Iron-saturated bovine lactoferrin: a promising chemopreventive agent for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a tumor with minimal chance of cure due to underlying liver diseases, late diagnosis, and inefficient treatments. Thus, HCC treatment warrants the development of additional strategies. Lactoferrin (Lf) is a mammalian multifunctional iron-binding glycoprotein of the innate immune response and can be found as either a native low iron form (native-Lf) or a high iron form (holo-Lf). Bovine Lf (bLf), which shares many functions with human Lf (hLf), is safe for humans and has several anticancer activities, including chemotherapy boost in cancer. We found endogenous hLf is downregulated in HCC tumors compared with normal liver, and decreased hLf levels in HCC tumors are associated with shorter survival of HCC patients. However, the chemoprotective effect of 100% iron saturated holo-bLf on experimental hepatocarcinogenesis has not yet been determined. We aimed to evaluate the chemopreventive effects of holo-bLf in different HCC models. Remarkably, a single dose (200 mg kg-1) of holo-bLf was effective in preventing early carcinogenic events in a diethylnitrosamine induced HCC in vivo model, such as necrosis, ROS production, and the surge of facultative liver stem cells, and eventually, holo-bLf reduced the number of preneoplastic lesions. For an established HCC model, holo-bLf treatment significantly reduced HepG2 tumor burden in xenotransplanted mice. Finally, holo-bLf in combination with sorafenib, the advanced HCC first-line treatment, synergistically decreased HepG2 viability by arresting cells in the G0/G1 phase of the cell cycle. Our findings provide the first evidence suggesting that holo-bLf has the potential to prevent HCC or to be used in combination with treatments for established HCC.

Steady Laminar Flow Decreases Endothelial Glycolytic Flux While Enhancing Proteoglycan Synthesis and Antioxidant Pathways.

Endothelial cells in steady laminar flow assume a healthy, quiescent phenotype, while endothelial cells in oscillating disturbed flow become dysfunctional. Since endothelial dysfunction leads to atherosclerosis and cardiovascular disease, it is important to understand the mechanisms by which endothelial cells change their function in varied flow environments. Endothelial metabolism has recently been proven a powerful tool to regulate vascular function. Endothelial cells generate most of their energy from glycolysis, and steady laminar flow may reduce endothelial glycolytic flux. We hypothesized that steady laminar but not oscillating disturbed flow would reduce glycolytic flux and alter glycolytic side branch pathways. In this study, we exposed human umbilical vein endothelial cells to static culture, steady laminar flow (20 dynes/cm2 shear stress), or oscillating disturbed flow (4 ± 6 dynes/cm2 shear stress) for 24 h using a cone-and-plate device. We then measured glucose and lactate uptake and secretion, respectively, and glycolytic metabolites. Finally, we explored changes in the expression and protein levels of endothelial glycolytic enzymes. Our data show that endothelial cells in steady laminar flow had decreased glucose uptake and 13C labeling of glycolytic metabolites while cells in oscillating disturbed flow did not. Steady laminar flow did not significantly change glycolytic enzyme gene or protein expression, suggesting that glycolysis may be altered through enzyme activity. Flow also modulated glycolytic side branch pathways involved in proteoglycan and glycosaminoglycan synthesis, as well as oxidative stress. These flow-induced changes in endothelial glucose metabolism may impact the atheroprone endothelial phenotype in oscillating disturbed flow.

Defective mitochondria remodelling in B cells leads to an aged immune response.

The B cell response in the germinal centre (GC) reaction requires a unique bioenergetic supply. Although mitochondria are remodelled upon antigen-mediated B cell receptor stimulation, mitochondrial function in B cells is still poorly understood. To gain a better understanding of the role of mitochondria in B cell function, here we generate mice with B cell-specific deficiency in Tfam, a transcription factor necessary for mitochondrial biogenesis. Tfam conditional knock-out (KO) mice display a blockage of the GC reaction and a bias of B cell differentiation towards memory B cells and aged-related B cells, hallmarks of an aged immune response. Unexpectedly, blocked GC reaction in Tfam KO mice is not caused by defects in the bioenergetic supply but is associated with a defect in the remodelling of the lysosomal compartment in B cells. Our results may thus describe a mitochondrial function for lysosome regulation and the downstream antigen presentation in B cells during the GC reaction, the dysruption of which is manifested as an aged immune response.

Lesiones cervicales no cariosas: una revisión sistemática / Non carious cervical lesions: a systematic review

Introducción: las lesiones cervicales no cariosas (NCCL, por sus siglas en inglés) son un grupo de lesiones que afectan el área cervical del órgano dental causando hipersensibilidad dentinaria y defectos estéticos. Objetivo: analizar la literatura sobre las lesiones cervicales no cariosas, su etiología, consideraciones anatómicas, características morfológicas de la lesión y tratamientos no restaurativos. Material y métodos: se realizó una búsqueda en la base de datos PubMed, utilizando las palabras clave: non-carious cervical lesions OR noncarious cervical lesions OR tooth wear OR tooth erosion OR dental abfraction OR abfraction, recopilando un total de 78 artículos. Resultados: es necesario determinar la etiología antes de seleccionar las estrategias de tratamiento para las lesiones cervicales no cariosas. Conocer los distintos tipos de tejidos que componen al órgano dentario facilita la comprensión de los factores que participan en el desarrollo de las lesiones cervicales no cariosas. Esto permite que el tratamiento se enfoque más en la causa del problema que en los síntomas. Con esto podemos modificar diversos factores de manera interceptiva, los tratamientos de terapia con láser y compuestos tópicos son una estrategia mínimamente invasiva. Conclusiones: la mejor manera de describir a las lesiones cervicales no cariosas sería como una enfermedad multifactorial. Se debe prestar especial atención en los métodos de diagnóstico, identificando cofactores que propicien el avance de la lesión, como son la fricción y la biocorrosión. Esta revisión brinda datos que asocian a los factores oclusales como una de las principales causas de una enfermedad que afecta a más de la mitad de la población adulta (AU)

Introduction: non-carious cervical lesions (NCCL) are a group of lesions that affect the cervical area of the dental organ causing dentin hypersensitivity and cosmetic defects. Objective: to know, through a systematic review, the current state of non-carious cervical lesions. Material and methods: a search was conducted in the PubMed database, using the keywords: non-carious cervical lesions OR noncarious cervical lesions OR tooth wear OR tooth erosion OR dental abfraction OR abfraction, compiling a total of 78 articles. Results: determining etiology is necessary before selecting treatment strategies for non-carious cervical lesions (NCCL). Know the different types of tissues that make up the dentary organ, facilitate the understanding of the factors involved in the development of noncarious al cervical lesions. This allows treatment to focus more on the cause of the problem than on symptoms. With this we can modify various factors in an interceptive way, laser therapy treatments and topical compounds, are a minimally invasive strategy. Conclusions: the best way to describe non-carious al cervical lesions would be as a multifactorial disease to which special attention should be paid to both diagnostic methods, identifying cofactors that promote the progression of injury, such as friction and biocorrosion. This review provides data that associates occlusal factors as one of the main causes of a disease that affects more than half of the adult population (AU)

Something to eat: experiences of food insecurity on the farm.

The health of farm owners and farmworkers has significant impacts on farm businesses, farming families, and local rural communities where agriculture is an important driver of social and economic activity. Rural residents and farmworkers have higher rates of food insecurity, but little is known about food insecurity among farm owners and the collective experiences of farm owners and farmworkers. Researchers and public health practitioners have stressed the need for policies that target the health and well-being of farm owners and farmworkers while remaining sensitive to the nature of life on the farm, yet farm owner and farmworker lived experiences have been understudied, especially in relation to one another. In-depth qualitative interviews were conducted with 13 farm owners and 18 farmworkers in Oregon. Modified grounded theory was used to analyze interview data. Data were coded using a three-stage process to identify salient core characteristics of food insecurity. Farm owner and farmworker meanings and interpretations of their food insecurity were often contradicted by evaluated food security scores using validated quantitative measures. According to such measures, 17 experienced high food security, 3 had marginal food security, and 11 had low food security, but narrative experiences suggested higher rates. Narrative experiences were categorized by core characteristics of food insecurity, including seasonal food shortages, resource stretching, working extended hours most days of the week, limited use of food assistance, and the tendency to downplay hardship. These unique factors have important implications for developing responsive policies and programs to support the health and well-being of farm livelihoods whose work enables health and well-being among consumers. Future studies to test the relationships between the core characteristics of food insecurity identified in this study and farm owner and farmworker meanings and interpretations of food insecurity, hunger, and nourishment are warranted.

Variation of muscle recruitment during exercises performed below horizontal arm elevation that target the lower trapezius: A repeated measures cross-sectional study on asymptomatic individuals.

The gold standard exercise for recruitment of the lower trapezius is the Y prone exercise which is performed above 90° of shoulder elevation. However, clinicians often prescribe exercises that avoid high elevation postures during early stages of rehabilitation. Comparatively little data exists on relative muscle recruitment during lower arm elevation exercises. This study examined the EMG activity of four shoulder girdle muscles during four exercises accomplished below 90° of shoulder elevation and compared them to the Y prone while considering sex effects. Variance across exercises of the ratio between upper trapezius and lower trapezius was also explored. 32 healthy participants completed standardized muscle-specific MVCs and two repetitions of each exercise. The side lying external rotation and the wall slide exercises produced the highest peak EMG for the lower trapezius, both 33 and 29% lower than the Y Prone. For the upper trapezius to lower trapezius ratio, the side lying external rotation elicited the lowest value, followed by the Y prone and wall slide (53 and 59% respectively higher). Sex influenced some EMG values, typically interacting with exercise type. Thus, side lying external rotation and the wall slide are recommended for targeting the lower trapezius muscle during early rehabilitation.

Quantification of Intracellular ATP Content in Ex Vivo GC B Cells.

The study of immunometabolism is an important and emerging field in immunology. B-cell activation upon antigen recognition induces profound metabolic changes in the cell, leading to an increase in ATP production to sustain cell proliferation and differentiation. Current methods available to determine the amount of ATP are time-consuming, require extensive sample processing, and need a large amount of starting material. We set up an easy follow-up protocol to determine the relative amount of ATP in living cells, combining cell surface staining with quinacrine. This acridine dye emits a green fluorescent signal in the presence of intracellular ATP. This protocol allows us to determine ATP in small populations of cells using flow cytometry, such as the germinal center.

Pandemic Demand for SARS-CoV-2 Testing Led to Critical Supply and Workforce Shortages in U.S. Clinical and Public Health Laboratories.

COVID-19 has brought unprecedented challenges to clinical and public health laboratories. While U.S. laboratories have continued striving to provide quality test results during the pandemic, the uncertainty and lack of supplies became a significant hurdle, hindering day-to-day laboratory operations and the ability to increase testing capacity for both SARS-CoV-2 and non-COVID-19 testing. In addition, long-standing laboratory workforce shortages became apparent, hindering the ability of clinical and public health laboratories to rapidly increase testing. The American Society for Microbiology, the College of American Pathologists, the National Coalition of STD Directors, and the Emerging Infections Network independently conducted surveys in 2020 and early 2021 to assess the capacity of the nation's clinical laboratories to respond to the increase in demand for testing during the COVID-19 pandemic. The results of these surveys highlighted the shortages of crucial supplies for SARS-CoV-2 testing and supplies for other routine laboratory diagnostics, as well as a shortage of trained personnel to perform testing. The conclusions are based on communications, observations, and the survey results of the clinical laboratory, public health, and professional organizations represented here. While the results of each survey considered separately may not be representative of the entire community, when considered together they provide remarkably similar results, further validating the findings and highlighting the importance of laboratory supply chains and the personnel capable of performing these tests for any response to a large-scale public health emergency.

Implementing Opt-Out HIV Testing in the Alameda County Jails.

Incorporating routine opt-out HIV testing in correctional settings is a critical component of an effective strategy to end the HIV/AIDS epidemic. Between 2012 and 2017, Alameda County jails implemented opt-out HIV testing to identify new cases, link those who were newly diagnosed to care, and reengage those who were previously diagnosed but not in care. Over a 6-year period, 15,906 tests were conducted, with a positivity rate of 0.55% for both newly diagnosed cases and previously diagnosed but out of care. Nearly 80% of those who tested positive were linked to care within 90 days. The high positivity and successful linkage and reengagement with care underscores the need to support HIV testing programs in correctional settings.

Predictive value of patency capsule and magnetic resonance enterography for capsule endoscopy retention in patients with established Crohn's disease.

INTRODUCTION: retention is the most common adverse event of the small bowel capsule endoscopy procedure. Patency capsule (Medtronic, Dublin, Ireland) and magnetic resonance enterography are two diagnostic methods that can prevent small bowel capsule endoscopy retention. The aim of this study was to evaluate the predictive value of these two diagnostic methods. MATERIAL AND METHODS: a prospective, comparative and observational study was performed in patients with established Crohn's disease. All patients had undergone magnetic resonance enterography and patency capsule procedures. If the patency capsule was not retained, the patient underwent a small bowel capsule endoscopy; otherwise, double balloon enteroscopy was performed to locate the stenosis. Magnetic resonance enterography predictive criteria for retention were analyzed in all cases. Sensitivity, specificity, positive predictive value and negative predictive value of the patency capsule and magnetic resonance enterography compared to small bowel capsule endoscopy or double balloon enteroscopy were calculated. RESULTS: forty patients were included (24 female, 55 ± 13 years old). Retention criteria with capsule endoscopy or double balloon enteroscopy were found in six patients, agreeing in five cases with patency capsule and in three cases with magnetic resonance enterography. Sensitivity, specificity, positive predictive value, negative predictive value and Kappa coefficient for predicting retention with the patency capsule were 83 %, 100 %, 100 % and 97 %, respectively, and 50 %, 91 %, 50 % and 91 %, respectively, with magnetic resonance enterography. CONCLUSIONS: patency capsule has a higher sensitivity and positive predictive value than magnetic resonance enterography for preventing small bowel capsule endoscopy retention in Crohn's disease patients.

Imatinib plasma levels in patients with chronic myeloid leukaemia under routine clinical practice conditions.

INTRODUCTION: The addition of imatinib to the therapeutic arsenal for chronic myeloid leukaemia (CML) has changed the natural course of the disease, in such a way that it is now considered a chronic pathology. However, to achieve therapeutic success, it is necessary to reach adequate plasma concentrations to ensure efficacy and safety.In this study, we aimed to evaluate the plasma concentration of imatinib, analysing its influence on effectiveness and safety in patients with CML. METHODS: We performed a descriptive, multicentre study in which imatinib plasma levels from patients diagnosed with CML between 2019-2020 were analysed. An optimal therapeutic range of 750-1500 ng/mL was established for the stratification of patients, according to their minimum plasma concentrations measured at steady state (Cssmin). RESULTS: A total of 28 patients were included, of whom only 39.3% (n = 11) showed Cssmin within the therapeutic range. 100% of patients with Cssmin >750 ng/mL achieved an optimal molecular response, while only 50% of patients with Cssmin <750 ng/mL achieved an optimal molecular response (p = 0.0004). The toxicity rate was 36.4% for patients with Cssmin >1500 ng/mL and 5.9% for those with Cssmin <1500 ng/mL (p = 0.039). CONCLUSIONS: This study aimed to describe the correlation between the toxicity and effectiveness of imatinib according to its Cssmin in routine clinical practice conditions. Based on our findings, it would be certainly justified to monitor patient plasma concentrations of imatinib on a daily routine basis in our hospitals.

Predictive value of patency capsule and magnetic resonance enterography for capsule endoscopy retention in patients with established Crohn’s disease

Introduction: retention is the most common adverse event of the small bowel capsule endoscopy procedure. Patency capsule (Medtronic, Dublin, Ireland) and magnetic resonance enterography are two diagnostic methods that can prevent small bowel capsule endoscopy retention. The aim of this study was to evaluate the predictive value of these two diagnostic methods. Material and methods: a prospective, comparative and observational study was performed in patients with established Crohn’s disease. All patients had undergone magnetic resonance enterography and patency capsule procedures. If the patency capsule was not retained, the patient underwent a small bowel capsule endoscopy; otherwise, double balloon enteroscopy was performed to locate the stenosis. Magnetic resonance enterography predictive criteria for retention were analyzed in all cases. Sensitivity, specificity, positive predictive value and negative predictive value of the patency capsule and magnetic resonance enterography compared to small bowel capsule endoscopy or double balloon enteroscopy were calculated. Results: forty patients were included (24 female, 55 ± 13 years old). Retention criteria with capsule endoscopy or double balloon enteroscopy were found in six patients, agreeing in five cases with patency capsule and in three cases with magnetic resonance enterography. Sensitivity, specificity, positive predictive value, negative predictive value and Kappa coefficient for predicting retention with the patency capsule were 83 %, 100 %, 100 % and 97 %, respectively, and 50 %, 91 %, 50 % and 91 %, respectively, with magnetic resonance enterography. Conclusions: patency capsule has a higher sensitivity and positive predictive value than magnetic resonance enterography for preventing small bowel capsule endoscopy retention in Crohn’s disease patients (AU)

Vancomycin versus daptomycin for the treatment of confirmed gram-positive catheter-related bloodstream infections in oncology patients.

OBJECTIVE: To analyse the effectiveness and safety of daptomycin versus vancomycin on the management catheter-related bloodstream  nfections in oncology patients. METHOD: A retrospective study was carried out including all patients admitted  at the Medical Oncology Unit between 2010 and 2018 with positive blood  cultures confirmed catheter-related bloodstream infections due to gram- positive microorganism, who were treated with either vancomycin or  daptomycin. The primary end point was all cause 30-days mortality, 30-days  hospital readmission and length of hospital stay (length of hospital stay). Results: A total of 70 patients with catheter-related bloodstream infections were included in the present study: vancomycin was administered to  61.4% (n = 43) and daptomycin to 38.6% (n = 27) of  patients. 78.5% (n = 55) of isolated bacteria showed a vancomycin minimum  inhibitory concentration ≤ 1 µg/ml. No differences were observed  between the two groups of patients regarding the 30-day mortality rate rate  (32.6% [n = 14] versus 29.6% [n = 8]; p = 0.797), the 30-day re-admission rate (30.2% [n = 13] versus 29.6% [n = 8]; p = 0.957) or the length of  hospital stay (18.9 versus 16.5 days; p = 0.562). Nephrotoxicity rate was  equivalent in both groups: a 7% (n = 3) of vancomycin goup versus a 7.4% (n  = 2) of daptomycin group (p = 0.946). CONCLUSIONS: Our results show that both antibiotics are equivalent in their  safety and effectiveness. Therefore, vancomycin should continue being the  treatment of chose for gram-positive catheter-related bloodstream infections,  in particular at hospital centres with a low prevalence of strains that show  diminished susceptibility to vancomycin.

OBJETIVO: Analizar la eficacia y seguridad de la daptomicina frente a la  vancomicina en el tratamiento de las infecciones del torrente sanguíneo asociadas a catéter vascular en pacientes oncológicos.Método: Se realizó un estudio retrospectivo que incluyó a los pacientes ingresados en la Unidad de Oncología-Médica entre 2010-2018 con infección del torrente sanguíneo asociada a catéter vascular causada por  grampositivos, y que fueron tratados con vancomicina o daptomicina. Como  objetivos principales se determinaron la tasa de mortalidad por todas las  causas a los 30 días, el reingreso hospitalario a los 30 días y la duración de la  estancia hospitalaria. RESULTADOS: El estudio incluyó 70 pacientes con infecciones del torrente sanguíneo asociadas a catéter vascular: el 61,4% (n = 43) recibió  vancomicina y el 38,6% (n = 27) daptomicina. El 78,5% (n = 55) de las  bacterias aisladas presentaron una concentración mínima inhibitoria de  vancomicina ≤ 1 µg/ml. No se observaron diferencias entre ambos grupos de  pacientes en cuanto a la tasa de mortalidad a 30 días (32,6% [n = 14]  frente al 29,6% [n = 8]; p = 0,797), la tasa de reingreso a 30 días (30,2% [n  = 13] frente al 29,6% [n = 8]; p = 0,957) o la duración de la hospitalización (18,9 frente a 16,5 días; p = 0,562). La tasa de nefrotoxicidad fue equivalente  en ambos grupos: 7% (n = 3) para vancomicina frente al 7,4% (n = 2) para  daptomicina (p = 0,946). CONCLUSIONES: Nuestros resultados muestran que ambos antibióticos son equivalentes en su seguridad y eficacia. Por ello, vancomicina debería seguir siendo el tratamiento de elección para la infección del torrente sanguíneo asociada a catéter vascular, especialmente en centros con  una baja prevalencia de cepas con una susceptibilidad disminuida a  ancomicina.

Critical Consciousness for Connectivity: Decoding Social Isolation Experienced by Latinx and LGBTQ+ Youth Using a Multi-Stakeholder Approach to Health Equity.

Systemic oppression creates a context in which Latinx LGBTQ+ youth experience social isolation. Social isolation has been associated with mental and physical health disparities, including disproportionate levels of depression, substance use, self-harm, and attempted suicide. These disparities are often magnified in rural and suburban areas with fewer identity-affirming spaces. This community-engaged study reports on the formative process of developing a Latinx LGBTQ+ telenovela (soap opera) allyship intervention based on critical consciousness theory. We conducted eight focus groups with community advisory boards, which included Latinx LGBTQ+ youth (n = 12), health and social service providers serving LGBTQ+ youth (n = 10), 4-H Latinx alumni youth (n = 12), and 4-H Latinx parents (n = 8). We interviewed nine Latinx LGBTQ+ youth enrolled in a film-making workshop. As a result of our multi-stakeholder approach, we: (1) described how stakeholders reflected on and decoded intersectional isolation on the individual, community, and structural levels; and (2) identified ways that stakeholders suggested taking action by improving access to resources to address social isolation, provide culturally competent healthcare, and co-create an enabling social environment. Our study indicated the importance of tapping into core values and intersectional identities to build solidarity among and within marginalized groups to dismantle oppressive systems.

The role of SNAP and WIC participation and racialized legal status in U.S. farmworker health.

BACKGROUND: Policies that restrict access to and use of the Supplemental Nutrition Assistance Program (SNAP) and Special Supplemental Nutrition Assistance Program for Women, Infants, and Children (WIC) by legal status may disproportionately disadvantage particular racial and ethnic groups. While immigrant legal status, race, and ethnicity are recognized as independent social determinants of health, studies examining the extent to which legal status structures racial and ethnic health disparities are limited. Research is needed to identify factors that mitigate disparate health outcomes, such as SNAP and WIC. METHODS: Cross-sectional data from the 2009/2010 National Agricultural Workers Survey (N = 3,961) were analyzed. Chi-square tests and logistic regressions examined associations among self-reported health, race, ethnicity, legal status, and SNAP/WIC participation. RESULTS: Farmworkers reporting excellent or good health were more likely to be non-Hispanic White, U.S. citizen, aged 18-25, single, male, educated beyond primary school, living above the poverty level, without chronic health conditions, and located in the Midwest. Hispanic farmworkers had lower odds of reporting excellent or good health (OR 0.27, 95% CI 0.12-0.62). Among SNAP/WIC participants, Hispanic farmworkers had higher odds of reporting excellent or good health (OR 6.74, 95% CI 1.54-29.57) compared to non-Hispanic White farmworkers. There was no significant association between self-reported health and legal status. DISCUSSION: This study complements the extant literature showing racial and ethnic health disparities among the U.S. farmworker population. Results provide valuable insight on the health-protective potential of programs like SNAP and WIC, particularly among Hispanic farmworkers, who may be both less likely to be eligible and more hesitant to participate. These findings underscore the need to expand U.S. farmworkers' eligibility and participation in SNAP and WIC.

The COVID-19 Mirage: A Young Biologist With an Atypical Presentation of a Zoonotic Disease During the COVID-19 Pandemic.

COVID-19 has become one of the main causes of febrile illness among emergency department patients and is always a differential diagnosis to keep in mind. Nonetheless, some patients with a history of exposure, persistent fever, and suspicion of COVID-19 end up having entirely different etiologies. Here, we present the case of a 29-year-old male biologist with an uncommon presentation of a zoonotic disease, characterized by unspecific signs and symptoms, which led to a delayed diagnosis, causing significant emotional distress in the patient. We also coin the term "COVID-19 Mirage," to serve as a constant reminder for clinicians of the effect that COVID-19 has caused on the differential diagnosis of fever of unknown etiology.

Multiscale modeling of presynaptic dynamics from molecular to mesoscale.

Chemical synapses exhibit a diverse array of internal mechanisms that affect the dynamics of transmission efficacy. Many of these processes, such as release of neurotransmitter and vesicle recycling, depend strongly on activity-dependent influx and accumulation of Ca2+. To model how each of these processes may affect the processing of information in neural circuits, and how their dysfunction may lead to disease states, requires a computationally efficient modelling framework, capable of generating accurate phenomenology without incurring a heavy computational cost per synapse. Constructing a phenomenologically realistic model requires the precise characterization of the timing and probability of neurotransmitter release. Difficulties arise in that functional forms of instantaneous release rate can be difficult to extract from noisy data without running many thousands of trials, and in biophysical synapses, facilitation of per-vesicle release probability is confounded by depletion. To overcome this, we obtained traces of free Ca2+ concentration in response to various action potential stimulus trains from a molecular MCell model of a hippocampal Schaffer collateral axon. Ca2+ sensors were placed at varying distance from a voltage-dependent calcium channel (VDCC) cluster, and Ca2+ was buffered by calbindin. Then, using the calcium traces to drive deterministic state vector models of synaptotagmin 1 and 7 (Syt-1/7), which respectively mediate synchronous and asynchronous release in excitatory hippocampal synapses, we obtained high-resolution profiles of instantaneous release rate, to which we applied functional fits. Synchronous vesicle release occurred predominantly within half a micron of the source of spike-evoked Ca2+ influx, while asynchronous release occurred more consistently at all distances. Both fast and slow mechanisms exhibited multi-exponential release rate curves, whose magnitudes decayed exponentially with distance from the Ca2+ source. Profile parameters facilitate on different time scales according to a single, general facilitation function. These functional descriptions lay the groundwork for efficient mesoscale modelling of vesicular release dynamics.

Vulvar Neurodermatitis in a Postmenopausal African-American Patient: A Case Report.

Lichen simplex chronicus commonly presents as a distressing vaginal lesion caused by severe, cyclical itch-scratch behavior. Lichen simplex chronicus is diagnosed by obtaining a detailed medical history, performing a physical exam, and recording of self-reported symptoms. Lichen simplex chronicus can be treated by corticosteroids, immunomodulators, antiepileptics, antihistamines, antidepressants, and phototherapy. Our case describes a 55-year-old female patient who presented to a clinic with recurrent vaginal itching, combined with compulsive scratching behavior that disrupted daily functioning. Physical examination revealed hypertrophic nodules located on the labia minora with scaling and hyperpigmentation. And the patient was diagnosed with lichen simplex chronicus. Empirical treatment with behavioral modifications and clobetasol propionate cream with an occlusive dressing produced significant improvements in symptoms at a six-month follow-up. Lichen simplex chronicus can have unusual presentations and; therefore, must be carefully differentiated from infectious and malignant skin lesions.

Will Polycrystalline Platinum Tip Sliding on a Gold(111) Surface Produce Regular Stick-Slip Friction?

Friction measurements by an atomic force microscope (AFM) frequently showed regular stick-slip friction signals with atomic-scale resolutions. Typically, for an AFM metal tip sliding on a metal crystal surface, the microstructure of the tip made from the thermally evaporated metal coating on a silicon cantilever was polycrystalline. Our detailed molecular dynamics(MD) simulations of a polycrystalline Pt tip (R = 10 nm in radius) sliding on an Au(111) surface revealed how the geometry of the polycrystalline tip took effect on the friction behavior at the contact interface. We found that the apex of the Pt tip with multiple grains near the edge of contact could induce severe plastic deformations of the gold substrate, leading to irregular stick-slip frictions upon sliding. Simulation results showed that in order to achieve a clear stick-slip friction signal with single atomic slips, the apex of the Pt tip must adopt a single crystalline protrusion without any neighboring grains involved in the metal contact. We showed that such a single crystalline protrusion, which presumably could be achieved during initial run-in or wear-out of high-energy Pt atoms in the neighboring grains, was passivated by a large number of gold atoms due to metal adhesion in the contact periphery. Using such a crystalline protrusion tip, we demonstrated that the stick-slip friction produced was very "tolerant" to the adhesion of a large number of gold atoms on the tip apex. We further showed that AFM tip mass used in MD simulations also played an important role in determining the transition between friction regimes, which could be well explained by the Prandtl-Tomlinson thermal activation model.

Vancomicina frente a daptomicina como tratamiento de las bacteriemias asociadas a catéter y causadas por grampositivos en el paciente oncológico / Vancomycin versus daptomycin for the treatment of confirmed gram-positive catheter-related bloodstream infections in oncology patients

Objetivo: Analizar la eficacia y seguridad de la daptomicina frente ala vancomicina en el tratamiento de las infecciones del torrente sanguíneoasociadas a catéter vascular en pacientes oncológicos.Método: Se realizó un estudio retrospectivo que incluyó a los pacientesingresados en la Unidad de Oncología-Médica entre 2010-2018 coninfección del torrente sanguíneo asociada a catéter vascular causadapor grampositivos, y que fueron tratados con vancomicina o daptomicina.Como objetivos principales se determinaron la tasa de mortalidad portodas las causas a los 30 días, el reingreso hospitalario a los 30 días yla duración de la estancia hospitalaria.Resultados: El estudio incluyó 70 pacientes con infecciones del torrentesanguíneo asociadas a catéter vascular: el 61,4% (n = 43) recibió vancomicinay el 38,6% (n = 27) daptomicina. El 78,5% (n = 55) de las bacteriasaisladas presentaron una concentración mínima inhibitoria de vancomicina≤ 1 μg/ml. No se observaron diferencias entre ambos grupos depacientes en cuanto a la tasa de mortalidad a 30 días (32,6% [n = 14] frente al 29,6% [n = 8]; p = 0,797), la tasa de reingreso a 30 días (30,2%[n = 13] frente al 29,6% [n = 8]; p = 0,957) o la duración de la hospitalización(18,9 frente a 16,5 días; p = 0,562). La tasa de nefrotoxicidadfue equivalente en ambos grupos: 7% (n = 3) para vancomicina frente al7,4% (n = 2) para daptomicina (p = 0,946).Conclusiones: Nuestros resultados muestran que ambos antibióticos sonequivalentes en su seguridad y eficacia. Por ello, vancomicina deberíaseguir siendo el tratamiento de elección para la infección del torrentesanguíneo asociada a catéter vascular, especialmente en centros con unabaja prevalencia de cepas con una susceptibilidad disminuida a vancomicina.

Objective: To analyse the effectiveness and safety of daptomycin versusvancomycin on the management catheter-related bloodstream infectionsin oncology patients.Method: A retrospective study was carried out including all patientsadmitted at the Medical Oncology Unit between 2010 and 2018 withpositive blood cultures confirmed catheter-related bloodstream infectionsdue to gram-positive microorganism, who were treated with either vancomycinor daptomycin. The primary end point was all cause 30-daysmortality, 30-days hospital readmission and length of hospital stay (lengthof hospital stay).Results: A total of 70 patients with catheter-related bloodstream infectionswere included in the present study: vancomycin was administeredto 61.4% (n = 43) and daptomycin to 38.6% (n = 27) of patients.78.5% (n = 55) of isolated bacteria showed a vancomycin minimuminhibitory concentration ≤ 1 μg/ml. No differences were observed betweenthe two groups of patients regarding the 30-day mortality rate rate (32.6% [n = 14] versus 29.6% [n = 8]; p = 0.797), the 30-day re-admissionrate (30.2% [n = 13] versus 29.6% [n = 8]; p = 0.957) or the lengthof hospital stay (18.9 versus 16.5 days; p = 0.562). Nephrotoxicity ratewas equivalent in both groups: a 7% (n = 3) of vancomycin goup versus a7.4% (n = 2) of daptomycin group (p = 0.946).Conclusions: Our results show that both antibiotics are equivalent intheir safety and effectiveness. Therefore, vancomycin should continuebeing the treatment of chose for gram-positive catheter-related bloodstreaminfections, in particular at hospital centres with a low prevalence ofstrains that show diminished susceptibility to vancomycin.