Laparoscopic versus Open Surgery in Complicated Appendicitis in Children Less Than 5 Years Old: A Six-Year Single-Centre Experience

Introduction. Acute appendicitis is the most common surgical emergency in the pediatric population. The peak incidence occurs in the first decade of life, while it is uncommon to face appendicitis in children younger than 5 years of age. Laparoscopy is now demonstrated to be the optimal approach also to treat complicated appendicitis, but in very young children this standardized operation is not always easy to perform. Material and Methods. From January 2009 to December 2015 we operated on 525 acute appendicitis, with 120 patients less than 5 years of age. Results. 90 children had a complicated appendicitis (localized or diffuse peritonitis): 43 (48%) were operated on by open approach and 47 (52%) by laparoscopy. The overall incidence of postoperative complications was greater in the open appendectomy group (63% versus 26%) and all severe complications requiring reintervention (6% of cases: 3 postoperative abscesses resolved with ultrasound guided percutaneous abscess drainage; 1 tubal surgery for salpingitis; 1 adhesion-related ileus requiring relaparotomy) were mostly associated with open surgery. Conclusions. Laparoscopic surgery resulted as the best approach for treating complicated appendicitis also in younger children, with minor and less severe postoperative complications compared to open surgery

Systemic Exosomal Delivery of shRNA Minicircles Prevents Parkinsonian Pathology

The development of new therapies to slow down or halt the progression of Parkinson's disease is a health care priority. A key pathological feature is the presence of alpha-synuclein aggregates, and there is increasing evidence that alpha-synuclein propagation plays a central role in disease progression. Consequently, the downregulation of alpha-synuclein is a potential therapeutic target. As a chronic disease, the ideal treatment will be minimally invasive and effective in the long-term. Knockdown of gene expression has clear potential, and siRNAs specific to alpha-synuclein have been designed; however, the efficacy of siRNA treatment is limited by its short-term efficacy. To combat this, we designed shRNA minicircles (shRNA-MCs), with the potential for prolonged effectiveness, and used RVG-exosomes as the vehicle for specific delivery into the brain. We optimized this system using transgenic mice expressing GFP and demonstrated its ability to downregulate GFP protein expression in the brain for up to 6 weeks. RVG-exosomes were used to deliver anti-alpha-synuclein shRNA-MC therapy to the alpha-synuclein preformed-fibril-induced model of parkinsonism. This therapy decreased alpha-synuclein aggregation, reduced the loss of dopaminergic neurons, and improved the clinical symptoms. Our results confirm the therapeutic potential of shRNA-MCs delivered by RVG-exosomes for long-term treatment of neurodegenerative diseases

Discourse markers activate their, <i>like</i>, cohort competitors

Speech in everyday conversations is riddled with discourse markers (DMs), such as well, you know, and like. However, in many lab-based studies of speech comprehension, such DMs are typically absent from the carefully articulated and highly controlled speech stimuli. As such, little is known about how these DMs influence online word recognition. The present study specifically investigated the online processing of DM like and how it influences the activation of words in the mental lexicon. We specifically targeted the cohort competitor (CC) effect in the Visual World Paradigm: Upon hearing spoken instructions to “pick up the beaker,” human listeners also typically fixate—next to the target object—referents that overlap phonologically with the target word (cohort competitors such as beetle; CCs). However, several studies have argued that CC effects are constrained by syntactic, semantic, pragmatic, and discourse constraints. Therefore, the present study investigated whether DM like influences online word recognition by activating its cohort competitors (e.g., lightbulb). In an eye-tracking experiment using the Visual World Paradigm, we demonstrate that when participants heard spoken instructions such as “Now press the button for the, like … unicycle,” they showed anticipatory looks to the CC referent (lightbulb)well before hearing the target. This CC effect was sustained for a relatively long period of time, even despite hearing disambiguating information (i.e., the /k/ in like). Analysis of the reaction times also showed that participants were significantly faster to select CC targets (lightbulb) when preceded by DM like. These findings suggest that seemingly trivial DMs, such as like, activate their CCs, impacting online word recognition. Thus, we advocate a more holistic perspective on spoken language comprehension in naturalistic communication, including the processing of DMs

Efficient Non-viral Gene Delivery into Human Hematopoietic Stem Cells by Minicircle Sleeping Beauty Transposon Vectors

The Sleeping Beauty (SB) transposon system is a non-viral gene delivery platform that combines simplicity, inexpensive manufacture, and favorable safety features in the context of human applications. However, efficient correction of hematopoietic stem and progenitor cells (HSPCs) with non-viral vector systems, including SB, demands further refinement of gene delivery techniques. We set out to improve SB gene transfer into hard-to-transfect human CD34 + cells by vectorizing the SB system components in the form of minicircles that are devoid of plasmid backbone sequences and are, therefore, significantly reduced in size. As compared to conventional plasmids, delivery of the SB transposon system as minicircle DNA is 3c20 times more efficient, and it is associated with up to a 50% reduction in cellular toxicity in human CD34 + cells. Moreover, providing the SB transposase in the form of synthetic mRNA enabled us to further increase the efficacy and biosafety of stable gene delivery into hematopoietic progenitors ex vivo. Genome-wide insertion site profiling revealed a close-to-random distribution of SB transposon integrants, which is characteristically different from gammaretroviral and lentiviral integrations in HSPCs. Transplantation of gene-marked CD34 + cells in immunodeficient mice resulted in long-term engraftment and hematopoietic reconstitution, which was most efficient when the SB transposase was supplied as mRNA and nucleofected cells were maintained for 4\u20138 days in culture before transplantation. Collectively, implementation of minicircle and mRNA technologies allowed us to further refine the SB transposon system in the context of HSPC gene delivery to ultimately meet clinical demands of an efficient and safe non-viral gene therapy protocol. Ivics and collegues refined the Sleeping Beauty transposon system for gene transfer in human hematopoietic stem and progenitor cells by vectorizing the transposon components as minicircle DNA and synthetic mRNA. The advanced vector system enables efficient and safe non-viral engineering of hematopoietic cells that can be transplanted into immunodeficient mice

Heritage language anxiety and majority language anxiety among Turkish immigrants in the Netherlands

Aims and objectives: This study examines the language anxiety that occurs in immigrants’ daily lives when speaking the heritage language and the majority language, both in their host country and during visits to their home country. It compares the levels of heritage language anxiety and majority language anxiety across three generations of the Turkish immigrant community in the Netherlands and explores the link between immigrants’ language anxiety, and sociobiographical (i.e. generation, gender, education) and language background variables (i.e. age of acquisition, self-perceived proficiency, frequency of language use). Design: A Likert scale-based questionnaire was administered to 116 participants across three generations who reported their language anxiety levels when speaking the heritage language and the majority language in three social contexts (i.e. family, friendship and speaking with native speakers). Findings: Statistical analyses revealed that heritage language anxiety and majority language anxiety were prevalent in immigrants’ daily life, and that levels of both forms of anxiety differed across generations, and in different daily life situations. First- and second-generation immigrants typically experienced majority language anxiety, while second- and predominantly third-generation immigrants suffered from heritage language anxiety. Relationships emerged between language background variables and both forms of anxiety, but only in certain situations. These findings suggest that language background variables on their own may be insufficient to explain immigrant language anxiety in certain social contexts (i.e. within family). Rather than merely language background factors, a variety of other issues within social, cultural and national currents must be considered when examining language anxiety in the immigrant context. Implications: Taking an interdisciplinary approach that combines language contact and foreign language anxiety/second language anxiety research, this study suggests that the concept of foreign language anxiety/second language anxiety should be expanded beyond the confines of the classroom in order to include daily interactions immigrant or minority communities. Originality: This study contributes to the limited body of evidence on the topic of language anxiety in immigrant contexts and presents a new construct ‘majority language anxiety’

GESTIONE PERIOPERATORIA DEI BAMBINI AFFETTI DA NEUROBLASTOMA E IPERTENSIONE TUMORE-DIPENDENTE: STUDIO DEL GRUPPO ITALIANO DI CHIRURGIA ONCOLOGICA PEDIATRICA (GICOP).

Il Neuroblastoma (NB) con sintomatologia ipertensiva riveste un\u2019esigua percentuale dei tumori neuroblastici trattati ogni anno, attualmente in letteratura esistono unicamente due studi (1,2), che riportano un\u2019incidenza di sintomatologia ipertensiva del 10-19% dei casi. Il follow-up dei pazienti studiati risulta breve, inoltre il meccanismo fisiopatologico non \ue8 stato tuttora dimostrato, ipotizzando una combinazione tra la compressione del peduncolo vascolare renale e la secrezione di catecolamine urinarie. Per quanto riguarda il management intra-operatorio, che pu\uf2 risultare difficoltoso a causa di picchi iper\ipotensivi durante la manipolazione della massa, esistono unicamente case reports (3,4). Lo scopo dello studio \ue8 valutare l\u2019approccio diagnostico e la gestione perioperatoria del bambino affetto da NB con sintomatologia ipertensiv