Deep self-supervised learning for biosynthetic gene cluster detection and product classification.

Natural products are chemical compounds that form the basis of many therapeutics used in the pharmaceutical industry. In microbes, natural products are synthesized by groups of colocalized genes called biosynthetic gene clusters (BGCs). With advances in high-throughput sequencing, there has been an increase of complete microbial isolate genomes and metagenomes, from which a vast number of BGCs are undiscovered. Here, we introduce a self-supervised learning approach designed to identify and characterize BGCs from such data. To do this, we represent BGCs as chains of functional protein domains and train a masked language model on these domains. We assess the ability of our approach to detect BGCs and characterize BGC properties in bacterial genomes. We also demonstrate that our model can learn meaningful representations of BGCs and their constituent domains, detect BGCs in microbial genomes, and predict BGC product classes. These results highlight self-supervised neural networks as a promising framework for improving BGC prediction and classification.

Common data elements for arthrogryposis multiplex congenita: An international framework.

AIM: To facilitate multisite studies and international clinical research, this study aimed to identify consensus-based, standardized common data elements (CDEs) for arthrogryposis multiplex congenita (AMC). METHOD: A mixed-methods study comprising of several focus group discussions and three rounds of modified Delphi surveys to achieve consensus using two tiered-rating scales were conducted. RESULTS: Overall, 45 clinical experts and adults with lived experience (including 12 members of an AMC consortium) participated in this study from 11 countries in North America, Europe, and Australia. The CDEs include 321 data elements and 19 standardized measures across various domains from fetal development to adulthood. Data elements pertaining to AMC phenotypic traits were mapped according to the Human Phenotype Ontology. A universal governance structure, local operating protocols, and sustainability plans were identified as the main facilitators, whereas limited capacity for data sharing and the need for a federated informatics infrastructure were the main barriers. INTERPRETATION: Collection of systematic data on AMC using CDEs will allow investigations on etiological pathways, describe epidemiological profile, and establish genotype-phenotype correlations in a standardized manner. The proposed CDEs will facilitate international multidisciplinary collaborations by improving large-scale studies and opportunities for data sharing, knowledge translation, and dissemination.

Modulation of Synaptic Plasticity Genes Associated to DNA Damage in a Model of Huntington's Disease.

Huntington's disease (HD) is a disease characterized by the progressive degeneration of nerve cells in the brain. DNA damage has been implicated in many neurological disorders; however, the association between this damage and the impaired signaling related to neurodegeneration is still unclear. The transcription factor c-AMP-responsive element binding protein (CREB) has a relevant role in the neuronal plasticity process regulating the expression of several genes, including brain-derived neurotrophic factor (BDNF). Here we analyzed the direct link between DNA damage and the expression of genes involved in neuronal plasticity. The study was performed in model cell lines STHdhQ7 (wild type) and STHdhQ111 (HD model). Treatment with Etoposide (Eto) was used to induce double-strand breaks (DSBs) to evaluate the DNA damage response (DDR) and the expression of synaptic plasticity genes. Eto treatment induced phosphorylation of ATM (p-ATM) and H2AX (γH2AX), markers of DDR, in both cell lines. Interestingly, upon DNA damage, STHdhQ7 cells showed increased expression of activity-regulated cytoskeleton associated protein (Arc) and BDNF when compared to the HD cell line model. Additionally, Eto induced CREB activation with a differential localization of its co-activators in the cell types analyzed. These results suggest that DSBs impact differentially the gene expression patterns of plasticity genes in the normal cell line versus the HD model. This effect is mediated by the impaired localization of CREB-binding protein (CBP) and histone acetylation in the HD model. Our results highlight the role of epigenetics and DNA repair on HD and therefore we suggest that future studies should explore in depth the epigenetic landscape on neuronal pathologies with the goal to further understand molecular mechanisms and pinpoint therapeutic targets.

Changes in general and abdominal obesity in children at 4, 6 and 9 years of age and their association with other cardiometabolic risk factors.

Temporary changes in childhood obesity and their association with cardiometabolic risk factors have been receiving increased attention. The objective of this study was to evaluate changes in general (GO) and abdominal (AO) obesity in children from 4 to 9 years of age and their associations with cardiometabolic risk factors at 9 years of age. This study includes 1344 children from the Longitudinal Childhood Obesity Study (ELOIN). Physical examinations performed at 4, 6 and 9 years of age and a blood sample was only taken at 9 years of age. Changes in obesity from 4 to 9 years of age were estimated using Body Mass Index and waist circumference. Participants were classified into four groups according to GO and AO: (1) stable without obesity (no obesity at all three measurements); (2) remitting obesity at 9 years (obesity at 4 and/or 6 years but not at 9 years); (3) incident or recurrent obesity at 9 years (obesity only at 9 years, at 4 and 9 years or at 6 and 9 years); and (4) stable or persistent with obesity (obesity at 4, 6 and 9 years). Dyslipidemia and dysglycemia were defined by the presence of at least one altered parameter of the lipid or glycemic profile. Odds ratios (OR) were estimated using logistic regression. Compared with children without GO at all ages, those with persistent GO had an OR of 3.66 (95% CI: 2.06-6.51) for dyslipidemia, 10.61 (95% CI: 5.69-19.79) for dysglycemia and 8.35 (95% CI: 4.55-15.30) for high blood pressure. The associations were fairly similar in the case of AO, with ORs of 3.52 (95% CI: 1.96-6.34), 17.15 (95% CI: 9.09-32.34) and 8.22 (95% CI: 4.46-15.15), respectively, when comparing persistent versus stable without AO. Children with incident obesity at 9 years presented a moderate cardiometabolic risk that was nevertheless higher compared to those stable without obesity, whereas those with remitting obesity did not show any significant associations. CONCLUSION: Incident, and especially, persistent obesity, is associated with an increased cardiometabolic risk. The very early prevention of obesity, with a focus on nutrition, physical activity and sedentary behaviour, as well as tracking growth from birth to age 5, should be a priority to prevent the burden of cardiometabolic disease with consequences for adulthood. WHAT IS KNOWN: • General and abdominal obesity has been shown to be associated with other cardiometabolic risk factors such as dyslipidemia, insulin resistance and hypertension. • Temporary changes in obesity and their associations with cardiometabolic risk factors have not been sufficiently explored in childhood. WHAT IS NEW: • Children with incident, and especially persistent, general and/or abdominal obesity, had an increased risk of dyslipidemia, dysglycemia and high blood pressure. •Remitting obesity was not associated with an increased cardiometabolic risk.

Persistently expressed human chorionic gonadotropin induces premature luteinization and progressive alterations on the reproductive axis in female mice.

The hypothalamic-pituitary-gonadal axis plays a fundamental role in the endocrine regulation of the reproductive function in mammals. Any change in the function of the participating hormones or their receptors can lead to alterations in sexual differentiation, the onset of puberty, infertility, cancer development, and other dysfunctions. In this study, we analyzed the influence of persistently elevated levels of the human chorionic gonadotropin hormone (hCG), a powerful agonist of pituitary luteinizing hormone (LH), on the reproductive axis of female mice. As a consequence of chronic hCG hypersecretion through a global expression of the hCGbeta-subunit in transgenic (TG) female mice, a series of events perturbed the prepubertal to juvenile transition. The imbalance in gonadotropin action was first manifested by precocious puberty and alterations in gonadal hormone production, with the consequent ovarian function disruption and infertility in adulthood. The expansion of cumulus cells in vivo and in vitro, ovulatory capacity, and gene expression of ovulation-related marker genes after hormone stimulation were normal in 3-week-old TG females. However, the expression of genes related to steroidogenesis and luteinization such as Lhcgr, Prlr, and the steroidogenic enzymes Cyp11a1, Cyp17a1, and Cyp19a1 were significantly elevated in the TG females. This study demonstrates that the excessive secretion of hCG in concert with high prolactin, induced premature luteinization, and enhanced ovarian steroidogenesis, as was shown by the up-regulation of luteal cell markers and progesterone synthesis in the TG mice. Furthermore, progressively impaired reproductive function of the TG females occurred from the peripubertal stage to adulthood, thus culminating in infertility.

Current Trends of Bacterial and Fungal Optoproteins for Novel Optical Applications.

Photoproteins, luminescent proteins or optoproteins are a kind of light-response protein responsible for the conversion of light into biochemical energy that is used by some bacteria or fungi to regulate specific biological processes. Within these specific proteins, there are groups such as the photoreceptors that respond to a given light wavelength and generate reactions susceptible to being used for the development of high-novel applications, such as the optocontrol of metabolic pathways. Photoswitchable proteins play important roles during the development of new materials due to their capacity to change their conformational structure by providing/eliminating a specific light stimulus. Additionally, there are bioluminescent proteins that produce light during a heatless chemical reaction and are useful to be employed as biomarkers in several fields such as imaging, cell biology, disease tracking and pollutant detection. The classification of these optoproteins from bacteria and fungi as photoreceptors or photoresponse elements according to the excitation-emission spectrum (UV-Vis-IR), as well as their potential use in novel applications, is addressed in this article by providing a structured scheme for this broad area of knowledge.

An Overview of the Role of MicroRNAs on Carcinogenesis: A Focus on Cell Cycle, Angiogenesis and Metastasis.

In recent years, the importance of epigenetic markers in the carcinogenesis of different malignant neoplasms has been demonstrated, also demonstrating their utility for understanding metastatic spread and tumor progression in cancer patients. Among the different biomarkers, microRNAs represent a set of non-coding RNAs that regulate gene expression, having been involved in a wide variety of neoplasia acting in different oncogenic pathways. Both the overexpression and downregulation of microRNAs represent a complex interaction with various genes whose ultimate consequence is increased cell proliferation, tumor invasion and interaction with various driver markers. It should be noted that in current clinical practice, even though the combination of different microRNAs has been shown to be useful by different authors at diagnostic and prognostic levels, there are no diagnostic kits that can be used for the initial approach or to assess recurrences of oncological diseases. Previous works have cited microRNAs as having a critical role in several carcinogenic mechanisms, ranging from cell cycle alterations to angiogenesis and mechanisms of distant metastatic dissemination. Indeed, the overexpression or downregulation of specific microRNAs seem to be tightly involved in the modulation of various components related to these processes. For instance, cyclins and cyclin-dependent kinases, transcription factors, signaling molecules and angiogenic/antiangiogenic products, among others, have been recognized as specific targets of microRNAs in different types of cancer. Therefore, the purpose of this article is to describe the main implications of different microRNAs in cell cycle alterations, metastasis and angiogenesis, trying to summarize their involvement in carcinogenesis.

Burden of overweight and obesity in Mexico from 1990 to 2021.

BACKGROUND: Overweight and obesity (OW/OB) represent a serious challenge in Mexico, with effects on health, society and economy. Demographic, epidemiological, nutritional, social and economic factors have exacerbated this problem. OBJECTIVE: To analyze mortality and years of healthy life lost in Mexico due to OW/OB in the 1990-2021 period. MATERIAL AND METHODS: The Global Burden of Disease and Risk Factors 2021 study was used to analyze data on elevated body mass index (BMI) as a risk factor and its evolution in Mexico. RESULTS: In 2021, 118 thousand deaths attributable to high BMI were recorded, which accounted for 10.6% of total deaths and more than 4.2 million disability-adjusted life years lost. CONCLUSIONS: The obesogenic environment, influenced by social determinants of health, has had a significant impact on mortality, burden of disease, and economic costs. Addressing OW/OB requires multisector interventions to strengthen the Mexican health system.

ANTECEDENTES: El sobrepeso y la obesidad constituyen un grave desafío en México, con efectos en la salud, sociedad y economía. Factores demográficos, epidemiológicos, nutricionales, sociales y económicos han agravado esta problemática. OBJETIVO: Analizar la mortalidad y los años de vida saludable perdidos en México por sobrepeso y obesidad en el período de 1990 a 2021. MATERIAL Y MÉTODOS: Se utilizó el Global Burden of Disease 2021 para analizar los datos sobre índice de masa corporal elevado como factor de riesgo y su evolución en México. RESULTADOS: En 2021 se registraron 118 mil muertes atribuibles a índice de masa corporal elevado, que representaron 10.6 % del total de muertes y más de 4.2 millones de años de vida perdidos ajustados por discapacidad. CONCLUSIONES: El ambiente obesogénico, influido por determinantes sociales, ha tenido un impacto significativo en la mortalidad, la carga de enfermedad y los costos económicos. Abordar el sobrepeso y la obesidad requiere intervenciones multisectoriales para fortalecer el sistema de salud mexicano.

Food grade nanoemulsion development to control food spoilage microorganisms on bread surface.

In this study, the effect of emulsifier mixture and their concentrations on the development of nanoemulsion was studied. The impact of sonication and microfluidization processing conditions on the physicochemical properties and in vitro antimicrobial activity was also evaluated. The optimal nanoemulsion formulation was then evaluated on bread surface against B. subtilis. Results showed that a hydrophilic-lipophilic balance HLB = 12 and emulsifier: oil ratio of 1:1 allowed the formation of stable nanoemulsion. Also, both microfluidization and sonication allowed the formation of nanoscale-emulsion. Sonication treatment for 10 min allowed a maintain the total flavonoid content and a slight reduction of total phenol content. Furthermore, employing sonication resulted to the lowest polydispersity index suggesting more stable nanoemulsion. Nanoscale-emulsion showed a good in vitro antimicrobial activity against L. monocytogenes and E. coli. The application of nanoemulsion on bread surface inoculated with B. subtilis showed a delay of the decay. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05660-5.

Parents can reliably and accurately detect trunk asymmetry using an inclinometer smartphone app.

PURPOSE: An inclinometer smartphone application has been developed to enable the measurement of the angle of trunk inclination (ATI) to detect trunk surface asymmetry. The objective was to determine the reliability and validity of the smartphone app in the hands of non-professionals. METHODS: Three non-professional observers and one expert surgeon measured maximum ATI twice in a study involving 69 patients seen in the spine clinics to rule out scoliosis or for regular follow-up (10-18 y.o., Cobb [0°-58°]). Observers were parents not familiar with scoliosis screening nor use of an inclinometer. They received training from a 4-minute video. Intra and inter-observer reliability was determined using the generalizability theory and validity was assessed from intraclass correlation coefficients (ICC), agreement with the expert on ATI measurements using Bland-Altman analysis, and correct identification of the threshold for consultation (set to ≥6° ATI). RESULTS: Intra-observer and inter-observer reliability coefficients were excellent ϕ = 0.92. The standard error of measurement was 1.5° (intra-observer, 2 measurements) meaning that a parent may detect a change of 4° between examinations 95% of the time. Comparison of measurements between non-professionals and the expert resulted in ICC varying from 0.82 [0.71-0.88] to 0.84 [0.74-0.90] and agreement on the decision to consult occurred in 83 to 90% of cases. CONCLUSION: The use of a smartphone app resulted in excellent reliability, sufficiently low standard error of measurement (SEM) and good validity in the hands of non-professionals. The device and the instructional video are adequate means to allow detection and regular examination of trunk asymmetries by non-professionals.

[Scores obtained by physicians in the national health services admission contest between 2016 and 2020]. / Resultados del sistema de puntuación del Concurso Nacional de Ingreso a los Servicios de Salud entre 2016 y 2020.

BACKGROUND: Medical specialists are an essential resource for the functioning of the health system and in Chile there is a growing deficit of these specialists. To address this shortage, the government has strategies for training health professionals, such as a national public contest for medical scholarships, named CONISS, which stands out for its high capacity to produce medical specialists. The scoring system of this contest is used for the allocation of training resources to the best candidates. AIM: To describe the results of the CONISS scoring system between 2016 and 2020. MATERIAL AND METHODS: Analysis of public registries of physicians participating in the CONISS contest between 2016 and 2020. RESULTS: During the study period 7,373 physicians participated in this contest (49% females). Annual participation increased progressively. The participants graduated from 21 Chilean universities and a variable number from foreign universities. The scores obtained by participants improved by 1.47 points between the first and last year of the study period. CONCLUSIONS: Interpretation of these results is complicated by the characteristics and limitations of the measurements of the CONISS scoring system. This precludes establishing whether this system effectively filters out the best candidates for medical specialization programs.

Effective glutamate clearance from the systemic circulation by hemodialysis: Potential relevance for cerebral ischemia management.

High glutamate levels after head trauma or cerebral ischemia have neurotoxic effects. The objective of the present study was to evaluate the efficacy of hemodialysis to remove glutamate from the blood and to assess the behavior of this small molecule. Ten patients with end-renal disease on hemodialysis were included in the study. Glutamate clearance was evaluated within the first hour of hemodialysis on a midweek dialysis day on five patients who underwent low flux hemodialysis, whereas the other five patients underwent highly efficient hemodialysis (high flux hemodialysis on one day and online hemodiafiltration on another day). Glutamate clearance with hemodialysis was very effective and did not show any differences between the techniques (low flux: 214 [55], high flux: 204 [37], online hemodiafiltration: 202 [16], median (interquartile range), P = .7). Glutamate clearance was almost equivalent to vascular access plasma flow and it was not affected by dialyzer permeability or ultrafiltration rate. After a hemodialysis session, a significant decrease in glutamate blood level was observed (prehemodialysis: 59.7 [36.1], posthemodialysis 37.0 [49.2], P = .005). Dialysis performed under fasting condition showed higher glutamate reduction rate (60%) than that under feeding condition (20%). Hemodialysis may be an effective method to reduce glutamate blood levels, and the molecule clearance does not differ between the different techniques used. Considering previous results in experimental models, hemodialysis without hemodynamic stress, could be considered for reducing glutamate neurotoxic effects in acute ischemic strokes of patients in chronic hemodialysis programs.

Meeting Treatment Goals in Patients on Extramural Dialysis in Health Social Security in Mexico.

INTRODUCTION: For the majority of renal replacement therapy history, the main treatment option for patients with end-stage renal disease (ESRD) in Mexico has been peritoneal dialysis. However, the use of hemodialysis is overwhelmingly increasing, driving public health care institutions to subrogate this service. Even when the actual hiring model for subrogation is accurate, there is a lack of quality control points in the hemodialysis prescription, poor adherence to clinical practice guidelines, and a few or no record of outcomes in hemodialysis patients of these subrogated services. The objective of this work is to fill this information gap to allow for uniform and safe hemodialysis for patients of Mexico. MATERIAL AND METHODS: An observational and cross-sectional study was performed, including all patients receiving chronic hemodialysis treatment in subrogated units of Mexican Social Security Institute (IMSS) in the northern region of Mexico City. Clinical and biochemical data as well as hemodialysis dose by Kt/V and urea reduction rate were collected and evaluated. To determine distribution, mean or median and SD or interquartile range were used; for nominal variables, the difference in proportions was estimated using the χ2 test; proportions were analyzed for biochemical values using the statistical package SPSS version 25. RESULTS: In our study, >60% (485) of the patients were anemic with an average hemoglobin of 9.39 mg/dL (SD ± 1.83); serum calcium was found below 8.4 mg/dL in 51.3% (383) of patients, and only in 45.8% (342) was at an optimal level of this parameter. Only 33.5% of patients have arteriovenous fistula for dialysis access. The hemodialysis dose was optimal in >75% of patients. CONCLUSIONS: It is necessary to enhance and monitor treatment of comorbidities in patients with ESRD in subrogated hemodialysis units in México. We observed adequate prescription of hemodialysis in a majority of patients, achieving quality control points for removal of nitrogen products. Yet, there is a lack of quality control of comorbidities; therefore, we should aim to optimize treatment for mineral-bone disorder, anemia, and nutritional status.

Is hepatitis C direct-acting antiviral therapy a risk factor for the development and recurrence of hepatocellular carcinoma? Narrative literature review and clinical practice recommendations.

The development of direct-acting antivirals (DAAs) has been a turning point in chronic hepatitis C treatment. With an efficacy rate on viral eradication close to 100% and an excellent safety profile, they have replaced interferon-based treatments as first-line therapy for hepatitis C virus (HCV). Following the encouraging results observed during the first years with these treatments, new publications suggested an unexpectedly high incidence of hepatocellular carcinoma (HCC) in patients previously treated with DAAs as well as a higher HCC recurrence rate in them. The possible interaction between DAAs and HCC and its impact on HCC incidence and recurrence still remains controversial. The aim of the present work is to review the current state of the matter by analyzing studies that evaluate the association between chronic hepatitis C treatment with DAAs and the development of HCC either de novo or as a recurrence. Following this, clinical practice recommendations are done.

Becoming what you are seeking: Building Relational Self-Awareness in emerging adults.

Emerging adults are attempting to navigate a rapidly shifting and immensely complicated landscape of modern love, often without meaningful sex and relationship education. Although individually oriented relationship education programs for emerging adults make a difference in the knowledge, attitudes, and beliefs of the recipients (Simpson et al., Journal of Youth and Adolescence, 2018, 47, 477) and most emerging adults report they yearn for relationship education (Weissbourd et al., The talk: How adults can promote young people's healthy relationships and prevent misogyny and sexual harassment, 2017), these programs are not widely available. Educators who are working with emerging adults in a classroom or psychoeducational setting are well-positioned to help emerging adults identify and enact healthy and purposeful relational and sexual choices. The first part of the paper orients readers to the "topography" of the modern love landscape by describing four macro cultural themes that impact the intimate lives of emerging adults. The second part of the paper introduces relationship educators to Relational Self-Awareness (Solomon, Loving Bravely: 20 lessons of self-discovery to help you get the love you want, New Harbinger, 2017), an integrative approach to helping emerging adults understand the self-in-relationship. Each of the five pillars of Relational Self-Awareness is defined and operationalized, and specific recommendations are provided for how educators can integrate these pillars into their existing curricula. Clinical implications and future directions are offered.

Los adultos emergentes están intentando orientarse ante un panorama de amor moderno rápidamente cambiante e inmensamente complicado, generalmente sin sexo significativo ni educación sobre las relaciones. Aunque los programas de educación sobre las relaciones para adultos emergentes con orientación individual marcan una diferencia en el conocimiento, las actitudes y las creencias de los destinatarios (Simpson et al., 2018), y la mayoría de los adultos emergentes informan que desean recibir educación sobre las relaciones (Weissbourd et al., 2017), estos programas no son ampliamente accesibles. Los educadores que trabajan con adultos emergentes en un aula o en un entorno psicoeducativo están bien posicionados para ayudarlos a identificar y a adoptar elecciones sexuales y relacionales saludables y significativas. La primera parte del artículo guía a los lectores por la "topografía" del panorama del amor moderno mediante la descripción de cuatro temas macroculturales que repercuten en las vidas íntimas de los adultos emergentes. En la segunda parte del artículo se presenta la autoconciencia relacional (Solomon, 2017) a los educadores sobre relaciones, un enfoque integrador para ayudar a los adultos emergentes a comprender el yo en las relaciones. Se definen y se operacionalizan cada uno de los cinco pilares de la autoconciencia relacional, y se dan recomendaciones específicas sobre cómo los educadores pueden integrar estos pilares en sus planes de estudio existentes. Se comentan las consecuencias clínicas y las futuras direcciones del estudio.

Lack of the aryl hydrocarbon receptor accelerates aging in mice.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, largely known for its role in xenobiotic metabolism and detoxification as well as its crucial role as a regulator of inflammation. Here, we have compared a cohort wild-type and AhR-null mice along aging to study the relationship between this receptor and age-associated inflammation, termed as "inflammaging," both at a systemic and the CNS level. Our results show that AhR deficiency is associated with a premature aged phenotype, characterized by early inflammaging, as shown by an increase in plasma cytokines levels. The absence of AhR also promotes the appearance of brain aging anatomic features, such as the loss of the white matter integrity. In addition, AhR-/- mice present an earlier spatial memory impairment and an enhanced astrogliosis in the hippocampus when compared with their age-matched AhR+/+ controls. Importantly, we have found that AhR protein levels decrease with age in this brain structure, strongly suggesting a link between AhR and aging.-Bravo-Ferrer, I., Cuartero, M. I., Medina, V., Ahedo-Quero, D., Peña-Martínez, C., Pérez-Ruíz, A., Fernández-Valle, M. E., Hernández-Sánchez, C., Fernández-Salguero, P. M., Lizasoain, I., Moro, M. A. Lack of the aryl hydrocarbon receptor accelerates aging in mice.

A Protocol-Driven Reduction in Surgical Site Infections After Colon Surgery.

BACKGROUND: Surgical site infection (SSI) is an established quality indicator and predictor for adverse patient outcomes. Multiple strategies have been established to reduce SSI; however, optimum protocol remains unclear. The aim of the study was to assess the impact of established protocol on SSI after colon surgery. METHODS: We established a colon SSI bundle in 2017, which includes a chlorhexidine prescrub followed by chloraPrep, betadine wound wash, antibiotic infused irrigation, use of closure tray, and incision coverage with silver impregnated dressing. Retrospective analysis of a 2-y (2016-2017) prospectively collected before and after analysis of all patients undergoing elective colon surgery was performed. Patients were divided into two groups: preprotocol (PP: year 2016) and postprotocol (PoP: year 2017). Patients in the two groups were matched using propensity score matching for age, gender, comorbidities, Anesthesiology Severity Score, indication of procedure, and procedure type. Outcome measures were SSI, hospital length of stay, and readmission rate. RESULTS: A total of 328 patients were analyzed, and after propensity matching, 94 patients (PP:47 and PoP:47) were included. The mean age was 63.7 ± 16.4 y, 43.6% male, and 44.6% of procedures were performed laparoscopically. There was no difference in demographics, comorbidities, and procedure details between two groups. PoP patients had significantly lower superficial (odds ratio: 0.91 [0.74-0.98]; P = 0.045) and deep SSI (odds ratio:0.97 [0.65-0.99]; P = 0.048) than PP patients. PoP patient had shorter length of stay (P = 0.049) and trend toward lower readmission rate (P = 0.098) compared with PP patients and an 85% reduction in the Centers for Medicare and Medicaid Services standardized infection rate. CONCLUSIONS: Protocol-driven patient care improves patient outcomes. SSI bundle reduced SSI in patient undergoing colon surgery. Establishing national SSI bundles will help standardize care and help optimize patient outcomes.

Odontogenic cutaneous sinus tracts due to infection with nontuberculous mycobacteria: a report of three cases.

BACKGROUND: Soft tissue or skin infections due to nontuberculous mycobacteria (NTM) have been reported frequently and are mostly associated with trauma or cosmetic interventions like plastic surgery. However, infection with NTM as a result of a dental procedure have rarely been described and the lack of clinical suspicion and a clear clinical manifestation makes diagnosis challenging. CASE PRESENTATION: We report on three patients with a facial cutaneous sinus tract of dental origin, due to an infection with respectively Mycobacterium fortuitum, M. abscessus and M. peregrinum. The infection source was the dental unit waterlines (DUWLs), which were colonized with NTM. CONCLUSIONS: Water of the DUWL can pose a health risk. This report emphasizes the need for quality control and certification of water flowing through DUWLs, including the absence of NTM. Our report also shows the need for a rapid recognition of NTM infections and accurate laboratory diagnosis in order to avoid long-term ineffective antibiotic treatment.

Telemedicine, drug-resistant epilepsy, and ketogenic dietary therapies: A patient survey of a pediatric remote-care program during the COVID-19 pandemic.

OBJECTIVE: The purpose of this study was to assess parent satisfaction with the management of ketogenic diet therapies (KDTs) through telemedicine using WhatsApp as the main tool. METHODS: Parent satisfaction was longitudinally evaluated through questionnaires. The survey was developed with Google Questionnaire forms and sent via WhatsApp. The questionnaire consisted of 13 items concerning the management of KDTs using telemedicine in the context of the coronavirus disease 2019 (COVID-19) pandemic. Our population of patients has limited financial resources and low levels of education. Given that many families did not have either computers or WIFI, or any other access to information or communication technology, WhatsApp was chosen as a tool as it was available on the cell phones of all families and the professionals. RESULTS: Our survey showed that 96.3% of the parents were satisfied with the management of KDTs through telemedicine. The main benefits observed were the possibility of continuing treatment during the COVID-19 pandemic and the ease of accessing the professional team from the comfort of their home. Overall, 72.2% of the families would recommend using telemedicine for KDTs in any situation regardless of the pandemic. None of the families reported that they would recommend against treatment by telemedicine. The availability of a social support network (parents WhatsApp group) coordinated by professionals from the KDT team was considered to be useful by most respondents (90%). CONCLUSIONS: Our study suggests that management of children with DRE on KDTs through telemedicine is feasible, well accepted by the families, and probably as safe as conventional medicine. WhatsApp may be an interesting telemedicine tool to start and maintain KDTs.

Combined Therapy for Alzheimer's Disease: Tacrine and PAMAM Dendrimers Co-Administration Reduces the Side Effects of the Drug without Modifying its Activity.

Alzheimer's disease has become a public health priority, so an investigation of new therapies is required. Tacrine (TAC) was licensed for treatments; however, its oral administration caused hepatotoxicity, so it is essential to reduce the side effects. PAMAM dendrimer generation 4.0 and 4.5 (DG4.0 and DG4.5) can be used as drug delivery systems and as nanodrugs per se. Our work aims to propose a combined therapy based on TAC and PAMAM dendrimer co-administration. TAC and dendrimer interactions were studied by in vitro drug release, drug stability, and FTIR. The toxicity profile of co-administration was evaluated in human red blood cells, in Neuro-2a cell culture, and in zebrafish larvae. Also, the anti-acetylcholinesterase activity was studied in cell culture. It was possible to obtain DG4.0-TAC and DG4.5-TAC suspensions, without reducing the drug solubility and stability. FTIR and in vitro release studies confirmed that interaction between TAC and DG4.5 was of the electrostatic type. No toxicity effects on human red blood cells were observed, whereas the co-administration with DG4.5 reduced cytotoxicity of TAC on the Neuro-2a cell line. Moreover, in vivo co-administration of both DG4.0-TAC and DG4.5-TAC reduced the morphological and hepatotoxic effects of TAC in zebrafish larvae. The reduction of TAC toxicity was not accompanied by a reduction in its activity since the anti-acetylcholinesterase activity remains when it is co-administrated with dendrimers. In conclusion, the co-administration of TAC with both DG4.0 and DG4.5 is a novel therapy since it was less-toxic, was more biocompatible, and has the same effectiveness than the free drug. Graphical abstract.