Short bowel syndrome (SBS) is a rare malabsorptive disorder as a result of the loss of bowel mass mostly secondary to surgical resection of the small intestine. Other causes are vascular diseases, ...neoplasms or inflammatory bowel disease. The spectrum of the disease is widely variable from single micronutrient malabsorption to complete intestinal failure, depending on the remaining length of the small intestine, the anatomical portion of intestine and the function of the remnant bowel. Over the last years, the management of affected patients has remarkably improved with the increase in patients’ quality of life and survival, mainly thanks to advances in home-based parenteral nutrition (PN). In the last ten years new treatment strategies have become available together with increasing experience and the encouraging results with new drugs, such as teduglutide, have added a new dimension to the management of SBS.
This review aims to summarize the knowledge available in the current literature on SBS epidemiology, pathophysiology, and its surgical (including intestinal lengthening procedures and intestinal transplantation) and medical management with emphasis on the recent advances.
Moreover, this review attempts to provide the new understanding and recent approaches to SBS complications such as sepsis, catheter thrombosis, and intestinal failure-associated liver disease.
Hepatitis C virus infection (HCV) represents a unique model to characterize, from early to late stages of infection, the T cell differentiation process leading to exhaustion of human CD8+ T cells. ...Here we show that in early HCV infection, exhaustion-committed virus-specific CD8+ T cells display a marked upregulation of transcription associated with impaired glycolytic and mitochondrial functions, that are linked to enhanced ataxia-telangiectasia mutated (ATM) and p53 signaling. After evolution to chronic infection, exhaustion of HCV-specific T cell responses is instead characterized by a broad gene downregulation associated with a wide metabolic and anti-viral function impairment, which can be rescued by histone methyltransferase inhibitors. These results have implications not only for treatment of HCV-positive patients not responding to last-generation antivirals, but also for other chronic pathologies associated with T cell dysfunction, including cancer.
Infections of the ears, paranasal sinuses, nose and throat are very common and represent a serious issue for the healthcare system. Bacterial biofilms have been linked to upper respiratory tract ...infections and antibiotic resistance, raising serious concerns regarding the therapeutic management of such infections. In this context, novel strategies able to fight biofilms may be therapeutically beneficial and offer a valid alternative to conventional antimicrobials. Biofilms consist of mixed microbial communities, which interact with other species in the surroundings and communicate through signaling molecules. These interactions may result in antagonistic effects, which can be exploited in the fight against infections in a sort of "bacteria therapy". Streptococcus salivarius and Streptococcus oralis are α-hemolytic streptococci isolated from the human pharynx of healthy individuals. Several studies on otitis-prone children demonstrated that their intranasal administration is safe and well tolerated and is able to reduce the risk of acute otitis media. The aim of this research is to assess S. salivarius 24SMB and S. oralis 89a for the ability to interfere with biofilm of typical upper respiratory tract pathogens.
To investigate if soluble substances secreted by the two streptococci could inhibit biofilm development of the selected pathogenic strains, co-cultures were performed with the use of transwell inserts. Mixed-species biofilms were also produced, in order to evaluate if the inhibition of biofilm formation might require direct contact. Biofilm production was investigated by means of a spectrophotometric assay and by confocal laser scanning microscopy.
We observed that S. salivarius 24SMB and S. oralis 89a are able to inhibit the biofilm formation capacity of selected pathogens and even to disperse their pre-formed biofilms. Diffusible molecules secreted by the two streptococci and lowered pH of the medium revealed to be implied in the mechanisms of anti-biofilm activity.
S. salivarius 24SMB and S. oralis 89a possess desirable characteristics as probiotic for the treatment and prevention of infections of the upper airways. However, the nature of the inhibition appear to be multifactorial and additional studies are required to get further insights.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The exact semantic processes subserving the formation of false memories are still poorly understood. Here, we directly probed the semantic origins of false memories in a typical ...Deese-Roediger-McDermott (DRM) task, by predicting participants' performance in this task through data-driven distributional semantic models. Participants were required to study lists of words and then to perform a recognition task. Our findings indicate that the participants' performance is better accounted for by a local rather than a global strategy on the task at hand: the single lists composing the task activate specific semantic clusters that are responsible for the occurrence of false memories. In particular, memory performance followed a continuous semantic gradient, with higher false recognitions occurring for higher sematic similarity between the lures (i.e., the false memory items) and the words in the relative lists. Crucially, our findings also show that semantic memory is differently involved in veridical and false memories, with this pattern being consistent across two reanalyses of data from previous studies and being replicated in an independent experiment. We thus outline an empirically-driven theoretical framework to account for the semantic processes supporting veridical and false memories formation.
We present a 3D method to numerically design a realizable metasurface, which transforms a given incident field into a radiated field that satisfies mask-type (inequality) constraints. The method is ...based on an integral equation formulation, with local impedance boundary condition (IBC) approximation. The procedure yields the spatial distribution of the impedance, yet the process involves the synthesis of the equivalent current only. This current is constrained to correspond to a realizable surface impedance, i.e., passive, lossless, and with reactance values bounded by practical realizability limits. The current-based design avoids any solution of the forward problem, and the impedance is obtained from the synthesized current only at the end of the process. The procedure is gradient-based, with the gradient expressed in closed form. This allows handling large metasurfaces, with full spatial variability of the impedance in two dimensions. The method requires no a priori information, and all relevant operations in the iterative process can be evaluated with O ( N log N ) complexity. Application examples concentrate on the case of on-surface excitation and far-field pattern specifications; they show designs of circular and rectangular metasurface antennas of 20 wavelengths in size, with pencil- and shaped-beam patterns, and for both circular and linear polarization.
Public policy scholars have recently focused on the mechanisms accounting for the sustainability of major policy changes. Among the strategies by which policy entrepreneurs may try to avoid future ...backlash institutionalization is certainly one of the most used. Yet, it can foster ossification and eventually jeopardize policy effectiveness. Such a potential trade‐off between institutionalization and long‐term effectiveness is particularly intense in policies concerning technological innovation because the necessity to create winning coalitions can undermine the required absorption capacity needed by government to engage the innovation ecosystems. This paper explores such a trade‐off with a case study on the Italian policy for public sector's digital transformation. The case is theoretically promising because over three decades institutionalization has always represented the main overall strategy adopted by policymaker, but only the 2016 initiative emerged as a “success.” In this sense, the case study can focus on the mechanisms activated by policy entrepreneurs to trigger and entrench change.
Resumen
Los estudiosos de las políticas públicas se han centrado recientemente en los mecanismos que dan cuenta de la sostenibilidad de los principales cambios de política. Entre las estrategias mediante las cuales los empresarios de políticas pueden tratar de evitar futuras reacciones adversas, la institucionalización es sin duda una de las más utilizadas. Sin embargo, puede fomentar la osificación y, finalmente, poner en peligro la eficacia de las políticas. Tal compensación potencial entre la institucionalización y la efectividad a largo plazo es particularmente intensa en las políticas relacionadas con la innovación tecnológica porque la necesidad de crear coaliciones ganadoras puede socavar la capacidad de absorción requerida por el gobierno para involucrar a los ecosistemas de innovación. Este documento explora tal compensación con un estudio de caso sobre la política italiana para la transformación digital del sector público. El caso es teóricamente prometedor porque durante tres décadas la institucionalización siempre ha representado la principal estrategia general adoptada por los formuladores de políticas, pero solo la iniciativa de 2016 surgió como un “éxito”. En este sentido, el estudio de caso puede centrarse en los mecanismos activados por los empresarios de políticas para desencadenar y afianzar el cambio.
摘要
公共政策学者近期聚焦于重大政策变革的可持续性背后的机制。在政策企业家用于试图避免未来冲突的策略中, 制度化一定是最常用的策略之一。然而,它能促进僵化并最终破坏政策的有效性。在关于技术创新的政策中, 制度化和长期有效性之间的潜在得失尤其强烈,因为建立获胜联盟的必要性可能会破坏政府用于参与创新生态系统所需的吸收能力。本文以意大利公共部门数字转型政策为例, 探究了这种得失。该案例在理论上是有前景的,因为在过去的30年里, 制度化一直代表了决策者所采纳的主要总体战略,但只有2016年的倡议取得了“成功”。照此, 该案例研究能聚焦于政策企业家为触发和巩固变革而启动的机制。
The autonomic nervous system (ANS) is one of the main biological systems that regulates the body's physiology. Autonomic nervous system regulatory capacity begins before birth as the sympathetic and ...parasympathetic activity contributes significantly to the fetus' development. In particular, several studies have shown how vagus nerve is involved in many vital processes during fetal, perinatal, and postnatal life: from the regulation of inflammation through the anti-inflammatory cholinergic pathway, which may affect the functioning of each organ, to the production of hormones involved in bioenergetic metabolism. In addition, the vagus nerve has been recognized as the primary afferent pathway capable of transmitting information to the brain from every organ of the body. Therefore, this hypothesis paper aims to review the development of ANS during fetal and perinatal life, focusing particularly on the vagus nerve, to identify possible "critical windows" that could impact its maturation. These "critical windows" could help clinicians know when to monitor fetuses to effectively assess the developmental status of both ANS and specifically the vagus nerve. In addition, this paper will focus on which factors-i.e., fetal characteristics and behaviors, maternal lifestyle and pathologies, placental health and dysfunction, labor, incubator conditions, and drug exposure-may have an impact on the development of the vagus during the above-mentioned "critical window" and how. This analysis could help clinicians and stakeholders define precise guidelines for improving the management of fetuses and newborns, particularly to reduce the potential adverse environmental impacts on ANS development that may lead to persistent long-term consequences. Since the development of ANS and the vagus influence have been shown to be reflected in cardiac variability, this paper will rely in particular on studies using fetal heart rate variability (fHRV) to monitor the continued growth and health of both animal and human fetuses. In fact, fHRV is a non-invasive marker whose changes have been associated with ANS development, vagal modulation, systemic and neurological inflammatory reactions, and even fetal distress during labor.
To evaluate the ability of
HN001 and
BB536 to colonize the intestinal environment of healthy subjects and modify the gut microbiota composition.
Twenty healthy Italian volunteers, eight males and ...twelve females, participated in the study. Ten subjects took a sachet containing 4 × 10
colony-forming units (CFU) of
BB536 and 10
CFU of
HN001, 30 min before breakfast (pre-prandial administration), while ten subjects took a sachet of probiotic product 30 min after breakfast (post-prandial administration). The ability of
HN001 and
BB536 to colonize human gut microbiota was assessed by means of quantitative real-time PCR, while changes in gut microbiota composition were detected by using Ion Torrent Personal Genome Machine.
Immediately after 1-mo of probiotic administration,
BB536 and
HN001 load was increased in the majority of subjects in both pre-prandial and post-prandial groups. This increase was found also 1 mo after the end of probiotic oral intake in both groups, if compared to samples collected before probiotic consumption. At phyla level a significant decrease in
abundance was detected immediately after 1-mo of
BB536 and
HN001 oral intake. This reduction persisted up to 1 mo after the end of probiotic oral intake together with a significant decrease of
abundance if compared to samples collected before probiotic administration. Whereas, at species level, a higher abundance of
,
and
was observed, together with a reduction of
,
,
and
abundance. In addition, during follow-up period we observed a further reduction in
and
, together with a decrease in
and
abundance. Conversely, the abundance of
was increased if compared to samples collected at the beginning of the experimental time course.
BB536 and
HN001 showed the ability to modulate the gut microbiota composition, leading to a significant reduction of potentially harmful bacteria and an increase of beneficial ones. Further studies are needed to better understand the specific mechanisms involved in gut microbiota modulation.
The aim of this study was to determine the long-term effects and determinants of success of cardiac pacing in patients affected by reflex syncope enrolled in the Syncope Unit Project 2 (SUP 2) study. ...Initial results have validated the effectiveness of a standardized guideline-based algorithm which can be used in clinical practice in order to select suitable candidates for cardiac pacing.
In this prospective, multicentre, observational study, patients aged >40 years, affected by severe unpredictable recurrent reflex syncope, underwent carotid sinus massage (CSM), followed by tilt testing (TT) if CSM was negative, followed by implantation of an implantable loop recorder (ILR) if TT was negative. Those who had an asystolic response to one of these tests received a dual-chamber pacemaker. Of 281 patients who met the inclusion criteria, 137 (49%) received a pacemaker and were followed up for a mean of 26 ± 11 months: syncope recurred in 25 (18%) of them. At 3 years, the actuarial syncope recurrence rate was 20% 95% confidence interval (CI) 12-30 and was significantly lower than in 142 patients who did not receive a pacemaker and were observed by means of an ILR 43% (95% CI 29-57), P = 0.01. The 3-year recurrence rate was not different among 78 CSM+, 38 TT+, and 21 ILR+ patients, whereas it was lower in 20 patients with negative TT 5% (95% CI 0-15) than in 61 patients with positive TT 24% (95% CI 10-38).
The benefit of cardiac pacing is maintained at 3 years, irrespective of the index diagnostic test, and is maximum in patients with negative TT.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01509534.
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