Factors Influencing Inappropriate Use of Antibiotics in Infants under 3 Years of Age in Primary Care: A Qualitative Study of the Paediatricians' Perceptions.

Antibiotic consumption in infants of less than three years is higher than average the average consumption for general population. The aim of this study was to explore paediatricians' opinions regarding factors influencing inappropriate use of antibiotics in early infancy in primary care. A qualitative study based on the grounded theory using convenience sampling was conducted in Murcia Region, Spain. Three focal discussion groups were developed with 25 participants from 9 health areas (HA) of Murcia Region. Paediatricians perceived that health care pressure was an influential factor in the prescribing behaviour, forcing them to prescribe antibiotics for a rapid cure in unjustified circumstances. Participants believed that antibiotic consuming was related to parents' self-medication due to their perceptions about the curative potential of antibiotics together with facilities to obtain these agents from pharmacies without prescription. The misuse of antibiotics by paediatricians was associated to the lack of education on antibiotic prescription and the limited use of clinical guidelines. Not prescribing an antibiotic in the presence of a potentially severe disease generated more fear than an unnecessary prescription. The clinical interaction asymmetry was more evident, when paediatricians use trapping risk strategies as a mechanism to justify a restrictive prescribing behaviour. The rational model of clinical decision-making in antibiotic prescribing among paediatricians was determined by factors associated with health care management, social awareness and knowledge of the population and pressure of families' demands. The present findings have contributed to the design and implementation of health interventions in the community for improving awareness of the appropriate use of antibiotics, as well as for a better quality of prescription by peadiatricians.

Type I but Not Type II Calreticulin Mutations Activate the IRE1α/XBP1 Pathway of the Unfolded Protein Response to Drive Myeloproliferative Neoplasms.

Approximately 20% of patients with myeloproliferative neoplasms (MPN) harbor mutations in the gene calreticulin (CALR), with 80% of those mutations classified as either type I or type II. While type II CALR-mutant proteins retain many of the Ca2+ binding sites present in the wild-type protein, type I CALR-mutant proteins lose these residues. The functional consequences of this differential loss of Ca2+ binding sites remain unexplored. Here, we show that the loss of Ca2+ binding residues in the type I mutant CALR protein directly impairs its Ca2+ binding ability, which in turn leads to depleted endoplasmic reticulum (ER) Ca2+ and subsequent activation of the IRE1α/XBP1 pathway of the unfolded protein response. Genetic or pharmacologic inhibition of IRE1α/XBP1 signaling induces cell death in type I mutant but not type II mutant or wild-type CALR-expressing cells, and abrogates type I mutant CALR-driven MPN disease progression in vivo. SIGNIFICANCE: Current targeted therapies for CALR-mutated MPNs are not curative and fail to differentiate between type I- versus type II-driven disease. To improve treatment strategies, it is critical to identify CALR mutation type-specific vulnerabilities. Here we show that IRE1α/XBP1 represents a unique, targetable dependency specific to type I CALR-mutated MPNs. This article is highlighted in the In This Issue feature, p. 265.

Levels of low-molecular-weight hyaluronan in periodontitis-treated patients and its immunostimulatory effects on CD4+ T lymphocytes.

OBJECTIVES: During periodontitis, chronic inflammation triggers soft tissue breakdown, and hyaluronan is degraded into fragments of low molecular weight (LMW-HA). This investigation aimed to elucidate whether LMW-HA fragments with immunogenic potential on T lymphocytes remain in periodontal tissues after periodontal treatment. MATERIALS AND METHODS: GCF samples were obtained from 15 periodontitis-affected patients and the LMW-HA, RANKL, and OPG levels were analyzed before and after 6 months of periodontal treatment by ELISA. Eight healthy individuals were analyzed as controls. Besides, human T lymphocytes were purified, exposed to infected dendritic cells, and pulsed with LMW-HA. Non-treated T lymphocytes were used as control. The expression levels of the transcription factors and cytokines that determine the Th1, Th17, and Th22 lymphocyte differentiation and function were analyzed by RT-qPCR. Similarly, the expression levels of RANKL and CD44 were analyzed. RESULTS: In the GCF samples of periodontitis-affected patients, higher levels of LMW-HA were detected when compared with those of healthy individuals (52.1 ± 15.4 vs. 21.4 ± 12.2, p < 0.001), and these increased levels did not decrease after periodontal therapy (52.1 ± 15.4 vs. 45.7 ± 15.9, p = 0.158). Similarly, the RANKL levels and RANKL/OPG ratios did not change after periodontal therapy. Furthermore, in human T lymphocytes, LMW-HA induced higher expression levels of the Th1, Th17, and Th22-related transcription factors and cytokines, as well as CD44 and RANKL, as compared with non-treated cells. CONCLUSIONS: In some patients, increased levels of LMW-HA persist in periodontal tissues after conventional periodontal therapy, and these remaining LMW-HA fragments with immunostimulatory potential could induce the polarization of a pathologic Th1/Th17/Th22-pattern of immune response on T lymphocytes. CLINICAL RELEVANCE: The persistence of increased levels of LMW-HA in periodontal tissues after periodontal therapy could favor the recurrence of the disease and further breakdown of periodontal supporting tissues.

Identification of Gait Events in Healthy Subjects and With Parkinson's Disease Using Inertial Sensors: An Adaptive Unsupervised Learning Approach.

Automatic identification of gait events is an essential component of the control scheme of assistive robotic devices. Many available techniques suffer limitations for real-time implementations and in guaranteeing high performances when identifying events in subjects with gait impairments. Machine learning algorithms offer a solution by enabling the training of different models to represent the gait patterns of different subjects. Here our aim is twofold: to remove the need for training stages using unsupervised learning, and to modify the parameters according to the changes within a walking trial using adaptive procedures. We developed two adaptive unsupervised algorithms for real-time detection of four gait events, using only signals from two single-IMU foot-mounted wearable devices. We evaluated the algorithms using data collected from five healthy adults and seven subjects with Parkinson's disease (PD) walking overground and on a treadmill. Both algorithms obtained high performance in terms of accuracy ( F1 -score ≥ 0.95 for both groups), and timing agreement using a force-sensitive resistors as reference (mean absolute differences of 66 ± 53 msec for the healthy group, and 58 ± 63 msec for the PD group). The proposed algorithms demonstrated the potential to learn optimal parameters for a particular participant and for detecting gait events without additional sensors, external labeling, or long training stages.

¿Qué palabras conozco?: propiedades psicométricas de una prueba de vocabulario para niños y niñas de nivel primario / Which words do I know? Psychometric properties of a vocabulary test for primary school children

El vocabulario es el conocimiento acerca de las palabras que maneja y conoce una persona. Juega un rol preponderante en el desarrollo y la ejecución de gran cantidad de habilidades cognitivas. El objetivo de este trabajo consistió en mostrar las propiedades psicométricas de un instrumento para la evaluación de la amplitud y profundidad del vocabulario (¿Qué palabras conozco? [QPC]), y su desempeño en niños y niñas de 3ro a 7mo grado de escuela primaria, de distinto nivel socioeconómico. Con este propósito se administró la prueba a 1327 niños y niñas de nivel socioeconómico medio y bajo. Las puntuaciones obtenidas mostraron evidencias muy satisfactorias de consistencia interna de los ítems y estabilidad temporal. Con respecto a las de validez, se obtuvo una correlación significativa con la tarea de vocabulario del WISC IV. Asimismo se observó que los niños y niñas de nivel socioeconómico medio presentaron un desempeño significativamente mayor que los niños y niñas de nivel socioeconómico bajo.

Vocabulary is the knowledge about words that a person uses and understands. It plays a preponderated role in the development and execution of a large number of cognitive abilities. The aim of this study was to show the psychometric properties of an instrument for the assessment of vocabulary breadth and depth (¿Qué Palabras Conozco? [QPC]), and its performance in children from 3rd to 7th grade in primary school, from different socioeconomic status. For this purpose, the test was administered to 1327 children of medium and low socioeconomic status. The scores obtained showed a very satisfactory evidence of internal consistency of the items as well as temporal stability. Regarding its validity, a significant correlation was obtained with the vocabulary task of the WISC IV. Likewise it was observed that the children from medium socioeconomic status showed a significantly higher performance than the children from low socioeconomic status.

Immunostimulatory activity of low-molecular-weight hyaluronan on dendritic cells stimulated with Aggregatibacter actinomycetemcomitans or Porphyromonas gingivalis.

OBJECTIVES: Periodontitis is a chronic inflammatory disease characterized by tooth-supporting tissue destruction, which is elicited by the host's immune response triggered against periodonto-pathogen bacteria. During periodontal tissue destruction, extracellular matrix components are metabolized and fragmented. Some extracellular matrix component-derived fragments, such as low-molecular-weight hyaluronan (LMW-HA), have potent immunogenic potential, playing a role as damage-associated molecular patterns (DAMPs) during activation of immune cells. Dendritic cells (DCs) play a central role in the host's immune response displayed during periodontitis; thus, this study aimed to analyze whether LMW-HA has an immunostimulatory activity on DCs when stimulated with periodonto-pathogen bacteria. MATERIALS AND METHODS: LMW-HA-treated and non-treated DCs were stimulated with Aggregatibacter actinomycetemcomitans or Porphyromonas gingivalis and the mRNA expression for cytokines tumor necrosis factor-α (TNF-alpha), interleukin-1ß (IL-1B), interleukin-6 (IL-6), and interleukin-23 (IL-23A) was quantified by RT-qPCR. In addition, transcription factors interferon regulatory factor 4 (IRF4), interferon regulatory factor 8 (IRF8), neurogenic locus notch homolog protein 2 (NOTCH2), and basic leucine zipper ATF-like transcription factor 3 (BATF3), involved in DC activation, were analyzed. RESULTS: Higher expression levels of TNF-alpha, IL-1B, IL-6, and IL-23A were detected in LMW-HA-treated DCs after bacterial infection, as compared with non-treated DCs. When LMW-HA-treated DCs were infected with A. actinomycetemcomitans, higher levels of IRF4, NOTCH2, and BATF3 were detected compared with non-treated cells; whereas against P. gingivalis infection, increased levels of IRF4 and NOTCH2 were detected. CONCLUSION: LMW-HA plays an immunostimulatory role on the immune response triggered by DCs during infection with A. actinomycetemcomitans or P. gingivalis. CLINICAL RELEVANCE: Detection of extracellular matrix component-derived fragments produced during periodontal tissue destruction, such as LMW-HA, could explain at least partly unsuccessful periodontal treatment and the chronicity of the disease.

Alveolar bone resorption and Th1/Th17-associated immune response triggered during Aggregatibacter actinomycetemcomitans-induced experimental periodontitis are serotype-dependent.

BACKGROUND: Aggregatibacter actinomycetemcomitans expresses several virulence factors that may contribute to the pathogenesis of periodontitis. Based on the antigenicity of the O-polysaccharide component of the lipopolysaccharide (LPS), different A. actinomycetemcomitans serotypes have been described. Among them, serotype b has demonstrated a stronger capacity to trigger Th1 and Th17-associated cytokine, CC-chemokine, and CC-chemokine receptor production on immune cells in vitro. With a murine model of experimental periodontitis, this investigation aimed to analyze the alveolar bone resorption and the pattern of immune response triggered by the different A. actinomycetemcomitans serotypes within periodontal lesions. METHODS: For periodontal lesion induction, mice were orally infected with the different A. actinomycetemcomitans serotypes or their purified LPS. Alveolar bone resorption was analyzed using microcomputed tomography and scanning electron microscopy. Bacterial infection, receptor activator of nuclear factor-kappa B ligand (RANKL) and Th1 and Th17-associated cytokine, CC-chemokine, and CC-chemokine receptor levels were quantified by quantitative polymerase chain reaction (qPCR). T lymphocytes isolated from periodontal lesions were analyzed by flow cytometry. RESULTS: In periodontal lesions, serotype b of A. actinomycetemcomitans induced higher alveolar bone resorption and expression of RANKL compared with the other serotypes. In addition, serotype b induced greater levels of Th1- and Th17-related cytokines, CC-chemokines, and CC-chemokine receptors than the others. Similarly, higher numbers of infiltrating Th1 and Th17 lymphocytes were detected in serotype b-induced periodontal lesions. CONCLUSIONS: These results demonstrate that periodontal lesions induced with different A. actinomycetemcomitans serotypes elicited distinct alveolar bone resorption and immune response. In particular, serotype b was more pathogenic than the others and induced stronger Th1 and Th17 patterns of immune responses during experimental periodontitis.

Impedance Control for Robotic Rehabilitation: A Robust Markovian Approach.

The human-robot interaction has played an important role in rehabilitation robotics and impedance control has been used in the regulation of interaction forces between the robot actuator and human limbs. Series elastic actuators (SEAs) have been an efficient solution in the design of this kind of robotic application. Standard implementations of impedance control with SEAs require an internal force control loop for guaranteeing the desired impedance output. However, nonlinearities and uncertainties hamper such a guarantee of an accurate force level in this human-robot interaction. This paper addresses the dependence of the impedance control performance on the force control and proposes a control approach that improves the force control robustness. A unified model of the human-robot system that considers the ankle impedance by a second-order dynamics subject to uncertainties in the stiffness, damping, and inertia parameters has been developed. Fixed, resistive, and passive operation modes of the robotics system were defined, where transition probabilities among the modes were modeled through a Markov chain. A robust regulator for Markovian jump linear systems was used in the design of the force control. Experimental results show the approach improves the impedance control performance. For comparison purposes, a standard [Formula: see text] force controller based on the fixed operation mode has also been designed. The Markovian control approach outperformed the [Formula: see text] control when all operation modes were taken into account.

Comparison of kinematic and EMG parameters between unassisted, fixed- and adaptive-stiffness robotic-assisted ankle movements in post-stroke subjects.

In this paper, we present an assist-as-needed scheme that effectively adapted the assistance provided by an ankle rehabilitation robot according to patient's participation and performance during therapeutic movements. We performed an error-based estimation of the ankle impedance as a valid measure of the patient participation. Then, we computed the amount of robotic assistance by three steps: normalization of the combined patient-robot stiffness, optimization of patientrobot interaction, and finally, adaptation of the level of the robotic assistance according to patient's performance while playing a serious game. Four post-stroke patients evaluated our methodology using an impedance controlled robotic system to assist alternated open-ended dorsi/plantarflexion movements in sitting position. Experimental results indicated that the proposed adaptive-stiffness method improves patient participation and performance compared to a fixed-stiffness assistive method and to an unassisted baseline. We also found that adaptive assistance could optimize the patient's muscular activity during movements. Our strategy effectively assisted with a lower stiffness allowing more kinematic variability in motions leaded by patient, decreasing the total amount of provided assistance without compromising the overall performance during therapy.

Presentación atípica de la enfermedad de Alexander infantil sin macrocefalia / An atypical presentation of Infantile Alexander disease lacking macrocephaly

Resumen: Introducción: La enfermedad de Alexander consiste en una forma de leucodistrofia poco frecuente que afecta principalmente a los astrocitos; tiene un patrón de herencia autosómica recesiva y es causada por mutaciones en el gen GFAP, localizado en el cromosoma 17q21. Puede presentarse a cualquier edad y la forma infantil se caracteriza por macrocefalia, crisis convulsivas, retraso motor y cognitivo grave y espasticidad o ataxia progresivas. Caso clínico: Paciente de sexo femenino de 8 meses evaluada por retraso psicomotor y crisis convulsivas motoras focales no provocadas. En la exploración física, con perímetro cefálico normal, respuesta motora incrementada ante estímulos táctiles y al ruido, signos piramidales y ausencia de visceromegalias. Se observó hipodensidad generalizada de la sustancia blanca en la resonancia magnética y punción lumbar con hiperproteinorraquia. Se descartó enfermedad de Krabbe mediante ensayo enzimático y secuenciación del gen GALC. En la reevaluación del caso, las alteraciones en la neuroimagen hicieron sospechar de enfermedad de Alexander, y la secuenciación del gen GFAP reportó una mutación en el exón 4 c.716G > A, lo que ocasionó un cambio de arginina por histidina en la posición 239 de la proteína (p.Arg239His). Conclusiones: Los signos radiológicos en la resonancia fueron determinantes para el diagnóstico, que posteriormente se confirmó con estudio molecular. Es importante considerar que ciertas mutaciones no se asocian con macrocefalia, lo cual puede ocasionar retraso en el diagnóstico.

Abstract: Background: Alexander disease is a rare form of leukodystrophy that involves mainly astrocytes; it is inherited in an autosomal recessive manner and occurs by mutations in the GFAP gene, located on chromosome 17q21. It can occur at any age and its infantile form is characterized by macrocephaly, seizures, severe motor and cognitive delay, and progressive spasticity or ataxia. Case report: An 8-month-old female was evaluated with a history of neurodevelopmental delay and unprovoked focal motor seizures. Physical examination showed normal head circumference, increased motor responses to tactile and noise stimuli, pyramidal signs and no visceromegalies. Widespread hypodense white matter was found on magnetic resonance and lumbar puncture showed hyperproteinorrachia. Krabbe disease was ruled out by enzymatic assay and gene sequencing of GALC. In the reassessment of the case, abnormalities in neuroimaging lead to suspicion of Alexander disease, and GFAP gene sequencing reported a pathogenic mutation in exon 4 c.716G > A, which caused a change of arginine to histidine at position 239 of the protein (p.Arg239His). Conclusions: The radiographic signs observed in the resonance were decisive for the diagnosis, later confirmed by molecular study. It is important to consider that certain mutations are not associated with macrocephaly, which may cause delay in diagnosis.

The Use of Cellulose Membrane to Eliminate Burst Release from Intravaginal Rings.

Burst release was observed when ethylene vinyl acetate copolymer (EVA) intravaginal rings were tested for progesterone release in our previous work (Helbling et al. Pharm Res. 31(3):795-808, 2014). Burst release is undesirable in controlled delivery devices because release is uncontrollable and higher levels of active pharmaceutical ingredient could lead to the occurrence of adverse effect. The present contribution is about the use of membranes to coat EVA rings to eliminate burst release. Physicochemical state of progesterone in uncoated rings and the solubility and diffusion coefficient in membrane were studied. Hormone delivery from several rings of different sizes was compared. A mathematical model was used to analyze the effects of membrane properties on delivery rate. No chemical interactions were detected between hormone and polymer. Hormone was mainly forming amorphous aggregates inside rings, and migration to membrane was not observed during storage. Diffusion coefficient was smaller in membrane (∼10(-8) cm(2) s(-1)) than in matrix (∼10(-7) cm(2) s(-1)). Zero-order release kinetics were obtained for coated rings, and release rate decreases as the thickness of the coat increases. Cellulose membrane successfully eliminates burst release and controls the delivery from EVA rings. The equations developed can be used to determine the appropriate coat thickness to produce specific release rate.

[An atypical presentation of Infantile Alexander disease lacking macrocephaly]. / Presentación atípica de la enfermedad de Alexander infantil sin macrocefalia.

BACKGROUND: Alexander disease is a rare form of leukodystrophy that involves mainly astrocytes; it is inherited in an autosomal recessive manner and occurs by mutations in the GFAP gene, located on chromosome 17q21. It can occur at any age and its infantile form is characterized by macrocephaly, seizures, severe motor and cognitive delay, and progressive spasticity or ataxia. CASE REPORT: An 8-month-old female was evaluated with a history of neurodevelopmental delay and unprovoked focal motor seizures. Physical examination showed normal head circumference, increased motor responses to tactile and noise stimuli, pyramidal signs and no visceromegalies. Widespread hypodense white matter was found on magnetic resonance and lumbar puncture showed hyperproteinorrachia. Krabbe disease was ruled out by enzymatic assay and gene sequencing of GALC. In the reassessment of the case, abnormalities in neuroimaging lead to suspicion of Alexander disease, and GFAP gene sequencing reported a pathogenic mutation in exon 4 c.716G>A, which caused a change of arginine to histidine at position 239 of the protein (p.Arg239His). CONCLUSIONS: The radiographic signs observed in the resonance were decisive for the diagnosis, later confirmed by molecular study. It is important to consider that certain mutations are not associated with macrocephaly, which may cause delay in diagnosis.

Síndrome compartimental poscirculación extracorpórea / Compartment syndrome after extracorporeal circulation

Introducción: el síndrome compartimental en cirugía cardiovascular tiene diferentes causas, entre ellas las que se derivan del fenómeno isquemia reperfusión luego de un tiempo de circulación extracorpórea y pinzamiento aórtico prolongado, sobretodo si se canulan los vasos femorales. Objetivo: presentar un caso clínico de Síndrome Compartimental poscirculación extracorpórea. Desarrollo: se trata de un paciente masculino de 28 años, con antecedentes de intervenciones cardiacas previas, al que se le realizó nuevamente sustitución protésica aórtica, por incompetencia de la prótesis valvular. Durante la intervención se canuló por la arteria y vena femoral derechas para realización de la circulación extracorpórea, con tiempo prolongado de paro y de circulación extracorpórea. Se tomaron medidas de protección cerebral con hiportermia profunda y se trasladó para la terapia, ventilado, bajo los efectos anestésicos. Luego de la recuperación y extubación, refirió dolor intenso en el miembro inferior derecho, con aumento progresivo del volumen del mismo, sobretodo en la región posterior de la pierna, que se hizo tensa, con disminución de los pulsos pedios y gradiente térmico. Paralelamente se encontró aumento del potasio sérico, que se trató enérgicamente, así como cifras de CPK muy elevadas, mioglobinuria y oligoanuria, tratándose según protocolo de protección renal. Por el cuadro presentado se diagnosticó un síndrome compartimental y se solicitó valoración por el Servicio de Angiología. Se confirmó el diagnóstico y se realizó fasciotomía descompresiva. Tuvo una evolución favorable, lográndose salvar el miembro afectado. Conclusiones: el diagnóstico y la actuación precoz permiten limitar y disminuir las complicaciones del síndrome compartimental(AU)

Introduction: compartment syndrome associated to cardiovascular surgery may result from various factors, among them the ischemia-reperfusion phenomenon following a period of extracorporeal circulation and prolonged aortic clamping, especially when the femoral vessels are cannulated. Objective: present a clinical case of compartment syndrome after extracorporeal circulation. Method: a male 28-year-old patient with a history of cardiac surgery underwent prosthetic aortic replacement once again due to prosthetic valve incompetence. Cannulation was performed during surgery via the right femoral artery and vein to set up extracorporeal circulation, with prolonged cardiac arrest and extracorporeal circulation time. Cerebral protection measures were taken with the use of deep hypothermia, and the patient was transferred to the therapy ward ventilated and under the effect of anesthetics. After recovery and extubation, the patient referred intense pain on his right lower limb, whose volume had gradually increased, especially the posterior region of the leg, which turned tense, with reduced pedal pulses and thermal gradient. An increase in serum potassium was also observed, which was treated energetically, as well as very high CPK values, myoglobinuria and oligonuria, all of which were approached in compliance with the renal protection protocol. The patient's condition was diagnosed as compartment syndrome, and an assessment was requested from the Angiology Service. The diagnosis was confirmed and decompressive fasciotomy was performed. The patient evolved favorably and the affected limb was preserved. Conclusions: early diagnosis and management make it possible to limit and reduce the complications of compartment syndrome(AU)

Síndrome compartimental poscirculación extracorpórea / Compartment syndrome after extracorporeal circulation

Introducción: el síndrome compartimental en cirugía cardiovascular tiene diferentes causas, entre ellas las que se derivan del fenómeno isquemia reperfusión luego de un tiempo de circulación extracorpórea y pinzamiento aórtico prolongado, sobretodo si se canulan los vasos femorales. Objetivo: presentar un caso clínico de Síndrome Compartimental poscirculación extracorpórea. Desarrollo: se trata de un paciente masculino de 28 años, con antecedentes de intervenciones cardiacas previas, al que se le realizó nuevamente sustitución protésica aórtica, por incompetencia de la prótesis valvular. Durante la intervención se canuló por la arteria y vena femoral derechas para realización de la circulación extracorpórea, con tiempo prolongado de paro y de circulación extracorpórea. Se tomaron medidas de protección cerebral con hiportermia profunda y se trasladó para la terapia, ventilado, bajo los efectos anestésicos. Luego de la recuperación y extubación, refirió dolor intenso en el miembro inferior derecho, con aumento progresivo del volumen del mismo, sobretodo en la región posterior de la pierna, que se hizo tensa, con disminución de los pulsos pedios y gradiente térmico. Paralelamente se encontró aumento del potasio sérico, que se trató enérgicamente, así como cifras de CPK muy elevadas, mioglobinuria y oligoanuria, tratándose según protocolo de protección renal. Por el cuadro presentado se diagnosticó un síndrome compartimental y se solicitó valoración por el Servicio de Angiología. Se confirmó el diagnóstico y se realizó fasciotomía descompresiva. Tuvo una evolución favorable, lográndose salvar el miembro afectado. Conclusiones: el diagnóstico y la actuación precoz permiten limitar y disminuir las complicaciones del síndrome compartimental.

Introduction: compartment syndrome associated to cardiovascular surgery may result from various factors, among them the ischemia-reperfusion phenomenon following a period of extracorporeal circulation and prolonged aortic clamping, especially when the femoral vessels are cannulated. Objective: present a clinical case of compartment syndrome after extracorporeal circulation. Method: a male 28-year-old patient with a history of cardiac surgery underwent prosthetic aortic replacement once again due to prosthetic valve incompetence. Cannulation was performed during surgery via the right femoral artery and vein to set up extracorporeal circulation, with prolonged cardiac arrest and extracorporeal circulation time. Cerebral protection measures were taken with the use of deep hypothermia, and the patient was transferred to the therapy ward ventilated and under the effect of anesthetics. After recovery and extubation, the patient referred intense pain on his right lower limb, whose volume had gradually increased, especially the posterior region of the leg, which turned tense, with reduced pedal pulses and thermal gradient. An increase in serum potassium was also observed, which was treated energetically, as well as very high CPK values, myoglobinuria and oligonuria, all of which were approached in compliance with the renal protection protocol. The patient's condition was diagnosed as compartment syndrome, and an assessment was requested from the Angiology Service. The diagnosis was confirmed and decompressive fasciotomy was performed. The patient evolved favorably and the affected limb was preserved. Conclusions: early diagnosis and management make it possible to limit and reduce the complications of compartment syndrome.

The optimization of an intravaginal ring releasing progesterone using a mathematical model.

PURPOSE: Progering® is the only intravaginal ring intended for contraception therapies during lactation. It is made of silicone and releases progesterone through the vaginal walls. However, some drawbacks have been reported in the use of silicone. Therefore, ethylene vinyl acetate copolymer (EVA) was tested in order to replace it. METHODS: EVA rings were produced by a hot-melt extrusion procedure. Swelling and degradation assays of these matrices were conducted in different mixtures of ethanol/water. Solubility and partition coefficient of progesterone were measured, together with the initial hormone load and characteristic dimensions. A mathematical model was used to design an EVA ring that releases the hormone at specific rate. RESULTS: An EVA ring releasing progesterone in vitro at about 12.05 ± 8.91 mg day(-1) was successfully designed. This rate of release is similar to that observed for Progering®. In addition, it was observed that as the initial hormone load or ring dimension increases, the rate of release also increases. Also, the device lifetime was extended with a rise in the initial amount of hormone load. CONCLUSIONS: EVA rings could be designed to release progesterone in vitro at a rate of 12.05 ± 8.91 mg day(-1). This ring would be used in contraception therapies during lactation. The use of EVA in this field could have initially several advantages: less initial and residual hormone content in rings, no need for additional steps of curing or crosslinking, less manufacturing time and costs, and the possibility to recycle the used rings.

Application of the Refined Integral Method in the mathematical modeling of drug delivery from one-layer torus-shaped devices.

A mathematical modeling of controlled release of drug from one-layer torus-shaped devices is presented. Analytical solutions based on Refined Integral Method (RIM) are derived. The validity and utility of the model are ascertained by comparison of the simulation results with matrix-type vaginal rings experimental release data reported in the literature. For the comparisons, the pair-wise procedure is used to measure quantitatively the fit of the theoretical predictions to the experimental data. A good agreement between the model prediction and the experimental data is observed. A comparison with a previously reported model is also presented. More accurate results are achieved for small A/C(s) ratios.

Modeling of dispersed-drug delivery from planar polymeric systems: optimizing analytical solutions.

Analytical solutions for the case of controlled dispersed-drug release from planar non-erodible polymeric matrices, based on Refined Integral Method, are presented. A new adjusting equation is used for the dissolved drug concentration profile in the depletion zone. The set of equations match the available exact solution. In order to illustrate the usefulness of this model, comparisons with experimental profiles reported in the literature are presented. The obtained results show that the model can be employed in a broad range of applicability.

Role of the Nfo and ExoA apurinic/apyrimidinic endonucleases in repair of DNA damage during outgrowth of Bacillus subtilis spores.

Germination and outgrowth are critical steps for returning Bacillus subtilis spores to life. However, oxidative stress due to full hydration of the spore core during germination and activation of metabolism in spore outgrowth may generate oxidative DNA damage that in many species is processed by apurinic/apyrimidinic (AP) endonucleases. B. subtilis spores possess two AP endonucleases, Nfo and ExoA; the outgrowth of spores lacking both of these enzymes was slowed, and the spores had an elevated mutation frequency, suggesting that these enzymes repair DNA lesions induced by oxidative stress during spore germination and outgrowth. Addition of H2O2 also slowed the outgrowth of nfo exoA spores and increased the mutation frequency, and nfo and exoA mutations slowed the outgrowth of spores deficient in either RecA, nucleotide excision repair (NER), or the DNA-protective alpha/beta-type small acid-soluble spore proteins (SASP). These results suggest that alpha/beta-type SASP protect DNA of germinating spores against damage that can be repaired by Nfo and ExoA, which is generated either spontaneously or promoted by addition of H2O2. The contribution of RecA and Nfo/ExoA was similar to but greater than that of NER in repair of DNA damage generated during spore germination and outgrowth. However, nfo and exoA mutations increased the spontaneous mutation frequencies of outgrown spores lacking uvrA or recA to about the same extent, suggesting that DNA lesions generated during spore germination and outgrowth are processed by Nfo/ExoA in combination with NER and/or RecA. These results suggest that Nfo/ExoA, RecA, the NER system, and alpha/beta-type SASP all contribute to the repair of and/or protection against oxidative damage of DNA in germinating and outgrowing spores.

Illicit drug use research in Latin America: epidemiology service use, and HIV.

The purpose of this article is to review the research status of illicit drug use and its data sources in Latin America, with particular attention to the research that has been produced in the past 15 years in epidemiology of illicit drug use services utilization, and relationship between HIV and drug use. This article complements the series of articles that are published in this same volume which examine drug abuse research (epidemiology, prevention, and treatment) and HIV prevention in Latinos residing in the United States. This review resulted from extensive international and national searches using the following databases: Current Contents Connect, Social and Behavioral Sciences; EBSCO; EMBASE(R) Psychiatry; Evidence Based Medicine (through OVID); Medline, Neurosciences, PsychINFO, Pubmed, BIREME/PAHO/WHO--Virtual Health Library, and SciELO. Papers selected for further review included those published in Spanish, English, and Portuguese in peer-reviewed journals. From the evidence reviewed, it was found that the published research literature is heavily concentrated on descriptive epidemiologic surveys, providing primarily prevalence rates and general information on associated factors. Evidence on patterns of service delivery and HIV prevention and treatment is limited. The cumulative scope of this research clearly indicates variability in quantity and quality of research across Latin American nations and the need for greater uniformity in data collection elements, methodologies, and the creation of international collaborative research networks.