Development, implementation and evaluation of a multinational FLS mentorship programme in Latin America.

Realising the benefits of systematic secondary fracture prevention requires supporting local sites to get started and becoming effective. We here describe the development, implementation and impact of a regional fracture liaison service (FLS) mentorship programme in Latin America that led to 64 FLS getting started and coverage of 17,205 patients. INTRODUCTION: Despite treatments and service models to deliver effective secondary fracture prevention, most patients are left untreated after a fragility fracture. To improve the capability to get FLS started and more effective, we describe the development, implementation and evaluation of an international programme to develop national communities of FLS mentors as part of the Capture the Fracture Partnership in Latin America. METHODS: The IOF regional team and the University of Oxford developed the curriculum and associated resources for training mentors in setting up FLS, service improvement and mentorship. Mentors were selected during a preparatory meeting, trained using live online sessions followed by regular mentor-led post-training meetings. The programme was evaluated using a pre-training needs assessment and post-training evaluation based on Moore's outcomes. RESULTS: The mentorship programme was initiated in Mexico, Brazil, Colombia and Argentina. The mentors were multidisciplinary, including orthopaedic surgery, rehabilitation, rheumatology, endocrinology, geriatrics, gynaecology and internal medicine. There was 100% participation in training sessions and reported satisfaction with the training. Since the initiation of the training programme, 22 FLS have been set up in Mexico, 30 in Brazil, 3 in Colombia and 9 in Argentina, in comparison with two in Chile and none in any other LATAM countries that were not involved in the mentorship programme. This equates to approximately 17,025 additional patients identified from 2019 to 2021 after initiation of mentorship. The mentors have engaged with 58 FLS for service development. Post-training activities include two published national best practice guidelines and other country-specific resources for FLS in the local language. CONCLUSION: Despite the COVID pandemic, the mentorship pillar of the Capture the Fracture Partnership has developed a community of FLS mentors with measurable improvement in national FLS provision. The programme is a potentially scalable platform to develop communities of mentors in other countries.

Relationship between cognition and age at onset of first-episode psychosis: comparative study between adolescents, young adults, and adults.

Psychotic disorders typically manifest from late adolescence to early adulthood, and an earlier onset might be associated with greater symptom severity and a worse long-term prognosis. This study aimed to compare the cognitive characteristics of patients with first-episode psychosis (FEP) by their age at onset. We included 298 patients diagnosed with FEP and classified them as having an early onset (EOS), youth onset (YOS), or adult onset (AOS) based on age limits of ≤ 18 years (N = 61), 19-24 years (N = 121), and ≥ 25 years (N = 116), respectively. Socio-demographic and clinical variables included age at baseline, gender, socio-economic status, antipsychotic medication, DSM-IV diagnoses assessed by clinical semi-structured interview, psychotic symptom severity, and age at onset. Neuropsychological assessment included six cognitive domains: premorbid intelligence, working memory, processing speed, verbal memory, sustained attention, and executive functioning. The EOS group had lower scores than the YOS or AOS groups in global cognition, executive functioning, and sustained attention. Although the scores in the YOS group were intermediate to those in the EOS and AOS groups for most cognitive factors, no statistically significant differences were detected between the YOS and AOS groups. Age at onset results in specific patterns of cognitive interference. Of note, impairment appears to be greater with EOS samples than with either YOS or AOS samples. A longitudinal study with a larger sample size is needed to confirm our findings.

Novel Nanotube Multiquantum Dot Devices.

Addressable quantum states well isolated from the environment are of considerable interest for quantum information science and technology. Carbon nanotubes are an appealing system, since a perfect crystal can be grown without any missing atoms and its cylindrical structure prevents ill-defined atomic arrangement at the surface. Here, we develop a reliable process to fabricate compact multielectrode circuits that can sustain the harsh conditions of the nanotube growth. Nanotubes are suspended over multiple gate electrodes, which are themselves structured over narrow dielectric ridges to reduce the effect of the charge fluctuators of the substrate. We measure high-quality double- and triple-quantum dot charge stability diagrams. Transport measurements through the triple-quantum dot indicate long-range tunneling of single electrons between the left and right quantum dots. This work paves the way to the realization of a new generation of condensed-matter devices in an ultraclean environment, including spin qubits, mechanical qubits, and quantum simulators.

Evaluation of Expanded Criteria Donors Using the Kidney Donor Profile Index and the Preimplantation Renal Biopsy.

The increasing comorbidity of kidney transplant (KT) donors make it necessary to develop scores to correctly assess the quality of kidney grafts. This study analyzes the usefulness of the preimplantation biopsy and the Kidney Donor Profile Index (KDPI) as indicators of KT survival from expanded criteria donors (ECD). Retrospective study of KT in our center between January 2010 to June 2019 who received a kidney from an ECD and underwent a preimplantation biopsy. 266 KT were included. Graft survival was categorized by KDPI quartiles: Q1 = 86%, Q2 = 95%, Q3 = 99% and Q4 = 100%. KT from KDPI Q1 presented better survival (p = 0.003) and Q4 donors had worse renal function (p = 0.018) and poorer glomerular filtration rate (3rd month; p = 0.017, 1st year; p = 0.010). KT survival was analyzed according to KDPI quartile and preimplantation biopsy score simultaneously: Q1 donors with biopsy score ≤3 had the best survival, especially comparing against Q3 with a biopsy score >3 and Q4 donors (p = 0.014). In multivariable analysis, hyaline arteriopathy, glomerulosclerosis, and KDPI Q4 were predictors for graft survival. High KDPI and a greater histological injury in the preimplantation biopsy, especially glomerular and vascular lesions, were related to a higher rate of KT loss from ECD.

Regulators of A20 (TNFAIP3): new drug-able targets in inflammation.

Persistent activation of the transcription factor Nuclear factor-κB (NF-κB) is central to the pathogenesis of many inflammatory disorders, including those of the lung such as cystic fibrosis (CF), asthma, and chronic obstructive pulmonary disease (COPD). Despite recent advances in treatment, management of the inflammatory component of these diseases still remains suboptimal. A20 is an endogenous negative regulator of NF-κB signaling, which has been widely described in several autoimmune and inflammatory disorders and more recently in terms of chronic lung disorders. However, the underlying mechanism for the apparent lack of A20 in CF, COPD, and asthma has not been investigated. Transcriptional regulation of A20 is complex and requires coordination of different transcription factors. In this review we examine the existing body of research evidence on the regulation of A20, concentrating on pulmonary inflammation. Special focus is given to the repressor downstream regulatory element antagonist modulator (DREAM) and its nuclear and cytosolic action to regulate inflammation. We provide evidence that would suggest the A20-DREAM axis to be an important player in (airway) inflammatory responses and point to DREAM as a potential future therapeutic target for the modification of phenotypic changes in airway inflammatory disorders. A schematic summary describing the role of DREAM in inflammation with a focus on chronic lung diseases as well as the possible consequences of altered DREAM expression on immune responses is provided.

A screening approach to improve water management practices in undeveloped shale plays, with application to the transboundary Eagle Ford Formation in northeast Mexico.

Hydraulic fracturing (HF) operations have transformed the unconventional energy industry, leading to a global increase in hydrocarbon production. Despite this, only the US, China, Canada and Argentina currently dominate production of unconventional resources, with the majority of shale basins globally remaining unprofitable to develop. An important gap in current water-energy nexus research, which this study addresses, is the assessment of potential water use to satisfy HF procedures in emergent plays. This work presents a screening tool for assessing first-order estimates of water impacts in undeveloped shale plays, testing the approach in the transboundary Eagle Ford (EF) play in northeast Mexico. We couple surface water and groundwater stress indicators derived from global hydrological variables to depict a baseline water stress index. Relative water stress is mapped for proposed blocks to be leased by the Mexican government in the future. We simulate four HF scenarios to assess new total water stress indicators for each block, considering shale production schemes using representative well drilling density (well lateral length(s) per unit area) and HF water intensity (HF water volume per unit lateral length) from existing EF development in Texas. Results suggest that the most feasible management scenario would consider the drilling of ∼1360 new unconventional wells/yr with projected HF water use of ∼57 Mm3/yr (0.7% of the total water withdrawals). The remaining scenarios will largely affect groundwater resources. Though applied to the EF in Mexico, this screening tool can assess water use constraints in emerging unconventional plays globally.

Individual trajectories of cognitive performance in first episode psychosis: a 2-year follow-up study.

Individual changes over time in cognition in patients with psychotic disorders have been studied very little, especially in the case of first episode psychosis (FEP). We aimed to establish whether change in individual trajectories in cognition over 2 years of a sample of 159 FEP patients was reliable and clinically significant, using the reliable change index (RCI) and clinically significant change (CSC) methods. We also studied a sample of 151 matched healthy controls. Patients and controls were assessed with a set of neuropsychological tests, as well as premorbid, clinical and functionality measures. We analysed the course of cognitive measures over time, using analysis of variance, and the individual trajectories in the cognitive measures with the regression-based RCI (RCISRB) and the CSC. The RCISRB showed that between 5.4 and 31.2% of the patients showed deterioration patterns, and between 0.6 and 8.8% showed improvement patterns in these tests over time. Patients showing better cognitive profiles according to RCISRB (worsening in zero to two cognitive measures) showed better premorbid, clinical and functional profiles than patients showing deterioration patterns in more than three tests. When combining RCISRB and CSC values, we found that less than 10% of patients showed improvement or deterioration patterns in executive function and attention measures. These results support the view that cognitive impairments are stable over the first 2 years of illness, but also that the analysis of individual trajectories could help to identify a subgroup of patients with particular phenotypes, who may require specific interventions.

Cryoneurolysis to treat the pain and symptoms of knee osteoarthritis: a multicenter, randomized, double-blind, sham-controlled trial.

OBJECTIVE: Evaluate the efficacy and safety/tolerability of cryoneurolysis for reduction of pain and symptoms associated with knee osteoarthritis (OA). DESIGN: Randomized, double-blind, sham-controlled, multicenter trial with a 6-month follow-up in patients with mild-to-moderate knee OA. Patients were randomized 2:1 to cryoneurolysis targeting the infrapatellar branch of the saphenous nerve (IPBSN) or sham treatment. The primary endpoint was the change from baseline to Day 30 in the Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain score adjusted by the baseline score and site. Secondary endpoints, including visual analogue scale (VAS) pain score and total WOMAC score, were tested in a pre-defined order. RESULTS: The intent-to-treat (ITT) population consisted of 180 patients (n = 121 active treatment, n = 59 sham treatment). Compared to the sham group, patients who received active treatment had a statistically significant greater change from baseline in the WOMAC pain subscale score at Day 30 (P = 0.0004), Day 60 (P = 0.0176), and Day 90 (P = 0.0061). Patients deemed WOMAC pain responders at Day 120 continued to experience a statistically significant treatment effect at Day 150. Most expected side effects were mild in severity and resolved within 30 days. The incidence of device- or procedure-related adverse events was similar in the two treatment groups with no occurrence of serious or unanticipated adverse device effects (ADE). CONCLUSIONS: Cryoneurolysis of the IPBSN resulted in statistically significant decreased knee pain and improved symptoms compared to sham treatment for up to 150 days, and appeared safe and well tolerated.

Insular pathology in young people with high-functioning autism and first-episode psychosis.

BACKGROUND: Autism Spectrum Disorders (ASD) and psychosis share deficits in social cognition. The insular region has been associated with awareness of self and reality, which may be basic for proper social interactions. METHODS: Total and regional insular volume and thickness measurements were obtained from a sample of 30 children and adolescents with ASD, 29 with early onset first-episode psychosis (FEP), and 26 healthy controls (HC). Total, regional, and voxel-level volume and thickness measurements were compared between groups (with correction for multiple comparisons), and the relationship between these measurements and symptom severity was explored. RESULTS: Compared with HC, a shared volume deficit was observed for the right (but not the left) anterior insula (ASD: p = 0.007, FEP: p = 0.032), and for the bilateral posterior insula: (left, ASD: p = 0.011, FEP: p = 0.033; right, ASD: p = 0.004, FEP: p = 0.028). A voxel-based morphometry (VBM) conjunction analysis showed that ASD and FEP patients shared a gray matter volume and thickness deficit in the left posterior insula. Within patients, right anterior (r = -0.28, p = 0.041) and left posterior (r = -0.29, p = 0.030) insular volumes negatively correlated with the severity of insight deficits, and left posterior insular volume negatively correlated with the severity of 'autistic-like' symptoms (r = -0.30, p = 0.028). CONCLUSIONS: The shared reduced volume and thickness in the anterior and posterior regions of the insula in ASD and FEP provides the first tentative evidence that these conditions share structural pathology that may be linked to shared symptomatology.

Dopaminergic regulation of olfactory type G-protein α subunit expression in the striatum.

BACKGROUND: In rodents, the olfactory type G-protein α subunit (Gαolf) couples the dopamine D1 receptor (D1R) to adenylyl cyclase, triggering intracellular signaling and neuronal activation. In the striatum, Gαolf is enriched in the striosomes. Changes in Gαolf protein levels have been observed after dopamine depletion. However, the regulation of Gαolf expression by dopamine and dopamine receptors is not fully understood. METHODS: To address this, Striatal Gαolf expression pattern was studied in wild-type and genetically engineered mice lacking D1R, D2R (D2 receptor), and downstream regulatory element antagonist modulator (DREAM) protein whose dopamine levels were manipulated. Dopamine depletion was accomplished by 6-hydroxydopamine (6-OHDA) or by Pitx3 ablation, and dopamine replacement by chronic levodopa (l-dopa). The Gαolf levels were analyzed by immunohistochemistry, Western blot, and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: Our results demostrate that Dopamine depletion or inactivation of D1R abolished the striosomal pattern of Gαolf expression and increased Gαolf protein levels. Dopamine replacement in wild-type lesioned mice reestablished both the expression pattern and protein levels, but paradoxically increased Gαolf messenger RNA (mRNA). In D1R(-/-) mice, dopamine depletion decreased striatal Gαolf expression, whereas l-dopa did not restore either Gαolf levels or its expression pattern. Inactivation of D2R or changes in the cAMP/PKA signaling pathway downstream of Gαolf did not modify its expression. CONCLUSION: Our results show a homeostatic, negative regulation of Gαolf by dopamine and by D1R stimulation, which are also required for the striosomal Gαolf pattern. These results shed light on the regulation of Gαolf by dopamine signaling that could be involved in the pathophysiology of the maladaptive response to chronic l-dopa treatment in Parkinson's disease.

Heart Rate Variability: a Follow-up in Elite Soccer Players Throughout the Season.

Heart rate variability (HRV) can provide useful information on physiological adaptations to training, but its role is unknown in professional soccer. The aim of this study was to determine an HRV profile in professional soccer over a season. A total of 504 records were made of the heart beat signal throughout a season from 22 professional soccer players. HRV was recorded in a sitting position, early morning and fasting for a period of 10 min. Standard deviation 1 and 2 (SD1, SD2), standard deviation of normal to normal R-R intervals (SDNN), Root Mean Square of the Successive Differences (rMSSD), percentage of RR intervals > 50 ms (pNN50), Sample Entropy (SampEn), Stress Score (SS) and sympathetic/parasympathetic ratio (S/PS ratio) were calculated. SDNN, rMSSD, pNN50, SD1 and SD2 showed an identical behaviour throughout the season, with lower values in the pre-season and the end of the season. SS and S/PS ratio indicated a sympathetic stress alert in the same periods. A weekly recording of the HRV over a 10 min period that includes a Poincaré plot with SS and S/PS ratio and at least one variable of the time domain is a useful tool for the follow-up of the individual assimilation of weekly workloads, including the game.

Bovine rabies cases in Ecuador: a retrospective cross-sectional observational study (2007 to 2020).

The hematophagous bats are usually the main reservoir of sylvatic rabies, being one of the most important viral zoonoses affecting humans and livestock in Latin America. Despite the most countries have already studied spatio-temporal distribution of bovine rabies, however, in Ecuador, little has been reported about the state of rabies in the country. Aiming to this objective, a descriptive observational study was realized from 2007 to 2020 based on the formal reports by WAHI-OIE and surveillance of bovine rabies retrieved from its official website. During the study period in Ecuador, some 895 cases of rabies were confirmed in cattle. In addition, in the total of bovine rabies cases seen in Andean and Coast regions (185 effected bovines), Loja and Esmeraldas had 95 (6.16% cases per 10,000 animals) and 51 (1.7% cases per 10,000 animals), respectively. Furthermore, the Amazon region indicated higher rabies cases in cattle than to the observed in other regions (710 rabies cases) while it was highly fluctuating with respect to the years (9.74 to 42.82% cases per 10,000 animals). However, Zamora (292 rabies cases), Orellana (115 rabies cases) and Sucumbíos (113 rabies cases) yielded the highest incidence rates than other provinces (9 to 42% cases per 10,000 animals). Based on this evidence, it has been fundamental to assess the current national program for preventing and control of the sylvatic rabies, being also necessary to include concept of the ecology of the vampire bat. Regardless of these results, vaccination is vital for control programs to prevent rabies in livestock and need to be widely increased for limiting their geographic and temporal spread.

[There is no difference in clinical outcomes in patients with distal Neer II and Neer V clavicle fractures treated with or without coracoclavicular augmentation systems]. / No existe diferencia en desenlaces clínicos en pacientes con fracturas de clavícula distal Neer II y Neer V tratados con o sin sistemas de aumentación coracoclavicular.

INTRODUCTION: the use of coracoclavicular augmentation systems together with locking plates in the treatment of unstable distal clavicle fractures (Neer II and Neer V) is controversial. MATERIAL AND METHODS: patients with unstable distal clavicle fractures treated between 2013-2022 were retrospectively reviewed. The patients were divided into two groups: patients treated with locking plates (P group) and patients treated with locking plates and coracoclavicular augmentation systems (PCC group). Postoperative complications, modified preoperative and final coracoclavicular distance (CC), and outcomes on the Visual Analog Scale (VAS) and Quick Disabilities of the Arm, Shoulder, and Hand (Quick DASH) were recorded. RESULTS: 16 of 23 patients were treated with plates only, and 7 of 23 were treated with plates and coracoclavicular augmentation systems. One case showed no fracture consolidation, and there was one case of cutaneous infection. The mean final CC distance was 23.7 in the P group and 22.1 in the PCC group. The mean VAS score was 1.3 in both the P and PCC groups, while the mean Quick DASH score was 5.5 in the P group and 8.1 in the PCC group. No significant differences were found in CC distance, VAS or Quick DASH scores. CONCLUSION: the use of locking plates is likely sufficient in the management of unstable distal clavicle fractures, as there were no significant differences in functional outcomes in this study when coracoclavicular augmentation systems were used together with locking plates.

INTRODUCCIÓN: el uso de sistemas de aumentación coracoclaviculares en combinación con placas bloqueadas en el tratamiento de las fracturas de clavícula distal inestables es controvertido. MATERIAL Y MÉTODOS: se han revisado retrospectivamente los pacientes con fracturas distales de clavícula inestables tratados entre 2013-2022 en Hospital Clínic de Barcelona. Se dividieron a los pacientes en dos grupos: pacientes tratados con placas bloqueadas (grupo P) y pacientes tratados con placas bloqueadas y sistemas de aumentación coracoclaviculares (grupo PCC). Se registraron las complicaciones postoperatorias, distancia CC (coracoclavicular) modificada preoperatoria y final, así como los resultados en la escala visual analógica (EVA) y en el Quick Disabilities of the Arm, Shoulder and Hand (Quick DASH). RESULTADOS: de un total de 23 pacientes, 16 se trataron sólo con placas y siete con placas y sistemas de aumentación coracoclaviculares. Se observó ausencia de consolidación en un caso e infección cutánea en otro. La distancia CC final media fue de 23.7 mm en el grupo P y de 22.1 mm en el grupo PCC. La media de la EVA fue de 1.3 en ambos grupos, mientras que el Quick DASH tuvo media de 5.5 en el grupo P y de 8.1 en el grupo PCC. No se encontraron diferencias significativas en la distancia CC, en la EVA ni en el Quick DASH. CONCLUSIÓN: los resultados sugieren que el uso de placas bloqueadas es probablemente suficiente en el manejo de las fracturas de clavícula distales inestables, sin observar diferencias significativas en los resultados funcionales al agregar sistemas de aumentación coracoclavicular.

[Functional results of a rapid recovery program compared to the usual protocol in total knee arthroplasty]. / Resultados funcionales de un programa de recuperación rápida comparado con el protocolo habitual en artroplastía total de rodilla.

INTRODUCTION: rapid recovery programs in joint replacement surgery are effective in developed countries; The objective of this study was to evaluate the functional outcomes of a rapid recovery program in our population and to compare them with the results of the usual protocol. MATERIAL AND METHODS: a randomized single blinded clinical trial was conducted with patients who were candidates for total knee arthroplasty (n = 51) recruited from May 2018 to December 2019. group A (n = 24) received a rapid recovery program and group B (n = 27) received the usual protocol, with follow-up for 12 months. For statistical analysis, the Student's t test (parametric continuous variables), Kruskal-Wallis (nonparametric continuous variables) and the chi-square test (categorical variables) were used. RESULTS: statistically significant differences were found between groups in pain at two months (group A 3.4 ± 1.3 vs group B 4.2 ± 1.4, p = 0.04) and six months (1 ± 0.8 vs 1.7 ± 1.2, p = 0.01), with the WOMAC questionnaire at two months (group A 74.5 ± 7.2 vs group B 67.2 ± 7.5, p 0.01), six months (88.7 ± 5.3 vs 83.0 ± 4.8, p 0.01) and 12 months (90.1 ± 4.5 vs 86.7 ± 4.3, p 0.01), and with the IDKC questionnaire at two months (group A 62.9 ± 7.0 vs group B 55.9 ± 6.1, p 0.01), six months (74.3 ± 2.7 vs 71.1 ± 3.9, p 0.01) and 12 months (75.4 ± 3.0 vs 72.6 ± 3.5, p 0.01). CONCLUSIONS: the results obtained in this study suggest that the implementation of these programs can be a safe and effective alternative in terms of reducing pain and functional capacity in our population.

INTRODUCCIÓN: los programas de recuperación rápida en cirugía de reemplazo articular son eficaces en países desarrollados; el objetivo de este estudio fue evaluar los resultados funcionales de un programa de recuperación rápida en nuestra población y comprarlos con los resultados del protocolo habitual. MATERIAL Y MÉTODOS: se realizó un ensayo clínico no ciego simple aleatorizado con pacientes candidatos a artroplastía total de rodilla (n = 51) reclutados de Mayo de 2018 a Diciembre de 2019. El grupo A (n = 24) recibió un programa de recuperación rápida y el grupo B (n = 27) recibió el protocolo habitual, con seguimiento durante 12 meses. Para el análisis estadístico se utilizó la prueba de t de Student (variables continuas paramétricas), Kruskal-Wallis (variables continuas no paramétricas) y la prueba de 2 (variables categóricas). RESULTADOS: se encontraron diferencias estadísticamente significativas entre grupos en el dolor a los dos meses (grupo A 3.4 ± 1.3 versus grupo B 4.2 ± 1.4, p = 0.04) y seis meses (1 ± 0.8 versus 1.7 ± 1.2, p = 0.01), con el cuestionario WOMAC a los dos meses (grupo A 74.5 ± 7.2 versus grupo B 67.2 ± 7.5, p 0.01), seis meses (88.7 ± 5.3 versus 83.0 ± 4.8, p 0.01) y 12 meses (90.1 ± 4.5 versus 86.7 ± 4.3, p 0.01) y con el cuestionario IDKC a los dos meses (grupo A 62.9 ± 7.0 versus grupo B 55.9 ± 6.1, p 0.01), seis meses (74.3 ± 2.7 versus 71.1 ± 3.9, p 0.01) y 12 meses (75.4 ± 3.0 versus 72.6 ± 3.5, p 0.01). CONCLUSIONES: los resultados obtenidos en este estudio sugieren que la implementación de estos programas puede ser una alternativa segura y eficaz en cuanto a la disminución del dolor y a la capacidad funcional en nuestra población.

Social Cognition in Autism and Schizophrenia Spectrum Disorders: The Same but Different?

Social cognition impairment is a core shared phenotype in both schizophrenia spectrum disorders (SSD) and autism spectrum disorders (ASD). This study compares social cognition performance through four different instruments in a sample of 147 individuals with ASD or SSD and in healthy controls. We found that both clinical groups perform similarly to each other and worse than healthy controls in all social cognition tasks. Only performance on the Movie for the Assessment of Social Cognition (MASC) test was independent of age and intelligence. Proportionately, individuals in the control group made significantly more overmentalization errors than both patients group did and made fewer undermentalization errors than patients with SSD did. AUC analyses showed that the MASC was the instrument that best discriminated between the clinical and control groups. Multivariate analysis showed negative symptom severity as a potential mediator of the association between social cognition deficit and poor global functioning.

Eruption of the nevado del ruiz volcano, Colombia, on 13 november 1985: tephra fall and lahars.

A small Plinian eruption of the Nevado del Ruiz volcano in Colombia ejected 3.5 x 10(10) kilograms of mixed dacite and andesite tephra on 13 November 1985, with a maximum column height of 31 kilometers above sea level. Small pyroclastic flows and surges, generated during the initial stage of the eruption, caused surface melting of approximately 10% of the volcano's ice cap, leading to meltwater floods. The erosive floods incorporated soils and loose sediments from the volcano's flanks and developed into lahars, which claimed at least 25,000 lives.

Prevalence of peripheral neuropathy associated with chemotherapy in four oncology centers of Colombia. / Prevalencia de neuropatia periferica asociada a quimioterapia en cuatro centros oncologicos de Colombia.

INTRODUCTION: Chemotherapy-induced peripheral neuropathy is a common adverse reaction in a variety of medications frequently used for a great number of cancer treatments. This condition consists of mainly sensory-type symptoms, motor components and autonomic changes. Reported prevalence ranges from 30-68%, after the completion of chemotherapy in non-Latin American people with different populations and socioeconomic levels. AIM: To determine the prevalence of chemotherapy-induced peripheral neuropathy in a Colombian population. PATIENTS AND METHODS: A real-world evidence cross-sectional retrospective study was performed in all patients from oncological clinical centers in Colombia, which received pharmacological therapy for any cancer between January 2015 and December 2016, with taxanes (paclitaxel, docetaxel), alkylators (oxaliplatin), proteasome inhibitors (bortezomib), and epothilone B analogs (ixabepilone). RESULTS: A total of 1,551 patients in four cities were included, and 11,280 doses were applied; predominantly females (n = 1,094; 70.5%), with a mean age of 57 ± 13 years old. Paclitaxel was the most commonly prescribed drug (n = 788; 50.8%). Chemotherapy-induced peripheral neuropathy was developed in 48.9% of paclitaxel, 58.5% of oxaliplatin, 50.5% of docetaxel, 43.7% of bortezomib and 95.2% of ixabepilone patients. Thirty-three patients were treated with two of these medications simultaneously. CONCLUSIONS: Chemotherapy-induced peripheral neuropathy is a frequent adverse reaction to daily cancer therapy in Colombian patients managed with taxanes, alkylators, proteasome inhibitors, and epothilone B analogs. Hence, it is necessary to establish more successful diagnostic methods and incorporate validated scales in the routine evaluation of all patients receiving these medications in our environment.

TITLE: Prevalencia de neuropatia periferica asociada a quimioterapia en cuatro centros oncologicos de Colombia.Introduccion. La neuropatia periferica inducida por quimioterapia es una reaccion comun a una variedad de medicamentos usados en el tratamiento del cancer, que consiste principalmente en sintomas sensitivos, con componentes motores y cambios autonomicos. La prevalencia es del 30-68% despues de terminar la quimioterapia en paises no latinoamericanos. Objetivo. Determinar la prevalencia de la neuropatia periferica inducida por quimioterapia en la poblacion colombiana. Pacientes y metodos. Estudio retrospectivo con evidencia del mundo real en la totalidad de pacientes atendidos en cuatro centros oncologicos de Colombia, quienes recibieron terapia farmacologica para algun tipo de cancer entre enero de 2015 y diciembre de 2016 con taxanos (paclitaxel, docetaxel), agentes alquilantes (oxaliplatino), inhibidores de proteasoma (bortezomib) y analogos de epotilona B (ixabepilona). Resultados. Se siguio a un total de 1.551 pacientes en cuatro ciudades a quienes se les aplicaron 11.280 dosis, con predominio femenino (n = 1.094; 70,5%) y una edad media de 57 ± 13 años. El paclitaxel fue el farmaco mas prescrito (n = 788; 50,8%). La neuropatia inducida por quimioterapia se presento en el 48,9% de los pacientes con paclitaxel, el 58,5% de los pacientes con oxaliplatino, el 50,5% de los pacientes con docetaxel, el 43,7% de los pacientes con bortezomib y el 95,2% de los pacientes con ixabepilona. Se trato a 33 pacientes con dos de estos medicamentos simultaneamente. Conclusiones. La neuropatia periferica inducida por quimioterapia es una reaccion adversa frecuente en pacientes con cancer en Colombia tratados con taxanos, alquilantes, inhibidores de proteasoma e ixabepilona. Es necesario establecer metodos diagnosticos efectivos e incorporar escalas validadas en la evaluacion rutinaria de los pacientes que reciben estas medicaciones.

Molecular pathways of pain: Fos/Jun-mediated activation of a noncanonical AP-1 site in the prodynorphin gene.

Noxious stimulation provokes the activation of genes that are thought to play a crucial role in the phenomena of stress and pain. Among these is the prodynorphin gene. By double-labeling in situ hybridization/immunohistochemistry, we show that increased prodynorphin gene expression is preceded, in the same neurons, by an early induction of c-fos. Inspection of the prodynorphin promoter region revealed the presence of several AP-1-like sequences. We demonstrate that only one of these sites is a functional AP-1 element. It is constituted by the noncanonical TGACAAACA sequence, in which the palindromic structure is partly conserved by the 3' terminal CA dinucleotide. Transfection experiments in NCB20 neuroblastoma cells indicated that this site is a target of Fos/Jun trans-activation. Our results suggest that Fos/Jun oncoproteins may function as third messengers in the signal transduction mechanisms of stress/pain processes.

Transcriptional response to cAMP in brain: specific distribution and induction of CREM antagonists.

Changes in cAMP levels are often associated with the modulation of neuronal function. The CREM gene encodes both antagonists and activators of the cAMP-dependent transcriptional response by alternative splicing. CREM transcripts in rat brain show a characteristic pattern of expression, being specific for the inner layer of the cerebral cortex, anterior thalamus, hippocampus, and hypothalamus. Strikingly, the CREM transcripts correspond to the antagonist isoforms in these areas, suggesting a down-regulatory role for CREM in brain; in contrast, the expression of CREM tau and CREB activators is more diffuse and generalized. In the supraoptic nucleus, CREM expression is induced after osmotic stimulus. Importantly, this demonstrates physiological inducibility of CREM, which is novel within the CRE/ATF family.

Molecular mechanisms of pain: serotonin1A receptor agonists trigger transactivation by c-fos of the prodynorphin gene in spinal cord neurons.

By using spinal cord neurons cultured in chemically defined medium, a double labeling procedure, and blockage with antisense oligonucleotides, we show that induction of c-fos and the subsequent transactivation of the prodynorphin gene are coupled events, triggered by serotonin1A receptor agonists. Addition of the specific 1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) to the culture, at concentrations similar to that needed for transactivation of the prodynorphin gene, also significantly increases cAMP levels. Furthermore, in rats depleted of serotonin by intrathecal administration of 5,7-dihydroxytryptamine, the induction of prodynorphin after noxious stimulation is dramatically decreased compared with the induction in sham-operated rats. These results suggest that the expression of the prodynorphin gene in spinal cord is under the control of the raphe-spinal efferents containing serotonin.