Assessment of bioactive peptides derived from laminin-111 as prospective breast cancer-targeting agents.

Breast cancer remains a pressing public health issue primarily affecting women. Recent research has spotlighted bioactive peptides derived from laminin-111, implicated in breast tumor development. Remarkably, the sequences IKVAV, YIGSR, and KAFDITYVRLKF from the α1, ß1, and γ1 chains, respectively, have garnered significant attention. This study aims to assess the potential of these radiolabeled peptides as targeting agents for breast cancer. The three peptides were synthesized using the Fmoc strategy, purified via reversed-phase high-performance liquid chromatography (RP-HPLC), and characterized through mass spectrometry. Iodine-131 (131I) radiolabeling was performed using the chloramine T method, exhibiting high radiochemical yield and stability for [131I]I-YIKVAV and [131I]I-YIGSR. Conversely, [131I]I-KAFDITYVRLKF demonstrated low radiochemical yield and stability and was excluded from the biological studies. The lipophilicity of the compounds ranged from - 2.12 to - 1.10. Serum protein binding assay for [131I]I-YIKVAV and [131I]I-YIGSR reached ≅ 48% and ≅ 25%, respectively. Affinity for breast cancer cells was evaluated using MDA-MB-231 and MCF-7 tumor cell lines, indicating the affinity of the radiopeptides with these tumor cells. Ex vivo biodistribution profiles of the radiopeptides were assessed in the MDA-MB-231 breast tumor animal model, revealing tumor tissue accumulation, supported by a high tumor-to-contralateral muscle ratio and autoradiography. These results signify the effective penetration of YIKVAV and YIGSR into tumor tissue. Therefore, the synthesized α1 and ß1 peptide fragments exhibit favorable characteristics as potential breast cancer-targeting agents, promising future exploration as radiopharmaceuticals for breast cancer.

Radiochemical and biological assessments of a PSMA-I&S cold kit for fast and inexpensive 99mTc-labeling for SPECT imaging and radioguided surgery in prostate cancer.

The expression of prostate-specific membrane antigen (PSMA) is upregulated in prostate cancer (PCa) cells and PSMA-ligands have been radiolabeled and used as radiopharmaceuticals for targeted radionuclide therapy (TRT), single photon emission computed tomography (SPECT) or positron emission tomography (PET) molecular imaging, and radioguided surgery in PCa patients. Herein, we aimed at radiolabeling the PSMA-I&S cold kit with 99mTc, resulting in a radiopharmaceutical with high radiochemical yield (RCY) and stability for SPECT imaging and radioguided surgery in PCa malignancies. Various pre-clinical assays were conducted to evaluate the [99mTc]Tc-PSMA-I&S obtained by the cold kit. These assays included assessments of RCY, radiochemical stability in saline, lipophilicity, serum protein binding (SPB), affinity for LNCaP-PCa cells (binding and internalization studies), and ex vivo biodistribution profile in naive and LNCaP-PCa-bearing mice. The radiopharmaceutical was obtained with good RCY (92.05% ± 2.20%) and remained stable for 6 h. The lipophilicity was determined to be -2.41 ± 0.06, while the SPB was ∼97%. The binding percentages to LNCaP cells were 9.41% ± 0.57% (1 h) and 10.45% ± 0.45% (4 h), with 63.12 ± 0.93 (1 h) and 65.72% ± 1.28% (4 h) of the bound material being internalized. Blocking assays, employing an excess of unlabeled PSMA-I&S, resulted in a reduction in the binding percentage by 2.6 times. The ex vivo biodistribution profile confirmed high accumulation of [99mTc]Tc-PSMA-I&S in the tumor and the tumor-to-contralateral muscle ratio was ∼6.5. In conclusion, [99mTc]Tc-PSMA-I&S was successfully obtained by radiolabeling the cold kit using freshly eluted [99mTc]NaTcO4, exhibiting good RCY and radiochemical stability. The preclinical assays demonstrated that the radiopharmaceutical shows favorable characteristics for SPECT imaging and radioguided surgery in PCa patients.

Pentoxifylline reduces inflammation and prevents myocardial perfusion derangements in experimental chronic Chagas' cardiomyopathy.

BACKGROUND: Myocardial perfusion defect (MPD) is common in chronic Chagas cardiomyopathy (CCC) and is associated with inflammation and development of left ventricular systolic dysfunction. We tested the hypothesis that pentoxifylline (PTX) could reduce inflammation and prevent the development of MPD in a model of CCC in hamsters. METHODS AND RESULTS: We investigated with echocardiogram and rest myocardial perfusion scintigraphy at baseline (6-months after T. cruzi infection/saline) and post-treatment (after additional 2-months of PTX/saline administration), female Syrian hamsters assigned to 3 groups: T. cruzi-infected animals treated with PTX (CH + PTX) or saline (CH + SLN); and uninfected control animals (CO). At the baseline, all groups showed similar left ventricular ejection fraction (LVEF) and MPD areas. At post-treatment evaluation, there was a significant increase of MPD in CH + SLN group (0.8 ± 1.6 to 9.4 ± 9.7%), but not in CH + PTX (1.9 ± 3.0% to 2.7 ± 2.7%) that exhibited MPD area similar to CO (0.0 ± 0.0% to 0.0 ± 0.0%). The LVEF decreased in both infected groups. Histological analysis showed a reduced inflammatory infiltrate in CH + PTX group (395.7 ± 88.3 cell/mm2), as compared to CH + SLN (515.1 ± 133.0 cell/mm2), but larger than CO (193.0 ± 25.7 cell/mm2). The fibrosis and TNF-α expression was higher in both infected groups. CONCLUSIONS: The prolonged use of PTX is associated with positive effects, including prevention of MPD development and reduction of inflammation in the chronic hamster model of CCC.

Hypertonic saline infusion does not improve the chance of primary fascial closure after damage control laparotomy: a randomized controlled trial.

BACKGROUND: Previous observational studies showed higher rates of abdominal wall closure with the use of hypertonic saline in trauma patients with abdominal injuries. However, no randomized controlled trials have been performed on this matter. This double-blind randomized clinical trial assessed the effect of 3% hypertonic saline (HS) solution on primary fascial closure and the timing of abdominal wall closure among patients who underwent damage control laparotomy for bleeding control. METHODS: Double-blind randomized clinical trial. Patients with abdominal injuries requiring damage control laparotomy (DCL) were randomly allocated to receive a 72-h infusion (rate: 50 mL/h) of 3% HS or 0.9 N isotonic saline (NS) after the index DCL. The primary endpoint was the proportion of patients with abdominal wall closure in the first seven days after the index DCL. RESULTS: The study was suspended in the first interim analysis because of futility. A total of 52 patients were included. Of these, 27 and 25 were randomly allocated to NS and HS, respectively. There were no significant differences in the rates of abdominal wall closure between groups (HS: 19 [79.2%] vs. NS: 17 [70.8%]; p = 0.71). In contrast, significantly higher hypernatremia rates were observed in the HS group (HS: 11 [44%] vs. NS: 1 [3.7%]; p < 0.001). CONCLUSION: This double-blind randomized clinical trial showed no benefit of HS solution in primary fascial closure rates. Patients randomized to HS had higher sodium concentrations after the first day and were more likely to present hypernatremia. We do not recommend using HS in patients undergoing damage control laparotomy. Trial registration The trial protocol was registered in clinicaltrials.gov (identifier: NCT02542241).

Radiosynthesis Standardization and Preclinical Assessment of the [68Ga]Ga-DOTA-Ubiquicidin29-41: A Translational Study Targeting Differential Diagnosis of Infectious Processes.

Human bacterial infections significantly contribute to the increase in healthcare-related burdens. This scenario drives the study of novel techniques for the early and precise diagnosis of infectious processes. Some alternatives include Nuclear Medicine- and Molecular Imaging-based strategies. However, radiopharmaceuticals that are available for routine assessments are not specific to differentiating infectious from aseptic inflammatory processes. In this context, [68Ga]Ga-DOTA-Ubiquicidin29-41 was synthesized using an automated module and radiochemical; in vivo and in vitro studies were performed. The radiopharmaceutical remained stable in saline (up to 180 min) and in rodent serum (up to 120 min) with radiochemical purities > 99 and 95%, respectively. Partition coefficient and serum protein binding at 60 min were determined (-3.63 ± 0.17 and 44.06 ± 1.88%, respectively). Ex vivo biodistribution, as well as in vivo microPET/CT images in mice, showed rapid blood clearance with renal excretion and reduced uptake in other organs in Staphylococcus aureus-infected animals. Higher uptake was observed in the target as compared to the non-target tissue (p < 0.0001) at 60 min post administration. The presented in-human clinical case demonstrates uptake of the radiopharmaceutical by Staphyloccocus aureus bacteria. These results indicate the potential of [68Ga]Ga-DOTA-Ubiquicidin29-41 as a radiopharmaceutical that can be obtained in a hospital radiopharmacy for the diagnosis of infectious processes using PET/CT.

Alteration of hippocampal Egr3, GABA A receptors, Il-1ß, Il6 and Ccl3 expression in audiogenic tremor mice after seizure.

Neuroinflammation plays a protective role in the brain; however, in neurological diseases such as epilepsy, overactivated neuroinflammation, along with overexpression of inflammatory mediators, can cause neuronal tissue damage, which can trigger seizures due to loss of ionic or neurotransmitter homeostasis. Therefore, we aimed to evaluate mRNA expression levels of proinflammatory cytokines, early growth response factor 3 (Egr3), and GABA A receptors in the hippocampus of naive audiogenic mutant tremor mice, and stimulated tremor mice after a seizure. Gene expression of Il-1ß, Il-6, Tnf-α, Ccl2, Ccl3, Egr3, Gabra1, and Gabra4 from hippocampal samples of naive and stimulated tremor mice were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Relative to resistant mice, Ccl3 gene expression was increased and Il6 was decreased in the hippocampus of naïve tremor mice. Thirty minutes after a seizure, Ccl3 and Il-1ß mRNA expression were decreased (p < 0.0001; p = 0.0034, respectively) while Il6 was increased (p = 0.0052) in stimulated tremor mice, relative to naïve animals. In addition, Egr3, Gabra1, and Gabra4 mRNA expression was decreased in the hippocampus of naive tremor mice, relative to resistant mice, which increased 30 minutes after a seizure (p = 0.0496; p = 0.0447, and p = 0.0011, respectively), relative to naïve animals. In conclusion, overexpression of Ccl3 in the hippocampus of naive tremor mice, followed by downregulation soon after seizure in stimulated tremor mice, could be involved in changes in the blood-brain barrier (BBB) permeability in epilepsy. Il-1ß may be involved in hippocampal downregulation of GABA A receptors of naive tremor mice, characterizing an important mechanism in audiogenic seizures triggering. Hippocampal alterations of proinflammatory cytokines, Egr3, and GABA A receptors in tremor mice reinforce them as an alternative tool to modeling temporal lobe epilepsy.

Evaluation of Urine and Vaginal Self-Sampling versus Clinician-Based Sampling for Cervical Cancer Screening: A Field Comparison of the Acceptability of Three Sampling Tests in a Rural Community of Cuenca, Ecuador.

Self-sampling methods for HPV testing have been demonstrated to be highly sensitive and specific. The implementation of these methods in settings with a lack of infrastructure or medical attention has been shown to increase the coverage of cervical cancer screening and detect cervical abnormalities in the early stages. The aim of this study is to compare the acceptability of urine and vaginal self-sampling methods versus clinician sampling among rural women. A total of 120 women participated. Each participant self-collected urine and vaginal samples and underwent clinician sampling for Pap smear and HPV testing. After the sample collection, a questionnaire to qualify the device, technique, and individual acceptability was applied, and the additional overall preference of three sample tests was evaluated. Results: The characteristics of the participants were as follows: median age of 35 years; 40.8% were married; 46.7% had a primary level of education; median age of sexual onset of 17.6 years. Compared with clinician sampling, both vaginal self-sampling, OR 20.12 (7.67-52.8), and urine sampling, OR 16.63 (6.79-40.72), were more comfortable; granted more privacy: vaginal self-sampling, OR 8.07 (3.44-18.93), and urine sampling, OR 19.5 (5.83-65.21); were less painful: vaginal self-sampling, OR 0.07 (0.03-0.16), and urine sampling, OR 0.01 (0-0.06); were less difficult to apply: vaginal self-sampling, OR 0.16 (0.07-0.34), and urine sampling, OR 0.05 (0.01-0.17). The overall preference has shown an advantage for vaginal self-sampling, OR 4.97 (2.71-9.12). No statistically significant preference was demonstrated with urine self-sampling versus clinician sampling. Conclusions: Self-sampling methods have a high acceptance in rural communities. Doubts on the reliability of self-sampling often appear to be a limitation on its acceptability. However, the training and education of the community could increase the uptake of these methods.

The miR-181 family regulates colonic inflammation through its activity in the intestinal epithelium.

The intestinal epithelium is a key physical interface that integrates dietary and microbial signals to regulate nutrient uptake and mucosal immune cell function. The transcriptional programs that regulate intestinal epithelial cell (IEC) quiescence, proliferation, and differentiation have been well characterized. However, how gene expression networks critical for IECs are posttranscriptionally regulated during homeostasis or inflammatory disease remains poorly understood. Herein, we show that a conserved family of microRNAs, miR-181, is significantly downregulated in IECs from patients with inflammatory bowel disease and mice with chemical-induced colitis. Strikingly, we showed that miR-181 expression within IECs, but not the hematopoietic system, is required for protection against severe colonic inflammation in response to epithelial injury in mice. Mechanistically, we showed that miR-181 expression increases the proliferative capacity of IECs, likely through the regulation of Wnt signaling, independently of the gut microbiota composition. As epithelial reconstitution is crucial to restore intestinal homeostasis after injury, the miR-181 family represents a potential therapeutic target against severe intestinal inflammation.

Role of Self-Sampling for Cervical Cancer Screening: Diagnostic Test Properties of Three Tests for the Diagnosis of HPV in Rural Communities of Cuenca, Ecuador.

BACKGROUND: HPV primary screening has shown effectiveness for cancer prevention; however, gynaecological examination is considered uncomfortable. Self-sampling methods increase the acceptance of screening. The aim of this study is to compare the sensitivity and specificity of clinician sampling versus vaginal and urine self-sampling for HPV diagnosis. METHODS: A diagnostic test study was conducted in a rural parish of Cuenca, Ecuador. A total of 120 women participated. Each participant self-collected urine and vaginal samples and underwent clinician sampling for HPV testing. The latter was considered as the golden standard. All three samples were processed with the same amplification and hybridization protocol for HPV detection (Hybribio) following the manufacturer's instructions. RESULTS: Characteristics of the participants were: median age 35 years; 40.8% married; 46.7% had a primary level of education; and median age of sexual onset, 17.6 years. The prevalence of any type of HPV with clinician sampling was 15.0%, 17.5% with urine sampling and 18.3% with vaginal self-sampling. Self-sampling sensitivity reached 94.4% (IC 74.2-99.9), and specificity 92.1% (IC 85.2-95.9). Urine sampling had a sensitivity of 88.8% (IC 67.2, 96.9), and specificity 94.1% (IC 67.2-96.9). The negative predictive value was 98.9% (IC 94.2-99.8) for vaginal self-sampling and 97.6% (IC 92.6-99.4) for urine sampling. CONCLUSIONS: This study shows that vaginal and urine self-sampling methods have similar sensitivity and specificity compared with clinician sampling for the diagnosis of HPV. The correlation between HPV genotypes among the three tests is satisfactory.

Comparative Evaluation of Radiochemical and Biological Properties of 131I- and [99mTc]Tc(CO)3-Labeled RGD Analogues Planned to Interact with the αvß3 Integrin Expressed in Glioblastoma.

Radiolabeled peptides with high specificity for overexpressed receptors in tumor cells hold great promise for diagnostic and therapeutic applications. In this work, we aimed at comparing the radiolabeling efficiency and biological properties of two different RGD analogs: GRGDYV and GRGDHV, labeled with iodine-131 (131I) and technetium-99m-tricarbonyl complex [99mTc][Tc(CO)3]+. Additionally, we evaluated their interaction with the αvß3 integrin molecule, overexpressed in a wide variety of tumors, including glioblastoma. Both peptides were chemically synthesized, purified and radiolabeled with 131I and [99mTc][Tc(CO)3]+ using the chloramine-T and tricarbonyl methodologies, respectively. The stability, binding to serum proteins and partition coefficient were evaluated for both radioconjugates. In addition, the binding and internalization of radiopeptides to rat C6 glioblastoma cells and rat brain homogenates from normal animals and a glioblastoma-induced model were assessed. Finally, ex vivo biodistribution studies were carried out. Radiochemical yields between 95-98% were reached for both peptides under optimized radiolabeling conditions. Both peptides were stable for up to 24 h in saline solution and in human serum. In addition, the radiopeptides have hydrophilic characteristics and a percentage of binding to serum proteins around 35% and 50% for the [131I]I-GRGDYV and [99mTc]Tc(CO)3-GRGDHV fragments, respectively. Radiopeptides showed the capacity of binding and internalization both in cell culture (C6) and rat brain homogenates. Biodistribution studies corroborated the results obtained with brain homogenates and confirmed the different binding characteristics due to the exchange of radionuclides and the presence of the tricarbonyl complex. Thereby, the results showed that both radiopeptides might be considered for future clinical applications.

Meningoencefalitis por Listeria monocytogenes / Meningoencephalitis due to Listeria monocytogenes

RESUMEN La neurolisteriosis se presenta principalmente como meningitis o meningoencefalitis, en menor frecuencia romboencefalitis o absceso cerebral. Es la principal causa de muerte entre todas las meningitis bacterianas y se asocia con una alta tasa de discapacidad neurológica. Para su diagnóstico se deben tener en cuenta la edad y los factores de riesgo, principalmente individuos mayores de 50 años y con condiciones de inmunosupresión. Las ayudas diagnósticas son clave para lograr el aislamiento de Lm, donde el cultivo de LCR tiene la mejor sensibilidad. Aunque faltan estudios que demuestren la superioridad de los estudios moleculares, el FilmArray-MEP parece ser prometedor en el aislamiento rápido y preciso de los principales microorganismos involucrados en la meningitis piógena, entre estos Lm. La IRM cerebral es el estudio de elección para el diagnóstico de romboencefalitis. La piedra angular del tratamiento sigue siendo ampicilina, cuya asociación con aminoglucósido podría disminuir la mortalidad.

SUMMARY Neurolisteriosis presents mainly as meningitis or meningoencephalitis, to a lesser extent rhombencephalitis or brain abscess frequency. It is the leading cause of death among all Bacterial meningitis and is associated with a high rate of neurological disability. For your diagnosis must take into account age and risk factors, mainly over 50 years and with immunosuppression conditions. Diagnostic aids are key to achieving the isolation of Lm, where CSF culture has the best sensitivity. Although studies are lacking demonstrating the superiority of molecular studies, the Film Array-MEP appears to be promising in fast and accurate isolation of the main microorganisms involved in pyogenic meningitis, among these Lm. Brain MRI is the study of choice for the diagnosis of rhombencephalitis. The cornerstone of treatment remains ampicillin, and its association with aminoglycoside could decrease mortality.

Standardization of the [68Ga]Ga-PSMA-11 Radiolabeling Protocol in an Automatic Synthesis Module: Assessments for PET Imaging of Prostate Cancer.

Prostate-specific membrane antigen (PSMA) is a glycoprotein present in the prostate, that is overexpressed in prostate cancer (PCa). Recently, PSMA-directed radiopharmaceuticals have been developed, allowing the pinpointing of tumors with the Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) imaging techniques. The aim of the present work was to standardize and validate an automatic synthesis module-based radiolabeling protocol for [68Ga]Ga-PSMA-11, as well as to produce a radiopharmaceutical for PET imaging of PCa malignancies. [68Ga]Ga-PSMA-11 was evaluated to determine the radiochemical purity (RCP), stability in saline solution and serum, lipophilicity, affinity to serum proteins, binding and internalization to lymph node carcinoma of the prostate (LNCaP) cells, and ex vivo biodistribution in mice. The radiopharmaceutical was produced with an RCP of 99.06 ± 0.10%, which was assessed with reversed-phase high-performance liquid chromatography (RP-HPLC). The product was stable in saline solution for up to 4 h (RCP > 98%) and in serum for up to 1 h (RCP > 95%). The lipophilicity was determined as -3.80 ± 0.15, while the serum protein binding (SPB) was <17%. The percentages of binding to LNCaP cells were 4.07 ± 0.51% (30 min) and 4.56 ± 0.46% (60 min), while 19.22 ± 2.73% (30 min) and 16.85 ± 1.34% (60 min) of bound material was internalized. High accumulation of [68Ga]Ga-PSMA-11 was observed in the kidneys, spleen, and tumor, with a tumor-to-contralateral-muscle ratio of >8.5 and a tumor-to-blood ratio of >3.5. In conclusion, an automatic synthesis module-based radiolabeling protocol for [68Ga]Ga-PSMA-11 was standardized and the product was evaluated, thus verifying its characteristics for PET imaging of PCa tumors in a clinical environment.

Papel pronóstico de factores asociados con lesión isquémica de la circulación anterior: estudio de cohorte / Prognosis role of factors associated with anterior circulation stroke: a cohort study

RESUMEN INTRODUCCIÓN: La enfermedad cerebrovascular constituye un problema de salud pública. Esta entidad representa una importante causa de discapacidad permanente en el adulto, además de tener impacto social, económico y sanitario. Los altos costos que demanda la atención sanitaria desde su momento diagnóstico, el manejo inicial del evento y la posterior rehabilitación-paliación de las secuelas, obligan al conocimiento de características del individuo y factores pronósticos. Esto como insumo de planificación de servicios de prevención para personas en riesgo y atención de pacientes con ataque cerebrovascular. OBJETIVO: Identificar el papel pronóstico que tienen algunos factores asociados con la lesión isquémica, con respecto al grado de discapacidad y mortalidad en el infarto cerebral de la circulación anterior. METODOLOGÍA: Estudio observacional analítico, prospectivo de cohorte, con un análisis anidado de casos y controles. Se identificó la escala del National Institute of Health Stroke Scale (NIHSS) para determinar el compromiso neurológico al ingreso. A los tres meses del evento, se obtuvo la escala Rankin modificado (mRS, variable dependiente) en busca de discapacidad residual y mortalidad; se consideraron casos los mRS desfavorables (puntajes: 3, 4, 5 y 6), y controles los mRS favorables (puntajes: 0, 1, 2). RESULTADOS: Se incluyeron 93 pacientes con ACV-i de circulación anterior; la mediana para la edad fue 67 años RIC (57-76); el NIHSS más frecuente fue moderado (50 pacientes, 53,8 %) y la mediana de tiempo transcurrido para el inicio de manejo médico fue de 5 horas RIC (3-24 horas). La identificación de la etiología del ACVi fue posible en 33 pacientes (35,5 %, más frecuente el cardioembólico). Luego de 90 días del ACVi, la clasificación mRS más frecuente fue de tres puntos "moderado" (22 pacientes, 23,7 %) y la mortalidad fue de siete pacientes (7,5 %). En el análisis bivariado la ubicación del infarto en el hemisferio izquierdo fue una variable desfavorable en términos de discapacidad a los tres meses en comparación con el hemisferio derecho (OR: 2,51; IC 95 %: 1,06 - 5,9; p = 0,03). CONCLUSIONES: La población de estudio fue predominantemente de sexo masculino, con una limitación funcional moderada (NIHSS 5-15) al ingreso a urgencias. Tres meses después del evento, la mayoría de los pacientes cursó con movilidad reducida, algún compromiso de las funciones mentales, pero esencialmente independientes en su vida diaria. La lesión del hemisferio izquierdo se comportó como un factor de mal pronóstico en la recuperación funcional de los pacientes.

SUMMARY INTRODUCTION: Cerebrovascular disease constitutes a public health problem. This entity represents an important cause of permanent disability in adults, social, economic and health impact as well. The high costs demanded by health care from the moment of diagnosis, initial management of the event, and subsequent rehabilitation-palliation of the sequelae, requires knowledge of population characteristics and possible prognostic factors. This can be useful as an input for planning prevention services for people at risk and care of stroke patients. OBJECTIVE: To identify the prognostic role that some factors associated with the ischemic lesion have regarding the degree of disability and mortality, in the cerebral infarction of the anterior circulation. Methods: Observational, analytical, prospective cohort study was performed, with a nested case-control analysis. Neurological involvement was measured at admission with the NIHSS scale. At three months post-event, the modified Rankin scale (mRS: dependent variable) was measured, pursuing residual disability and mortality; cases: patient with unfavorable mRS score (score: 3, 4, 5, 6); controls: patient with favorable mRS score (score: 0, 1, 2). RESULTS: 93 patients with diagnosis of ischemic stroke of anterior circulation were included. Median age was 67 years RIQ (57-76); most frequent NIHSS was moderate (50; 53.8 %) and the median evolution time to medical management was 5 hours RIQ (3-24 hours). Etiology was identified in 33 patients (35.5 %, cardio-embolic the most). After 90 days since ischemic injury, most frequent mRS was "3: moderate" (22; 23.7 %) and 7 (7.5 %) patients died. Bivariate analysis identified left hemisphere stroke as an unfavorable variable in terms of disability at three months compared to the right hemisphere (OR 2.51, 95 % CI 1.06-5.9, p = 0.03). CONCLUSIONS: The population with ischemic stroke was predominantly males with multiple comorbidities, with a moderate neurological compromise on admission (NIHSS score: 5-15). After three months post event, patients were predominantly with reduced mobility, some mental functions affection, but essentially independent in activities of daily living. The involvement of left hemisphere is projected as poor prognostic factor in the functional recovery of our patients.

Recommendations of the Colombian Consensus Committee for the Management of Traumatic Brain Injury in Prehospital, Emergency Department, Surgery, and Intensive Care (Beyond One Option for Treatment of Traumatic Brain Injury: A Stratified Protocol [BOOTStraP]).

Background Traumatic brain injury (TBI) is a global public health problem. In Colombia, it is estimated that 70% of deaths from violence and 90% of deaths from road traffic accidents are TBI related. In the year 2014, the Ministry of Health of Colombia funded the development of a clinical practice guideline (CPG) for the diagnosis and treatment of adult patients with severe TBI. A critical barrier to the widespread implementation was identified-that is, the lack of a specific protocol that spans various levels of resources and complexity across the four treatment phases. The objective of this article is to present the process and recommendations for the management of patients with TBI in various resource environments, across the treatment phases of prehospital care, emergency department (ED), surgery, and intensive care unit. Methods Using the Delphi methodology, a consensus of 20 experts in emergency medicine, neurosurgery, prehospital care, and intensive care nationwide developed recommendations based on 13 questions for the management of patients with TBI in Colombia. Discussion It is estimated that 80% of the global population live in developing economies where access to resources required for optimum treatment is limited. There is limitation for applications of CPGs recommendations in areas where there is low availability or absence of resources for integral care. Development of mixed methods consensus, including evidence review and expertise points of good clinical practices can fill gaps in application of CPGs. BOOTStraP (Beyond One Option for Treatment of Traumatic Brain Injury: A Stratified Protocol) is intended to be a practical handbook for care providers to use to treat TBI patients with whatever resources are available. Results Stratification of recommendations for interventions according to the availability of the resources on different stages of integral care is a proposed method for filling gaps in actual evidence, to organize a better strategy for interventions in different real-life scenarios. We develop 10 algorithms of management for building TBI protocols based on expert consensus to articulate treatment options in prehospital care, EDs, neurological surgery, and intensive care, independent of the level of availability of resources for care.

Bench Validation of a Handcrafted Prototype Catheter for Intra-gastric Pressure Monitoring.

BACKGROUND: Abdominal compartment syndrome is a sustained intra-abdominal pressure (IAP) >20 mm Hg associated with new organ dysfunction. In order to prevent its development and related complications, IAP monitoring should be performed in patients with risk factors. Although techniques for its monitoring have been developed, they are of high cost and not always available in low- and lower-middle-income countries. Therefore, we aim to develop and validate in a bench model a handcrafted catheter to be used as an alternative method to measure the intra-gastric pressure (IGP) as a surrogate of the IAP. METHODS: We used an acrylic water container as a model of the abdomen and four handcrafted catheters made of a 16 Fr Levin tube with a globe finger tied with silk in the distal end, inflated with 1 cm of air. They were placed on the bottom of the container where the water pressure was directly measured as a gold standard. The agreement between the two measures was assessed with the Bland-Altman method. RESULTS: We performed 120 simultaneous measures. The mean pressure difference was 0.218 (95% CI 0.074 to 0.363). CONCLUSIONS: The handcrafted prototype catheter and the direct measure were highly correlated. The new catheter is a reliable and reproducible tool for pressure monitoring. However, before it can be used in the clinical setting for IAP monitoring, validation in human models in a real clinical setting needs to be performed.

Behavioral and neurochemical characterization of the spontaneous mutation tremor, a new mouse model of audiogenic seizures

The tremor mutant phenotype results from an autosomal recessive spontaneous mutation arisen in a Swiss–Webster mouse colony. The mutant mice displayed normal development until three weeks of age when they began to present motor impairment comprised by whole body tremor, ataxia, and decreased exploratory behavior. These features increased in severity with aging suggesting a neurodegenerative profile. In parallel, they showed audiogenic generalized clonic seizures. Results from genetic mapping identified the mutation tremor on chromosome 14, in an interval of 5 cM between D14Mit37 (33.21cM) and D14Mit115 (38.21cM), making Early Growth Response 3 (Egr3) the main candidate gene. Comparing with wild type (WT) mice, the tremor mice showed higher hippocampal gene expression of Egr3 and Gabra1 and increased concentrations of noradrenalin (NOR; p=.0012), serotonin (5HT; p=.0083), 5-hydroxyindoleacetic acid (5-HIAA; p=.0032), gama-amino butyric acid (GABA; p=.0123), glutamate (p=.0217) and aspartate (p=.0124). In opposition, the content of glycine (p=.0168) and the vanillylmandelic acid (VMA)/NOR ratio (p=.032) were decreased. Regarding to dopaminergic system, neither dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) contents nor the turnover rate of DA showed statistically significant differences between WT and mutant mice. Data demonstrated that audiogenic seizures of tremor mice are associated with progressive motor impairment as well as to hippocampal alterations of the Egr3 and Gabra1 gene expression and amino acid and monoamine content. In addition, the tremor mice could be useful for study of neurotransmission pathways as modulators of epilepsy and the pathogenesis of epilepsies occurring with generalized clonic seizures.

Use of silver nanoparticles to control Vibrio fluvialis in cultured angelfish Pterophyllum scalare.

Nanoparticles have multiple applications, among which is their use as antimicrobial agents in aquaculture. The objective of this work was to determine the antibacterial effect of silver nanoparticles (AgNPs) against Vibrio fluvialis in cultured angelfish Pterophyllum scalare. AgNPs were synthetized through chemical reduction and characterized by UV-visible and infrared spectroscopy. Particle size ranged from 60 to 170.8 nm, and scanning electron microscopy revealed cubic and spherical forms. A minimal inhibitory concentration of 222.5 ppm was determined, as well as inhibition halos between 8.66 and 14.3 mm. Inhibition of V. fluvialis growth was observed upon contact with AgNPs. An 88% survival of infected fish was obtained when treated with AgNPs, in contrast to 100% mortality of fish that were not treated. No damage to internal or external organs was observed in fish exposed to AgNPs. We conclude that AgNPs exert an antimicrobial effect against V. fluvialis, and thus represent a new alternative to control diseases caused by this microorganism in P. scalare culture.

Alteraciones neuropsicológicas y funciones ejecutivas superiores en adolescentes de padres con alcoholismo, vistos desde el modelo de adaptación de Roy / Neuropsychological disorders and higher executive functions in teens of parents with alcoholism, seen from the Roy Adaptation Model

El alcoholismo por parte de los padres está estrechamente ligado a causar alteraciones cognitivas tanto a la persona dependiente de la sustancia como a las personas con las que convive éste todos los días, existen habilidades cognitivas de tipo superior llamadas funciones ejecutivas, las cuales regulan las acciones complejas del ser humano para llevar una conducta social aceptada, dichas funciones se desarrollan en la adolescencia, etapa en la cual el cerebro alcanza su tamaño igual al del adulto y por ende, su madurez. Callista Roy desarrolló un modelo del proceso cognitivo basado en las unidades funcionales del cerebro, se fundamenta en el conocimiento de la neurociencia y las observaciones en la práctica de enfermería, hace mención de las funciones ejecutivas y los cambios que sufre el adolescente

Regional Myocardial Perfusion Disturbance in Experimental Chronic Chagas Cardiomyopathy.

Altered myocardial perfusion is a common finding in chronic Chagas cardiomyopathy (CCC), but its underlying histologic changes have not been elucidated. We investigated the occurrence of myocardial perfusion defects (MPDs) and the correlated regional changes to histology in an experimental model of CCC in hamsters. Methods: Female Syrian hamsters (n = 34) were infected with 3.5 × 104 to 105 trypomastigote forms of Trypanosoma cruzi, Y strain, and 6-10 mo afterward underwent in vivo imaging including resting 99mTc-sestamibi SPECT, segmental and global left ventricular function assessment using 2-dimensional echocardiography, and 18F-FDG PET for evaluation of myocardial viability. Histologic analysis included quantification of fibrosis, inflammatory infiltration, and the diameter and density of myocardial microcirculation. Results: MPDs were present in 17 (50%) of the infected animals. Histologic analysis revealed no transmural scar in segments with an MPD, and normal or mildly reduced 18F-FDG uptake, indicating viable myocardium. Infected animals with an MPD, in comparison to infected animals without an MPD and control animals, showed a lower left ventricular ejection fraction (P = 0.012), a higher wall motion score index (P = 0.004), and a higher extent of inflammatory infiltration (P = 0.018) but a similar extent of fibrosis (P = 0.15) and similar microvascular diameter and density (P > 0.05). Segments with an MPD (n = 65), as compared with normally perfused regions in the same animal (n = 156), showed a higher wall motion score index (P = 0.005) but a similar extent of inflammatory infiltration, a similar extent of fibrosis, and a similar microvascular diameter and density. Conclusion: Resting MPDs are frequent in experimental CCC and are associated with myocardial inflammation but do not designate scar tissue, corresponding to regions with metabolically viable myocardium.