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.

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.

[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.

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.

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.

The natural history of perforated foregut ulcers after repair by omental patching or primary closure.

BACKGROUND: The treatment of perforated foregut ulcers by omental patching (OP) or primary closure has mostly replaced vagotomy and pyloroplasty/antrectomy (VPA). We sought to determine the natural history and recurrence rate of ulceration in patients treated by omental patching or primary closure. STUDY DESIGN: An 11-year retrospective study. RESULTS: From 2004 through 2015, 94 patients had perforated foregut ulcers, 53 gastric, and 41 duodenal. 77 (82%) were treated by OP alone (study group) and 17 (18%) were treated with VPA (comparison group). All OP patients were discharged on PPIs, but only 86% took the drugs for a median of 22 months (1-192, SD 40). Endoscopy in the OP group showed recurrent ulcers in nine (12% recurrence rate) and gastritis in three (4%) This group also had three later recurrent perforations. Another recurrent ulcer hemorrhaged causing death (3% late mortality). Two other patients required non-emergent re-do ulcer operations for recurrent disease/symptoms (surgical re-intervention rate 4%). Total length of follow-up was median 44 months (1-192, SD 40) and was complete in 82 (87%). 18 (23%) patients in the OP group developed recurrent abdominal pain attributed to ulcer disease during follow-up, compared to 2 (12%) in the VPA group (p = 0.15). No patient in the VPA group had an endoscopic recurrence or re-intervention. CONCLUSION: Omental patching does not correct the underlying disease process which causes foregut perforation, and has a 12% endoscopically proven recurrent ulceration rate and a 23% incidence of recurrent symptoms within 44 months. Patients tend to stop taking PPIs after 22 months at which time their risk increases.

Relación entre el transporte y las características nutricionales de la carne porcina para consumo humano en el valle de aburrá (colombia) / Relationship between transport and nutritional characteristics of pork meat for human consumption in the valle de aburrá (colombia)

RESUMEN La carne de cerdo se considera fuente de alto valor nutritivo por su alto contenido de proteína; sin embargo, su transporte representa un eslabón crítico, por cuanto genera pérdidas económicas, cuando se producen alteraciones en el bienestar animal que repercuten en los parámetros nutricionales, disminuyen la capacidad de retención de agua y ocasionan pérdidas de proteína. El objetivo de este estudio fue relacionar las características de los transportes con las características nutricionales de la carne porcina destinada a consumo humano en el Valle de Aburrá (Antioquia, Colombia) en 2017. Se visitaron tres plantas de sacrificio del Valle de Aburrá con muestreo probabilístico estratificado por planta y afijación igual, obteniendo información de 338 animales. Se analizaron los parámetros nutricionales de las muestras cárnicas, así como variables sociodemográficas, de infraestructura, bienestar animal y prácticas de conducción de los transportistas. Se realizaron pruebas de ji-cuadrado (χ 2) para variables cualitativas dicotómicas, regresión logística para variables cualitativas politómicas y U de Mann-Whitney para variables cuantitativas. Se encontró asociación entre varios de los parámetros indagados con valores p estadísticamente significativos (p = 0,000; así, no tener suministro de agua permanente para los animales incrementa en 46,55 veces (IC 18,08 - 120,07) la posibilidad de presentar carnes nutricionalmente inadecuadas. Se concluye que factores como la falta de suministro de agua a los cerdos, el mal estado de pisos y separadores, la deficiente capacitación de los transportistas, la falta de supervisión a los animales, no tener el certificado técnico-mecánico y la velocidad promedio de 80 km/h, se asocian con la generación de productos cárnicos nutricionalmente inadecuados.

ABTRACT Pork meat is considered a source of high nutritional value due to its high protein content, however, transport is a critical link to generate economic losses by producing alterations in animal welfare, which have an impact on nutritional parameters, decreasing the capacity of water retention, and generating protein losses. The objective of this study was to relate the characteristics of transport, with the nutritional characteristics of pork for human consumption in the Valle de Aburrá (Antioquia, Colombia) in 2017. In this location, three slaughterhouses were visited with probabilistic sampling stratified by plant and equal affixation, obtaining information from 338 animals. The nutritional parameters of the meat samples and sociodemographic variables, infrastructure, animal welfare and driving practices of the transporters were analyzed. ji-square (χ 2) tests were performed for dichotomous qualitative variables, logistic regression for qualitative polytomous variables and Mann-Whitney U test for quantitative variables. An association was found between several of the parameters investigated with statistically significant p values (p = 0,000), where, having no permanent water supply for the animals increases in 46.55 times (IC 18.08 - 120.07) the possibility of presenting nutritionally inadequate meats. It was concluded that factors such as lack of water supply to pigs, poor condition of the floors and separators, lack of training in transporters, lack of supervision of animals, lack of mechanical technical certification and average speed of 80 km/h are associated with the generation of nutritionally inadequate meat products.

A novel approach in the treatment of acute whiplash syndrome: Ultrasound-guided needle percutaneous electrolysis. A randomized controlled trial.

INTRODUCTION: Whiplash associated disorders are currently a common musculoskeletal problem. Besides the high incidence in western countries, the costs derived from prolonged treatment and medicolegal compensation, make this entity a challenging problem for clinicians and insurance companies. To date, no conservative treatment has shown clear superiority in the management of acute cases. HYPOTHESIS: Percutaneous needle electrolysis (PNE) is an effective approach for the treatment of Quebec type II acute whiplash syndrome (AWS). PNE consists in the application of brief galvanic currents into a damaged structure, producing a local controlled inflammatory response, with subsequent tissular healing enhancement. MATERIALS AND METHODS: One hundred AWS patients were randomized into: (a) standard physiotherapy intervention for AWS; (b) a standardized PNE protocol for AWS. Both groups were assessed for treatment outcome at the 5th week mark. RESULTS: Both groups showed a statistically significant improvement according to the Northwick Park Neck Questionnaire, visual analogic scale and pressure pain threshold. The improvement was similar in both groups, except for the pain pressure threshold, with a 56.6% reduction vs. 44.4% reduction in favour of the PNE group (P=0.035). In addition, the physio group consumed a mean treatment time of 20hours, while the PNE intervention averaged less than 1 hour in total. DISCUSSION: PNE can be considered as an effective treatment option for AWS. Importantly, the technique is highly cost-effective, with limited equipment required and a notable treatment time reduction, compared to more comprehensive physiotherapy protocols. TYPE OF STUDY: Randomized controlled trial. LEVEL OF PROOF: 1b.

The effects of second-generation antipsychotics on food intake, resting energy expenditure and physical activity.

Second-generation antipsychotics (SGA) are associated with weight gain and metabolic alterations including hyperglycemia, dyslipidemia, hypertension and metabolic syndrome. These metabolic side effects increase cardiovascular risk and are related to medication non-compliance. Patients without previous exposure to these or other antipsychotic drugs (naive patients) seem to be more prone to develop these metabolic abnormalities. The mechanisms behind weight gain can be an increase in food intake and/or a decrease in energy expenditure. This review comprehensively examines the current knowledge on the impact of these drugs on food intake and energy expenditure. The influence of these drugs on appetite and food intake (total caloric intake and food sources) is reviewed as well as the evidence of abnormal eating behaviors. The studies evaluating the effect on resting energy expenditure are critically examined, taking into account the influence of body composition and previous exposure to antipsychotics (naive vs non-naive patients). Finally, the influence of these drugs on physical activity is also discussed. The knowledge of the mechanisms of weight gain in patients starting these drugs may be useful to further prompt research in this field and ameliorate the metabolic side effects associated with these treatments.

A neuroprotective phase precedes striatal degeneration upon nucleolar stress.

The nucleolus is implicated in sensing and responding to cellular stress by stabilizing p53. The pro-apoptotic effect of p53 is associated with several neurodegenerative disorders, including Huntington's disease (HD), which is characterized by the progressive loss of medium spiny neurons (MSNs) in the striatum. Here we show that disruption of nucleolar integrity and function causes nucleolar stress and is an early event in MSNs of R6/2 mice, a transgenic model of HD. Targeted perturbation of nucleolar function in MSNs by conditional knockout of the RNA polymerase I-specific transcription initiation factor IA (TIF-IA) leads to late progressive striatal degeneration, HD-like motor abnormalities and molecular signatures. Significantly, p53 prolongs neuronal survival in TIF-IA-deficient MSNs by transient upregulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a tumor suppressor that inhibits mammalian target of rapamycin signaling and induces autophagy. The results emphasize the initial role of nucleolar stress in neurodegeneration and uncover a p53/PTEN-dependent neuroprotective response.

[Macular hole surgery without postoperatory <> down positioning. Pilot study]. / Cirugía de agujero macular sin posición <> postoperatoria. Estudio piloto.

PURPOSE: To evaluate the visual and anatomical outcomes of macular hole surgery using phacoemulsification, vitrectomy and intraocular gas tamponade without the use of postoperative face down positioning. METHODS: Phacoemulsification with an intraocular lens implant, followed by vitrectomy with internal limiting membrane peeling and perfluoropropane (C3F8), was performed in patients with stage 3 or 4 macular holes. After surgery, patients had to avoid the supine position for 15 days. Patients with a gas level <50% during the first week had a fluid-gas exchange. Visual acuity and closure of the macular hole were evaluated after 1 year of follow-up. RESULTS: 20 eyes of 20 patients, aged 60 to 75 years (median age 68 years), were included in this study. The best initial visual acuity ranged from 0.05 to 0.13 (ETDRS), with the median being 0.06. The final visual acuity was 0.05 to 0.30 with a median of 0.10. A statistically significant improvement (p=0.001, Wilcoxon) was found. The anatomic postoperative results revealed 90% (n=18) of the macular holes were closed while 10% (n=2) were not. CONCLUSIONS: Macular hole surgery has, in general, good results and patients can achieve improvement in their visual acuity without the need for uncomfortable and unbearable post operative posture positions.

Perfluorocarbon-perfused vitrectomy: a new method for vitrectomy--a safety and feasibility study.

PURPOSE: To evaluate the safety and feasibility of perfluorocarbon-perfused vitrectomy (PCPV) as a technique during vitrectomy for proliferative diabetic retinopathy (PDR) and rhegmatogenous retinal detachment (RRD). METHODS: In an experimental, prospective, noncomparative and interventional study, 28 eyes of 28 patients were submitted to vitrectomy with the PCPV technique, 18 eyes with PDR and 10 with RRD. In this technique we replaced the traditional balanced saline solution (BSS) in the infusion line (conventional vitrectomy) by perfluorocarbon liquids (PCL). Some patients with PDR were treated with oxygenated PCL. Clinical evaluation, electroretinography (ERG), and endothelial cell count (ECC) were used to assess the safety of this procedure. An arbitrary grading system (grades 0-5) was used to classify the surgery and maneuvers to assess feasibility. RESULTS: No eyes had a significant decrease in ECC, and the patients in whom we could obtain ERG postoperatively showed no significant differences from preoperative ERG. In the PDR group (using oxygenated and nonoxygenated PCL), 77.8% were graded 5/5; in the RRD group 90% were 5/5. PCPV allowed better visualization of vitreous and intraocular structures, rapid retinal reattachment, less blood in the vitreous cavity, subretinal fluid resolution, blood confinement, retinal stabilization, and easier dissection of epiretinal membranes. In all cases at least one surgical step was eliminated. CONCLUSIONS: PCPV in humans is a safe and feasible technique. Probably in selected cases the use of PCL offers several advantages over BSS, because of their properties (gravitational forces, immiscibility with bodily fluids, and ability to transport oxygen). Prospective and comparative studies are necessary to establish formal indications and possible contraindications.

[Bilateral macular cysts secondary to electric current strike. A case report]. / Quistes maculares bilaterales inducidos por descarga eléctrica. Presentación de un caso.

OBJECTIVE: To report the clinical and tomographic findings in a case of maculopathy secondary to high-tension electric current strike. CASE REPORT: A 27-year-old male refers a reduction in his visual acuity after electric strike. Visual acuity was 0.05 in both eyes. Circular reddish macular lesions measuring 400 micro m in RE and 200 micro m in LE were evident. Optical coherence tomography (OCT) showed intraretinal foveal cysts. At the third month follow-up visit, visual acuity had improved to 0.4 in RE and 0.5 in LE. Clinical and tomographic evaluation showed a reduction of the foveal cysts. DISCUSSION: Electricity affects retinal pigment epithelium and retina by thermal denaturation. OCT provides a conclusive diagnosis.

Subretinal, viscoelastic-assisted, endoscope-guided photothermal ablation of choroidal neovascular membranes by Erbium:YAG laser.

BACKGROUND AND OBJECTIVE: The efficacy of endoscope-guided Erbium:YAG laser, assisted by viscoelastic macular detachment, in subretinal ablation of choroidal neovascular membranes (CNVs) is evaluated. PATIENTS AND METHODS: A high-repetition, midinfrared erbium:YAG laser was used subretinally to ablate CNVs in 2 patients. Ablation followed pars plana vitrectomy and macular retinal detachment using a viscoelastic substance, and was guided by a high resolution endoscope. RESULTS: Visual acuity improved from 6/90 to 6/20, six months after treatment in 1 patient, and from finger counting from 1 meter to 6/30, three months after treatment in the other. The membranes showed no angiographic signs of activity postoperatively. However, a zone of stippled hyperfluorescence appeared in both patients, corresponding with the macular detachment area. This gradually diminished in size in both patients. CONCLUSIONS: The surgical procedure was found effective in our preliminary research. The use of viscoelastic substance and endoscope is felt to contribute to the favorable outcome. The cause and significance of the retinal pigment epithelium damage are yet to be determined.

Interleukin 3-dependent activation of DREAM is involved in transcriptional silencing of the apoptotic Hrk gene in hematopoietic progenitor cells.

The apoptotic protein Hrk is expressed in hematopoietic progenitors after growth factor deprivation. Here we identify a silencer sequence in the 3' untranslated region of the hrk gene that binds to the transcriptional repressor DREAM in interleukin-3 (IL-3)-dependent hematopoietic progenitor cells, and abrogates the expression of reporter genes when located downstream of the open reading frame. In addition, the binding of DREAM to the hrk gene is reduced or eliminated when cells are cultured in the absence of IL-3 or treated with a calcium ionophore or a phosphatidylinositol 3-kinase-specific inhibitor, suggesting that both calcium mobilization and phosphorylation can regulate the transcriptional activity of DREAM. Furthermore, we have shown that DREAM is phosphorylated by a phosphatidylinositol 3-kinase-dependent, but Akt-independent pathway. In all cases, loss of the DREAM-DNA binding complex was correlated with increased levels of Hrk and apoptosis. These data suggest that IL-3 may trigger the activation of DREAM through different signaling pathways, which in turn binds to a silencer sequence in the hrk gene and blocks transcription, avoiding inappropriate cell death in hematopoietic progenitors.

Successful erbium: YAG laser-induced chorioretinal venous anastomosis for the management of ischemic central retinal vein occlusion. A report of two cases.

BACKGROUND: Central retinal vein occlusion (CRVO) is a disorder with potentially blinding complications, particularly when associated with retinal ischemia. There is no reliable treatment for ischemic CRVO. METHODS: We developed a new approach for ischemic cases of CRVO consisting of vitrectomy, posterior hyaloid detachment, and four erbium:YAG laser-induced chorioretinal anastomoses, one in each quadrant. RESULTS: We report two cases of ischemic CRVO treated with this approach, with initial visual acuity of count fingers at 30 cm and hand movements respectively. After the surgery, there was resolution of hemorrhages and macular edema and visual improvement to 20/400 in the first case and to 20/180 in the second case. In both cases, there was successful creation of chorioretinal anastomoses, and there was no anterior segment neovascularization or other complications related to the surgery. CONCLUSION: This treatment shows promise in the management of the ischemic cases of CRVO, and further evaluation is justified.

The DREAM-DRE interaction: key nucleotides and dominant negative mutants.

Transcriptional repressor DREAM, an EF-hand containing calcium-binding protein, blocks basal expression of target genes through specific interaction with DRE sites in the DNA. The sequence GTCA forms the central core of the DRE site, whereas flanking nucleotides contribute notably to the affinity for DREAM. Release of binding of DREAM from the DRE results in derepression, a process that is regulated by Ca(2+). Change of two amino acids within an EF-hand in DREAM blocks Ca(2+)-induced derepression and results in potent dominant negative mutants of endogenous DREAM.

DREAM-alphaCREM interaction via leucine-charged domains derepresses downstream regulatory element-dependent transcription.

Protein kinase A-dependent derepression of the human prodynorphin gene is regulated by the differential occupancy of the Dyn downstream regulatory element (DRE) site. Here, we show that a direct protein-protein interaction between DREAM and the CREM repressor isoform, alphaCREM, prevents binding of DREAM to the DRE and suggests a mechanism for cyclic AMP-dependent derepression of the prodynorphin gene in human neuroblastoma cells. Phosphorylation in the kinase-inducible domain of alphaCREM is not required for the interaction, but phospho-alphaCREM shows higher affinity for DREAM. The interaction with alphaCREM is independent of the Ca(2+)-binding properties of DREAM and is governed by leucine-charged residue-rich domains located in both alphaCREM and DREAM. Thus, our results propose a new mechanism for DREAM-mediated derepression that can operate independently of changes in nuclear Ca(2+).

Microbiological water purification without the use of chemical disinfection.

OBJECTIVE: Point-of-use (POU) water treatment systems are self-contained units that can be used by recreational enthusiasts who normally obtain drinking water from untreated sources (i.e., rivers, lakes, etc). Microbiological water purifier units are capable of removing all waterborne pathogens. The purpose of this study was to evaluate a new technology (Structured Matrix) capable of micro-biologically purifying the water without the use of chemical disinfectants or an external power requirement. METHODS: Each of 3 identical portable water filtration units were evaluated for their ability to remove Klebsiella terrigena, poliovirus type 1, rotavirus SA-11, and Cryptosporidium parvum oocysts. Units were operated according to the manufacturer's instructions to process 378 L of water. Each unit was challenged with test organisms after 0, 94, 190, 227, 284, 340, and 378 L had passed through it. For the 227-L and 284-L challenges, a "worst-case" water quality (4 degrees C, pH 9, and turbidity 30 NTU) was used that contained 1500 mg/L dissolved solids and 10 mg/L humid acid. At 340-L and 378-L challenges, worst-case water quality was adjusted to pH 5.0. Units were tested after stagnation for 48 hours following passage of 190, 340, and 378 L of water. RESULTS: The geometric average removal exceeded 99.9999% for bacteria, 99.99% for viruses, and 99.9% for Cryptosporidium parvum oocysts. CONCLUSION: These units comply with the criteria guidelines for microbial removal under the United States Environmental Protection Agency's "Guide Standard and Protocol for Testing Microbiological Water Purifiers."

DREAM is a Ca2+-regulated transcriptional repressor.

Fluxes in amounts of intracellular calcium ions are important determinants of gene expression. So far, Ca2+-regulated kinases and phosphatases have been implicated in changing the phosphorylation status of key transcription factors and thereby modulating their function. In addition, direct effectors of Ca2+-induced gene expression have been suggested to exist in the nucleus, although no such effectors have been identified yet. Expression of the human prodynorphin gene, which is involved in memory acquisition and pain, is regulated through its downstream regulatory element (DRE) sequence, which acts as a location-dependent gene silencer. Here we isolate a new transcriptional repressor, DRE-antagonist modulator (DREAM), which specifically binds to the DRE. DREAM contains four Ca2+-binding domains of the EF-hand type. Upon stimulation by Ca2+, DREAM's ability to bind to the DRE and its repressor function are prevented. Mutation of the EF-hands abolishes the response of DREAM to Ca2+. In addition to the prodynorphin promoter, DREAM represses transcription from the early response gene c-fos. Thus, DREAM represents the first known Ca2+-binding protein to function as a DNA-binding transcriptional regulator.