Fattori predittivi precoci nella pancreatite acuta: indici prognostici multiparametrici e ruolo di nuovi marcatori molecolari

La pancreatite acuta è un processo infiammatorio acuto del pancreas in cui si sviluppa una autodigestione della ghiandola pancreatica da parte degli enzimi digestivi in essa contenuti e che può coinvolgere i tessuti circostanti od organi distanti. L’evoluzione della patologia è spesso imprevedibile e varia da una completa risoluzione del quadro clinico e funzionale, allo sviluppo di complicanze locali e/o sistemiche fino all’insufficienza multiorgano e al decesso. Numerosi sono gli indici prognostici utilizzati per individuare i pazienti a richio di sviluppare una pancreatite acuta severa. Nello studio sono stati valutati i più comuni indici prognostici (Ranson score, APACHE II score e Balthazar score) confrontandoli con nuovi marcatori molecolari: la proteina C reattiva (PCR: proteina di fase acuta) e la metalloproteinasi-9 (MMP-9: gelatenasi coinvolta nella degradazione della matrice extracellulare e nella migrazione dei polimorfonucleati) con l’obiettivo di individuare gli indici più accurati e precoci utili alla stratificazione del rischio. Sono stati arruolati nello studio 65 pazienti con acquisizione prospettica dei dati relativi a Ranson, APACHE II, Balthazar score e PCR dosata a 0 e 48 ore dal ricovero. In un sottogruppo di 26 pazienti è stata dosata la MMP-9 al tempo 0 e in 11 di questi pazienti l’MMP-9 a 48 ore dal ricovero. I pazienti sono stati considerati affetti da pancreatite acuta lieve o severa in accordo con i criteri di Atlanta del 1992. Tutti gli indici prognostici hanno mostrato valori medi significativamente superiori nei casi di PA severa, rispetto ai casi di PA lieve tranne per quanto riguarda i valori di MMP-9 dosata a 48 ore dal ricovero. L’ulteriore analisi statistica eseguita mediante la stima di un modello di regressione logistica multivariata applicato al totale dei 65 pazienti, ha individuato la PCR dosata a 48 ore e il Ranson score, quali indici prognostici indipendenti più sensibili nell’individuazione dei pazienti con maggiore rischio di pancreatite acuta severa. Un simile modello statistico stimato sul sottogruppo di 26 pazienti, ha individuato l’MMP-9 dosata al tempo 0, e ancora il Ranson score, come i due indici prognostici indipendenti più sensibili, e in particolare l’MMP-9 come l’indice prognostico più precoce nell’individuazione dei pazienti candidati a sviluppare una pancreatite acuta severa. Ulteriori studi, su un numero più ampio di pazienti, saranno necessari per confermare il dato e valutare l’ambito di applicazione di questo nuovo indice prognostico

Human neural stem cell transplantation in ALS: initial results from a phase I trial

We report the initial results from a phase I clinical trial for ALS. We transplanted GMP-grade, fetal human neural stem cells from natural in utero death (hNSCs) into the anterior horns of the spinal cord to test for the safety of both cells and neurosurgical procedures in these patients. The trial was approved by the Istituto Superiore di Sanit\ue0 and the competent Ethics Committees and was monitored by an external Safety Board

Needlestick injuries, glove perforation and round-tipped blunt needles

We read with great interest the article by Battersby et al. [1] about the impairment of surgical knot quality due to double gloving. The practice to wearing two pairs of gloves during surgical procedures to reduce the risks of exposure to patient’s blood and transmission of infectious organisms has been recommended worldwide, by several healthcare authorities, also on the basis of a Cochrane review showing the absence of compromised dexterity as a result of double gloving [2]. The study performed by Battersby and Colleagues clearly shows that double gloving reduces the quality of surgical knots by 24%, no matter the suture type used. A wider reduction of knot quality (50%) was noted with 4.0 sutures. These results question the safety of surgical knots tied wearing double gloves and, as a consequence, push surgeons to consider other precautions to reduce bloody contamination during surgery ..

Binary Biocompatible CNC–Gelatine Hydrogel as 3D Scaffolds Suitable for Cell Culture Adhesion and Growth

Binary nano-biocomposite 3D scaffolds of cellulose nanocrystals (CNCs)—gelatine were fabricated without using chemical crosslinking additives. Controlled oxidative treatment allowed introducing carboxyl or carbonyl functionalities on the surface of CNCs responsible for the crosslinking of gelatine polymers. The obtained composites were characterized for their physical-chemical properties. Their biocompatibility towards different cell cultures was evaluated through MTT and LDH assays, cellular adhesion and proliferation experiments. Gelatine composites reinforced with carbonyl-modified CNCs showed the most performing swelling/degradation profile and the most promising adhesion and proliferation properties towards cell lines, suggesting their potential application in the field of tissue engineering

Functional Characterization of Two Variants at the Intron 6-Exon 7 Boundary of the KCNQ2 Potassium Channel Gene Causing Distinct Epileptic Phenotypes

Pathogenic variants in KCNQ2 encoding for Kv7.2 potassium channel subunits have been found in patients affected by widely diverging epileptic phenotypes, ranging from Self-Limiting Familial Neonatal Epilepsy (SLFNE) to severe Developmental and Epileptic Encephalopathy (DEE). Thus, understanding the pathogenic molecular mechanisms of KCNQ2 variants and their correlation with clinical phenotypes has a relevant impact on the clinical management of these patients. In the present study, the genetic, biochemical, and functional effects prompted by two variants, each found in a non-familial SLNE or a DEE patient but both affecting nucleotides at the KCNQ2 intron 6-exon 7 boundary, have been investigated to test whether and how they affected the splicing process and to clarify whether such mechanism might play a pathogenetic role in these patients. Analysis of KCNQ2 mRNA splicing in patient-derived lymphoblasts revealed that the SLNE-causing intronic variant (c.928-1G > C) impeded the use of the natural splice site, but lead to a 10-aa Kv7.2 in frame deletion (Kv7.2 p.G310Δ10); by contrast, the DEE-causing exonic variant (c.928G > A) only had subtle effects on the splicing process at this site, thus leading to the synthesis of a full-length subunit carrying the G310S missense variant (Kv7.2 p.G310S). Patch-clamp recordings in transiently-transfected CHO cells and primary neurons revealed that both variants fully impeded Kv7.2 channel function, and exerted strong dominant-negative effects when co-expressed with Kv7.2 and/or Kv7.3 subunits. Notably, Kv7.2 p.G310S, but not Kv7.2 p.G310Δ10, currents were recovered upon overexpression of the PIP2-synthesizing enzyme PIP5K, and/or CaM; moreover, currents from heteromeric Kv7.2/Kv7.3 channels incorporating either Kv7.2 mutant subunits were differentially regulated by changes in PIP2 availability, with Kv7.2/Kv7.2 G310S/Kv7.3 currents showing a greater sensitivity to PIP2 depletion when compared to those from Kv7.2/Kv7.2 G310Δ10/Kv7.3 channels. Altogether, these results suggest that the two variants investigated differentially affected the splicing process at the intron 6-exon 7 boundary, and led to the synthesis of Kv7.2 subunits showing a differential sensitivity to PIP2 and CaM regulation; more studies are needed to clarify how such different functional properties contribute to the widely-divergent clinical phenotypes

Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma

Transformed stem cells have been isolated from some human cancers. We report that, unlike other brain cancers, the lethal glioblastoma multiforme contains neural precursors endowed with all of the critical features expected from neural stem cells. Similar, yet not identical, to their normal neural stem cell counterpart, these precursors emerge as unipotent (astroglial) in vivo and multipotent (neuronal-astroglial-oligodendroglial) in culture. More importantly, these cells can act as tumor-founding cells down to the clonal level and can establish tumors that closely resemble the main histologic, cytologic, and architectural features of the human disease, even when challenged through serial transplantation. Thus, cells possessing all of the characteristics expected from tumor neural stem cells seem to be involved in the growth and recurrence of adult human glioblastomas multiforme

Gabapentin treatment in a patient with KCNQ2 developmental epileptic encephalopathy

De novo variants in KCNQ2 encoding for Kv7.2 voltage-dependent neuronal potassium (K+) channel subunits are associated with developmental epileptic encephalopathy (DEE). We herein describe a the clinical and electroencephalographic (EEG) features of a child with early-onset DEE caused by the novel KCNQ2 p.G310S variant. In vitro experiments demonstrated that the mutation induces loss-of-function effects on the currents produced by channels incorporating mutant subunits; these effects were counteracted by the selective Kv7 opener retigabine and by gabapentin, a recently described Kv7 activator. Given these data, the patient started treatment with gabapentin, showing a rapid and sustained clinical and EEG improvement over the following months. Overall, these results suggest that gabapentin can be regarded as a precision therapy for DEEs due to KCNQ2 loss-of-function mutations

Uso de suplementos alimentares em praticantes de artes marciais em uma academia em Fortaleza-CE

Nos últimos anos as pessoas têm despertado para a necessidade de uma vida com mais qualidade, que é frequentemente buscada através de alimentação equilibrada aliada a exercícios físicos. Este aspecto vem crescendo tanto entre aqueles que antes só se preocupavam com a estética, quanto nos grupos que teve maior preocupação em relação à saúde. Diante disso, o presente estudo teve como objetivo promover uma avaliação sobre o uso de suplementos alimentares por praticantes de artes marciais. Para tanto, realizou-se um estudo de natureza descritiva e quantitativa com abordagem exploratória. Tendo sido utilizado como ferramenta de coleta de dados um questionário com perguntas objetivas contendo identificação, arte marcial e uso de suplementação. O público-alvo são alunos praticantes de Jiu Jiutsu e Muay Thai em uma academia localizada em Fortaleza-CE. Constatou-se, por meio deste estudo, que menos da metade dos participantes da pesquisa recorrem a profissionais qualificados para receberem a indicação do uso de suplementos alimentares. E que por esta razão podem acabar seguindo uma recomendação errada, tendo em vista que cada organismo é diferente, bem como os treinos e as dietas. Portanto, é ressaltado que somente um profissional qualificado, por meio de avaliação e exames, pode indicar o melhor suplemento e suas quantidades, bem como advertir o usuário sobre os possíveis riscos, preparando-o para um uso consciente do produto

Uso de suplementos alimentares em praticantes de artes marciais em uma academia em Fortaleza-CE

In recent years people have been awakening to the need for a higher quality life, which is often sought through balanced diet combined with physical exercise. This aspect has been growing both among those who previously only concerned themselves with aesthetics, and among the groups that had the greatest concern regarding health. Given this, the present study aimed to promote an assessment of the use of dietary supplements by practitioners of martial arts. Therefore, a descriptive and quantitative study with exploratory approach was performed. Having been used as a data collection tool a questionnaire with objective questions containing identification, martial art and use of supplementation. The target audience are practicing students of Jiu Jiutsu and Muay Thai at a gym located in Fortaleza-CE. It was found from this study that less than half of the survey participants use qualified professionals to receive the indication of the use of dietary supplements. And for this reason they may end up following a wrong recommendation, as each body is different, as well as training and diets. Therefore, it is emphasized that only a qualified professional, through evaluation and examinations, can indicate the best supplement and its quantities, as well as warn the user about possible risks, preparing him for conscious use of the product.Nos últimos anos as pessoas têm despertado para a necessidade de uma vida com mais qualidade, que é frequentemente buscada através de alimentação equilibrada aliada a exercícios físicos. Este aspecto vem crescendo tanto entre aqueles que antes só se preocupavam com a estética, quanto nos grupos que teve maior preocupação em relação à saúde. Diante disso, o presente estudo teve como objetivo promover uma avaliação sobre o uso de suplementos alimentares por praticantes de artes marciais. Para tanto, realizou-se um estudo de natureza descritiva e quantitativa com abordagem exploratória. Tendo sido utilizado como ferramenta de coleta de dados um questionário com perguntas objetivas contendo identificação, arte marcial e uso de suplementação. O público-alvo são alunos praticantes de Jiu Jiutsu e Muay Thai em uma academia localizada em Fortaleza-CE. Constatou-se, por meio deste estudo, que menos da metade dos participantes da pesquisa recorrem a profissionais qualificados para receberem a indicação do uso de suplementos alimentares. E que por esta razão podem acabar seguindo uma recomendação errada, tendo em vista que cada organismo é diferente, bem como os treinos e as dietas. Portanto, é ressaltado que somente um profissional qualificado, por meio de avaliação e exames, pode indicar o melhor suplemento e suas quantidades, bem como advertir o usuário sobre os possíveis riscos, preparando-o para um uso consciente do produto