Vertical growth dynamics of biofilms.

During the biofilm life cycle, bacteria attach to a surface and then reproduce, forming crowded, growing communities. Many theoretical models of biofilm growth dynamics have been proposed; however, difficulties in accurately measuring biofilm height across relevant time and length scales have prevented testing these models, or their biophysical underpinnings, empirically. Using white light interferometry, we measure the heights of microbial colonies with nanometer precision from inoculation to their final equilibrium height, producing a detailed empirical characterization of vertical growth dynamics. We propose a heuristic model for vertical growth dynamics based on basic biophysical processes inside a biofilm: diffusion and consumption of nutrients and growth and decay of the colony. This model captures the vertical growth dynamics from short to long time scales (10 min to 14 d) of diverse microorganisms, including bacteria and fungi.

Electroencephalographic Abnormalities are Common in COVID-19 and are Associated with Outcomes.

OBJECTIVE: The aim was to determine the prevalence and risk factors for electrographic seizures and other electroencephalographic (EEG) patterns in patients with Coronavirus disease 2019 (COVID-19) undergoing clinically indicated continuous electroencephalogram (cEEG) monitoring and to assess whether EEG findings are associated with outcomes. METHODS: We identified 197 patients with COVID-19 referred for cEEG at 9 participating centers. Medical records and EEG reports were reviewed retrospectively to determine the incidence of and clinical risk factors for seizures and other epileptiform patterns. Multivariate Cox proportional hazards analysis assessed the relationship between EEG patterns and clinical outcomes. RESULTS: Electrographic seizures were detected in 19 (9.6%) patients, including nonconvulsive status epilepticus (NCSE) in 11 (5.6%). Epileptiform abnormalities (either ictal or interictal) were present in 96 (48.7%). Preceding clinical seizures during hospitalization were associated with both electrographic seizures (36.4% in those with vs 8.1% in those without prior clinical seizures, odds ratio [OR] 6.51, p = 0.01) and NCSE (27.3% vs 4.3%, OR 8.34, p = 0.01). A pre-existing intracranial lesion on neuroimaging was associated with NCSE (14.3% vs 3.7%; OR 4.33, p = 0.02). In multivariate analysis of outcomes, electrographic seizures were an independent predictor of in-hospital mortality (hazard ratio [HR] 4.07 [1.44-11.51], p < 0.01). In competing risks analysis, hospital length of stay increased in the presence of NCSE (30 day proportion discharged with vs without NCSE: HR 0.21 [0.03-0.33] vs 0.43 [0.36-0.49]). INTERPRETATION: This multicenter retrospective cohort study demonstrates that seizures and other epileptiform abnormalities are common in patients with COVID-19 undergoing clinically indicated cEEG and are associated with adverse clinical outcomes. ANN NEUROL 2021;89:872-883.

Tuberculosis treatment without rifampin in kidney/kidney-pancreas transplantation: A case series report.

BACKGROUND: The best approach to tuberculosis (TB) treatment in transplanted patients is still unknown. Current guidelines are based on evidence either extrapolated from other populations or observational. Rifampin-containing regimens have strong pharmacokinetic interactions with immunosuppressive regimens, with high rates of organ dysfunction and ∼20% mortality. This report describes the results obtained using non-rifampin-containing regimens to treat confirmed TB in adult patients with kidney/kidney-pancreas transplantation. METHODS: Retrospective data analysis from confirmed TB cases in adult kidney/kidney-pancreas transplant recipients (2006-2019), treated "de novo" with non-rifampin-containing regimens. RESULTS: Fifty-seven patients had confirmed TB. Thirty patients were treated "de novo" with non-rifampin-containing regimens. These patients' mean age was 49.24 (±11.50) years. Induction immunosuppression was used in 22 patients. Maintenance immunosuppression was tacrolimus-mycophenolate-steroids in 13 (43%), sirolimus-mycophenolate-steroids in 6 (20%), and other immunosuppressive regimens in 11 (36%). Belatacept was used in four patients. TB localizations: pulmonary 43%; disseminated 23%; extrapulmonary 33%. Twenty-seven (90%) patients completed treatment with isoniazid, ethambutol, and levofloxacin (12 months, 23; 9 months, 3; 6 months, 1); 12 of these patients also received pyrazinamide for the first 2 months and were cured with functioning grafts. One patient (3%) lost the graft while on treatment. Two patients (7%) died while on TB treatment. Median (range) follow-up after completion of TB treatment was 32 (8-150) months. No TB relapses were observed. CONCLUSIONS: Results with non-rifampin-containing TB treatments in this case series were better (in terms of mortality and graft dysfunction) than those previously described with rifampin-containing regimens in transplanted patients.

Tenant-Based Housing Voucher Programs: A Community Guide Systematic Review.

CONTEXT: Unaffordable or insecure housing is associated with poor health in children and adults. Tenant-based housing voucher programs (voucher programs) limit rent to 30% or less of household income to help households with low income obtain safe and affordable housing. OBJECTIVE: To determine the effectiveness of voucher programs in improving housing, health, and other health-related outcomes for households with low income. DESIGN: Community Guide systematic review methods were used to assess intervention effectiveness and threats to validity. An updated systematic search based on a previous Community Guide review was conducted for literature published from 1999 to July 2019 using electronic databases. Reference lists of included studies were also searched. ELIGIBILITY CRITERIA: Studies were included if they assessed voucher programs in the United States, had concurrent comparison populations, assessed outcomes of interest, were written in English, and published in peer-reviewed journals or government reports. MAIN OUTCOME MEASURES: Housing quality and stability, neighborhood opportunity (safety and poverty), education, income, employment, physical and mental health, health care use, and risky health behavior. RESULTS: Seven studies met inclusion criteria. Compared with low-income households not offered vouchers, voucher-using households reported increased housing quality (7.9 percentage points [pct pts]), decreased housing insecurity or homelessness (-22.4 pct pts), and decreased neighborhood poverty (-5.2 pct pts).Adults in voucher-using households had improved health care access and physical and mental health. Female youth experienced better physical and mental health but not male youth. Children who entered the voucher programs under 13 years of age had improved educational attainment, employment, and income in their adulthood; children's gains in these outcomes were inversely related to their age at program entry. CONCLUSION: Voucher programs improved health and several health-related outcomes for voucher-using households, particularly young children. Research is still needed to better understand household's experiences and contextual factors that influence achievement of desired outcomes.

Effectiveness of Two Targeted Temperature Management Methods After Pediatric Postcardiac Arrest: A Multicenter International Study.

OBJECTIVES: It is currently recommended that after return of spontaneous circulation following cardiac arrest, fever should be prevented using TTM through a servo-controlled system. This technology is not yet available in many global settings, where manual physical measures without servo-control is the only option. Our aim was to compare feasibility, safety and quality assurance of servo-controlled system versus no servo-controlled system cooling, TTM protocols for cooling, maintenance and rewarming following return of spontaneous circulation after cardiac arrest in children. DESIGN: Prospective, multicenter, nonrandomized, study. SETTING: PICUs of 20 hospitals in South America, Spain, and Italy, 2012-2014. PATIENTS: Under 18 years old with a cardiac arrest longer than 2 minutes, in coma and surviving to PICU admission requiring mechanical ventilation were included. METHODS: TTM to 32-34°C was performed by prospectively designed protocol across 20 centers, with either servo-controlled system or no servo-controlled system methods, depending on servo-controlled system availability. We analyzed clinical data, cardiac arrest, temperature, mechanical ventilation duration, length of hospitalization, complications, survival, and neurologic outcomes at 6 months. PRIMARY OUTCOME: feasibility, safety and quality assurance of the cooling technique and secondary outcome: survival and Pediatric Cerebral Performance Category at 6 months. MEASUREMENTS AND MAIN RESULTS: Seventy patients were recruited, 51 of 70 TTM (72.8%) with servo-controlled system. TTM induction, maintenance, and rewarming were feasible in both groups. Servo-controlled system was more effective than no servo-controlled system in maintaining TTM (69 vs 60%; p = 0.004). Servo-controlled system had fewer temperatures above 38.1°C during the 5 days of TTM (0.1% vs 2.9%; p < 0.001). No differences in mortality, complications, length of mechanical ventilation and of stay, or neurologic sequelae were found between the two groups. CONCLUSIONS: TTM protocol (for cooling, maintenance and rewarming) following return of spontaneous circulation after cardiac arrest in children was feasible and safe with both servo-controlled system and no servo-controlled system techniques. Achieving, maintaining, and rewarming within protocol targets were more effective with servo-controlled system versus no servo-controlled system techniques.

Strongyloidiasis Outside Endemic Areas: Long-term Parasitological and Clinical Follow-up After Ivermectin Treatment.

Background: Strongyloides stercoralis affects 30-100 million people worldwide. The first-line therapy is ivermectin. Cure is defined as the absence of larvae by parasitological methods 1 year after treatment. To date, no longitudinal parasitological studies for longer periods of time have been conducted to confirm its cure. Here, we evaluated treatment response in long-term follow-up patients with chronic infection using parasitological and molecular methods for larvae or DNA detection. Methods: A prospective, descriptive, observational study was conducted between January 2009 and September 2015 in Buenos Aires, Argentina. Twenty-one patients with S. stercoralis diagnosis were evaluated 30, 60, and 90 days as well as 1, 2, 3, and/or 4 years after treatment by conventional methods (fresh stool, Ritchie method, agar plate culture), S. stercoralis-specific polymerase chain reaction (PCR) in stool DNA, and eosinophil values. Results: During follow-up, larvae were detected by conventional methods in 14 of 21 patients. This parasitological reactivation was observed starting 30 days posttreatment (dpt) and then at different times since 90 dpt. Eosinophil values decreased (P = .001) 30 days after treatment, but their levels were neither associated with nor predicted these reactivations. However, S. stercoralis DNA was detected by PCR in all patients, both in their first and subsequent stool samples, thus reflecting the poor efficacy of ivermectin at eradicating parasite from host tissues. Asymptomatic eosinophilia was the most frequent clinical form among chronically infected patients. Conclusions: These results suggest that the parasitological cure is unlikely. Strongyloidiasis must be considered a chronic infection and ivermectin administration schedules should be reevaluated.

Reweighted autoencoded variational Bayes for enhanced sampling (RAVE).

Here we propose the reweighted autoencoded variational Bayes for enhanced sampling (RAVE) method, a new iterative scheme that uses the deep learning framework of variational autoencoders to enhance sampling in molecular simulations. RAVE involves iterations between molecular simulations and deep learning in order to produce an increasingly accurate probability distribution along a low-dimensional latent space that captures the key features of the molecular simulation trajectory. Using the Kullback-Leibler divergence between this latent space distribution and the distribution of various trial reaction coordinates sampled from the molecular simulation, RAVE determines an optimum, yet nonetheless physically interpretable, reaction coordinate and optimum probability distribution. Both then directly serve as the biasing protocol for a new biased simulation, which is once again fed into the deep learning module with appropriate weights accounting for the bias, the procedure continuing until estimates of desirable thermodynamic observables are converged. Unlike recent methods using deep learning for enhanced sampling purposes, RAVE stands out in that (a) it naturally produces a physically interpretable reaction coordinate, (b) is independent of existing enhanced sampling protocols to enhance the fluctuations along the latent space identified via deep learning, and (c) it provides the ability to easily filter out spurious solutions learned by the deep learning procedure. The usefulness and reliability of RAVE is demonstrated by applying it to model potentials of increasing complexity, including computation of the binding free energy profile for a hydrophobic ligand-substrate system in explicit water with dissociation time of more than 3 min, in computer time at least twenty times less than that needed for umbrella sampling or metadynamics.

Esophageal Cancer Outcomes After Definitive Chemotherapy With Intensity Modulated Proton Therapy.

Purpose: The effectiveness of intensity-modulated proton therapy (IMPT) for esophageal cancer treated with definitive concurrent chemoradiation therapy remains inadequately explored. We investigated long-term outcomes and toxicity experienced by patients who received IMPT as part of definitive esophageal cancer treatment. Patients and Methods: We retrospectively identified and analyzed 34 patients with locally advanced esophageal cancer who received IMPT with concurrent chemotherapy as a definitive treatment regimen at The University of Texas MD Anderson Cancer Center from 2011 to 2021. The median IMPT dose was 50.4 GyRBE in 28 fractions; concurrent chemotherapy consisted of fluorouracil and/or taxane and/or platinum. Survival outcomes were determined by the Kaplan-Meier method, and toxicity was scored according to the Common Terminology Criteria for Adverse Events version 4.0. Results: The median age of all patients was 71.5 years. Most patients had stage III (cT3 cM0) adenocarcinoma of the lower esophagus. At a median follow-up time of 39 months, the 5-year overall survival rate was 41.1%; progression-free survival, 34.6%; local regional recurrence-free survival, 78.1%; and distant metastasis-free survival, 65.0%. Common acute chemoradiation therapy-related toxicities included hematologic toxicity, esophagitis (and late-onset), fatigue, weight loss, and nausea (and late-onset); grade 3 toxicity rates were 26.0% for hematologic, 18.0% for esophagitis and 9.0% for nausea. No patient had grade ≥3 wt loss or radiation pneumonitis, and no patients had pulmonary fibrosis or esophageal fistula. No grade ≥4 events were observed except for hematologic toxicity (lymphopenia) in 2 patients. Conclusion: Long-term survival and toxicity were excellent after IMPT for locally advanced esophageal cancer treated definitively with concurrent chemoradiation therapy. When available, IMPT should be offered to such patients to minimize treatment-related cardiopulmonary toxicity without sacrificing outcomes.

Emergence and maintenance of stable coexistence during a long-term multicellular evolution experiment.

The evolution of multicellular life spurred evolutionary radiations, fundamentally changing many of Earth's ecosystems. Yet little is known about how early steps in the evolution of multicellularity affect eco-evolutionary dynamics. Through long-term experimental evolution, we observed niche partitioning and the adaptive divergence of two specialized lineages from a single multicellular ancestor. Over 715 daily transfers, snowflake yeast were subjected to selection for rapid growth, followed by selection favouring larger group size. Small and large cluster-forming lineages evolved from a monomorphic ancestor, coexisting for over ~4,300 generations, specializing on divergent aspects of a trade-off between growth rate and survival. Through modelling and experimentation, we demonstrate that coexistence is maintained by a trade-off between organismal size and competitiveness for dissolved oxygen. Taken together, this work shows how the evolution of a new level of biological individuality can rapidly drive adaptive diversification and the expansion of a nascent multicellular niche, one of the most historically impactful emergent properties of this evolutionary transition.

Examining the role of oxygen-binding proteins on the early evolution of multicellularity.

Oxygen availability is a key factor in the evolution of multicellularity, as larger and more sophisticated organisms often require mechanisms allowing efficient oxygen delivery to their tissues. One such mechanism is the presence of oxygen-binding proteins, such as globins and hemerythrins, which arose in the ancestor of bilaterian animals. Despite their importance, the precise mechanisms by which oxygen-binding proteins influenced the early stages of multicellular evolution under varying environmental oxygen levels are not yet clear. We addressed this knowledge gap by heterologously expressing the oxygen binding proteins myoglobin and myohemerythrin in snowflake yeast, a model system of simple, undifferentiated multicellularity. These proteins increased the depth and rate of oxygen diffusion, increasing the fitness of snowflake yeast growing aerobically. Experiments show that, paradoxically, oxygen-binding proteins confer a greater fitness benefit for larger organisms under high, not low, O2 conditions. We show via biophysical modeling that this is because facilitated diffusion is more efficient when oxygen is abundant, transporting a greater quantity of O2 which can be used for metabolism. By alleviating anatomical diffusion limitations to oxygen consumption, the evolution of O2-binding proteins in the oxygen-rich Neoproterozoic may have been a key breakthrough enabling the evolution of increasingly large, complex multicellular metazoan lineages.

Gene expression profiling of circulating tumor cells captured by MicroCavity Array is superior to enumeration in demonstrating therapy response in patients with newly diagnosed advanced and locally advanced non-small cell lung cancer.

Background: Circulating tumor cells (CTCs) are a promising non-invasive tool for monitoring therapy response. The only Food and Drug Administration (FDA)-approved test is limited to enumeration of epithelial CTC without further characterization and is not approved for the management of non-small cell lung cancer (NSCLC). Here we use a MicroCavity Array (MCA) system to capture CTC agnostic of epithelial markers for further molecular testing in NSCLC. Methods: CTCs were enumerated by fluorescent microscopy as longitudinal sampling throughout disease management from 213 NSCLC patients. CTC-enriched samples from a subset of 127 patients were interrogated for gene expression by reverse transcription polymerase chain reaction (RT-PCR) using a customized pre-selected panel of 20 genes. Results: At least 1 CTC was detected by enumeration in 53.8% of samples. Most patients had fewer than 5 CTCs (91%) and the highest observed count was 35 CTCs. Enumeration of single CTCs was not prognostic, although detection of CTC clusters at any time point was associated with increased risk of progression [hazard ratio (HR) 3.00, 95% confidence interval (CI): 1.1-8.2, P=0.0318]. In contrast, 124 (97.6%) patients with samples interrogated for gene expression had at least 1 gene detectable in at least 1 sample, and 101 (79.5%) had at least one elevated epithelial gene in at least one timepoint. High expression of BCL2, CD274 [programmed death-ligand 1 (PD-L1)], CDH1, EPCAM, FGFR1, FN1, KRT18, MET and MUC1 were associated with poor prognosis. Patients with CTCs positive for at least 3 epithelial genes at baseline all progressed within 10 months (HR 8.2, P<0.001, 95% CI: 3.2-21.1). BCL2, CD274 (PD-L1), EPCAM and MUC1 remained significant independent prognostic factors in multivariate, time-dependent analyses of progression and death. Conclusions: The selective profile of CTC genes and identification of CTC clusters better correlated with prognosis than enumeration of enriched CTC in NSCLC patients in this study.

Emergence and maintenance of stable coexistence during a long-term multicellular evolution experiment.

The evolution of multicellular life spurred evolutionary radiations, fundamentally changing many of Earth’s ecosystems. Yet little is known about how early steps in the evolution of multicellularity transform eco-evolutionary dynamics, e.g., via niche expansion processes that may facilitate coexistence. Using long-term experimental evolution in the snowflake yeast model system, we show that the evolution of multicellularity drove niche partitioning and the adaptive divergence of two distinct, specialized lineages from a single multicellular ancestor. Over 715 daily transfers, snowflake yeast were subject to selection for rapid growth in rich media, followed by selection favoring larger group size. Both small and large cluster-forming lineages evolved from a monomorphic ancestor, coexisting for over ~4,300 generations. These small and large sized snowflake yeast lineages specialized on divergent aspects of a trade-off between growth rate and survival, mirroring predictions from ecological theory. Through modeling and experimentation, we demonstrate that coexistence is maintained by a trade-off between organismal size and competitiveness for dissolved oxygen. Taken together, this work shows how the evolution of a new level of biological individuality can rapidly drive adaptive diversification and the expansion of a nascent multicellular niche, one of the most historically-impactful emergent properties of this evolutionary transition.

Varied solutions to multicellularity: The biophysical and evolutionary consequences of diverse intercellular bonds.

The diversity of multicellular organisms is, in large part, due to the fact that multicellularity has independently evolved many times. Nonetheless, multicellular organisms all share a universal biophysical trait: cells are attached to each other. All mechanisms of cellular attachment belong to one of two broad classes; intercellular bonds are either reformable or they are not. Both classes of multicellular assembly are common in nature, having independently evolved dozens of times. In this review, we detail these varied mechanisms as they exist in multicellular organisms. We also discuss the evolutionary implications of different intercellular attachment mechanisms on nascent multicellular organisms. The type of intercellular bond present during early steps in the transition to multicellularity constrains future evolutionary and biophysical dynamics for the lineage, affecting the origin of multicellular life cycles, cell-cell communication, cellular differentiation, and multicellular morphogenesis. The types of intercellular bonds used by multicellular organisms may thus result in some of the most impactful historical constraints on the evolution of multicellularity.

Pharmacotherapy for Nonconvulsive Seizures and Nonconvulsive Status Epilepticus.

Most seizures in critically ill patients are nonconvulsive. A significant number of neurological and medical conditions can be complicated by nonconvulsive seizures (NCSs) and nonconvulsive status epilepticus (NCSE), with brain infections, hemorrhages, global hypoxia, sepsis, and recent neurosurgery being the most prominent etiologies. Prolonged NCSs and NCSE can lead to adverse neurological outcomes. Early recognition requires a high degree of suspicion and rapid and appropriate duration of continuous electroencephalogram (cEEG) monitoring. Although high quality research evaluating treatment with antiseizure medications and long-term outcome is still lacking, it is probable that expeditious pharmacological management of NCSs and NCSE may prevent refractoriness and further neurological injury. There is limited evidence on pharmacotherapy for NCSs and NCSE, although a few clinical trials encompassing both convulsive and NCSE have demonstrated similar efficacy of different intravenous (IV) antiseizure medications (ASMs), including levetiracetam, valproate, lacosamide and fosphenytoin. The choice of specific ASMs lies on tolerability and safety since critically ill patients frequently have impaired renal and/or hepatic function as well as hematological/hemodynamic lability. Treatment frequently requires more than one ASM and occasionally escalation to IV anesthetic drugs. When multiple ASMs are required, combining different mechanisms of action should be considered. There are several enteral ASMs that could be used when IV ASM options have been exhausted. Refractory NCSE is not uncommon, and its treatment requires a very judicious selection of ASMs aiming at reducing seizure burden along with management of the underlying condition.

Unexplained Anemia in the Elderly.

Anemia is frequently diagnosed in elderly patients, and it is a key indicator of many reactive and clonal conditions. Furthermore, the older age is the most common presenting age for myelodysplastic syndromes (MDS). Anemia in older age may be attributed to an inflammatory state due to senescence, comorbidities, nutritional deficiencies, or primary bone marrow conditions. As diagnostic possibilities and life expectancy increase, the prevalence of anemia of the elderly increases as well. The etiology has a direct impact on the treatment and quality of life of these patients, in whom is a usual clinical challenge as it may be due to a multifactorial origin. In a minority group, when no etiology is identified, it is classified as unexplained anemia (UA) or clonal cytopenia of unknown significance (CCUS). The underlying cause of anemia remains unexplained in 30% of cases, and a great part of unexplained cytopenia may account for myeloid neoplasms. Anemia in the elderly is associated with worse cognitive and functional outcomes and increased mortality.

Incidence, Mortality, and Survival Trends of Primary CNS Tumors in Cali, Colombia, From 1962 to 2019.

PURPOSE: Global studies have shown varying trends of CNS tumors within geographic regions. In Colombia, the epidemiologic characteristics of CNS neoplasms are not well elucidated. We aimed to provide a summary of the descriptive epidemiology of primary CNS tumors among the urban population of Cali, Colombia. METHODS: We conducted a time-trend study from 1962 to 2019 using the Population-Based Cali Cancer Registry. The age-standardized rates per 100,000 person-years were obtained by direct method using the world standard population. Results were stratified by sex, age group at diagnosis, and histologic subtype. We used Joinpoint regression analysis to detect trends and obtain annual percentage change (APC) with 95% CIs. We estimated 5-year net survival using the Pohar-Perme method. RESULTS: During 1962 to 2016, 4,732 new cases of CNS tumors were reported. From 1985 to 2019, a total of 2,475 deaths from malignant CNS tumors were registered. A statistically significant increase in the trends of incidence (APC, 2.8; 95% CI, 2.1 to 3.5) and mortality (APC, 1.5; 95% CI, 1.1 to 2.0) rates was observed during the study. The most common malignant CNS tumor was glioblastoma (17.8% of all tumors), and the most frequent benign tumor was meningioma (17.2%). Malignancy was more common in males than in females. Unspecified malignant neoplasms represented 32% of all cases. The highest 5-year net survival was 31.4% during 2012 to 2016. CONCLUSION: Our findings demonstrate an increasing burden of primary CNS tumors for the last 60 years, with a steady rate from the early 2010s. There was an improvement of 5-year net survival for the last decade. Males had higher mortality than did females. Additional efforts are needed to fully explore the geographic, environmental, and genetic contributors of CNS malignancies within the region.

Vaccination of rabbits with immunodominant antigens from Sarcoptes scabiei induced high levels of humoral responses and pro-inflammatory cytokines but confers limited protection.

BACKGROUND: Vaccination is an attractive ecological alternative to the use of acaricides for parasite control. However, effective anti-parasite vaccines against sarcoptic mange have not yet been developed. The purpose of this study was first to identify Sarcoptes scabiei immunodominant antigens and second to evaluate them as vaccine candidates in a rabbit/S. scabiei var. cuniculi model. METHODS: The S. scabiei Ssλ15 immunodominant antigen was selected by immunoscreening of a S. scabiei var. hominis cDNA. The full-length cDNA was sequenced and cloned into the pGEX vector and the recombinant protein expressed in BL21 (DE3) cells and purified. A vaccination trial was performed consisting of a test group (n = 8) immunised with recAgs (a mix of two recombinant antigens, Ssλ15 and the previously described Ssλ20∆B3) and a control group (n = 8) immunised with PBS. All analyses were performed with R Statistical Environment with α set at 0.050. RESULTS: The full-length open reading frame of the 1,821 nt cloned cDNA encodes a 64 kDa polypeptide, the sequence of which had 96 % identity with a hypothetical protein of S. scabiei. Ssλ15 was localised by immunostaining of skin sections in the tegument surrounding the mouthparts and the coxa in the legs of mites. Rabbit immunisation with recAgs induced high levels of specific IgG (P < 0.010) and increased levels of total IgEs. However, no significant clinical protection against S. scabiei challenge was detected. Unexpectedly, the group immunised with the recAgs mix had significantly higher lesion scores (P = 0.050) although lower mean mite densities than those observed in the control group. These results might indicate that the lesions in the recAgs group were due not only to the mites density but also to an exacerbated immunological response after challenge, which is in agreement with the specific high levels of pro-inflammatory cytokines (IL-1 and TNFα) detected after challenge in this group. CONCLUSIONS: The selected antigens delivered as recombinant proteins had no clinical protective efficacy against S. scabiei infestation although immunisation reduced mite density. However, these results pave the way for future studies on alternative production systems, adjuvants, delivery methods and combinations of antigens in order to manage stimulation of clinical protective immune responses.

Tratamiento integral de fisura palatina con injerto de lengua: reporte de caso / Sinus floor elevation with a lateral window technique and simultaneous dental implants placement: case report

RESUMEN: La fisura labio palatina (FLP) es una alteración del desarrollo, congénita, de etiología desconocida. La fístula oronasal es la complicación más común de la reparación del paladar con fisura. Los problemas más comunes incluyen hipernasalidad al hablar y el pase de fluidos y comida hacia la cavidad nasal. El caso corresponde a un paciente de 16 años de edad, sexo masculino, con fístula buconasal de 2,1 cm de diámetro mayor en sentido transversal, como secuela de FLP unilateral derecha. Además relata problemas en la alimentación, traspaso de fluidos a la cavidad nasal, problemas de habla por insuficiencia velo faríngea (IVF) valor 9, alteraciones en sus relaciones interpersonales y baja autoestima. Se realizó el injerto de lengua en fístula buconasal, tratamiento de ortodoncia y rehabilitación oral para dar solución estética y funcional. El éxito del tratamiento integral le permitió al paciente mejorar sus relaciones sociales debido a una mayor autoestima.

ABSTRACT: The cleft lip and palate (CLP) is a developmental and congenital anomaly of unknown etiology. The oronasal fistula is the most common complication of the cleft palate reparation. The most common problems are hypernasality on speech and the passage of fluids and food to the nasal cavity. This case is about a sixteen- year-old boy with a 2,1 cm diameter oronasal fistula due to a right unilateral CLP sequel. He also presented alimentation problems, fluid passage to the nasal cavity, speech defects by velopharyngeal insufficiency (VFI), relationships problems and low self-esteem. A tongue graft in the oronasal fistula, orthodontic treatment and oral rehabilitation were made to give an aesthetic and functional solution. The success of the treatment allowed the patient to improve his relationships due to a greater self-esteem.

Prevalencia de sustancias psicoactivas asociadas con muertes violentas en Cali / Prevalence of psychoactive substances associated with violent deaths in Cali

Introducción: El consumo de sustancias psicoactivas se considera un problema mundial que repercute tanto en el sector social, económico y político como en el de salud. Según diferentes estudios, las muertes por violencia tales como accidentes de tránsito, suicidios y homicidios, se fundamentan en el hecho que existe una fuerte influencia del alcohol y otras sustancias psicoactivas. Objetivo: Estimar la prevalencia de sustancias psicoactivas en las muestras biológicas obtenidas durante el procedimiento de necropsia, que fueron analizadas en el laboratorio de Toxicología del Instituto Nacional de Medicina Legal y Ciencias Forenses Regional Suroccidente de Cali, Colombia. Métodos: Estudio transversal de los casos de muerte violenta ocurridos en Cali durante el período de enero de 1998 a junio de 2002 donde se efectuaron 17.434 necropsias, en las cuales se realizó un muestreo aleatorio sistemático y se analizaron 404 casos. Resultados: Del total de las muertes, 50/100 se presentaron en menores de 30 años y 84.8/100 eran hombres. La manera más frecuente de muerte fue por homicidio (53.7/100), seguida por muerte natural (17.8/100), accidente de tránsito (15.5/100), accidental (6.7/100) y suicidio (6.2/100). La prevalencia de sustancias psicoactivas (alcoholemia más drogas de abuso y tóxicas) fue 31.9/100, alcoholemia 23.7/100 y drogas de abuso y sustancias tóxicas 29.2/100. La cocaína (21.2/100) y la marihuana (14.1/100) fueron las drogas de abuso más prevalentes. En 47.4/100 de los suicidios se encontró evidencias de sustancias psicoactivas siendo muy variadas las drogas utilizadas. En homicidio, 35.2/100 tuvo hallazgo de psicotrópicos. Conclusión: La tercera parte de las muertes violentas ocurridas en Cali se asociaron con el consumo de sustancias psicoactivas. Sin lugar a dudas es un llamado de atención para implementar medidas preventivas que enfrenten este problema de salud pública que interesa a todos los sectores