The road ahead to successful BBB opening and drug-delivery with focused ultrasound.

This review delves into the innovative technology of Blood-Brain Barrier (BBB) opening with low-intensity focused ultrasound in combination with microbubbles (LIFU-MB), a promising therapeutic modality aimed at enhancing drug delivery to the central nervous system (CNS). The BBB's selective permeability, while crucial for neuroprotection, significantly hampers the efficacy of pharmacological treatments for CNS disorders. LIFU-MB emerges as a non-invasive and localized method to transiently increase BBB permeability, facilitating the delivery of therapeutic molecules. Here, we review the procedural stages of LIFU-MB interventions, including planning and preparation, sonication, evaluation, and delivery, highlighting the technological diversity and methodological challenges encountered in current clinical applications. With an emphasis on safety and efficacy, we discuss the crucial aspects of ultrasound delivery, microbubble administration, acoustic feedback monitoring and assessment of BBB permeability. Finally, we explore the critical choices for effective BBB opening with LIFU-MB, focusing on selecting therapeutic agents, optimizing delivery methods, and timing for delivery. Overcoming existing barriers to integrate this technology into clinical practice could potentially revolutionize CNS drug delivery and treatment paradigms in the near future.

A Scoping Review of Focused Ultrasound Enhanced Drug Delivery for Across the Blood-Brain Barrier for Brain Tumors.

BACKGROUND AND OBJECTIVES: Previous mechanisms of opening the blood-brain barrier (BBB) created a hypertonic environment. Focused ultrasound (FUS) has recently been introduced as a means of controlled BBB opening. Here, we performed a scoping review to assess the advances in drug delivery across the BBB for treatment of brain tumors to identify advances and literature gaps. METHODS: A review of current literature was conducted through a MEDLINE search inclusive of articles on FUS, BBB, and brain tumor barrier, including human, modeling, and animal studies written in English. Using the Rayyan platform, 2 reviewers (J.P and C.Y) identified 967 publications. 224 were chosen to review after a title screen. Ultimately 98 were reviewed. The scoping review was designed to address the following questions: (1) What FUS technology improvements have been made to augment drug delivery for brain tumors? (2) What drug delivery improvements have occurred to ensure better uptake in the target tissue for brain tumors? RESULTS: Microbubbles (MB) with FUS are used for BBB opening (BBBO) through cavitation to increase its permeability. Drug delivery into the central nervous system can be combined with MB to enhance transport of therapeutic agents to target brain tissue resulting in suppression of tumor growth and prolonging survival rate, as well as reducing systemic toxicity and degradation rate. There is accumulating evidence demonstrating that drug delivery through BBBO with FUS-MB improves drug concentrations and provides a better impact on tumor growth and survival rates, compared with drug-only treatments. CONCLUSION: Here, we review the role of FUS in BBBO. Identified gaps in the literature include impact of tumor microenvironment and extracellular space, improved understanding and control of MB and drug delivery, further work on ideal pharmacologics for delivery, and clinical use.

Hyperkalemia-Induced T Wave Oversensing in an Implantable Cardioverter Defibrillator.

A 66-year-old female with end-stage renal disease and heart failure with reduced ejection fraction, status post implantable cardioverter defibrillator (ICD) presented to the emergency department with dizziness and fatigue. An electrocardiogram showed sinus rhythm, complete atrioventricular block, and ventricular paced rhythm at 30 beats per minute (bpm). Device interrogation revealed a programmed VVI mode with a lower rate limit of 40 bpm and evidence of T wave oversensing. Serologic studies were remarkable for hyperkalemia (7.9 mmol/dL). The device was initially reprogrammed to provide a higher pacing rate and symptomatic improvement. Both complete AV block and T wave oversensing resolved after correction of hyperkalemia. This case highlights the need for vigilant monitoring of electrolyte imbalances in ICD patients.

Fully automated high-throughput immuno-µPlaque assay for live-attenuated tetravalent dengue vaccine development.

Dengue fever has remained a continuing global medical threat that impacts half of the world's population. Developing a highly effective dengue vaccine, with live-attenuated tetravalent vaccines as leading candidates, remains essential in preventing this disease. For the development of live virus vaccines (LVVs), potency measurements play a vital role in quantifying the active components of vaccine drug substance as well as drug product during various stages of research, development, and post-licensure evaluations. Traditional plaque-based assays are one of the most common potency test methods, but they generally take up to weeks to complete. Less labor and time-intensive potency assays are thus called for to aid in the acceleration of vaccine development, especially for multivalent LVVs. Here, we introduce a fully automated, 96-well format µPlaque assay that has been optimized as a high-throughput tool to evaluate process and formulation development of a live-attenuated tetravalent dengue vaccine. To the best of our knowledge, this is the first report of a miniaturized viral plaque method for dengue with full automation via an integrated robotic system. Compared to the traditional manual plaque assay, this newly developed method substantially reduces testing time by approximately half and allows for the evaluation of over ten times more samples per run. The fully automated workflow, from cell culture to plaque counting, significantly minimizes analyst hands-on time and improves assay repeatability. The study presents a pioneering solution for the rapid measurement of LVV viral titers, offering promising prospects for advancing vaccine development through high-throughput analytics.

Automated segmentation of ablated lesions using deep convolutional neural networks: A basis for response assessment following laser interstitial thermal therapy.

BACKGROUND: Laser interstitial thermal therapy (LITT) of intracranial tumors or radiation necrosis enables tissue diagnosis, cytoreduction, and rapid return to systemic therapies. Ablated tissue remains in situ, resulting in characteristic post-LITT edema associated with transient clinical worsening and complicating post-LITT response assessment. METHODS: All patients receiving LITT at a single center for tumors or radiation necrosis from 2015 to 2023 with ≥9 months of MRI follow-up were included. An nnU-Net segmentation model was trained to automatically segment contrast-enhancing lesion volume (CeLV) of LITT-treated lesions on T1-weighted images. Response assessment was performed using volumetric measurements. RESULTS: Three hundred and eighty four unique MRI exams of 61 LITT-treated lesions and 6 control cases of medically managed radiation necrosis were analyzed. Automated segmentation was accurate in 367/384 (95.6%) images. CeLV increased to a median of 68.3% (IQR 35.1-109.2%) from baseline at 1-3 months from LITT (P = 0.0012) and returned to baseline thereafter. Overall survival (OS) for LITT-treated patients was 39.1 (9.2-93.4) months. Lesion expansion above 40% from volumetric nadir or baseline was considered volumetric progression. Twenty-one of 56 (37.5%) patients experienced progression for a volumetric progression-free survival of 21.4 (6.0-93.4) months. Patients with volumetric progression had worse OS (17.3 vs 62.1 months, P = 0.0015). CONCLUSIONS: Post-LITT CeLV expansion is quantifiable and resolves within 6 months of LITT. Development of response assessment criteria for LITT-treated lesions is feasible and should be considered for clinical trials. Automated lesion segmentation could speed the adoption of volumetric response criteria in clinical practice.

Implementing a Pharmacogenomic-driven Algorithm to Guide Antiplatelet Therapy among Caribbean Hispanics: A non-randomized prospective cohort study.

Background: After percutaneous coronary intervention (PCI), clopidogrel resistant patients are at an increased risk of major adverse cardiovascular and cerebrovascular events (MACCEs). We aimed to assess whether genotype-guided selection of oral antiplatelet drugs using a clinical decision support (CDS) algorithm reduces the occurrence of these ischemic events and improves outcomes among Caribbean Hispanic patients from Puerto Rico, who are underrepresented in clinical pharmacogenomic (PGx)-guided implementation studies. Methods: Individual platelet function testing (PRU) measures, CYP2C19*2 and PON1 rs662 genotypes, clinical and demographic data from 8 medical facilities were included. Patients were separated into standard of care (SoC) and genotype-guided groups (150 each). Risk scores were calculated based on a previously developed CDS risk prediction algorithm designed to make actionable treatment recommendations for each patient. Alternative therapy with ticagrelor was recommended for patients with a high risk score ≥2. Statistical associations between patient time free of MACCEs and predictor variables (i.e., treatment groups, risk scores) were tested in this population using Kaplan-Meier survival analyses and Cox proportional-hazards regression models. Results: Median age of participants is 67 years; BMI: 27.8; 48% women; 14% smokers; 59% with type-2 diabetes mellitus (T2DM). Among patients with high-risk scores who were free from MACCE events 6 months after coronary stenting, genotype-driven guidance of antiplatelet therapy showed superiority over SoC in terms of reducing the incidence rate of atherothrombotic events. Conclusions: The clinical utility of our PGx-driven CDS algorithm to reduce the incidence rate of MACCEs among post-PCI Caribbean Hispanic patients on clopidogrel was externally demonstrated. Clinical Trial Registration Unique Identifier: NCT03419325.

Treatment with an Anti-CK2 Synthetic Peptide Improves Clinical Response in COVID-19 Patients with Pneumonia. A Randomized and Controlled Clinical Trial.

The instrumental role of CK2 in the SARS-CoV-2 infection has pointed out this protein kinase as promising therapeutic target in COVID-19. Anti-SARS-CoV-2 activity has been reported by CK2 inhibitors in vitro; however, no anti-CK2 clinical approach has been investigated in COVID-19. This trial aimed to explore the safety and putative clinical benefit of CIGB-325, an anti-CK2 peptide previously assessed in cancer patients. A monocentric, controlled, and therapeutic exploratory trial of intravenous CIGB-325 in adults hospitalized with COVID-19 was performed. Twenty patients were randomly assigned to receive CIGB-325 (2.5 mg/kg/day during 5-consecutive days) plus standard-of-care (10 patients) or standard-of-care alone (10 patients). Adverse events were classified by the WHO Adverse Reaction Terminology. Parametric and nonparametric statistical analyses were performed according to the type of variable. Considering the small sample size, differences between groups were estimated by Bayesian analysis. CIGB-325 induced transient mild and/or moderate adverse events such as pruritus, flushing, and rash in some patients. Both therapeutic regimens were similar with respect to SARS-CoV-2 clearance in nasopharynx swabs over time. However, CIGB-325 significantly reduced the median number of pulmonary lesions (9.5 to 5.5, p = 0.042) at day 7 and the proportion of patients with such an effect was also higher according to Bayesian analysis (pDif > 0; 0.951). Also, CIGB-325 significantly reduced the CPK (p = 0.007) and LDH (p = 0.028) plasma levels at day 7. Our preliminary findings suggest that this anti-CK2 clinical approach could be combined with standard-of-care in COVID-19 in larger studies.

Characterization and antimicrobial effect of a bioinspired thymol coating formed on titanium surface by one-step immersion treatment.

OBJECTIVE: To develop an antimicrobial and anti-adherent thymol (TOH)-containing coating on titanium (Ti) by a bioinspired one-step biocompatible method. METHODS: A nanolayer of adsorbed TOH (TOH-NL-Ti) was formed by an easy deep coating method on Ti surface. The treatment consists in a simple one-step immersion process in a TOH-containing solution. Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (ATR-FTIR), potentiodynamic electrochemical technique, open circuit potential records, Atomic Force Microscopy (AFM) and measurements of TOH release were used to characterize TOH-NL-Ti. Live/Dead staining and plate counting were employed to quantify attached and living adhered bacteria, respectively. Biocompatibility and cytotoxicity in fibroblastic and pre-osteoblastic cell lines were evaluated by acridine orange staining and MTT assay, respectively. RESULTS: TOH adsorbed on TOH-NL-Ti was detected by ATR-FTIR and electrochemical techniques. ATR-FTIR results showed that TOH nanofilms development involves spontaneous production of ketonic structures on Ti surface. AFM analysis revealed that the thickness of the TOH-NL was below 80 nm. Finally, microbiological assays confirmed that TOH-NL-Ti can inhibit the adhesion and kill attached bacteria leading to the eradication of leaving cells on its surface. After 24 h of biocidal release, the antimicrobial effect is also significant (a decrease of 3 orders in the number of attached bacteria). SIGNIFICANCE: The formation of TOH-NL-Ti nanolayer is a simple strategy able to be applied by not specially trained personnel, to reduce implant infection risks, ensure highly effective antimicrobial action and inhibition of bacterial adhesion on Ti surfaces without showing toxic effects for pre-osteoblastic and fibroblastic cells.

Implementing a pharmacogenetic-driven algorithm to guide dual antiplatelet therapy (DAPT) in Caribbean Hispanics: protocol for a non-randomised clinical trial.

INTRODUCTION: Minority populations in the USA are disproportionately affected by cardiovascular conditions. Reduced responsiveness to clopidogrel among carriers of CYP2C19 variants has been reported in patients with either coronary artery disease (CAD) or acute coronary syndrome (ACS) after the percutaneous coronary intervention (PCI). Previous studies have evaluated CYP2C19 genotyping-guided antiplatelet therapy in selected populations; however, this has yet to be tested among Hispanics. Given the paucity of clinical research on CYP2C19 and antiplatelet clinical outcomes in Hispanics, our study will test the safety and efficacy of a genetic-driven treatment algorithm to guide dual antiplatelet therapy (DAPT) in Caribbean Hispanics. METHODS AND ANALYSIS: This is a multicentre, prospective, non-randomised clinical trial that proposes an assessment of pharmacogenomic-guided DAPT in post-PCI Caribbean Hispanic patients with ACS or CAD. We will recruit 250 patients to be compared with a matched non-concurrent cohort of 250 clopidogrel-treated patients (standard-of-care). Major adverse cardiovascular events (MACEs) such as all-cause death, myocardial infarction (MI), stroke, coronary revascularisation, stent thrombosis and bleedings over 6 months will be the study endpoints. Among the recruited, high-risk patients will be escalated to ticagrelor and low-risk patients will remain on clopidogrel. The primary objective is to determine whether genetic-guided therapy is superior to standard of care. The secondary objective will determine if clopidogrel treatment in low-risk patients is not associated with a higher rate of MACEs compared with escalated antiplatelet therapy in high-risk patients. Patients will be enrolled up to the group's completion. ETHICS AND DISSEMINATION: Approval was obtained from the Institutional Review Board of the University of Puerto Rico Medical Sciences Campus (protocol # A4070417). The study will be carried out in compliance with the Declaration of Helsinki and International Conference on Harmonization Good Clinical Practice Guidelines. Findings will be published in a peer-reviewed journal and controlled access to experimental data will be available. TRIAL REGISTRATION NUMBER: NCT03419325; Pre-results.

Sex differences in brain correlates of STEM anxiety.

Anxiety is known to dysregulate the salience, default mode, and central executive networks of the human brain, yet this phenomenon has not been fully explored across the STEM learning experience, where anxiety can impact negatively academic performance. Here, we evaluated anxiety and large-scale brain connectivity in 101 undergraduate physics students. We found sex differences in STEM-related and clinical anxiety, with longitudinal increases in science anxiety observed for both female and male students. Sex-specific relationships between STEM anxiety and brain connectivity emerged, with male students exhibiting distinct inter-network connectivity for STEM and clinical anxiety, and female students demonstrating no significant within-sex correlations. Anxiety was negatively correlated with academic performance in sex-specific ways at both pre- and post-instruction. Moreover, math anxiety in male students mediated the relation between default mode-salience connectivity and course grade. Together, these results reveal complex sex differences in the neural mechanisms driving how anxiety is related to STEM learning.

Effect of anodized zirconium implants on early osseointegration process in adult rats: a histological and histomorphometric study.

Since surface plays a key role in bioactivity, the response of the host to the biomaterial will determine the success or failure of the prosthesis. The purpose of this study is to make an exhaustive analysis of the histological and histochemical characteristics of new bone tissue around Zr implants anodized at 60 V (Zr60) supported by histomorphometric methods in a rat model. Fibrous tissue was observed around the control implants (Zr0) and osteoblasts were identified on the trabeculae close to the implantation site that showed typical cytological characteristics of active secretory cells, regardless of the surface condition. The histomorphometrical analysis revealed a significant increase in cancellous bone volume, trabecular thickness and in trabecular number together with a decrease in trabecular separation facing Zr60. TRAP staining showed that there was a relative increase in the number of osteoclasts for Zr60. In addition, a larger number of osteoclast with a greater number of nuclei were detected in the tibiae for Zr60. This research demonstrated that the new bone microarchitecture in contact with Zr60 is able to improve the early stages of the osseointegration process and consequently the primary stability of implants which is a crucial factor to reduce recovery time for patients.

Software educativo en el proceso de enseñanza-aprendizaje de la asignatura Ética y Bioética / Educative software in the teaching-learning process of the subject Ethics and Bioethics

Introducción: la enseñanza de la ética y bioética es una necesidad palpable, un problema no resuelto para la educación superior en todos sus centros y carreras, en los momentos actuales, puesto que el profesional egresado de las universidades médicas necesita abordar desde la reflexión ética el ámbito de la actividad profesional en la esfera de la salud donde se va a desarrollar, para así propiciar un acercamiento a los principios, normas y valores del quehacer salubrista en el contexto del proyecto socialista cubano. Objetivo: diseñar un medio de enseñanza, que contribuya al proceso de enseñanza_aprendizaje en la asignatura Ética y Bioética en la carrera de Licenciatura en Tecnología de la Salud, de la Filial Universitaria Municipal de Salud, Consolación del Sur. Material y método: el presente estudio se basó en un proyecto de innovación tecnológica, en el área de pregrado a partir de un enfoque investigativo integral teniendo como base metodológica el método dialéctico materialista. Por lo que se emplearon métodos teóricos, empíricos y estadísticos, dentro de los primeros, el histórico-lógico, sistémico-estructural y el análisis documental y en el segundo grupo encuestas, entrevistas y la observación. Resultados: se manifiesta en la carencia de medios de enseñanza apoyados por la tecnología educativa que satisfaga la asequibilidad en la asimilación de los contenidos y la motivación por el aprendizaje para contribuir al perfeccionamiento de la asignatura Ética y Bioética, insuficiente comprensión por parte de los estudiantes de la importancia de la asignatura para su actuación profesional, bajos niveles de motivación en la adquisición de habilidades en los estudiantes, elementos que atentan contra la efectividad y calidad del proceso de enseñanza aprendizaje de esta asignatura. Conclusiones: se diseñó un software educativo para el estudio de la asignatura Ética y Bioética, que permitirá a los estudiantes un aprendizaje activo, consciente y desarrollador, facilitando la adquisición de habilidades y conocimientos para el modo de actuación profesional. La consulta a los expertos confirmó la validez del Software Educativo para la asignatura Ética y Bioética, de la carrera Licenciatura en Tecnología de la Salud, y la viabilidad de su implementación en la Filial Universitaria Municipal de Salud, Consolación del Sur.

Introduction: the teaching of ethics and bioethics is a latent need, a non-solved problem for higher education in all institutions and majors in current times, since the personnel graduated from medical universities requires treating from the ethic perception the scope of professional activity in the health area where he or she will make career, and thus to provide an approach to the principals, standards and values of the health care services in the context of the Cuban socialist project. Objective: to design a teaching aid that contributes with the teaching-learning process in the subject Ethics and Bioethics in the major Bachelor in Health Technology of the Consolación del Sur Municipal University Health Venue. Material and method: the present study was based on a technologic innovation project in the undergraduate section, from a comprehensive research approach, having a methodological basis the dialectical materialistic method. Theoretical, empirical, and statistical methods were used; within the first ones, the logical-historical, systemic-structural and the bibliographic review; within the second ones, surveys, interviews and observation. Results: there is lack of teaching aids supported by the educative technology satisfying accessibility in the assimilation of contents and motivation for learning thus contributing to perfecting the subject Ethics and Bioethics, insufficient understanding by the students of the importance of the subject for their professional performance, low levels of acquisition of skill by the students, and elements affecting the quality of the teaching learning process of this subject. Conclusions: a educative software was designed for studying the subject Ethics and Bioethics, which will permit the student an active, conscious and developing learning, facilitating the acquisition of skills and knowledge for professional performance. Consultation to the experts confirmed the validity of the educative software for the subject Ethics and Bioethics of the major Bachelor of Health Technology, and viability of its implementation in Consolación del Sur Municipal University Health Venue.

Mortalidad por accidentes de tránsito en Bayamo, Cuba 2011 / Mortality in traffic accidents in Bayamo, Cuba 2011

Con el objetivo de describir la mortalidad por accidentes de tránsito en Bayamo, Cuba, en el año 2011 se realizó una revisión de los pacientes lesionados y fallecidos a causa de accidentes de tránsito, registrados en Hospital Carlos M. de Céspedes. Se atendieron en emergencias 1365 lesionados, predominando el grupo etario de 25 a 44 años con 372 pacientes (27,3%), y el sexo masculino con 1071 (78,5%). Fallecieron 46 personas, en su mayoría del mismo grupo de edad y de sexo masculino. Los traumatismos múltiples (52,6%) y cráneofaciales (34,2%) fueron las localizaciones predominantes. Se destacaron los atropellos por vehículo de motor con mortalidad del 26,3%. En conclusión, la mortalidad por accidentes de tránsito predomina en adultos jóvenes masculinos; cuyas consecuencias fatales son debido a traumatismos múltiples por atropellos.

With the objective of describing mortality from traffic accidents in Bayamo, Cuba, in 2011 a review was performed of injured and deceased patients due to traffic accidents, recorded in the Hospital Carlos M. de Céspedes. Of the 1,365 injured patients treated in the emergency room, the predominant groups were individuals aged 25 to 44 years comprising 372 patients (27.3%) and men comprising 1,071 (78.5%). 46 people died, most from the same age group and male. Multiple traumatisms (52.6%) and craniofacial trauma (34.2%) were the predominant injuries. Motor vehicle-pedestrian accidents stood out with a mortality of 26.3%. In conclusion, mortality from traffic accidents predominately occurs in young male adults, whose fatal consequences are due to multiple traumatisms from road accidents.

La promoción de salud dirigida a reducir los factores de riesgo de cáncer cérvico uterino / Health promotion aimed to reducing uterine cervical cancer risk factors

La primera Conferencia Internacional sobre la Promoción de la Salud celebrada en Ottawa, el 21 de noviembre de 1986, definió la promoción de la salud como “el proceso de permitir a la gente aumentar su control sobre su salud y por lo tanto mejorarla”. Se reconoce claramente que la promoción de la salud va más allá de los estilos de vida, en la cual la educación para la salud constituye, junto a la comunicación y a la participación social, herramientas necesarias para su instrumentación en el primer nivel de atención. En la práctica cotidiana se desconoce de forma reiterada el valor que tiene el reconocimiento adecuado de las dimensiones de la promoción de salud, desde una perspectiva holística, dirigidas a reducir los factores de riesgo de cáncer cérvico uterino. El propósito del estudio fue realizar una contribución teórica a la promoción de salud para contribuir al fortalecimiento del Programa Nacional de Diagnóstico Precoz del Cáncer Cérvico Uterino. Al considerar el valor de esta disciplina desde sus dimensiones, el profesional de la salud dispone de una base teórica que guíe las acciones dirigidas a la reducción de factores de riesgos de este tipo de cáncer en la población femenina.

The first International Conference on Health Promotion celebrated in Ottawa on November 21st, 1986, defined health promotion as “the process allowing people to increase the control on their health and therefore to improve it”. It is clearly understood that health promotion goes beyond life styles, and also includes education for health, communication and social participation, necessary tools for its instrumentation in the first health care level. In every day practice it is continually not recognized the value of the adequate acknowledgement of health promotion dimensions, from a holistic perspective, aimed to reducing the uterine cervical cancer risk factors. The purpose of the research was theoretically contributing to the strengthening of the National Program of Uterine Cervical Cancer Precocious Diagnosis. When considering the value of this discipline in all its dimensions, the health care professional has a theoretical base to guide the actions aimed to reducing the risk factors of this kind of cancer among the female population.

[Mortality in traffic accidents in Bayamo, Cuba 2011]. / Mortalidad por accidentes de tránsito en Bayamo, Cuba 2011.

With the objective of describing mortality from traffic accidents in Bayamo, Cuba, in 2011 a review was performed of injured and deceased patients due to traffic accidents, recorded in the Hospital Carlos M. de Céspedes. Of the 1,365 injured patients treated in the emergency room, the predominant groups were individuals aged 25 to 44 years comprising 372 patients (27.3%) and men comprising 1,071 (78.5%). 46 people died, most from the same age group and male. Multiple traumatisms (52.6%) and craniofacial trauma (34.2%) were the predominant injuries. Motor vehicle-pedestrian accidents stood out with a mortality of 26.3%. In conclusion, mortality from traffic accidents predominately occurs in young male adults, whose fatal consequences are due to multiple traumatisms from road accidents.

Chronic elevation of phosphocholine containing lipids in mice exposed to Gulf War agents pyridostigmine bromide and permethrin.

For two decades, 25% of the veterans who served in the 1991 Gulf War (GW) have been living with Gulf War Illness (GWI), a chronic multisymptom illness. Evidence suggests that brain structures involved in cognitive function may be affected in GWI. Gulf War agents such as the acetylcholinesterase (AChE) inhibitor pyridostigmine bromide (PB) and the pesticide permethrin (PER) are considered key etiogenic factors in GWI. We therefore developed a mouse model of GW agent exposure by co-administering PB and PER and showed that this model exhibits cognitive impairment and anxiety, and increased astrogliosis at chronic post-exposure time-points. Since GW agents inhibit AChE, we hypothesized that PB+PER exposure will modulate phosphatidylcholine (PC) and sphingomyelin (SM), which are reservoirs of phosphocholine required for endogenous ACh synthesis. Lipidomic analyses showed that PC and SM were elevated in the brains of exposed compared to control mice. Brain ether PC (ePC) species were increased but lyso-platelet activating factors (lyso-PAF) that are products of ePC were decreased in exposed animals compared to controls. Catalase expression (a marker for peroxisomes) was increased in GW agent exposed mice compared to controls. Ether PC and lyso-PAF modulation was also evident in the plasma of GW agent exposed mice compared to controls. These studies suggest peroxisomal and lysosomal dysfunction in the brain at a chronic post-exposure timepoint following GW agent exposure. Our studies provide a new direction for GWI research, which will be useful for developing suitable therapies for treating GWI.

Comportamiento circadiano del infarto agudo del miocardio en pacientes atendidos en el Hospital Abel Santamaría Cuadrado / Circadian behavior of Acute Myocardial Infarction in patients admitted at “Abel Santamaria Cuadrado” University Hospital

La hora de aparición de los eventos coronarios agudos toma en los últimos años una relevancia especial. Muchas investigaciones tratan de esclarecer las particularidades de su ritmo circadiano. El objetivo fue caracterizar la hora de comienzo de los síntomas del infarto agudo del miocardio en pacientes hospitalizados durante cinco años. El método fue el estudio transversal descriptivo. El universo estuvo conformado por los 1 432 pacientes atendidos en el Hospital General Docente Abel Santamaría Cuadrado de Pinar del Río, Cuba, entre los años 2005 y 2009. La muestra incluyó 340 pacientes, que fueron seleccionados de forma aleatoria. Utilizando frecuencias absolutas y relativas se describieron las variables hora de inicio de los síntomas, la edad, el sexo, el hábito de fumar, los antecedentes personales de hipertensión arterial y diabetes mellitus, así como la letalidad. Se ajustó con el modelo Cosinor la curva de hora de inicio de los síntomas. La hora de inicio del infarto muestra un ritmo circadiano con picos entre las 9:00-11:59 h y las 24:00-02:59 h. En todos los grupos de edades se encontró un ritmo circadiano, con una curva ajustada de aspecto sinusoidal. En los pacientes fumadores la curva adopta aspecto bimodal. La letalidad del infarto fue de un 15,6 por ciento. La hora de comienzo del infarto agudo del miocardio se comporta con ritmo circadiano. En el tabaquismo, a diferencia de la hipertensión y la diabetes, se encuentran variaciones en la hora comienzo. La letalidad es superior en los pacientes que se infartan al medio día(AU)

The hour of onset in acute coronary events takes a special relevance nowadays. Several researches try to clear up the distinctiveness of the circadian rhythm. The objective was to characterize the hour of the onset of symptoms in acute myocardial infarction of patients hospitalize in the last 5 years. The method used was cross sectional and descriptive study. The target group was comprised of 1432 patients who attended to Abel Santamaria Cuadrado University Hospital in Pinar del Rio, Cuba during 2005 and 2009. The sample included 340 patients who were chosen at random, describing the absolute and relative frequencies as well as the variables: hour of onset, age, sex, smoking, personal records of hypertension and diabetes mellitus together with lethality. The model of Cosinor was adjusted considering the curve of the onset of symptoms. The hour of onset for the infarction shows a circadian rhythm with peaks between 9:00-11:59 hours and 24:00-02:59 hours. A circadian rhythm with an adjusted curve of sinusoidal aspect was found in all groups of ages. In smokers the curve adopts a bimodal aspect. Lethality of Acute Myocardial Infarction reached 15,6 per cent. The hour of the infarction behaves with circadian rhythm. In smoking, in contrast to hypertension and diabetes, variations were found on the hour of onset. Lethality is higher in patients suffering from infarction at noon(AU)

Sepsis en la edad pediátrica: su caracterización / Sepsis in the pediatric age: its characterization

Se realizó un estudio epidemiológico descriptivo y transversal en el hospital Pediátrico Docente Raymundo Castro Morales del municipio Puerto Padre, en el período de enero de 2006 a enero de 2007, con el objetivo de caracterizar la sepsis en los niños que han sido diagnosticados e ingresados en la sala de terapia por el sistema de urgencias. El universo estuvo constituido por todos los niños de 10 días a 18 años de edad que ingresaron en la sala de terapia de esta institución, constituyendo la muestra 47 pacientes, siendo la edad más frecuente la de 10 días a 11 meses de nacido y el síndrome de respuesta inflamatoria sistémica el estadio más frecuente. Se llevó a cabo una terapéutica adecuada y la gran mayoría de los niños evolucionó a la curación(AU)

A descriptive and cross-sectional epidemiological study was carried out at Raymundo Castro Morales Pediatric Teaching hospital of Puerto Padre Municipality, in the period from January, 2006 to January, 2007. The study aimed at characterizing sepsis in the children who have been diagnosed and admitted at the therapy ward through the emergencies system. The universe was constituted by all the children from 10 days to 18 years old who were admitted at the therapy ward of the institution and the sample was formed by 47 patients. The most frequent age was that from 10 days to 11 months old and the systemic inflammatory response syndrome was the most frequent stage. A proper therapeutics was carried out and most of the children evolved to the cure(AU)

Factores de riesgo del intento suicida en adolescentes con esta conducta / Risk factors of attempted suicide in adolescents with this behavior

El suicidio constituye un problema importante de salud, un verdadero drama existencial del hombre, reconocido desde la antigüedad. Con el propósito de determinar algunos de los factores de riesgo del intento suicida en adolescentes con esta conducta tratados en el Centro para la Atención Integral al Adolescente del municipio Artemisa entre 2005 y 2009, se realizó un proyecto de investigación analítico de tipo caso - control pareado retrospectivo. Se consideró grupo estudio [64 casos de intento suicida] y grupo control [64 no intento suicida]. Se utilizó el método histórico –lógico y empírico que permitió utilizar las historias clínicas de los pacientes en estudio y obtenida la información necesaria crear así una base de datos con el paquete estadístico Medcalc, a través del cual se crearon las tablas y gráficos correspondientes. Para determinar si existieron diferencias significativas entre los dos grupos se utilizaron los estadígrafos chi cuadrado y el Odds ratio, además de la Probabilidad. Constituyeron factores de riesgo del intento suicida: los antecedentes psiquiátricos familiares (p < 0,05; OR: 2,94; P: 74,61 por ciento), la estructura familiar (p < 0,05; OR: 2,137; P: 68,12 por ciento), la dinámica familiar (p < 0,05; OR: 2,290; P: 71,56 por ciento) y la depresión (p < 0,05; OR: 2,142; P: 68,17 por ciento). Resulta evidente la necesidad de una identificación precoz de los factores anteriores, a fin de establecer un programa de prevención que disminuya el riesgo suicida en los adolescentes(AU)

Suicide is a major health problem, a real man ´s existential drama, recognized since the antiquity. An analytic case control and retrospective study was conducted to determine some of the risk factors of attempted suicide in adolescents treated at Integrated Care Center for Adolescents in the period 2005-2009 in Artemisa municipality. 64 cases of attempted suicide were considered, study group and 64 not attempted suicide, control group. Historical-logical method and the empiric one allowed to look up the patients´ medical records and obtained the need information to create a database using the statistical package Medcalc, that allowed to create tables and graphics. Probability, chi - square and Odds ratio allowed the calculus of the significant differences between the two groups. The risk factors of attempted suicide in the study were: family psyquiatric histories(p < 0,05; OR: 2,94; P: 74,61 percent), family relations(p < 0,05; OR: 2,137; P: 68,12 percent),family dynamics(p < 0,05; OR: 2,290; P: 71,56 percent) and depression (p < 0,05; OR: 2,142; P: 68,17 percent). Early identification of risk factors of attempted suicide, is a clear need to establish a prevention program for decreasing this risk in adolescents(AU)

Niveles de tratamiento y control de la hipertensión arterial en el Policlínico Turcios Lima / Treatment levels and hypertension control at the Turcios Lima polyclinic

Introducción y objetivo: El control farmacológico de la hipertensión arterial es un componente esencial en la estrategia para el control de las enfermedades cardiovasculares. El propósito de esta investigación fue determinar la tasa actual de control de la hipertensión arterial en la población que recibe atención médica en el consultorio médico N° 18 perteneciente al Policlínico Turcios Lima, del municipio de Pinar del Río. Método: Estudio descriptivo y transversal; el universo estuvo constituido por 1.589 pacientes mayores de 15 años de edad, y la muestra, por 504 pacientes seleccionados por muestreo probabilístico estratificado. Resultados: Se obtuvo una prevalencia del 21,2 por ciento de hipertensión arterial, mayor en el sexo masculino; se calculó una tasa de control de 45 por cada 100 pacientes bajo tratamiento terapéutico y un porcentaje de control del 65,3 por ciento entre los tratados. El 42,3 por ciento de la población presenta un riesgo cardiovascular moderado de sufrir un accidente cardiovascular en los próximos 10 años. Conclusiones: Se obtuvo un nivel de control de la hipertensión arterial más elevado que lo notificado previamente por estudios poblacionales realizados en otros países, esta enfermedad es mejor controlada en las pacientes femeninas. En cuanto al riesgo cardiovascular global, predominó la categoría de moderado seguida por la de bajo riesgo, sin desestimar la población clasificada como de alto riesgo(AU)