The OPEMW sri estimates, together with other precipitation products, are used as input to an operational hydrological model for flood alert forecast. This paper presents the validation of OPEMW against simultaneous ground-based observations from a network of 20 weather radar systems and a network of more than 3000 rain gauges distributed over the Italian Peninsula and main islands. The validation effort uses a data set covering one year (July 2011–June 2012). The effort evaluates dichotomous and continuous scores for the assessment of rain detection and quantitative estimate, respectively, investigating both spatial and temporal features. The analysis demonstrates 98% accuracy in correctly identifying rainy and non-rainy areas; it also quantifies the increased ability (with respect to random chance) to detect rainy and non-rainy areas (0.42–0.45 Heidke skill score) or rainy areas only (0.27–0.29 equitable threat score). Performances are better than average during summer, fall, and spring, while worse than average in the winter season. The spatial–temporal analysis does not show seasonal dependence except over the Alps and northern Apennines during winter. A binned analysis in the 0–15 mm h−1 range suggests that OPEMW tends to slightly overestimate sri values below 6–7 mm h−1 and underestimate sri above those values. With respect to rain gauges (weather radars), the correlation coefficient is larger than 0.8 (0.9). The monthly mean difference and standard deviation remain within ±1 and 2 mm h−1 with respect to rain gauges (respectively −2–0 and 4 mm h−1 with respect to weather radars)

Reconstruction of the nose. management of nasal cutaneous defects according to aesthetic subunit and defect size. a review

The nose represents the most common site for the presentation of cutaneous cancer, especially in sun-exposed areas: ala, dorsum, and tip. Even the smallest loss of substance can create aesthetic and psychosocial concerns for patients; therefore, surgeons who perform nasal reconstruction should be strictly confident with the pertinent surgical anatomy in order to tailor the procedure to the patient's condition and needs. Radical tumor excision and satisfactory aesthetic and functional results are primary targets. Restoring the original shape is the goal of any reconstruction: appropriate reshaping of three-dimensional geometry, proper establishment of symmetry, and excellent color and texture match to the adjacent structures are paramount features. Multiple options exist to re-establish functional and aesthetic integrity after surgical oncology; nevertheless, the management of nasal defects can be often challenging, and the gold standard is yet to be found. The current goal is to highlight some of the more common techniques used to reconstruct cutaneous defects of the nose with a specific focus on decision making based on the aesthetic subunit and defect size. The authors attempt to share common pitfalls and offer practical suggestions that they have found helpful in their clinical experience

ALLELE-SPECIFIC TRANSCRIPTIONAL ACTIVITY OF THE VARIABLE NUMBER OF TANDEM REPEATS OF THE INDUCIBLE NITRIC OXIDE SYNTHASE GENE IS ASSOCIATED WITH IDIOPATHIC ACHALASIA

Background: Polymorphisms of genes involved in the regulation of the immune response are risk factors for achalasia, but their contribution to disease pathogenesis is unknown. Nitric oxide is involved in both immune function and inhibitory neurotransmission. Objective: to assess the association and the functional relevance of the CCTTT inducible Nitric Oxide Synthase (NOS2) gene promoter polymorphism in achalasia. Methods: Genomic DNA was isolated from 181 achalasia patients and 220 controls. Genotyping of the (CCTTT)n repeats was performed by PCR and capillary electrophoresis, and data analyzed by considering the frequency of the different alleles. HT29 cells were transfected with iNOS luciferase promoter-reporter plasmids containing different (CCTTT)n. Results: The alleles’ distribution ranged from 7 to 18, with a peak frequency at 12 repeats. Analysis of the allele frequencies revealed that individuals carrying 10 and 13 CCTTT repeats were respectively less and more frequent in achalasia (OR 0.5, 95% CI 0.3-0.5 and OR 1.6, 95% CI 1-2.4, all p<0.05). Long repeats were also significantly associated with an earlier onset of the disease (OR 1.69, 95% CI 1.13-2.53, p=0.01). Transfection experiments’ revealed a similar allele-specific iNOS transcriptional activity. Conclusion: The functional polymorphism (CCTTT) of NOS2 promoter is associated with achalasia, likely by an allele-specific modulation of nitric oxide production