Evolutionary Pathways and Trajectories in Antibiotic Resistance.

Evolution is the hallmark of life. Descriptions of the evolution of microorganisms have provided a wealth of information, but knowledge regarding "what happened" has precluded a deeper understanding of "how" evolution has proceeded, as in the case of antimicrobial resistance. The difficulty in answering the "how" question lies in the multihierarchical dimensions of evolutionary processes, nested in complex networks, encompassing all units of selection, from genes to communities and ecosystems. At the simplest ontological level (as resistance genes), evolution proceeds by random (mutation and drift) and directional (natural selection) processes; however, sequential pathways of adaptive variation can occasionally be observed, and under fixed circumstances (particular fitness landscapes), evolution is predictable. At the highest level (such as that of plasmids, clones, species, microbiotas), the systems' degrees of freedom increase dramatically, related to the variable dispersal, fragmentation, relatedness, or coalescence of bacterial populations, depending on heterogeneous and changing niches and selective gradients in complex environments. Evolutionary trajectories of antibiotic resistance find their way in these changing landscapes subjected to random variations, becoming highly entropic and therefore unpredictable. However, experimental, phylogenetic, and ecogenetic analyses reveal preferential frequented paths (highways) where antibiotic resistance flows and propagates, allowing some understanding of evolutionary dynamics, modeling and designing interventions. Studies on antibiotic resistance have an applied aspect in improving individual health, One Health, and Global Health, as well as an academic value for understanding evolution. Most importantly, they have a heuristic significance as a model to reduce the negative influence of anthropogenic effects on the environment.

Ubiquitin binds the amyloid ß peptide and interferes with its clearance pathways.

Several lines of evidence point to a compromised proteostasis associated with a reduction of the Ubiquitin Proteasome System (UPS) activity in patients affected by Alzheimer's Disease (AD) and suggest that the amyloid ß peptide (Aß) is an important player in the game. Inspired also by many reports, underlining the presence of ubiquitin (Ub) in the amyloid plaques of AD brains, here we set out to test whether Ub may bind the Aß peptide and have any effect on its clearance pathways. By using an integrated array of MALDI-TOF/UPLC-HRMS, fluorescence, NMR, SPR, Microscale Thermophoresis (MST) and molecular dynamics studies, we consistently demonstrated that Aß40 binds Ub with a 1 : 1 stoichiometry and K d in the high micromolar range. In particular, we show that the N-terminal domain of the Aß peptide (through residues D1, E3 and R5) interacts with the C-terminal tail of Ub (involving residues K63 and E64), inducing the central region of Aß (14HQKLVFFAEDVGSNK28) to adopt a mixed α-helix/ß-turn structure. ELISA assays, carried out in neuroblastoma cell lysates, suggest that Aß competitively binds Ub also in the presence of the entire pool of cytosolic Ub binding proteins. Ub-bound Aß has a lower tendency to aggregate into amyloid-like fibrils and is more slowly degraded by the Insulin Degrading Enzyme (IDE). Finally, we observe that the water soluble fragment Aß1-16 significantly inhibits Ub chain growth reactions. These results evidence how the non-covalent interaction between Aß peptides and Ub may have relevant effects on the regulation of the upstream events of the UPS and pave the way to future in vivo studies addressing the role played by Aß peptide in the malfunction of proteome maintenance occurring in AD.

Infecção de sítio cirúrgico em revascularizações do miocárdio: estudo retrospectivo / Surgical site infection in myocardial revascularization: a retrospective study

Objetivo: analisar a incidência de infecção do sítio cirúrgico em revascularizações do miocárdio. Métodos: estudo quantitativo com 314 prontuários de pacientes submetidos às revascularizações no período de 2014 a 2016, do serviço de cirurgia cardíaca. Foram avaliadas as relações de variáveis operatórias com o aparecimento de infecção de sítio cirúrgico para determinar os fatores significativos. Para a coleta dos dados utilizou-se as fichas de circulação extracorpórea e para a análise as definições estabelecidas pela Agência Nacional de Vigilância Sanitária. Resultados: 66,2% eram do sexo masculino; 62,1%, brancos; 47,3%, hipertensos; 22,8%, diabéticos e 91,7%, cirurgias eletivas. Evidenciou-se que febre, edema local em 24 horas, dor, necrose em lesão operatória e (re)abordagem cirúrgica são os principais fatores para incidência de infecções relacionada ao tempo médio de circulação extracorpórea e de cirurgia. Conclusão: a infecção de sítio cirúrgico em revascularizações está relacionada com o tempo de cirurgia e de circulação extracorpórea.

Objective: to analyze the incidence of surgical site infection in myocardial revascularizations.Methods: a quantitative study with 314 medical records of patients submitted to revascularizationin the period from 2014 to 2016, of the cardiac surgery service. The relationships of operativevariables with the appearance of surgical site infection were evaluated to determine the significantfactors. Data collection was done using the cardiopulmonary bypass records and for the analysis thedefinitions established by the National Sanitary Surveillance Agency. Results: 66,2% were male;62,1% white; 47,3% hypertensive and 22,8% diabetic; 91.7% were elective surgeries. It was evidencedthat fever, local edema in 24 hours, pain, necrosis in operative lesion and surgical intervention are the main factors for the incidence of infections related to the mean time of extracorporealcirculation and surgery. Conclusion: the surgical site infection in revascularizations is related to thetime of surgery and extracorporeal circulation.

Hopf Bifurcations in Directed Acyclic Networks of Linearly Coupled Hindmarsh-Rose Systems.

This paper addresses the existence of Hopf bifurcations in a directed acyclic network of neurons, each of them being modeled by a Hindmarsh-Rose (HR) neuronal model. The bifurcation parameter is the small parameter corresponding to the ratio of time scales between the fast and the slow dynamics. We first prove that, under certain hypotheses, the single uncoupled neuron can undergo a Hopf bifurcation. Hopf bifurcation occurrences in a directed acyclic network of HR neurons are then discussed. Numerical simulations are carried out to observe these bifurcations and to illustrate the theoretical results.

Evaluation of Bone Mineral Density in Patients with Type 1 Gaucher Disease in Argentina.

The purpose of this study was to evaluate the frequency of osteoporosis (OP) in patients with Gaucher disease (GD) in Argentina. GD patients from 28 centers were consecutively included from April 2012 to 2014. Bone mineral density (BMD) was determined by dual X-ray absorptiometry in the lumbar spine and the femoral neck or the total proximal femur for patients ≥20 yr of age, and by whole-body scan in the lumbar spine in patients <20 yr of age. In children, mineral density was calculated using the chronological age and Z height. OP diagnosis was determined following adult and pediatric official position of the International Society for Clinical Densitometry. A total of 116 patients were included, of which 62 (53.5%) were women. The median age was 25.8 yr. All patients received enzyme replacement therapy, with a median time of 9.4 yr. Normal BMD was found in 89 patients (76.7%), whereas low bone mass (LBM) or osteopenia was found in 15 patients (13%) and OP in 12 patients (10.3%). The analysis of the pediatric population revealed that 4 patients (9.3%) had LBM and 3 (7%) had OP (Z-score ≤ -2 + fractures height-adjusted by Z), whereas in the adult population (n = 73), 11 patients (15%) had LBM or osteopenia and 9 (12.3%) had OP. Bone marrow infiltration and the presence of fractures were significantly correlated with the presence of OP (p = 0.04 and <0.001, respectively). This is the first study in Argentina and in the region describing the frequency of OP or LBM in GD patients treated with imiglucerase using the official position of the International Society for Clinical Densitometry.

The insulin degrading enzyme activates ubiquitin and promotes the formation of K48 and K63 diubiquitin.

We report an ATP-dependent ubiquitin conjugation with IDE which, in turn, promotes Ub-Ub linkages in tube tests. We propose a novel function for IDE as a non-canonical ubiquitin activating enzyme.

Evaluación del grado de buena prescripción médica en 5 Hospitales Universitarios de tercer nivel de la ciudad de La Paz (Bolivia) / Assesment of the degree of a good medical prescriptionin 5 third level University Hospitals in the city of La Paz - Bolivia

OBJETIVO: establecer el grado de cumplimiento de Buenas Prácticas de Prescripción Médica sugeridas por la Organización Mundial de la Salud (OMS) analizando recetas extendidas a pacientes de consulta externa e internados de 5 hospitales universitarios de la ciudad de La Paz (Bolivia), identificando limitaciones y deficiencias en su formulación. MÉTODOS: estudio descriptivo, retrospectivo de evaluación de recetas, según disposiciones de la ley No.1737 (1996) de Bolivia, las Normas Nacionales de Atención Clínica del Ministerio de Salud Boliviano (2013) y el Manual de la Buena Prescripción de la OMS. RESULTADOS: del análisis de 220 recetas se desprende que la proporción de recetas que cumple con la mayoría de parámetros sugeridos por la OMS para una buena prescripción médica es baja. Las recetas que tienen identificación del prescriptor son 37,27%; 66,82%, no señala el origen de la prescripción; 15% incumple con una adecuada filiación del paciente, incluyendo el nombre del paciente, 80,91% no incluían la edad del paciente, 10,91% no estaban con nombre genérico del medicamento; 11,82% estaban con nombre comercial, 5,45% no contaban con nombre completo ni firma del prescriptor; 13,64% no incluía fecha de la prescripción. Un 34,09% tenían letra poco legible y 29.54% letra no legible. Estos datos, entre otros, indican la necesidad de reflexión y actualización sobre este importante tema. CONCLUSIONES: Se registra un elevado índice de incumplimiento de las normas de buena prescripción señaladas por las regulaciones antes mencionadas, identificando la necesidad de re-orientar los hábitos de prescripción facultativa a fin que no repercutan negativamente en la salud y tratamiento de los pacientes y en las acciones del Sistema Nacional de Salud. El formato de receta médica utilizado en los diferentes servicios de salud objeto del estudio es deficiente en cuanto al modelo y guía sugerida por la OMS.

OBJECTIVE: to establish the degree of compliance with good medical prescription practices suggested by the World Health Organization (WHO) analyzing prescriptions issued to outpatients and admitted patients of 5 university hospitals in the city of La Paz (Bolivia), identifying limitations and deficiencies in its formulation. METHODS: descriptive, longitudinal, retrospective study of prescription assesment, according to provisions of Law No.1737 (1996) of Bolivia, the National Standards for Clinical Care Bolivian Ministry of Health (2013) and the Manual of Good Prescription the World Health Organization (WHO). RESULTS: analysis of 220 prescriptions show that the proportion of prescriptions that meet most of the parameters suggested by WHO for a good prescription is down. 37,27% of prescriptions have prescriber identification; 66.82%, do not indicate the origin of the prescription, 15% fail to comply with proper affiliation of the patient, including the patient's name, 80.91% did not have included patient age, 10.91% of prescriptions were not made by generic drug name; 11.82% were prescribed with trade name, 5.45% had no full name or signature of the prescriber; 13.64% did not include prescription date. 36.36% were made legibly a 34.09% with little legibly and 29.54% with no legible. These data, among others, indicate the need for reflection and update on this important topic. CONCLUSIONS: it has been registered a high rate of non-compliance with good prescription for the above mentioned regulations, identifying the need to re-direct professional prescription habits so that no negative impact on the health and treatment of patients and the actions of the National Health System (NHS) is done. The format of prescription used in various health services under study is deficient in terms of model and guide suggested by the WHO.

Emerging dynamics in neuronal networks of diffusively coupled hard oscillators.

Oscillatory networks are a special class of neural networks where each neuron exhibits time periodic behavior. They represent bio-inspired architectures which can be exploited to model biological processes such as the binding problem and selective attention. In this paper we investigate the dynamics of networks whose neurons are hard oscillators, namely they exhibit the coexistence of different stable attractors. We consider a constant external stimulus applied to each neuron, which influences the neuron's own natural frequency. We show that, due to the interaction between different kinds of attractors, as well as between attractors and repellors, new interesting dynamics arises, in the form of synchronous oscillations of various amplitudes. We also show that neurons subject to different stimuli are able to synchronize if their couplings are strong enough.

Conversion of spinal anesthesia into general anesthesia: an evaluation of more than 35,000 spinal anesthetics.

BACKGROUND: The aim of this study was to evaluate the number of conversions from spinal anesthesia (SA) into general anesthesia (GA) in a large number of patients who underwent surgery over a period of twenty-one years. METHODS: From the hospital's database, all surgical procedures performed under SA between January 1, 1988 and December 31, 2008 were retrieved. From this file, all SA cases converted into GA cases requiring endotracheal intubation were selected. Patients were divided in four groups, according to the reason for GA: IMPOSS (SA impossible to perform), FAIL (SA non profound enough for allowing surgery, even with light sedation), INSUFF (SA inadequate for unexpected prolonged duration of surgery), and COMPL (occurrence of complications associated with SA and requiring rapid control of ventilation). Anesthesiologists who performed SA were divided according their experience. The outcomes of patients converted to GA were compared with a matched sample of patients who received planned GA. RESULTS: A total of 35,960 SA cases were performed from 1988 to 2008; 29,220 and 6,740 SA cases were for elective and emergency surgery, respectively. Two hundred seventeen (0.6%) SA cases were converted into GA cases; 80.2% and 19.8% of the conversions were recorded in elective and emergency operations, respectively, with obstetric operations being the most prevalent (82/217). The primary reasons for the conversions, in a rank order, were INSUFF 107 (49.3%), FAIL 84 (38.7%), IMPOSS 13 (5.9%), and COMPL 13 (5.9%). Complications more frequently occurred in the aged population (P<0.05). Anesthesiologists with less experience had higher percentages of FAIL, IMPOSS, INSUFF, and COMPL SA cases in comparison with experienced anesthesiologists (odd ratios being 4.7, 3.0, 2.4, and 4.4, respectively). There was no difference in the frequency of complications compared to a matched sample of 1,000 patients who underwent GA (P=0.65). CONCLUSION: SA has been found to be a safe and highly effective technique. Failure of SA was infrequent in a large number of patients surveyed and most often occurred with less experienced anesthesiologists. Conversion to GA did not produced different outcomes in comparison with planned GA. Prospective studies with a definite protocol for recording data performed on a large number of patients may help in determining the factors associated with conversion from SA into GA and how to avoid these unexpected situations.

Refeeding syndrome in early pregnancy. Case report.

Refeeding syndrome is a very serious disorder that is not often observed today, as it is more common during times of mass starvation or war. Nowadays, it is sometimes found in patients suffering from anorexia nervosa or neoplastic diseases. A case recently treated in our Intensive Care Unit is described. The patient was pregnant and suffering from Crohn's disease. It is emphasized that although refeeding syndrome is often fatal if not treated early, it is easily prevented or treated with adequate nutritional support.

Medicamentos, embarazo y la clasificación de la Food and Drug Administration- FDA / Drugs, pregnancy and the FDA clasification

Recordemos que toda sustancia puede ser veneno todo depende de la dosis, es el este sentido que los medicamentos no son la excepción, por lo que el extremar todo tipo de cuidados en la adminsitración de medicamentos, es imprescindible, mucho más si hablamos de una etapa tan importante como es el embarazo. Este es un problema que se da a todo nivel, comenzando de la persona embarazada que se automedica, hasta llegar al personal de salud, que no toma encuenta la existencia de un posible embarazo y que el más "simple"de los fármacos puede afectar en el desarrollo del embrión o feto de acuerdo al caso, por lo que una evaluación del riesgo-beneficio es primordial antes de recomendar un medicamento. En este sentido la FDA (Food an Drug Administration) realizó una clasificación de los medicamentos de acuerdo a su potencial teratógenico, razon por la cual resulta importante tomar en cuenta la misma para conocer cuales son drogas que se ueden tomar durante el embarazo y cuales no.

El abc de la Ley y Política de competencia / sss

Esta publicación busca generar un conocimiento que podria ser util para identificar prácticas anti-competitivas en el mercado, tomar acción y retificar esta situación

[Assessment of operating theatre procedures and quality of perioperative anaesthesia using a computer system for collecting anaesthesiological data]. / Valutazione dell'efficienza delle procedure di Sala Operatoria e della qualità anestesiologica perioperatoria attraverso un sistema informatizzato di raccolta dei dati anestesiologici.

BACKGROUND: In order to manage the operating theatre and guarantee constant improvement in the quality of procedures, it is indispensable to be able to have available a computerised workstation to enable the team to collect data and analyse them. METHODS: We used our anaesthesia department's computer workstation to retrospectively analyse operating sessions over a 16 month period during which organisational adjustments were made to optimise patient turnover and maximise the utilisation of operating theatres. Meantime we studied and compared the trend in anaesthesiological quality through the use of certain structural, process and outcome indicators. RESULTS: During the period under study an improvement was noted in the efficiency of operating theatre procedures (reduction in entry time of the first patient into the theatre, time between one case and the next and subutilisation of the operating theatre, p<0.05). As regards data on the quality of anaesthesiological assistance to the patient, no significant differences were noted when comparing the four periods examined. CONCLUSIONS: To make the operating complex work more efficiently, it is necessary to have available a computer system that makes it possible to continuously monitor theatre operation. The improvement initiatives undertaken led to a more effective utilisation of the operating theatre but did not produce a significant increase in productivity. In spite of the increased work load, analysis of the trend in quality indicators as regards anaesthesiological procedures did not reveal any modification.

Nutricion infantil: realidades y distrosiones / Infant nutrition: realites and distortions

La promoción y la comercialización de los mal llamados substitutos de la leche materna, por parte de la poderosa industria transnacional de alimentos para bebés e infantes incluyendo la industria nacional, está incitando y estimulando el consumo de estos productos, aún a riesgo de exponer vidas de indefensoss infantes y niños, a través de promoción y estrategias de mercadeo agresivas. Cuanto mas prematuramente los lactantes son destetados y privados del mejor alimento "la leche materna" suministrado por sus madres, más se contribuye al saludable negocio que arriesga la apropiada nutrición infantil. el presente artículo analiza la situación de la comercialización y promoxión de los mal llamados substitutos de la leche materna en el país, a través de un monitorio realizado sobre el cumplimiento del Código Internacional, las Resoluciones subsecuentes de la Asamblea Mundial de la Salud y la reglamentación nacional al respecto. El estudio se realizo en 8 departamentos de Bolivia, en el marco de un estudio internacional

El uso racional de mucolíticos y expectorantes / The rational use of mucolitics and expectorants

Son numerosos los productos farmacéuticos con fines mucolíticos y/o expectorantes y su utilizacion es una pr'actica totalmente enraizada en el hábito terapéutico del méico, del farmacéutico y del mismo enfermo (automedicación). Frecuentemente éstos fármacos son utilizados injustificadamente como ocurre en la faringitis, faringoamigadalitis, laringitis, gripe, neumonía bronquitis aguda no complicada o asma y otras enfermedades, en las que no se demostró su efecto beneficioso y más aún en combinación con sustancias de otros grupos farmacológicos como: antimicrobianos, antihistamínicos, antitusígenos, descongestionantes , vitanimas, analgésicos, etc. cuyas formulaciones están prohibidas según las normas farmacológicas del país. el principal objetivo del presente trabajo es analizar la presencia de este tipo de productos en el mercado nacional, valorando su eficaci, y seguridad en base a la evidencia científica independiente internacional

Nutricion infantil: realidades y distorsiones

III Monitoreo codigo internacional de comercializacion de sucedaneos de la leche materna - OMS/UNICEF en Bolivia. El codigo internacional de sucedaneos de la leche materna mantiene la misma vigencia que hace 20 anos. Por eso los monitoreos periodicos que realizan la Red Internacional de Grupos Pro Alimentacion Infantil(IBFAN) y Accion Internacional por la Salud (A.I.S) en Bolivia, sobre el grado de cumplimiento y/o transgresiones de las medidas previstas en el codigo siempre despiertan interes y son motivo de especial reconocimiento

Donacion de medicamentos en Bolivia / Drug donations: the Bolivia's case

La donación de medicamentos, bien intencionada y bien efectuada es remarcable por su caracter humanitario y solidario.Sin embargo puede constituir un importante problema en nuestro país, particularmente ante la precaria situacion de salud y sufrimiento de diversas poblaciones en Bolivia, pues muchas de estas donaciones proporcionan los fármacos que se necesitan desesperadamente, para enfrentar situaciones de enfermedad y emergencia, mientras otros donativos contienen medicamentos que no siempre responden a las necesidades de la zona afectada, resultando ser más perjudiciales que utiles sea en situaciones de emergencia o para el tipo de morbilidad, o para el nivel de servicio disponible, o bien sencillamente resultan desconocidos por los profesionales de salud, ya que no cumplen con las políticas farmacéuticas del país. De esta forma,tanto los que reciben como los que ofrecen donativos en especie, deben tratar de mejorar sus acciones, ya que no conocen, a menudo, los problemas que pueden generar y se sienten confundidos cuando se notifica que el "regalo" no resultó útil, necesario, ni deseado

Derechos de los pacientes y estandarización de tratamiento contra la tuberculosis: un estudio de casos en servicios de salud de La Paz (Bolivia) / Patient's rights and standarized treatments against tuberculosis: a case study of health care facilities of La Paz (Bolivia)

Bolivia tiene una de las tasas de incidencia de Tuberculosis (TB) más altas del continente americano(1). El número de casos que se notifica anualmente es elevado y a pesar de los esfuerzoz no ha sufrido variaciones importantes en los últimos años. Las políticas de control de la enfermedad en el país están basadas en el concepto de contar con un programa amplio y comprensivo, ejercitado a escala nacional, a través de la red de servicios de salud existentes, en todos sus niveles y como parte de la atención primaria integral de salud. El tratamiento tiene el objetivo de curar al paciente diagnosticado y cortar la cadena de transmisión del bacilo en la comunidad. Sin embargo, a través del presente artículo se advierte que las medidas de promoción y prevención de la enfermedad, no se han puesto en práctica, han sido insuficientes o francamente han fracasado, asumiendo que esta situación es debida a que no hay consenso y/o conocimiento sobre las normas adoptadas, o bien que la supervisión y el establecimeitno de responsabilidades es inadecuado. Resulta el hecho preocupante e intolerable por las implicaciones epidemiológicas, sociales y económicas, no sólo para los pacientes, sino para un país pobre, con un exiguo presupuesto de salud, menoscabando así la credibilidad de los prefesionales responsables de la utilización o instauración de algún determinado esquema de tratamiento