Is Intraoperative Muscle Motor Evoked Potential Variability due to Fluctuating Lower Motor Neuron Background Excitability?

PURPOSE: This pilot study tests the contribution of fluctuating lower motor neuron excitability to motor evoked potential (MEP) variability. METHODS: In six pediatric patients with idiopathic scoliosis and normal neurologic examination, cascades of 30 intraoperative H-reflexes (HRs) and MEPs were evoked in the soleus muscle using constant-current stimulators and recorded through surface electrodes with a 20-second interstimulus interval. First, HRs were obtained with an intensity capable of evoking the maximum response. Subsequently, MEPs were obtained with double trains and an intensity of 700 to 900 mA. Coefficients of variation (CVs) of amplitude and area under the curve from HRs and MEPs were compared using a paired two-tailed Student t test. Coefficients of correlation between the mean CVs of HR and MEP parameters were also assessed. RESULTS: Pooling the results from the six patients, the mean CV of amplitude from the MEP (24.6 ± 3) was significantly higher than that from the HR (3.5 ± 4.4) (P = 0.000091). The mean CV of the MEP area under the curve (21.8 ± 4.8) was also statistically significantly higher than that from the HR area under the curve (3.4 ± 4.5) (P = 0.00091). The coefficients of correlation of the mean CV of the HR amplitude and area under the curve compared with the corresponding values of the MEP were low (r = 0.29) and very low (r = 0.03), respectively. CONCLUSIONS: Our results suggest that fluctuations in lower motor neuron excitability may be less important than previously thought to explain the magnitude of MEP variability. The efficacy of corticospinal volleys to recruit a larger and more stable lower motor neuron population would be critical to obtain reproducible MEPs.

Geriatric proximal femur fracture updates.

Proximal femur fractures in the aging population present a variety of challenges. Physiologically, patients incurring this fracture are typically frail, with significant medical comorbidities, yet require early surgical treatment to restore mobility to prevent deterioration. Socioeconomically, the occurrence of a fragility fracture may be the beginning of the loss of independence, and the burdens of rehabilitation and support are borne by the individual patient and health care systems.

Anthelmintic activity and chemical profile of native plant extracts from the Yucatan Peninsula against Toxocara canis.

Toxocara canis can produce the "larva migrans" syndrome in humans, and in puppies, it can cause severe digestive disorders. The most used treatments are based on anthelmintics, although there are reports of anthelmintic (AH) resistance. The Yucatan Peninsula has a great variety of plant species whose AH properties are still unknown. The objective of this study was to evaluate the in vitro AH activity of ethanolic (EE), methanolic (ME) and aqueous (AE) extracts from the leaves of five native plant species of the Yucatan Peninsula on T. canis eggs of dogs from Merida, Yucatan. As part of a screening, the EE of the plants Alseis yucatanensis, Calea jamaicensis, Cameraria latifolia, Macrocepis diademata, and Parathesis cubana were evaluated at doses of 2400 and 3600 µg/ml. The EE and AE of A. yucatanensis and M. diademata presented high percentages (≥ 91.3%) of inhibition of the larval development of T. canis after six days of exposure. The lowest LC50 and LC99 was presented by the ME from A. yucatanensis (255.5 and 629.06 µg/ml, respectively) and the ME from M. diademata (222.4 and 636.5 µg/ml, respectively), and the AE from A. yucatanenesis (LC50 of 535.9 µg/ml). Chemical profiling of the most potent AH extract (Alseis yucatanensis) was carried out by LC-UV-HRMS. Data from the ME and AE from this plant indicated the presence of the known glucosylngoumiensine, kaempferol 3,7-diglucosyde, uvaol, linoleic acid and linolenic acid together with unknown alkaloids. The EE, ME and AE from leaves of M. diademata and A. yucatanensis could be developed as natural alternatives to control T. canis.

Assessing the impact of various tuberculin PPD brands on bovine tuberculosis diagnosis.

Although several brands of tuberculin purified protein derivatives (PPDs) are available for diagnosing bovine tuberculosis (bTB), comparative studies to determine their diagnostic accuracy are infrequent. In Ecuador we compared two different PPD brands for bTB diagnosis using skin testing and measuring skin thickness increase. Additionally, we evaluated four PPD brands, including those used for skin testing, in the Bovine Tuberculosis Interferon Gamma Test (IFN-γ test) measuring IFN-γ induction in whole blood. The study included 17 naturally tuberculosis-infected PPD and IFN-γ test positive bovines. Both the field and laboratory results showed significant differences in classifying the 17 bovines as bTB positive or negative. We hypothesize that several factors, such as the genetic background of the cows, sensitization to environmental mycobacteria, M. bovis strains involved in the bTB infection, and the manufacturing procedures of the PPDs, could have influenced the immune reaction toward the different tuberculin PPD brands. Our study emphasizes the necessity for comparative studies aimed at determining the diagnostic accuracy of PPD brands for bTB diagnosis as well as the development of standardized methods for PPD production and potency determination.

Tobacco use and risk of acute stroke in 32 countries in the INTERSTROKE study: a case­control study

BACKGROUND Smoking is a major risk factor for the global burden of stroke. We have previously reported a global population attributable risk (PAR) of stroke of 12.4% associated with current smoking. In this study we aimed to explore the association of current tobacco use with different types of tobacco exposure and environmental tobacco smoke (ETS) exposure on the risk of stroke and stroke subtypes, and by regions and country income levels. METHODS The INTERSTROKE study is a case­control study of acute first stroke and was undertaken with 13,462 stroke cases and 13,488 controls recruited between January 11, 2007 and August 8, 2015 in 32 countries worldwide. Association of risk of tobacco use and ETS exposure were analysed with overall stroke, ischemic and intracerebral hemorrhage (ICH), and with TOAST etiological stroke subtypes (large vessel, small vessel, cardioembolism, and undetermined). FINDINGS Current smoking was associated with an increased risk of all stroke (odds ratio [OR] 1.64, 95% CI 1.46­1.84), and had a stronger association with ischemic stroke (OR 1.85, 95% CI 1.61­2.11) than ICH (OR 1.19 95% CI 1.00­1.41). The OR and PAR of stroke among current smokers varied significantly between regions and income levels with high income countries (HIC) having the highest odds (OR 3.02 95% CI 2.24­4.10) and PAR (18.6%, 15.1­22.8%). Among etiological subtypes of ischemic stroke, the strongest association of current smoking was seen for large vessel stroke (OR 2.16, 95% CI 1.63­2.87) and undetermined cause (OR 1.97, 95% CI 1.55­2.50). Both filtered (OR 1.73, 95% CI 1.50­1.99) and non-filtered (OR 2.59, 95% CI 1.79­3.77) cigarettes were associated with stroke risk. ETS exposure increased the risk of stroke in a dose-dependent manner, exposure for more than 10 h per week increased risk for all stroke (OR 1.95, 95% CI 1.69­2.27), ischemic stroke (OR 1.89, 95% CI 1.59­2.24) and ICH (OR 2.00, 95% CI 1.60­2.50). INTERPRETATION There are significant variations in the magnitude of risk and PAR of stroke according to the types of tobacco used, active and ETS exposure, and countries with different income levels. Specific strategies to discourage tobacco use by any form and to build a smoke free environment should be implemented to ease the global burden of stroke. FUNDING The Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from Astra Zeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MERCK, Sharp and Dohme, Swedish Heart and Lung Foundation, UK Chest, and UK Heart and Stroke.

The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen.

Tumor adaptation or selection is thought to underlie therapy resistance in glioma. To investigate longitudinal epigenetic evolution of gliomas in response to therapeutic pressure, we performed an epigenomic analysis of 132 matched initial and recurrent tumors from patients with IDH-wildtype (IDHwt) and IDH-mutant (IDHmut) glioma. IDHwt gliomas showed a stable epigenome over time with relatively low levels of global methylation. The epigenome of IDHmut gliomas showed initial high levels of genome-wide DNA methylation that was progressively reduced to levels similar to those of IDHwt tumors. Integration of epigenomics, gene expression, and functional genomics identified HOXD13 as a master regulator of IDHmut astrocytoma evolution. Furthermore, relapse of IDHmut tumors was accompanied by histologic progression that was associated with survival, as validated in an independent cohort. Finally, the initial cell composition of the tumor microenvironment varied between IDHwt and IDHmut tumors and changed differentially following treatment, suggesting increased neoangiogenesis and T-cell infiltration upon treatment of IDHmut gliomas. This study provides one of the largest cohorts of paired longitudinal glioma samples with epigenomic, transcriptomic, and genomic profiling and suggests that treatment of IDHmut glioma is associated with epigenomic evolution toward an IDHwt-like phenotype. SIGNIFICANCE: Standard treatments are related to loss of DNA methylation in IDHmut glioma, resulting in epigenetic activation of genes associated with tumor progression and alterations in the microenvironment that resemble treatment-naïve IDHwt glioma.

Novel Fluoroquinolones with Possible Antibacterial Activity in Gram-Negative Resistant Pathogens: In Silico Drug Discovery.

Antibiotic resistance is a global threat to public health, and the search for new antibacterial therapies is a current research priority. The aim of this in silico study was to test nine new fluoroquinolones previously designed with potential leishmanicidal activity against Campylobacter jejuni, Escherichia coli, Neisseria gonorrhoeae, Pseudomonas aeruginosa, and Salmonella typhi, all of which are considered by the World Health Organization to resistant pathogens of global concern, through molecular docking and molecular dynamics (MD) simulations using wild-type (WT) and mutant-type (MT) DNA gyrases as biological targets. Our results showed that compound 9FQ had the best binding energy with the active site of E. coli in both molecular docking and molecular dynamics simulations. Compound 9FQ interacted with residues of quinolone resistance-determining region (QRDR) in GyrA and GyrB chains, which are important to enzyme activity and through which it could block DNA replication. In addition to compound 9FQ, compound 1FQ also showed a good affinity for DNA gyrase. Thus, these newly designed molecules could have antibacterial activity against Gram-negative microorganisms. These findings represent a promising starting point for further investigation through in vitro assays, which can validate the hypothesis and potentially facilitate the development of novel antibiotic drugs.

Effectiveness of the Unified Protocol for the transdiagnostic treatment of emotional disorders in online and group format in Argentina: study protocol for a randomized controlled trial.

BACKGROUND: The Unified Protocol (UP) is a transdiagnostic intervention based on emotional regulation for the treatment of emotional disorders. Its application in individual and group formats has been studied worldwide, obtaining similar results to specific protocols but with a lower drop-out rate and improving the cost-benefit ratio, since a larger number of patients can benefit from it. Moreover, the inclusion of digital technologies in psychotherapy aims to improve the accessibility of treatments, especially since the pandemic of COVID-19 that forced the implementation of treatments through teletherapy increasing its use. To date, no studies have been carried out in Argentina on the application of the UP in a group format and through teletherapy. The aim of the present study is to evaluate the efficacy of the UP in a group format and through teletherapy in the Argentine population. METHODS: A parallel-group, controlled, randomized trial, with pre-post and repeated follow-up measures intergroup design will be conducted. One hundred eighty patients will be randomized to one of the following conditions: an online, group-based UP intervention or a waiting list. The Beck Depression Inventory-II and the Beck Anxiety Inventory will be used to compare primary outcomes and the Beck Hopelessness Scale, Difficulties in Emotion Regulation Scale, Positive Affect and Negative Affect Scale, and Multicultural Quality of Life Index will be administered for secondary outcomes at baseline, post-intervention, and 3 months follow-up. Ad-hoc questionnaires will be used to assess patients' experiences and treatment satisfaction. DISCUSSION: The purpose of this trial is to evaluate the efficacy of the online and group application of the UP in the Argentine population, as well as to evaluate the patient's experience and satisfaction with the treatment. It is expected that the findings of this study will be useful in reducing anxious and depressive symptomatology, will allow us to adapt the UP to our culture, and will improve accessibility to treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT05275322. Registered on 11 March 2022.

Sun exposure practices, attitudes and knowledge among students and teachers at a University School of Health Sciences in Ecuador.

Skin cancer incidence is increasing worldwide. Late adolescence and young adulthood are fundamental stages of life to acquire good sun exposure practices, regarding both personal involvement in skin cancer prevention and being a role model for others, especially in a health education environment. This descriptive cross-sectional study is based on the validated CHACES questionnaire to study sun exposure and photoprotection behavior among students and teachers at the School of Health Sciences in the National University of Chimborazo, Riobamba (Ecuador). University members (814 students (89.8 %) and 93 teachers (10.2 %)) were studied, with a predominance of females and light-skin phototypes in both groups. Similar results were obtained regarding sun exposure, with higher recreative exposure in the teachers' group and higher occupational exposure in students. However, students significantly showed lower avoiding midday sun (41.9 % vs 60.9 %), and lower use of sunglasses (10.1 % vs. 41.6 %). Attitudes towards the sun and photoprotection knowledge issues were also equivalent between students and teachers (6.1/10 vs 6.2/10). Students' sunburn rate last year reaches 88.4 % and 52.7 % in teachers (p < 0.001). Using a multivariable logistic regression model, we identified risk factors associated with a greater risk of sunburn in our population. This study highlights areas to be improved regarding knowledge, attitudes and, especially, practices of photoprotection, among students and teachers at the University of Chimborazo. These results point out that awareness-raising campaigns should be implemented to reduce sunburns, morbidity and mortality of skin cancer in this environment.

When Do Smartwatch Heart Rate Concerns in Children Indicate Arrhythmia?

OBJECTIVE: To determine the incidence and predictors of true arrhythmia in pediatric patients presenting with concerns about smartwatch cardiac data. STUDY DESIGN: Single-center, retrospective cohort study of children aged 10-18 years who had presented to a pediatric cardiology clinic between January 2018 and December 2021 with concerns related to smartwatch cardiac data. The primary study outcome was diagnosis of arrhythmia based on clinical evaluation or documentation of arrhythmia by clinical testing. RESULTS: There were 126 patients (mean age 15.6 ± 2.4 years) who presented with a smartwatch-based rhythm concern, with tachycardia in 89%. In all, 19 of 126 (15%) patients were diagnosed with true arrhythmia. The odds of a true arrhythmia diagnosis with symptoms vs no symptoms were 3.2 (95% CI 0.7-14.5), and with heart rate (HR) ≥190 beats/min vs HR <190 beats/min, it was 14.3 (95% CI 3.8-52.8). The positive predictive value of HR ≥190 beats/min and symptoms together to predict arrhythmia was only 39% (95% CI 28-52). The negative predictive value for arrhythmia having neither symptoms nor HR >190 was 95% (95% CI 75-99). CONCLUSION: The likelihood of a true arrhythmia in pediatric patients presenting with a smartwatch-based HR concern was low. Rarely, smartwatch electrograms or trend data were sufficient for arrhythmia diagnosis.

Prevalence and severity of molar-incisor hypomineralization, is there an association with socioeconomic status? A cross-sectional study in Chilean schoolchildren.

PURPOSE: Data about molar-incisor hypomineralization (MIH) prevalence and its severity remains limited for some Latin American countries. Furthermore, its association with socioeconomic status (SES) is still unclear. Thus, this study aims to determine the prevalence and severity of MIH in Santiago, Chile and explore its association with SES. METHODS: A cross-sectional study with schoolchildren between 6 and 12 years was conducted. Children were evaluated using the European Academy of Paediatric Dentistry to diagnose MIH, and the Mathu-Muju and Wright criteria to determine its severity. RESULTS: A total of 1,270 children were included. The MIH prevalence was 12.8% without association with gender (p = 0.609). Prevalence was higher among schoolchildren ages 8 and 9 (p = 0.002), and in lower SES (p = 0.007). MIH mild cases were the most prevalent (63%), and severity was not related to gender (p = 0.656), age (p = 0.060), or SES (p = 0.174). CONCLUSIONS: The prevalence of MIH in the province of Santiago, Chile is 12.8% and was found to have a higher incidence in 8-9-year-old students and among those categorized by low SES. Furthermore, MIH prevalence was associated with low SES. IMPLICATIONS: Public health policies to address MIH in Chile should start with schoolchildren aged 8 to 9, and with low SES.

First Case Reports of Nontuberculous Mycobacterial (NTM) Lung Disease in Ecuador: Important Lessons to Learn.

Nontuberculous mycobacteria (NTM) lung infections are often misdiagnosed as tuberculosis, which can lead to ineffective antibiotic treatments. In this report, we present three cases of NTM lung infections in Ecuador that were initially diagnosed and treated as tuberculosis based on the results of sputum smear microscopy. The patients, all male, included two immunocompetent individuals and one HIV-positive subject. Unfortunately, sputum culture was not initiated until late in the course of the disease and the cause of the lung infection, Mycobacterium avium complex (MAC), was only identified after the patients had either passed away or were lost to follow-up. These cases are the first documented cases of NTM lung infections in the English medical literature from Ecuador. We emphasize the importance of accurate diagnosis of NTM infections by culture and identification to species level. Sputum smear staining alone cannot differentiate between mycobacterial species, which can lead to misidentification and ineffective treatments. Additionally, reporting NTM pulmonary disease as a notifiable disease to national TB control programs is recommended to obtain accurate prevalence data. These data are critical in determining the importance of this public health problem and the necessary actions needed to address it.

Mesenchymal stromal cell-derived membrane particles: A novel cell-free therapy for inflammatory bowel diseases.

Inflammatory bowel diseases (IBD), including ulcerative colitis, are chronic and idiopathic inflammations of the gastrointestinal tract. A disruption of the epithelial barrier and an imbalance between Th1 and Th2 subsets are associated with the onset and progression of these diseases. Mesenchymal stromal cells (MSC) are a promising therapy for IBD. However, cell-tracking studies have shown that intravenously infused MSC localize to the lungs and present short-term survival. To reduce practical complexities arising from living cells, we generated membrane particles (MP) from MSC membranes, which possess some of the immunomodulatory properties of MSC. This study investigated the effect of MSC-derived MP and conditioned media (CM) as cell-free therapies in the dextran sulfate sodium (DSS)-induced colitis model. Acute colitis was induced in C57BL/6 mice by oral administration of 2% DSS in drinking water ad libitum from days 0 to 7. Mice were treated with MP, CM, or living MSC on days 2 and 5. Our findings revealed that MP, CM, and living MSC ameliorated DSS-induced colitis by reducing colonic inflammation, the loss of colonic goblet cells, and intestinal mucosa permeability, preventing apoptosis of damaged colonic cells and balancing Th1 and Th2 activity. Therefore, MSC-derived MP have high therapeutic potential for treating IBD, overcoming the deficiencies of living MSC therapy, and opening novel frontiers in inflammatory diseases medicine.

La cuestión del afrontamiento cadavérico en anatomía y la necesidad de una educación inclusiva / The question of coping with the cadavera in anatomy and the need for an inclusive education

El material cadavérico (MC) humano en la cursada de Anatomía de la carrera de Medicina es el recurso didáctico más antiguo y completo para la enseñanza. Este elemento conlleva importantes significaciones y múltiples atravesamientos (legales, éticos, procedimentales, culturales) que, a partir de la mitad del siglo XX tuvo cuestionamientos y posicionamientos pedagógicos antagónicos en cuanto a su uso. Su utilización genera reacciones emocionales en los estudiantes, a veces negativas, que son procesadas por los mecanismos de defensa y las estrategiasde afrontamiento con que el sujeto cuente. Cuando éstos son sobrepasados puede aparecer un cortejo sindromático que constituye el afrontamiento cadavérico negativo, el cual es un factor que ubica al alumno en un estado de vulnerabilidad con alteraciones en lo académico. Consideramos necesario para este grupo de estudiantes, como para aquellos en su proceso de afrontamiento, estrategias didácticas que los secunden en el proceso y tiendan a una educación inclusiva para que el afrontamiento cadavérico negativo no sea causal de deserción o riesgosidad.

SUMMARY: The human cadaveric material (CM) in the course of Anatomy of the Medicine career is the oldest and most complete didactic resource for teaching. This element carries important meanings and multiple crossings (legal, ethical, procedural, cultural) that, from the middle of the 20th century, had questions and antagonistic pedagogical positions regarding its use. Its use generates emotional reactions in students, often negative, which are processed by the defense mechanisms and coping strategies available to the subject. When these are exceeded, a syndromic courtship may appear that constitutes negative cadaveric coping, which is a factor that places the student in a state of vulnerability with academic alterations. We consider it necessary for this group of students, as well as for those in their coping process, didactic strategies that support them in the process and tend to an inclusive education so that negative cadaverous coping is not a cause of desertion or risk.

A randomized controlled trial to investigate the use of acute coronary syndrome therapy in patients hospitalized with COVID-19: the COVID-19 Acute Coronary Syndrome trial

BACKGROUND: patients hospitalised with covid-19 suffer thrombotic complications. risk factors for poor outcomes are shared with coronary artery disease. Objectives: to investigate efficacy of an acute coronary syndrome regimen in patients hospitalised with covid-19 and coronary disease risk factors. PATIENTS/METHODS: a randomised controlled open-label trial across acute hospitals (uk and brazil) added aspirin, clopidogrel, low-dose rivaroxaban, atorvastatin, and omeprazole to standard care for 28-days. primary efficacy and safety outcomes were 30-day mortality and bleeding. the key secondary outcome was a daily clinical status (at home, in hospital, on intensive therapy unit admission, death). RESULTS: 320 patients from 9 centres were randomised. the trial terminated early due to low recruitment. at 30 days there was no significant difference in mortality (intervention: 11.5% vs control: 15%, unadjusted or 0.73, 95%ci 0.38 to 1.41, p=0.355). significant bleeds were infrequent and not significantly different between the arms (intervention: 1.9% vs control 1.9%, p>0.999). using a bayesian markov longitudinal ordinal model, it was 93% probable that intervention arm participants were more likely to transition to a better clinical state each day (or 1.46, 95% cri 0.88 to 95 2.37, pr(beta>0) =93%; adjusted or 1.50, 95% cri 0.91 to 2.45, pr(beta>0) =95%) and median time to discharge home was two days shorter (95% cri -4 to 0, 2% probability that it was worse). CONCLUSIONS: acute coronary syndrome treatment regimen was associated with a 99 reduction in the length of hospital stay without an excess in major bleeding. a larger trial is needed to evaluate mortality.

To evaluate whether there is a relationship between occlusion and body posture as delineated by a stabilometric platform: A systematic review.

OBJECTIVE: To evaluate whether there is a relationship between occlusion and body posture evaluated using a stabilometric platform. METHODS: Observational studies that analyzed the relationship between dental occlusion (changes in mandibular position and/or dental malocclusion) and body posture evaluated with a stabilometric platform in patients older than 13 years without orthodontic or orthopedic intervention and systemically healthy were considered eligible for inclusion. PubMed, EMBASE, Science Direct, LILACS, and Google Scholar databases were searched to obtain articles published from September 2019 up to March 2020. RESULTS: Twelve articles met the inclusion criteria, of which 66.7% showed a relationship between dental occlusion and body posture, and 33.3% found no relationship. The marked heterogeneity between studies did not allow data to be combined for meta-analyses. CONCLUSION: For the mandibular positions, the postural changes were mainly in the mediolateral direction, while in the malocclusions, they were in the anteroposterior direction.

Acid-Promoted Iso-Nazarov Cyclization of Conjugated trans-Dienones and Dienals for the Synthesis of 2-Cyclopentenones.

The acid-promoted cyclization of all-trans linearly conjugated dienones and dienals constitutes a synthetic strategy for the construction of 2-cyclopentenones.

Vascular Safe Zone During Percutaneous Pinning of the Distal Femur.

PURPOSE: During percutaneous pinning of the pediatric distal femur, iatrogenic vascular damage in the medial thigh is a frequent concern. The proximity of a proximal-medial pin to these vessels has never been studied in children. This study describes a radiologic vascular safe zone that is easily visualized during surgery (wherein the superficial femoral vessels are safely posterior). METHODS: Patients ≤16 years old with magnetic resonance imaging of one or both femora between 2005 and 2020 were retrospectively reviewed. The "at-risk level" (ARL) was defined as the distal-most axial image with a femoral vessel anterior to the posterior condylar axis. A standardized retrograde lateral-to-medial pin was templated. A correlation matrix and least squares regression identified age and physeal width (PW) as ideal independent variables. A vascular safe zone above the medial femoral condyle (MFC) was modeled as a multiple of PW (i.e. x*PW) and needed to satisfy 3 age-dependent criteria: (1) at the ARL, the pin is medial to the vessels, (2) the pin exits the medial thigh before the ARL, and (3) the chosen "vascular safe zone" (x*PW) is always distal to the ARL. RESULTS: Forty-three patients averaging 7.1±3.9 (0.3-16) years old were included. Intra-Class correlation coefficients were excellent (0.92-0.98). All measurements strongly correlated with age ( r =0.76-0.92, P <0.001) and PW ( r =0.82-0.93, P <0.001). All patients satisfied criteria 1. Criteria 2 was satisfied in all patients ≥6 years old, 86% of children 4-5, and only 18% of children ≤3. In children >3 years old, the largest safe zone that satisfied criteria 3 was 2×PW. On average, the ARL was 2.5×PW (99% CI 2.3-2.7) above the MFC. The average ARL in children ≥6 years old was significantly higher than 2×PW (162 mm vs. 120 mm, P <0.001). CONCLUSION: During passage of a distal femur pin into the medial thigh, children ≥6 years old have a vascular safe zone that extends 2×PW proximal to the MFC. Surgeons should be cautious with medial pin placement in children 4-5 years old and, if possible, avoid this technique in children ≤3. LEVEL OF EVIDENCE: IV.

Replication and transmission features of two experimental vaccine candidates against bovine tuberculosis subcutaneously administrated in a murine model.

Cattle vaccination is an attractive approach in compliance with control and eradication programs against Bovine Tuberculosis (bTB). Today, there is no anti bTB vaccine licensed. Two vaccine candidates, MbΔmce2 and MbΔmce2-phoP previously designed were evaluated in BALB/c mice, including the parental M. bovis NCTC10772 and a M. bovis hypervirulent Mb04-303 strains as controls. Sentinel mice (non-inoculated) cohoused with subcutaneous inoculated mice. Persistence, visible tuberculosis lesions (VTL) in lungs and spleens and bacillary load were investigated subcutaneously delivered at 60 and 90 days after inoculation (dpi) as well as their potential transmission to naïve mice. While a 100% survival was observed at 90 dpi without VTL in all groups, transmission was not evidenced in the sentinels mice. Vaccine candidates and control strains were isolated from the spleen of all inoculated mice, while Mb04-303 was isolated from the lungs of one inoculated mouse. Vaccine candidate's attenuation considering survival, lung bacillary load and VTL was confirmed, administrated by the subcutaneous route. Future experiments are necessary to demonstrate whether the persistence of both mutants in the spleen, with low CFU, remains over time to increase the potential increasing risk of dissemination to organs and subsequent transmission to other animals by airborne or other routes.

Phylogeny and biogeography of the ancient spider family Filistatidae (Araneae) is consistent both with long-distance dispersal and vicariance following continental drift.

Filistatids, the crevice weavers, are an ancient family of cribellate spiders without extant close relatives. As one of the first lineages of araneomorph spiders, they present a complicated mixture of primitive and derived characters that make them a key taxon to elucidate the phylogeny of spiders, as well as the evolution of phenotypic characters in this group. Their moderate diversity (187 species in 19 genera) is distributed mainly in arid and semi-arid subtropical zones of all continents, except Antarctica. The objective of this paper is to generate a comprehensive phylogenetic hypothesis for this family to advance the understanding of its morphological evolution and biogeography, as well as lay the basis for a natural classification scheme. By studying the morphology using optical and electronic microscopy techniques, we produced a matrix of 302 morphological characters coded for a sample of 103 species of filistatids chosen to represent the phylogenetic diversity of the family. In addition, we included sequences of four molecular markers (COI, 16S, H3 and 28S; 3787 aligned positions) of 70 filistatid species. The analysis of the data (morphological, molecular, and combined) consistently indicates the separation of the Filistatidae into two subfamilies, Prithinae and Filistatinae, in addition to supporting several groups of genera: Filistata, Zaitunia and an undescribed genus from Madagascar; Sahastata and Kukulcania; all Prithinae except Filistatinella and Microfilistata; Antilloides and Filistatoides; a large Old World group including Pritha, Tricalamus, Afrofilistata, Labahitha, Yardiella, Wandella and putative new genera; and a South American group formed by Lihuelistata, Pikelinia and Misionella. Pholcoides is transferred to Filistatinae and Microfilistata is transferred to Prithinae, and each represents the sister group to the remaining genera of its own subfamily. Most genera are valid, although Pikelinia is paraphyletic with respect to Misionella, so we consider the two genera as synonyms and propose a few new generic combinations. Considering the new phylogenetic hypothesis, we discuss the evolution of some morphological character systems and the biogeography of the family. The ages of divergence between clades were estimated using a total-evidence tip-dating approach by including fossils of Filistatidae and early spider clades; this approach resulted in younger age estimates than those obtained with traditional node-dating. Filistatidae is an ancient family that started diversifying in the Mesozoic and most genera date to the Cretaceous. Clades displaying transcontinental distributions were most likely affected by continental drift, but at least one clade shows unequivocal signs of transoceanic long-distance dispersal.