In vivo restoration of dystrophin expression in mdx mice using intra-muscular and intra-arterial injections of hydrogel microsphere carriers of exon skipping antisense oligonucleotides

Duchenne muscular dystrophy (DMD) is a genetic disease caused by a mutation in the X-linked Dytrophin gene preventing the expression of the functional protein. Exon skipping therapy using antisense oligonucleotides (AONs) is a promising therapeutic strategy for DMD. While benefits of AON therapy have been demonstrated, some challenges remain before this strategy can be applied more comprehensively to DMD patients. These include instability of AONs due to low nuclease resistance and poor tissue uptake. Delivery systems have been examined to improve the availability and stability of oligonucleotide drugs, including polymeric carriers. Previously, we showed the potential of a hydrogel-based polymeric carrier in the form of injectable PEG-fibrinogen (PF) microspheres for delivery of chemically modified 2'-O-methyl phosphorothioate (2OMePs) AONs. The PF microspheres proved to be cytocompatible and provided sustained release of the AONs for several weeks, causing increased cellular uptake in mdx dystrophic mouse cells. Here, we further investigated this delivery strategy by examining in vivo efficacy of this approach. The 2OMePS/PEI polyplexes loaded in PF microspheres were delivered by intramuscular (IM) or intra-femoral (IF) injections. We examined the carrier biodegradation profiles, AON uptake efficiency, dystrophin restoration, and muscle histopathology. Both administration routes enhanced dystrophin restoration and improved the histopathology of the mdx mice muscles. The IF administration of the microspheres improved the efficacy of the 2OMePS AONs over the IM administration. This was demonstrated by a higher exon skipping percentage and a smaller percentage of centered nucleus fibers (CNF) found in H&E-stained muscles. The restoration of dystrophin expression found for both IM and IF treatments revealed a reduced dystrophic phenotype of the treated muscles. The study concludes that injectable PF microspheres can be used as a carrier system to improve the overall therapeutic outcomes of exon skipping-based therapy for treating DMD

RNAlysis: analyze your RNA sequencing data without writing a single line of code

Abstract Background Among the major challenges in next-generation sequencing experiments are exploratory data analysis, interpreting trends, identifying potential targets/candidates, and visualizing the results clearly and intuitively. These hurdles are further heightened for researchers who are not experienced in writing computer code since most available analysis tools require programming skills. Even for proficient computational biologists, an efficient and replicable system is warranted to generate standardized results. Results We have developed RNAlysis, a modular Python-based analysis software for RNA sequencing data. RNAlysis allows users to build customized analysis pipelines suiting their specific research questions, going all the way from raw FASTQ files (adapter trimming, alignment, and feature counting), through exploratory data analysis and data visualization, clustering analysis, and gene set enrichment analysis. RNAlysis provides a friendly graphical user interface, allowing researchers to analyze data without writing code. We demonstrate the use of RNAlysis by analyzing RNA sequencing data from different studies using C. elegans nematodes. We note that the software applies equally to data obtained from any organism with an existing reference genome. Conclusions RNAlysis is suitable for investigating various biological questions, allowing researchers to more accurately and reproducibly run comprehensive bioinformatic analyses. It functions as a gateway into RNA sequencing analysis for less computer-savvy researchers, but can also help experienced bioinformaticians make their analyses more robust and efficient, as it offers diverse tools, scalability, automation, and standardization between analyses

Empiric Usage of “Anti-Pseudomonal” Agents for Hospital-Acquired Urinary Tract Infections

Hospital-acquired urinary tract infection (HAUTI) is one of the most common hospital-acquired infections, and over 80% of HAUTI are catheter-associated (CAUTI). Pseudomonas aeruginosa, as well as other non-glucose fermenting Gram negative organisms (NGFGN, e.g., Acinetobacter baumannii), are frequently covered empirically with “anti-Pseudomonals” being administered for every HAUTI (and CAUTI). However, this common practice was never trialed in controlled settings in order to quantify its efficacy and its potential impacts on hospitalization outcomes. There were 413 patients with HAUTI that were included in this retrospective cohort study (2017–2018), 239 (57.9%) had CAUTI. There were 75 NGFGN infections (18.2% of HAUTI, 22.3% of CAUTI). P. aeruginosa was the most common NGFGN (82%). Despite multiple associations per univariable analysis, recent (3 months) exposure to antibiotics was the only independent predictor for NGFGN HAUTI (OR = 2.4, CI-95% = 1.2–4.8). Patients who received empiric anti-Pseudomonals suffered from worse outcomes, but in multivariable models (one for each outcome), none were independently associated with the empiric administration of anti-Pseudomonals. To conclude, approximately one of every five HAUTI (and CAUTI) are due to NGFGN, which justifies the practice of empiric anti-Pseudomonals for patients with HAUTI (and CAUTI), particularly patients who recently received antibiotics. The practice is not associated with independent deleterious impacts on outcomes

The Epidemiology of Multidrug-Resistant Sepsis among Chronic Hemodialysis Patients

Sepsis is one of the leading causes of hospitalization and death among hemodialysis patients. Infections due to multidrug-resistant organisms (MDROs) are common among these patients, but empiric broad-spectrum coverage for every septic patient is associated with unfavorable outcomes. A retrospective case–control study was conducted at Shamir Medical Center, Israel (July 2016–April 2020), to determine predictors of MDRO infections among septic (per SEPSIS-3) ambulatory adult hemodialysis patients with permanent dialysis access (i.e., fistula, graft, or tunneled Perm-A-Cath). MDROs were determined according to established definitions. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to construct a prediction score and determine its performance. Of 509 patients, 225 (44%) had microbiologically confirmed infection, and 79 patients (35% of 225) had MDROs. The eventual independent predictors of MDRO infections were Perm-A-Cath access (vs. fistula or graft, aOR = 3, CI-95% = 2.1–4.2) and recent hospitalization in the previous three months (aOR = 2.3, CI-95% = 1.6–3.3). The score to predict MDRO sepsis with the highest performances contained seven parameters and displayed an area under the receiver operating characteristic curve (ROC AUC) of 0.74. This study could aid in defining a group of hemodialysis patients for which empiric broad-spectrum agents could be safely avoided

The Impact of Differences in Surveillance Definitions of Hospital Acquired Urinary Tract Infections (HAUTI)

Hospital-acquired urinary tract infections (HAUTI) are common and most cases are related to catheters (CAUTI). HAUTI and CAUTI surveillance is mandatory in many countries as a measure to reduce the incidence of infections and appropriately direct the allocation of preventable resources. The surveillance criteria issued by the Israeli Ministry of Health (IMOH), differ somewhat from that of the U.S. Centers for Disease Control and Prevention (CDC). Our study aims were to query and quantify the impact of these differences. In a retrospective cohort study conducted at Shamir Medical Center, for calendar year 2017, the surveillance criteria of both IMOH and CDC were applied on 644 patient-unique adults with “positive” urine cultures (per similar definitions). The incidence of HAUTI per IMOH was significantly higher compared to CDC (1.24/1000 vs. 1.02/1000 patient-days, p = 0.02), with no impact on hospitalization’s outcomes. The agreement rate between methods was high for CAUTI (92%), but much lower for all HAUTI (83%). The major error rate, i.e., patients diagnosed with HAUTI per IMOH but had no UTI per CDC, was 31%. To conclude, in order for surveillance to reflect the relative situation and direct allocation of preventable resources based on scientific literature, the process should be uniform worldwide

Rapid implementation of teledentistry during the Covid-19 lockdown

Introduction: The current corona virus disease 2019 (COVID-19) outbreak set new challenges to nearly all health plans and large health organizations worldwide, including movement restrictions, strict limitations in healthcare services, especially in the dental profession, and patient fears regarding potential infection. Telehealth can serve as an effective platform for remote connection between dental healthcare providers and patients, and can help reduce the risk of infection when social distancing is required. Objective: The current study aimed to evaluate the quality of treatment provided via teledentistry, as perceived by patients using the service, as well as their willingness to use online distant medical consultation in the future. Methods: Since March 2020, a new online service was implemented in the Oral Medicine Unit and Oral and Maxillofacial Surgery Department in the Galilee Medical Center, to expand the range of services beyond merely emergency treatments. Results: The current study examined the quality of teledentistry services as perceived by 89 patients participating in at least one teleconsultation, and their acceptance of remote healthcare. Satisfaction rates were high in patients who received both full and partial solution to their chief complaint. Moreover, acceptance of the teledentistry platform was high, even in the older age groups. Conclusions: We propose to implement teledentistry services in current and future pandemics, as well as during routine times, to strengthen our health care system with digital technologies

Hacia una formación europea de la medicina china: su incorporación en el sistema universitario español

L'Acupuntura i la Medicina Tradicional Xina existeixen des de fa milers d'anys al seu país d'origen i àrea d'influència. A occident, aquestes disciplines s’han anat introduint gradualment, tot i així no és fins els últims 40 anys que la seva implantació ha aconseguit gran notorietat. Aquest fet ha generat una controvèrsia que va des de els seus més acèrrims defensors fins als detractors més entossudits, basant-se uns en les seves bondats i els altres en la seva falta d'evidència científica. L'Estratègia de l'OMS 2014-2023 sobre Medicina tradicional insta als països membres a la seva regulació, com a pas previ a la seva incorporació als Sistemes Nacionals de Salut de cada país. Encara així, la controvèrsia persisteix, si bé en els últims anys hem vist com es regulava en països com els EUA, Austràlia, Xile, Portugal, etc., en altres països està en procés de regulació més o menys avançada. En la present recerca es pretén, des de l'anàlisi de l'estat de la qüestió als diferents països del món i a Espanya, poder verificar si, com pensem, existeix una tendència a la regulació de la MTC de manera autònoma respecte de la medicina al·lopàtica occidental, al mateix temps que avança la pràctica de la denominada “medicina xinesa integrativa” (combinació de la medicina xinesa i la medicina al·lopàtica occidental) i els projectes d’investigació sobre aquest tema. 5 Aquest anàlisis ens ha de permetre inferir quin hauria de ser la seva ubicació en el sistema Universitari espanyol, en el marc del sistema educatiu europeu. A més a més, hem realitzat una recopilació i anàlisi comparada de la normativa existent en aquells països en els quals existeix regulació sobre aquest tema. Una revisió de la bibliografia existent (fonamentalment articles en revistes especialitzades, ponències en Congressos, estudis del sector i dades qualitatives i quantitatives publicades per organismes públics i organitzacions locals, nacionals i internacionals). Una revisió de sentències per intrusisme i de l'ordre contenciós administratiu a Espanya. I, finalment, una revisió d'estudis indicatius de la utilització de la MTC per la ciutadania. El treball s'ha dividit en vuit apartats: introducció, interdisciplinarietat de la recerca, anàlisi històrica-antropològica de la MTC a Xina, definicions i conceptes bàsics, evidències científiques, situació legal i real de l'exercici professional i els estudis de medicina xinesa als diferents països i a Espanya, situació dels estudis oficials sanitaris a Espanya, i conclusions i noves línies de recerca. La present recerca no pot ser més oportuna, ja que al moment de finalitzar la mateixa, s'acaba d'obrir a Espanya un debat sobre les medicines naturals, conseqüència de la presentació d'un Projecte No de Llei per part del partit polític Ciutadans sobre la necessitat de controlar el que ells criden “pseudociències”, posant en el mateix sac tot tipus de teràpies. Aquest fet sens dubte hauria d'acabar potenciant la regulació dels estudis (i per tant la pràctica professional) d'aquelles medicines naturals que acreditin la seva utilitat com a únic mecanisme de control eficaç per assegurar l'eficàcia, eficiència i seguretat dels seus tractaments per a la ciutadania.La Acupuntura y la Medicina Tradicional China existen desde hace miles de años en su país de origen y área de influencia. En occidente, se han ido introduciendo gradualmente, sin embargo, no es hasta los últimos 40 años que su implantación ha alcanzado gran notoriedad. Este hecho ha generado una controversia que va desde sus más acérrimos defensores hasta los detractores más empecinados, basándose unos en sus bondades y los otros en su falta de evidencia científica. La Estrategia de la OMS 2014-2023 sobre Medicina tradicional insta a los países miembros a su regulación, como paso previo a su incorporación en los Sistemas Nacionales de Salud de cada país. Aun así, la controversia persiste, si bien en los últimos años hemos visto como se regulaba en países como EEUU, Australia, Chile, Portugal, etc., en otros países está en proceso de regulación más o menos avanzada. En la presente investigación se pretende, desde el análisis del estado de la cuestión en los diferentes países del mundo y en España, poder verificar si, como pensamos, existe una tendencia a la regulación de las MTC de manera autónoma respecto de la medicina alopática occidental, al tiempo que avanza la práctica de la denominada “medicina china integrativa” (combinación de la medicina china y la medicina alopática occidental) y los proyectos de investigación al respecto. Este análisis nos ha de permitir inferir cuál debería ser su ubicación en el sistema Universitario español, en el marco del sistema educativo europeo. Además, hemos realizado una recopilación y análisis comparado de la normativa existente en aquellos países en los que existe regulación al respecto. Una revisión de la bibliografía existente (fundamentalmente artículos en revistas especializadas, ponencias en Congresos, estudios del sector y datos cualitativos y cuantitativos publicados por organismos públicos y organizaciones locales, nacionales e internacionales). Una revisión de sentencias por intrusismo y del orden contencioso administrativo en España. Y, por último, una revisión de estudios indicativos de la utilización de la MTC por la ciudadanía. El trabajo se ha dividido en ocho apartados: introducción, interdisciplinariedad de la investigación, análisis histórico-antropológico de la MTC en China, definiciones y conceptos básicos, evidencias científicas, situación legal y real del ejercicio profesional y 4 los estudios de medicina china en los diferentes países y en España, situación de los estudios oficiales sanitarios en España, y conclusiones y nuevas líneas de investigación. La presente investigación no puede ser más oportuna puesto que en el momento de finalizar la misma se acaba de abrir en España un debate sobre las medicinas naturales, consecuencia de la presentación de un Proyecto No de Ley por parte del partido político Ciudadanos, sobre la necesidad de controlar lo que ellos llaman “pseudociencias”, poniendo en el mismo saco todo tipo de terapias. Este hecho sin duda debería acabar potenciando la regulación de los estudios (y por ende la práctica profesional) de aquellas medicinas naturales que acrediten su utilidad como único mecanismo de control eficaz para asegurar la eficacia, eficiencia y seguridad de sus tratamientos para la ciudadanía.Acupuncture and Traditional Chinese Medicine have existed for thousands of years in their country of origin and area of influence. In the West, they have been introduced gradually, however it is not until the last 40 years that its implementation has achieved great notoriety. This fact has generated a controversy that goes from its most staunch defenders to the most stubborn detractors, the former based on its benefits and the latter based on its lack of scientific evidence. The WHO Strategy 2014-2023 on Traditional Medicine urges member countries to regulate it, as a step prior to their incorporation into the National Health Systems of each country. Even so, the controversy persists, although in recent years we have seen how it was regulated in countries like USA, Australia, Chile, Portugal, etc., in other countries it is in process of regulation more or less advanced. In the present investigation, it is intended, from the analysis of the situation of the topic in the different countries of the world and in Spain, to verify if, as we thought, there is a tendency to regulate TCM independently of Western allopathic medicine, at the same time as the practice of so-called "integrative Chinese medicine" (a combination of Chinese medicine and Western allopathic medicine) is progressing and the research projects on the subject. This analysis should allow us to infer what should be its location in the Spanish university system, within the framework of the European educational system. In addition, we have compiled and compared the existing regulations in those countries where there is regulation in this regard. A review of the existing bibliography (mainly articles in specialized journals, papers in Congresses, studies of the sector and qualitative and quantitative data published by public organisms and local, national and international organizations). A revision of sentences by professional intrusion and of the administrative contentious order in Spain. And, finally, a review of studies indicative of the use of the MTC by the citizenship. The work has been divided into eight sections: introduction, interdisciplinary research, historical-anthropological analysis of TCM in China, basic definitions and concepts, scientific evidence, legal and real situation of professional practice and studies of Chinese medicine in different Countries and in Spain, status of official health studies in Spain, and conclusions and new lines of research. This research could not be timelier because at the end of its completion, there has just opened in Spain a debate on natural medicines, a consequence of the presentation of a non-binding motion by the political party Citizens, on the necessity to control what they call "pseudoscience", putting in the same bag all kinds of therapies. This fact should undoubtedly strengthen the regulation of studies (and therefore the professional practice) of those natural medicines that prove their utility as the only effective control mechanism to ensure the effectiveness, efficiency and safety of their treatments for citizen