Endoscopic pilonidal sinus treatment versus total excision with primary closure for sacrococcygeal pilonidal sinus disease in the pediatric population

Purpose: To evaluate the effectiveness and safety of Endoscopic Pilonidal Sinus Treatment (EPSiT) in the pediatric population and compare it with excision followed by primary closure (EPC) regarding intra- and postoperative outcomes. Methods: A retrospective analysis of all patients with chronic sacrococcygeal pilonidal sinus submitted to EPSiT and EPC during a 12-month period in our institution was performed. Data concerning patients' demographics and surgical outcomes were collected and compared between the two groups. Results: We analyzed a total of 21 cases that underwent EPSiT and 63 cases of EPC, both groups with similar demographic characteristics. Operative time was similar for both groups (30 vs. 38 min; p > 0.05). No major intraoperative complications were reported. Wound infection rate was lower for EPSiT ((5.2% [n = 1] vs. 20.0% [n = 12]); p > 0.05). Healing time was similar for both groups (28 vs. 37.5 days). Recurrence occurred in 18,9% (n = 15), with 2 cases (10.5%) reported in the EPSiT group versus 13 (21.6%) in EPC. There were no differences between groups regarding postoperative complications, complete wound healing and recurrence rates or healing time (p > 0.05). Conclusions: Our results suggest that EPSiT is as viable as excision followed by primary closure in the management of sacrococcygeal pilonidal sinus in the pediatric population

Emerging biosensing technologies for neuroinflammatory and neurodegenerative disease diagnostics

Neuroinflammation plays a critical role in the onset and progression of many neurological disorders, including Multiple Sclerosis, Alzheimer’s and Parkinson’s diseases. In these clinical conditions the underlying neuroinflammatory processes are significantly heterogeneous. Nevertheless, a common link is the chronic activation of innate immune responses and imbalanced secretion of pro and anti-inflammatory mediators. In light of this, the discovery of robust biomarkers is crucial for screening, early diagnosis, and monitoring of neurological diseases. However, the difficulty to investigate biochemical processes directly in the central nervous system (CNS) is challenging. In recent years, biomarkers of CNS inflammatory responses have been identified in different body fluids, such as blood, cerebrospinal fluid, and tears. In addition, progress in micro and nanotechnology has enabled the development of biosensing platforms capable of detecting in real-time, multiple biomarkers in clinically relevant samples. Biosensing technologies are approaching maturity where they will become deployed in community settings, at which point screening programs and personalized medicine will become a reality. In this multidisciplinary review, our goal is to highlight both clinical and recent technological advances toward the development of multiplex-based solutions for effective neuroinflammatory and neurodegenerative disease diagnostics and monitoring.IM and AC acknowledge the financial support from the Marie Curie COFUND Programme Nano TRAIN for Growth from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no 600375. This article is a result of the project Nanotechnology based functional solutions (FEDERNORTE-01-0145-FEDER-000019), co-financed by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). PM acknowledges the Ph.D. fellowship from Fundação para a Ci?ncia e Tecnologia, Portugal (PD/BD/105751/2014)

mitoTALEN Eliminates Mutant mtDNA Genomes in Neurons

Mutations in the mitochondrial DNA (mtDNA) commonly cause severe encephalopathies. Because most of these mtDNA alterations are heteroplasmic, we used a mitochondrial-targeted TALEN (mitoTALEN) to specifically eliminate the mutant mtDNA in the CNS of a mouse model harboring a heteroplasmic mutation in the mitochondrial tRNA alanine gene (m.5024C>T). Delivery to neurons was achieved by using AAV-PHP.eB and neuronal expression was obtained by using a neuronal-specific synapsin promoter. We found that most CNS regions were effectively transduced and showed a significant reduction in mutant mtDNA. This reduction was accompanied by an increase in mitochondrial tRNA alanine level, which is drastically reduced by the mutation. These results showed, for the first time, that mitochondrial-targeted gene editing can be effective in reducing CNS mutant mtDNA in vivo, paving the way for clinical trials in patients with mitochondrial encephalopathies

Effective detection of human leukocyte antigen risk alleles in celiac disease using tag single nucleotide polymorphisms.

Background: The HLA genes, located in the MHC region on chromosome 6p21.3, play an important role in many autoimmune disorders, such as celiac disease (CD), type 1 diabetes (T1D), rheumatoid arthritis, multiple sclerosis, psoriasis and others. Known HLA variants that confer risk to CD, for example, include DQA1*05/DQB1*02 (DQ2.5) and DQA1*03/ DQB1*0302 (DQ8). To diagnose the majority of CD patients and to study disease susceptibility and progression, typing these strongly associated HLA risk factors is of utmost importance. However, current genotyping methods for HLA risk factors involve many reactions, and are complicated and expensive. We sought a simple experimental approach using tagging SNPs that predict the CD-associated HLA risk factors. Methodology: Our tagging approach exploits linkage disequilibrium between single nucleotide polymorphism (SNPs) and the CD-associated HLA risk factors DQ2.5 and DQ8 that indicate direct risk, and DQA1*0201/DQB1*0202 (DQ2.2) and DQA1*0505/DQB1*0301 (DQ7) that attribute to the risk of DQ2.5 to CD. To evaluate the predictive power of this approach, we performed an empirical comparison of the predicted DQ types, based on these six tag SNPs, with those executed with current validated laboratory typing methods of the HLA-DQA1 and -DQB1 genes in three large cohorts. The results were validated in three European celiac populations. Conclusion: Using this method, only six SNPs were needed to predict the risk types carried by .95% of CD patients. We determined that for this tagging approach the sensitivity was .0.991, specificity .0.996 and the predictive value .0.948. Our results show that this tag SNP method is very accurate an

RNA editing signature during myeloid leukemia cell differentiation

Adenosine deaminases acting on RNA (ADARs) are key proteins for hematopoietic stem cell self-renewal and for survival of differentiating progenitor cells. However, their specific role in myeloid cell maturation has been poorly investigated. Here we show that ADAR1 is present at basal level in the primary myeloid leukemia cells obtained from patients at diagnosis as well as in myeloid U-937 and THP1 cell lines and its expression correlates with the editing levels. Upon phorbol-myristate acetate or Vitamin D3/granulocyte macrophage colony-stimulating factor (GM-CSF)-driven differentiation, both ADAR1 and ADAR2 enzymes are upregulated, with a concomitant global increase of A-to-I RNA editing. ADAR1 silencing caused an editing decrease at specific ADAR1 target genes, without, however, interfering with cell differentiation or with ADAR2 activity. Remarkably, ADAR2 is absent in the undifferentiated cell stage, due to its elimination through the ubiquitin–proteasome pathway, being strongly upregulated at the end of the differentiation process. Of note, peripheral blood monocytes display editing events at the selected targets similar to those found in differentiated cell lines. Taken together, the data indicate that ADAR enzymes play important and distinct roles in myeloid cells

Core components for effective infection prevention and control programmes: new WHO evidence-based recommendations

Abstract Health care-associated infections (HAI) are a major public health problem with a significant impact on morbidity, mortality and quality of life. They represent also an important economic burden to health systems worldwide. However, a large proportion of HAI are preventable through effective infection prevention and control (IPC) measures. Improvements in IPC at the national and facility level are critical for the successful containment of antimicrobial resistance and the prevention of HAI, including outbreaks of highly transmissible diseases through high quality care within the context of universal health coverage. Given the limited availability of IPC evidence-based guidance and standards, the World Health Organization (WHO) decided to prioritize the development of global recommendations on the core components of effective IPC programmes both at the national and acute health care facility level, based on systematic literature reviews and expert consensus. The aim of the guideline development process was to identify the evidence and evaluate its quality, consider patient values and preferences, resource implications, and the feasibility and acceptability of the recommendations. As a result, 11 recommendations and three good practice statements are presented here, including a summary of the supporting evidence, and form the substance of a new WHO IPC guideline

Diallel analysis and inbreeding depression of commercial maize hybrids aiming the formation of base populations

The development of base populations derived from high yield commercial hybrids is considered one of the main strategies to initiate a maize breeding program, mainly because these hybrids have already been tested in many environments, and so, associating high yield and a large proportion of favorable loci fixed. Therefore, the objective of the present study is to estimate the combining abilities and inbreeding depression of commercial maize hybrids for agronomic traits. Eighteen commercial hybrids divided in two groups accordingly to their respective companies, seventy-two F combinations from a partial diallel scheme, eighteen S populations and one check were evaluated in a randomized complete block design in two experiments, both in Sementes Balu Experimental Unit, Sabáudia (PR), Brazil, for growing seasons from 2011/2012 and 2012/2013. The Griffing method (1956), adapted to a partial diallel by Geraldi and Miranda Filho (1988) was applied for the evaluation of the general com- bining ability (GCA) and specific combining ability (SCA). The hybrids P1630, P4285, 30B39Y and DKB370 showed increased yield, and hybrids P1630, 32R22H, and DKB615 showed reduced plant and ear height. These hybrids can be recommended for the extraction of inbred lines and formation of composites followed by intrapopulation selection. The combinations P1630 x DKB330, P4285 x DKB245, 30F53 x DKB370, and 32R22H x DKB370 showed desirable SCA effects for grain yield and are recommended for use in interpopulation breeding programs. Among the hybrids with desirable GCA effects, 30B39Y showed the lowest inbreeding depression effect for the analyzed traits