Perspectives on technology: urethral slings in a post-mesh world.

OBJECTIVES: To detail the history of synthetic mid-urethral slings (SMUSs) and fascial slings, their efficacy, associated complications, and changes to practice that have occurred after the issuing of the 2011 US Food and Drug Administration (FDA) Safety Communication statement on transvaginal mesh (TVM), and to highlight the need for surgical registries and high-quality randomised controlled data to guide recommendations for continence procedures, in view of current concerns regarding mesh. METHODS: A literature search was conducted in EMBASE, PubMed, and the Cochrane Database of systematic reviews to identify articles published from 2011 onward, following the FDA Safety Communication regarding TVM. RESULTS: Prior to the formal FDA Safety Communication in 2011, TVM was considered a safe option for the treatment of both pelvic organ prolapse (POP) and stress urinary incontinence (SUI). The 2011 FDA safety communications and ensuing widely publicised litigation against TVM manufacturers have shifted both surgeon and patient acceptance of mesh products. Several efforts by medical and government bodies have been made to establish ways to monitor the surgical outcomes and safety of mesh products. The Australasian Pelvic Floor Procedure Registry is one such example. Although SMUSs have a long and established safety profile, perceptions of mesh products for SUI have also been negatively affected. The extent of this, however, has yet to be adequately measured through qualitative and quantitative data. The available data suggest it has been difficult for patients and consumers to distinguish between TVM morbidity for POP vs SUI. Furthermore, there remains a lack of high-quality randomised or real-world registry data to definitively exclude the SMUS from the SUI treatment algorithm. Since SMUSs are a viable option for SUI treatment, the concept of a 'post-mesh world' remains contentious. CONCLUSION: Controversies surrounding SMUSs have changed the treatment landscape of SUI. Against the background of significant litigious action following the FDA warnings against mesh use, there has been significant reduction in the uptake of synthetic mesh products. Although there are ample data related to surgical outcomes and safety for both autologous fascial and retropubic SMUSs in carefully selected patients, informed consent and surgical training will be of paramount importance as newer synthetic materials reach clinical maturity.

The meaning of non-criteria clinical manifestations in a real-life primary antiphospholipid syndrome cohort.

OBJECTIVES: We aimed to evaluate the prevalence of non-criteria clinical features in patients with primary antiphospholipid syndrome (APS), and to assess their relationship to thrombosis and damage. METHODS: We retrospectively included 177 primary APS patients, and/or patients who only achieved the serological Sydney criteria but had thrombocytopenia and/or haemolytic anaemia. We registered demographics, serology, treatment, thrombotic/obstetric manifestations and non-criteria clinical manifestations (cutaneous, haematologic, renal, heart valve disease, and neurological). We scored the DIAPS and a modified SLICC index. We used logistic regression and reported OR with 95% CI. RESULTS: 78% were women with a median follow-up of 6.7 years. Thrombosis was found in 74% of patients, 29.3% had obstetric features, and 64% had non-criteria clinical manifestations. The frequency of the non-criteria clinical manifestation was: haematologic 40.1%, cutaneous 20.9%, neurologic 18%, cardiac 5% and renal 4.5%. Non-criteria features were associated with LA (OR 2.3, 95% 1.03-5.1) and prednisone use (OR 8.2, 95% CI 1.7-39.3). A DIAPS score ≥1 was associated with thrombosis (OR 53.1, 95% CI 17.8-15.2), prednisone use (OR 0.27, CI 95% 0.09-0.83) and neurological involvement (OR 6.4, 95% CI 1.05-39.8); whereas a modified SLICC ≥ 1 with thrombosis (OR 10.2; IC 95% 4.43-26.1), neurological involvement (OR 6.4, 95%CI 1.05-39.8), obstetric features (OR 0.32 CI 95% 0.12-0,81) and cutaneous features (OR 5.3, CI 95% 1.4-19), especially livedo reticularis (OR 5.45; IC 95% 1.49-19.8). CONCLUSIONS: Non-criteria clinical manifestations are common and associated with LA. Among them, neurologic involvement and the presence of livedo were associated with damage accrual.

Is there a link between inorganic polyphosphate (polyP), mitochondria, and neurodegeneration?

Mitochondrial dysfunction - including increased apoptosis, calcium and protein dyshomeostasis within the organelle, and dysfunctional bioenergetics and oxidative status - is a common, early feature in all the major neurodegenerative diseases, including Alzheimer's Disease (AD) and Parkinson's Disease (PD). However, the exact molecular mechanisms that drive the organelle to dysfunction and ultimately to failure in these conditions are still not well described. Different authors have shown that inorganic polyphosphate (polyP), an ancient and well-conserved molecule, plays a key role in the regulation of mitochondrial physiology under basal conditions. PolyP, which is present in all studied organisms, is composed of chains of orthophosphates linked together by highly energetic phosphoanhydride bonds, similar to those found in ATP. This polymer shows a ubiquitous distribution, even if a high co-localization with mitochondria has been reported. It has been proposed that polyP might be an alternative to ATP for cellular energy storage in different organisms, as well as the implication of polyP in the regulation of many of the mitochondrial processes affected in AD and PD, including protein and calcium homeostasis. Here, we conduct a comprehensive review and discussion of the bibliography available regarding the role of polyP in the mitochondrial dysfunction present in AD and PD. Taking into account the data presented in this review, we postulate that polyP could be a valid, innovative and, plausible pharmacological target against mitochondrial dysfunction in AD and PD. However, further research should be conducted to better understand the exact role of polyP in neurodegeneration, as well as the metabolism of the polymer, and the effect of different lengths of polyP on cellular and mitochondrial physiology.

Antifungal activity of Punicalagin-nystatin combinations against Candida albicans.

OBJECTIVES: Oral candidiasis is the most common opportunistic fungal infection of oral mucosa and results from an overgrowth of Candida, especially Candida albicans. The potential anti-C. albicans and cytotoxicity of punicalagin (PCG), isolated from Punica granatum, alone or with nystatin (NYS) were evaluated. METHODS: Activity of compounds alone or in combinations was determined against two C. albicans strains (ATCC 90028 and SC5314). Minimal inhibitory concentration (MIC)-50 and Minimum Fungicidal Concentration (MFC) were assessed by XTT assay and CFU counts, respectively. For combinations, determination of fractional inhibitory concentration index was performed. Ergosterol pathway was investigated as a possible PCG antifungal mechanism. Cytotoxicity assays were undertaken on human primary oral keratinocytes and gingival fibroblasts incubated with antifungal concentrations of PCG and/or NYS for 24 hr. RESULTS: Combination of NYS and PCG increased antifungal efficacy, compared with compounds tested alone. Combinations 4 (PCG-6.25 µg/ml; NYS-3.9 µg/ml) and 5 (PCG-12.5 µg/ml; NYS-1.95 µg/ml) were more effective since they reduced the MIC-50 of PCG (50 µg/ml) by 8 and 4 times, respectively, increased the candidal inhibition and nullified the PCG cytotoxicity for keratinocytes. PCG antifungal mechanism did not involve ergosterol biosynthesis pathway. CONCLUSIONS: The favorable outcomes for combination of PCG and NYS encourage further testing this therapeutic strategy against C. albicans.

Incidence, Predictive Factors and Preventive Measures for Inguinal Hernia following Robotic and Laparoscopic Radical Prostatectomy: A Systematic Review.

PURPOSE: Inguinal hernia is a known sequel of radical prostatectomy which contributes to patient morbidity and health care expenditure. In this systematic review we evaluated the incidence of inguinal hernia associated with minimally invasive radical prostatectomy, in addition to predictive factors and preventive measures. MATERIALS AND METHODS: We searched PubMed® and Embase® between 2000 and February 2018 using the search terms inguinal hernia and radical prostatectomy. RESULTS: In concordance with search terms and selection criteria we identified a total of 155 reports with 27 studies eligible for inclusion. Collated results demonstrated a variable prevalence of inguinal hernia after laparoscopic radical prostatectomy and robotic assisted radical prostatectomy ranging from 4.3% to 8.3% and from 3% to 19.4 %, respectively. There was a higher mean prevalence of inguinal hernia after robotic assisted prostatectomy. Factors predicting inguinal hernia following minimally invasive radical prostatectomy included low body mass index, poor stream and straining prior to prostatectomy detected on symptom score instruments, a patent processus vaginalis or an intraoperative incidental inguinal hernia. Herniotomy or herniorrhaphy with onlay mesh repair was the most commonly reported intraoperative repair technique at the time of minimally invasive radical prostatectomy. Recurrence of repaired incidental hernia is rare. CONCLUSIONS: Inguinal hernia is common after minimally invasive radical prostatectomy. There is a lack of high level evidence to clarify risk factors and preventive strategies for inguinal hernia after minimally invasive radical prostatectomy. There is a justification for randomized controlled trials to further evaluate this under recognized clinical problem.

The systematics of Lobophora (Dictyotales, Phaeophyceae) in the western Atlantic and eastern Pacific oceans: eight new species.

Lobophora is a common tropical to temperate genus of brown algae found in a plethora of habitats including shallow and deep-water coral reefs, rocky shores, mangroves, seagrass beds, and rhodoliths beds. Recent molecular studies have revealed that Lobophora species diversity has been severely underestimated. Current estimates of the species numbers range from 100 to 140 species with a suggested center of diversity in the Central Indo-Pacific. This study used three molecular markers (cox3, rbcL, psbA), different single-marker species delimitation methods (GMYC, ABGD, PTP), and morphological evidence to evaluate Lobophora species diversity in the Western Atlantic and the Eastern Pacific oceans. Cox3 provided the greatest number of primary species hypotheses(PSH), followed by rbcL and then psbA. GMYC species delimitation analysis was the most conservative across all three markers, followed by PTP, and then ABGD. The most informative diagnostic morphological characters were thallus thickness and number of cell layers in both the medulla and the dorsal/ventral cortices. Following a consensus approach, 14 distinct Lobophora species were identified in the Western Atlantic and five in the Eastern Pacific. Eight new species from these two oceans were herein described: L. adpressa sp. nov., L. cocoensis sp. nov., L. colombiana sp. nov., L. crispata sp. nov., L. delicata sp. nov., L. dispersa sp. nov., L. panamensis sp. nov., and L. tortugensis sp. nov. This study showed that the best approach to confidently identify Lobophora species is to analyze DNA sequences (preferably cox3 and rbcL) followed by comparative morphological and geographical assessment.

Citation indices for social media articles in urology.

OBJECTIVE: To evaluate the impact of publications on urological participation in social media (SoMe) by virtue of citations in the urological and non-urological literature. MATERIALS AND METHODS: On 15 March 2016, a PubMed search was undertaken using the names of the major SoMe platforms in current use and associated with the field of urology. The search term 'urolog*' was used to specifically capture articles that could be associated with 'urology', 'urologist' or 'urological'. Exclusion criteria for analysis included non-English language articles, articles published for the first time online in any form after 1 March 2015, articles irrelevant to the topic of SoMe, and letters of correspondence. Included articles were then searched in Google Scholar and citations analysed to determine if citations were from the urological literature or non-urological literature. Citations from non-urological journals were considered to be as such even if authored by urologists and on the subject of urology and SoMe. RESULTS: Prior to exclusions as defined in the methods, our PubMed search yielded 232 articles of which 17 were non-English language and 66 had been published after 1 March 2015. Allowing for 12 months after the most recent articles were published, we found that the mean number of total citations in any journal was 20.8. There were more citations in journals not specific to urology, with 8.3 citations in urological journals, compared to 12.6 citations in non-urological journals. CONCLUSION: Urological SoMe journal articles are highly cited, particularly in the non-urological literature. It is likely that the magnitude of citations has positively contributed to the impact factors of the almost all journals publishing these manuscripts.

Chloroplast genomes as a tool to resolve red algal phylogenies: a case study in the Nemaliales.

BACKGROUND: Obtaining strongly supported phylogenies that permit confident taxonomic and evolutionary interpretations has been a challenge in algal biology. High-throughput sequencing has improved the capacity to generate data and yields more informative datasets. We sequenced and analysed the chloroplast genomes of 22 species of the order Nemaliales as a case study in the use of phylogenomics as an approach to achieve well-supported phylogenies of red algae. RESULTS: Chloroplast genomes of the order Nemaliales are highly conserved, gene-dense and completely syntenic with very few cases of gene loss. Our ML estimation based on 195 genes recovered a completely supported phylogeny, permitting re-classification of the order at various taxonomic levels. Six families are recognised and the placement of several previously contradictory clades is resolved. Two new sub-orders are described, Galaxaurineae and Nemaliineae, based on the early-branching nature and monophyly of the groups, and presence or absence of a pericarp. Analyses of subsets of the data showed that >90 % bootstrap support can be achieved with datasets as small as 2500 nt and that fast and medium evolving genes perform much better when it comes to resolving phylogenetic relationships. CONCLUSIONS: In this study we show that phylogenomics is an efficient and effective approach to investigate phylogenetic relationships. The six currently circumscribed Nemaliales families are clustered into two evolutionary lineages with strong statistical support based on chloroplast phylogenomic analyses. The conserved nature of red algal chloroplast genomes is a convenient and accessible source of data to resolve their ancient relationships.

[Impact of diabetes on cardiovascular risk in patients with dyslipidemia]. / Impacto de la diabetes en el riesgo cardiovascular en pacientes con dislipidemia.

Objective: To determine the impact of diabetes on cardiovascular risk in patients with dyslipidemia. Method: Observational, cross-sectional and comparative study in which cardiovascular risk was determined at 10 years in 100 patients with dyslipidemia, of these, 50 non-diabetic patients and 50 diabetic patients. Results: Both groups had similar characteristics in terms of age, blood pressure figures, average body mass index, and HDL and LDL levels. It was observed that the diabetic group has almost double the risk compared to the dyslipidemia group, 13.7 vs. 7.9 (p = 0.014), and the calculated heart age is also higher in patients with diabetes, 80 vs. 66 years (p = 0.003). Even in patients with diabetes there is a greater difference between the real age and the age of the heart, 24 years vs. 15 years of patients without diabetes (p = 0.000). Conclusion: Having diabetes and dyslipidemia doubles the cardiovascular risk of patients. Little metabolic control was found in the population studied, which significantly increases complications at an early age and the economic burden on the health system and the families of patients, so it is necessary to rethink treatment strategies to improve metabolic control and with it the prognosis for the patient in the long term.

Objetivo: Determinar el impacto de la diabetes en el riesgo cardiovascular en pacientes con dislipidemia. Método: Estudio observacional, transversal y comparativo, en el que se determinó el riesgo cardiovascular en 100 pacientes con dislipidemia, de los cuales 50 eran diabéticos, sin complicaciones crónicas. Resultados: Ambos grupos tenían características similares en cuanto a edad, presión arterial, índice de masa corporal, niveles de c-HDL y c-LDL. Sin embargo, al comparar el porcentaje de riesgo cardiovascular, observamos que el grupo de diabéticos tenía casi el doble de riesgo cardiovascular, 13.7 contra 7.9 (p = 0.014), y la edad del corazón calculada también fue mayor en los pacientes con diabetes, 80 contra 66 años (p = 0.003). Incluso, en los pacientes diabéticos la diferencia entre la edad real y la edad del corazón fue mayor, 24 años contra 15 años (p = 0.000). Conclusión: Padecer diabetes y dislipidemia duplica el riesgo cardiovascular. En la población estudiada se encontró poco control metabólico, lo que aumenta significativamente las complicaciones en edades tempranas y la carga económica al sistema de salud y a las familias de los pacientes; por tanto, es necesario replantear las estrategias de tratamiento para mejorar el control metabólico y el pronóstico del paciente a largo plazo.

Ex vivo and in vivo evidence that cigarette smoke-exposed T regulatory cells impair host immunity against Mycobacterium tuberculosis.

Introduction: A strong epidemiologic link exists between cigarette smoke (CS) exposure and susceptibility to tuberculosis (TB). Macrophage and murine studies showed that CS and nicotine impair host-protective immune cells against Mycobacterium tuberculosis (MTB) infection. While CS and nicotine may activate T regulatory cells (Tregs), little is known about how CS may affect these immunosuppressive cells with MTB infection. Methods: We investigated whether CS-exposed Tregs could exacerbate MTB infection in co-culture with human macrophages and in recipient mice that underwent adoptive transfer of Tregs from donor CS-exposed mice. Results: We found that exposure of primary human Tregs to CS extract impaired the ability of unexposed human macrophages to control an MTB infection by inhibiting phagosome-lysosome fusion and autophagosome formation. Neutralizing CTLA-4 on the CS extract-exposed Tregs abrogated the impaired control of MTB infection in the macrophage and Treg co-cultures. In Foxp3+GFP+DTR+ (Thy1.2) mice depleted of endogenous Tregs, adoptive transfer of Tregs from donor CS-exposed B6.PL(Thy1.1) mice with subsequent MTB infection of the Thy1.2 mice resulted in a greater burden of MTB in the lungs and spleens than those that received Tregs from air-exposed mice. Mice that received Tregs from donor CS-exposed mice and infected with MTB had modest but significantly reduced numbers of interleukin-12-positive dendritic cells and interferon-gamma-positive CD4+ T cells in the lungs, and an increased number of total programmed cell death protein-1 (PD-1) positive CD4+ T cells in both the lungs and spleens. Discussion: Previous studies demonstrated that CS impairs macrophages and host-protective T effector cells in controlling MTB infection. We now show that CS-exposed Tregs can also impair control of MTB in co-culture with macrophages and in a murine model.

Levelling-up rhodolith-bed science to address global-scale conservation challenges.

Global marine conservation remains fractured by an imbalance in research efforts and policy actions, limiting progression towards sustainability. Rhodolith beds represent a prime example, as they have ecological importance on a global scale, provide a wealth of ecosystem functions and services, including biodiversity provision and potential climate change mitigation, but remain disproportionately understudied, compared to other coastal ecosystems (tropical coral reefs, kelp forests, mangroves, seagrasses). Although rhodolith beds have gained some recognition, as important and sensitive habitats at national/regional levels during the last decade, there is still a notable lack of information and, consequently, specific conservation efforts. We argue that the lack of information about these habitats, and the significant ecosystem services they provide, is hindering the development of effective conservation measures and limiting wider marine conservation success. This is becoming a pressing issue, considering the multiple severe pressures and threats these habitats are exposed to (e.g., pollution, fishing activities, climate change), which may lead to an erosion of their ecological function and ecosystem services. By synthesizing the current knowledge, we provide arguments to highlight the importance and urgency of levelling-up research efforts focused on rhodolith beds, combating rhodolith bed degradation and avoiding the loss of associated biodiversity, thus ensuring the sustainability of future conservation programs.

Effect of denture liners surface modification with Equisetum giganteum and Punica granatum on Candida albicans biofilm inhibition.

Aim: This study investigated the effect of denture liners surface modification with Equisetum giganteum (EG) and Punica granatum (PG) on Candida albicans biofilm inhibition supposing its usage as a sustained-release therapeutical delivery system for Candida-associated denture stomatitis. Materials & methods:C. albicans biofilm (SC5314 or ATCC 90028) was formed on soft liners superficially modified by a primer mixed to drugs at minimum inhibitory concentrations (0.100 g for EG and PG or 0.016 g for nystatin per ml of primer). After 24 h, 7 or 14 days, antibiofilm activity was evaluated by colony-forming unit counts. Results: Not all groups were equi-efficient to nystatin after 24 h and 7 days. After 14 days, EG and PG efficacies were not different from nystatin (almost 100% inhibition). Conclusion: The proposed protocol presents a promising option to allopathic drugs for Candida-associated denture stomatitis treatment.

Hypothesis: Alpha-1-antitrypsin is a promising treatment option for COVID-19.

No definitive treatment for COVID-19 exists although promising results have been reported with remdesivir and glucocorticoids. Short of a truly effective preventive or curative vaccine against SARS-CoV-2, it is becoming increasingly clear that multiple pathophysiologic processes seen with COVID-19 as well as SARS-CoV-2 itself should be targeted. Because alpha-1-antitrypsin (AAT) embraces a panoply of biologic activities that may antagonize several pathophysiologic mechanisms induced by SARS-CoV-2, we hypothesize that this naturally occurring molecule is a promising agent to ameliorate COVID-19. We posit at least seven different mechanisms by which AAT may alleviate COVID-19. First, AAT is a serine protease inhibitor (SERPIN) shown to inhibit TMPRSS-2, the host serine protease that cleaves the spike protein of SARS-CoV-2, a necessary preparatory step for the virus to bind its cell surface receptor ACE2 to gain intracellular entry. Second, AAT has anti-viral activity against other RNA viruses HIV and influenza as well as induces autophagy, a known host effector mechanism against MERS-CoV, a related coronavirus that causes the Middle East Respiratory Syndrome. Third, AAT has potent anti-inflammatory properties, in part through inhibiting both nuclear factor-kappa B (NFκB) activation and ADAM17 (also known as tumor necrosis factor-alpha converting enzyme), and thus may dampen the hyper-inflammatory response of COVID-19. Fourth, AAT inhibits neutrophil elastase, a serine protease that helps recruit potentially injurious neutrophils and implicated in acute lung injury. AAT inhibition of ADAM17 also prevents shedding of ACE2 and hence may preserve ACE2 inhibition of bradykinin, reducing the ability of bradykinin to cause a capillary leak in COVID-19. Fifth, AAT inhibits thrombin, and venous thromboembolism and in situ microthrombi and macrothrombi are increasingly implicated in COVID-19. Sixth, AAT inhibition of elastase can antagonize the formation of neutrophil extracellular traps (NETs), a complex extracellular structure comprised of neutrophil-derived DNA, histones, and proteases, and implicated in the immunothrombosis of COVID-19; indeed, AAT has been shown to change the shape and adherence of non-COVID-19-related NETs. Seventh, AAT inhibition of endothelial cell apoptosis may limit the endothelial injury linked to severe COVID-19-associated acute lung injury, multi-organ dysfunction, and pre-eclampsia-like syndrome seen in gravid women. Furthermore, because both NETs formation and the presence of anti-phospholipid antibodies are increased in both COVID-19 and non-COVID pre-eclampsia, it suggests a similar vascular pathogenesis in both disorders. As a final point, AAT has an excellent safety profile when administered to patients with AAT deficiency and is dosed intravenously once weekly but also comes in an inhaled preparation. Thus, AAT is an appealing drug candidate to treat COVID-19 and should be studied.

[Costs in hand amputations derived from labor injuries]. / Costos directos e indirectos por amputaciones en mano derivadas de accidentes de trabajo.

BACKGROUND: Hand injuries by labor accidents are first rank. It is necessary to have a multidisciplinary medical approach to frequently generated temporary and permanent disabilities that affect costs to an institution and to enterprise. OBJECTIVE: To determine the direct cost (DC) and the indirect cost (IC) of complete and partial amputations in hand caused by labor injuries. METHODS: An observational study was performed. The data was obtained from labor injuries with amputation of a finger or hand that received multidisciplinary management. The costs were calculated according to the list of Institutional Unit Costs. The IC were obtained with the "safety pays" program. RESULTS: We included 48 cases. The average age was 32.17 years; the cost of surgical operations was $767,470; and the payment of a partial disability permanent was $1,032,670; the DC of the sample of 48 workers was $2,955,007 with an IC of $3,250,507 and a total cost of $6,205,515, the average cost per worker of $51,741 for DC, $56,915 for IC and $108,657 for the total cost. CONCLUSIONS: Costs of hand injures requires the creation of prevention programs.

Differential Responses by Human Macrophages to Infection With Mycobacterium tuberculosis and Non-tuberculous Mycobacteria.

Mycobacterium tuberculosis (MTB) and non-tuberculous mycobacteria (NTM) are formidable causes of lung diseases throughout the world. While MTB is considered to be more virulent than NTM, host factors also play a key role in disease development. To elucidate whether there are differential immune responses to various mycobacteria, THP-1 macrophages were temporally infected with MTB H37Rv or with four different NTM species. We found that cells infected with MTB had greater bacterial burden and p65 nuclear factor-kappa B (NF-κB) activation than cells infected with NTM. There was also differential expression of mRNA for interleukin-1-ß (IL-1ß), IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α) with no distinct pattern of mRNA expression among the different mycobacteria. In contrast, at the protein level, some generalizations can be made of the cytokines and chemokines expressed. Compared to uninfected cells, the rapid-growing Mycobacterium smegmatis but not Mycobacterium abscessus induced significantly greater pro-inflammatory cytokines and IL-10, whereas both NTM individually induced greater levels of chemokines. Compared to uninfected control cells, the two slow-growing NTM and MTB differentially induced cytokine expression with Mycobacterium avium inducing more pro-inflammatory cytokines and IL-10, whereas M. avium, Mycobacterium intracellulare, and MTB inducing greater but similar levels of chemokines. MTB-infected THP-1 cells also demonstrated lower level of phagosome-lysosome fusion and apoptosis than NTM-infected cells while there were differences in these macrophage functions among the NTM species. Interestingly, M. intracellulare, M. avium, and MTB have similar levels of autophagosome formation, but the levels displayed by all three were lower than for M. smegmatis and M. abscessus. This study demonstrates the differences in bacterial burden and macrophage effector functions among several clinically relevant mycobacterial species. Such disparities may, in part, account for differences in clinical outcomes among patients infected with various species of NTM as has been seen for different strains of MTB.

The Systemic Sclerosis Questionnaire (SySQ): Validation of the translation of the original German version into Spanish and its relationship to the disease and to quality of life. / Cuestionario de funcionalidad para esclerosis sistémica (SySQ): validación en español del original en alemán y su relación con la enfermedad y la calidad de vida.

OBJECTIVE: Translation, transculturation and validity of the self-administered questionnaire for functionality (Systemic Sclerosis Questionnaires [SySQ]) for use in Spanish patients with systemic sclerosis and its relationship to the severity of the disease and to quality of life. PATIENTS AND METHODS: We conducted an observational analytical study to perform a cross-cultural validation of the self-administered questionnaire on functionality in scleroderma. The validity of the form and content was evaluated by an expert panel. The method included: a) adaptation into Spanish of the construct for translation and back translation, and transculturation; b) internal consistency with the SySQ (Cronbach's alpha), and c) reproducibility was assessed taking into account all occasions in which the test was performed with Cohen's kappa. Additionally, we calculated the Spearman correlation coefficient with the Medsger severity scale, Health Assessment Questionnaire score and SF-36 score. RESULTS: We included 70 patients with systemic sclerosis: age 17-78 (51±12) years, 65 (93%) were women, diffuse/limited subtype 64/36%, disease duration of 0.5-40 years. Optimal internal consistency for all categories of the final version of SySQ (Cronbach's α of 0.961) and intraobserver reliability in 2 tests over a 2-week interval (Cohen's kappa coefficient 0.618) and optimal interobserver reliability in 2 tests on the same day (Cohen's kappa coefficient 0.911). Moderate correlation between functionality by SySQ and by Health Assessment Questionnaire (r=0.573, P<.0001). Inverse correlation between SySQ and quality of life mental health domain SF-36 (r=-0.435, P<.001) and physical domain SF-36 (r=-0.638, P<.001). Medsger severity scale (tendon, heart, lung, vascular) also showed significant correlation with SySQ. CONCLUSIONS: SySQ in this validated Spanish version is a suitable instrument to measure functional status in patients with systemic sclerosis. Reduced functionality is related to greater tendon and peripheral vascular involvement and to a poorer quality of life.

Impacto de la diabetes en el riesgo cardiovascular en pacientes con dislipidemia / Impact of diabetes on cardiovascular risk in patients with dyslipidemia

Resumen Objetivo: Determinar el impacto de la diabetes en el riesgo cardiovascular en pacientes con dislipidemia. Método: Estudio observacional, transversal y comparativo, en el que se determinó el riesgo cardiovascular en 100 pacientes con dislipidemia, de los cuales 50 eran diabéticos, sin complicaciones crónicas. Resultados: Ambos grupos tenían características similares en cuanto a edad, presión arterial, índice de masa corporal, niveles de c-HDL y c-LDL. Sin embargo, al comparar el porcentaje de riesgo cardiovascular, observamos que el grupo de diabéticos tenía casi el doble de riesgo cardiovascular, 13.7 contra 7.9 (p = 0.014), y la edad del corazón calculada también fue mayor en los pacientes con diabetes, 80 contra 66 años (p = 0.003). Incluso, en los pacientes diabéticos la diferencia entre la edad real y la edad del corazón fue mayor, 24 años contra 15 años (p = 0.000). Conclusión: Padecer diabetes y dislipidemia duplica el riesgo cardiovascular. En la población estudiada se encontró poco control metabólico, lo que aumenta significativamente las complicaciones en edades tempranas y la carga económica al sistema de salud y a las familias de los pacientes; por tanto, es necesario replantear las estrategias de tratamiento para mejorar el control metabólico y el pronóstico del paciente a largo plazo.

Abstract Objective: To determine the impact of diabetes on cardiovascular risk in patients with dyslipidemia. Method: Observational, cross-sectional and comparative study in which cardiovascular risk was determined at 10 years in 100 patients with dyslipidemia, of these, 50 non-diabetic patients and 50 diabetic patients. Results: Both groups had similar characteristics in terms of age, blood pressure figures, average body mass index, and HDL and LDL levels. It was observed that the diabetic group has almost double the risk compared to the dyslipidemia group, 13.7 vs. 7.9 (p = 0.014), and the calculated heart age is also higher in patients with diabetes, 80 vs. 66 years (p = 0.003). Even in patients with diabetes there is a greater difference between the real age and the age of the heart, 24 years vs. 15 years of patients without diabetes (p = 0.000). Conclusion: Having diabetes and dyslipidemia doubles the cardiovascular risk of patients. Little metabolic control was found in the population studied, which significantly increases complications at an early age and the economic burden on the health system and the families of patients, so it is necessary to rethink treatment strategies to improve metabolic control and with it the prognosis for the patient in the long term.

Recruiting American Indian/Alaska Native Students to Medical School: A Multi-Institutional Alliance in the U.S. Southwest.

PROBLEM: Despite national efforts to diversify the physician workforce, American Indian/Alaska Native (AI/AN) individuals have the least representation of all major racial and ethnic groups. Limited resources at state medical schools present institution-level recruitment challenges. Unified efforts to engage AI/AN students in premedical education activities are needed. APPROACH: The medical schools at the Universities of Arizona (Phoenix and Tucson), Colorado, New Mexico, and Utah identified a collective need to increase student diversity, particularly with regard to AI/AN students. The schools partnered with the Association of American Indian Physicians to support AI/AN students applying to medical school and to grow the overall AI/AN applicant pool. Each year from 2011 to 2016, these institutions hosted a two-day preadmissions workshop (PAW) to prepare participants for applying to medical school. OUTCOMES: From 2011 to 2016, 130 AI/AN students participated in the PAWs. Of these, 113 were first-time attendees, 15 participated on two separate occasions, and 1 participated on three separate occasions. Nineteen (21%) of the 90 first-time participants from 2011 to 2015 matriculated to a U.S. medical school in the past five years. Twenty-two of 23 participants (96% response rate) in 2016 responded to the postworkshop survey. Results indicated that interview preparation, individual consultation, and writing preparation ranked as the three most beneficial sessions/activities. NEXT STEPS: Standardized evaluation of future PAWs will identify best practices for recruiting AI/AN students to medical school, and future initiatives will include more robust measures of success.