ABSTRACT
WikiPathways (wikipathways.org) is an open-source biological pathway database. Collaboration and open science are pivotal to the success of WikiPathways. Here we highlight the continuing efforts supporting WikiPathways, content growth and collaboration among pathway researchers. As an evolving database, there is a growing need for WikiPathways to address and overcome technical challenges. In this direction, WikiPathways has undergone major restructuring, enabling a renewed approach for sharing and curating pathway knowledge, thus providing stability for the future of community pathway curation. The website has been redesigned to improve and enhance user experience. This next generation of WikiPathways continues to support existing features while improving maintainability of the database and facilitating community input by providing new functionality and leveraging automation.
Subject(s)
Databases, FactualABSTRACT
INTRODUCCIÓN. La sepsis es un estado de disfunción multisistémica, que se produce por una respuesta desregulada del huésped a la infección. Diversos factores influyen en la gravedad, manifestaciones clínicas y progresión de la sepsis, tales como, heterogeneidad inmunológica y regulación dinámica de las vías de señalización celular. La evolución de los pacientes depende del tratamiento oportuno, las escalas de puntuación clínica permiten saber la mortalidad estimada. OBJETIVO. Evaluar la mortalidad en la unidad de cuidados intensivos; establecer el manejo y la utilidad de aplicar paquetes de medidas o "bundlers" para evitar la progresión a disfunción, fallo multiorgánico y muerte. METODOLOGÍA. Modalidad de investigación tipo revisión sistemática. Se realizó una búsqueda bibliográfica en bases de datos como Google académico, Mendeley, ScienceDirect, Pubmed, revistas como New England Journal Medicine, Critical Care, Journal of the American Medical Association, British Medical Journal. Se obtuvo las guías "Sobreviviendo a la sepsis" actualización 2021, 3 guías internacionales, 10 estudios observacionales, 2 estudios multicéntricos, 5 ensayos aleatorizados, 6 revisiones sistémicas, 5 metaanálisis, 1 reporte de caso clínico, 4 artículos con opiniones de expertos y actualizaciones con el tema mortalidad de la sepsis en UCI con un total de 36 artículos científicos. RESULTADOS. La mortalidad de la sepsis en la unidad de cuidados intensivos, fue menor en el hospital oncológico de Guayaquil, seguido de Australia, Alemania, Quito, Francia, Estados Unidos de Norteamérica y Vietnan, La mortalidad más alta se observa en pacientes con enfermedades del tejido conectivo. DISCUSIÓN. La aplicación de los paquetes de medidas o "bundlers" en la sepsis, se asocia con una mejor supervivencia y menores días de estancia hospitalaria. CONCLUSIÓN. Las escalas SOFA, APACHE II y SAPS II ayudan a predecir la mortalidad de forma eficiente, en la detección y el tratamiento temprano en pacientes con enfermedades agudas y de alto riesgo.
INTRODUCTION. Sepsis is a state of multisystem dysfunction, which is caused by a dysregulated host response to infection. Several factors influence the severity, clinical manifestations and progression of sepsis, such as immunological heterogeneity and dynamic regulation of cell signaling pathways. The evolution of patients depends on timely treatment, clinical scoring scales allow to know the estimated mortality. OBJECTIVE. To evaluate mortality in the intensive care unit; to establish the management and usefulness of applying bundlers to prevent progression to dysfunction, multiorgan failure and death. METHODOLOGY. Systematic review type research modality. A bibliographic search was carried out in databases such as Google Scholar, Mendeley, ScienceDirect, Pubmed, journals such as New England Journal Medicine, Critical Care, Journal of the American Medical Association, British Medical Journal. We obtained the guidelines "Surviving Sepsis" update 2021, 3 international guidelines, 10 observational studies, 2 multicenter studies, 5 randomized trials, 6 systemic reviews, 5 meta-analyses, 1 clinical case report, 4 articles with expert opinions and updates on the subject of sepsis mortality in ICU with a total of 36 scientific articles. RESULTS. The mortality of sepsis in the intensive care unit, was lower in the oncological hospital of Guayaquil, followed by Australia, Germany, Quito, France, United States of America and Vietnam, The highest mortality is observed in patients with connective tissue diseases. DISCUSSION. The application of bundlers in sepsis is associated with better survival and shorter days of hospital stay. CONCLUSIONS. The SOFA, APACHE II and SAPS II scales help to predict mortality efficiently in the early detection and treatment of patients with acute and high-risk disease.
Subject(s)
Humans , Male , Female , Tertiary Healthcare , Hospital Mortality , Systemic Inflammatory Response Syndrome , Sepsis , Organ Dysfunction Scores , Intensive Care Units , Vasodilator Agents , Drug Resistance, Multiple , Candida glabrata , Candida tropicalis , Ecuador , Hypotension , Immunosuppressive Agents , Multiple Organ FailureABSTRACT
Background: To prevent COVID-19 progression, low-cost alternatives that are available to all patients are needed. Diverse forms of thermotherapy have been proposed to prevent progression to severe/critical COVID-19. Objective: The aim of this study is to evaluate the efficacy and safety of local thermotherapy to prevent disease progression in hospitalized adult patients with mild-to-moderate COVID-19. Methods: A multicenter, open-label, parallel-group, randomized, adaptive trial is used to evaluate the efficacy and safety of local thermotherapy to prevent disease progression in hospitalized adult patients with mild-to-moderate COVID-19. Eligible hospitalized adult patients with symptoms of COVID-19 with ≤5 days from symptom onset, meeting criteria for mild or moderate COVID-19, were randomly assigned to the intervention consisting of local thermotherapy via an electric heat pad in the thorax (target temperature range 39.542°C) continuously for 90 min, twice daily, for 5 days, or standard care. The main outcome was the proportion of patients who progressed to severe-to-critical COVID-19 or death. Patients were randomized in a 1:1 ratio through a centralized computer-generated sequence of minimization with a random component of 20%. Participants and medical staff were not blinded to the intervention. Results: One-hundred and five participants (thermotherapy n = 54, control n = 51) with a median age of 53 (IQR: 4164) years were included for analysis after the early cessation of recruitment due to the closure of all temporal COVID-19 units (target sample size = 274). The primary outcome of disease progression occurred in 31.4% (16/51) of patients in the control group vs. 25.9% (14/54) of those receiving thermotherapy (risk difference = 5.5%; 95%CI: −11.822.7, p = 0.54). Thermotherapy was well tolerated with a median total duration of thermotherapy of 900 (IQR: 877.5900) min. Seven (13.7%) patients in the control group and seven (12.9%) in the thermotherapy group had at least one AE (p = 0.9), none of which were causally attributed to the intervention. No statistically significant differences in serum cytokines (IL-1ß, IL-6, IL-8, IL-10, IL-17, and IFN-γ) were observed between day 5 and baseline among groups. Conclusion: Local thermotherapy was safe and well-tolerated. A non-statistically significant lower proportion of patients who experienced disease progression was found in the thermotherapy group compared to standard care. Local thermotherapy could be further studied as a strategy to prevent disease progression in ambulatory settings.Clinical Trial registration: www.clinicaltrials.gov, identifier: NCT04363541.
ABSTRACT
One of the major drawbacks of the industrial implementation of enzymatic processes is the low operational stability of the enzymes under tough industrial conditions. In this respect, the use of thermostable enzymes in the industry is gaining ground during the last decades. Herein, we report a structure-guided approach for the development of novel and thermostable 2'-deoxyribosyltransferases (NDTs) based on the computational design of disulfide bonds on hot spot positions. To this end, a small library of NDT variants from Lactobacillus delbrueckii (LdNDT) with introduced cysteine pairs was created. Among them, LdNDTS104C (100% retained activity) was chosen as the most thermostable variant, displaying a six- and two-fold enhanced long-term stability when stored at 55 °C (t1/255 °C ≈ 24 h) and 60 °C (t1/260 °C ≈ 4 h), respectively. Moreover, the biochemical characterization revealed that LdNDTS104C showed >60% relative activity across a broad range of temperature (30−90 °C) and pH (5−7). Finally, to study the potential application of LdNDTS104C as an industrial catalyst, the enzymatic synthesis of nelarabine was successfully carried out under different substrate conditions (1:1 and 3:1) at different reaction times. Under these experimental conditions, the production of nelarabine was increased up to 2.8-fold (72% conversion) compared with wild-type LdNDT.
Subject(s)
Enzymes, Immobilized , Pentosyltransferases , Arabinonucleosides , Cysteine , Disulfides/chemistry , Enzyme Stability , Enzymes, Immobilized/chemistry , Pentosyltransferases/metabolism , Substrate Specificity , TemperatureABSTRACT
Nucleoside 2'-deoxyribosyltransferases (NDTs) catalyze the cleavage of glycosidic bonds of 2'-deoxynucleosides and the following transfer of the 2'-deoxyribose moiety to acceptor nucleobases. Here, we report the crystal structures and biochemical properties of the first tetrameric NDTs: the type I NDT from the mesophilic bacterium Enterococcus faecalis V583 (EfPDT) and the type II NDT from the bacterium Desulfotalea psychrophila (DpNDT), the first psychrophilic NDT. This novel structural and biochemical data permitted an exhaustive comparative analysis aimed to shed light into the basis of the high global stability of the psychrophilic DpNDT, which has a higher melting temperature than EfPDT (58.5 °C versus 54.4 °C) or other mesophilic NDTs. DpNDT possesses a combination of unusual structural motifs not present neither in EfPDT nor any other NDT that most probably contribute to its global stability, in particular, a large aliphatic isoleucine-leucine-valine (ILV) bundle accompanied by a vicinal disulfide bridge and also an intersubunit disulfide bridge, the first described for an NDT. The functional and structural features of DpNDT do not fit the standard features of psychrophilic enzymes, which lead us to consider the implication of (sub)cellular levels together with the protein level in the adaptation of enzymatic activity to low temperatures.
Subject(s)
Bacterial Proteins/chemistry , Models, Molecular , Pentosyltransferases/chemistry , Protein Conformation , Protein Multimerization , Adaptation, Physiological , Bacterial Proteins/isolation & purification , Catalytic Domain , Chemical Phenomena , Cold Temperature , Disulfides , Enzyme Activation , Enzyme Stability , Pentosyltransferases/isolation & purification , Recombinant Proteins/chemistry , Recombinant Proteins/isolation & purification , Spectrum Analysis , ThermodynamicsABSTRACT
Nowadays, enzymatic synthesis of nucleotides is an efficient and sustainable alternative to chemical methodologies. In this regard, after the biochemical characterization of wild-type and mutant uracil phosphoribosyltransferases from Toxoplasma gondii (TgUPRT, TgUPRT2, and TgUPRT3), TgUPRT2 was selected as the optimal candidate (69.5 IU mg-1, UMP synthesis) for structure-guided immobilization onto Ni2+ chelate (MNiUPRT2) and onto glutaraldehyde-activated microparticles (MGlUPRT2). Among resulting derivatives, MNiUPRT23 (6127 IU g-1biocat; 92% retained activity; 3-5 fold enhanced stability at 50-60 °C) and MGlUPRT2N (3711 IU g-1biocat; 27% retained activity; 8-20 fold enhanced stability at 50-60 °C) displayed the best operability. Moreover, the enzymatic synthesis of different pyrimidine NMPs was performed. Finally, the reusability of both derivatives in 5-FUMP synthesis (MNiUPRT23, 80% retained activity after 7 cycles, 5 min; MGlUPRT2N, 70% retained activity after 10 cycles, 20 min) was carried out at short times.
Subject(s)
Pyrimidine Nucleosides , Toxoplasma , Nucleotides , Pentosyltransferases/genetics , Toxoplasma/geneticsABSTRACT
Nowadays, pharmaceutical industry demands competitive and eco-friendly processes for active pharmaceutical ingredients (APIs) manufacturing. In this context, enzyme and whole-cell mediated processes offer an efficient, sustainable and cost-effective alternative to the traditional multi-step and environmentally-harmful chemical processes. Particularly, 2'-deoxyribosyltransferases (NDTs) have emerged as a novel synthetic alternative, not only to chemical but also to other enzyme-mediated synthetic processes. This review describes recent findings in the development and scaling up of NDTs as industrial biocatalysts, including the most relevant and recent examples of single enzymatic steps, multienzyme cascades, chemo-enzymatic approaches, and engineered biocatalysts. Finally, to reflect the inventive and innovative steps of NDT-mediated bioprocesses, a detailed analysis of recently granted patents, with specific focus on industrial synthesis of nucleoside-based APIs, is hereunder presented.
Subject(s)
Nucleosides , Pharmaceutical Preparations , Biocatalysis , Drug IndustryABSTRACT
Herein we report the first proof for the application of type II 2'-deoxyribosyltransferase from Lactobacillus delbrueckii (LdNDT) in suicide gene therapy for cancer treatment. To this end, we first confirm the hydrolytic ability of LdNDT over the nucleoside-based prodrugs 2'-deoxy-5-fluorouridine (dFUrd), 2'-deoxy-2-fluoroadenosine (dFAdo), and 2'-deoxy-6-methylpurine riboside (d6MetPRib). Such activity was significantly increased (up to 30-fold) in the presence of an acceptor nucleobase. To shed light on the strong nucleobase dependence for enzymatic activity, different molecular dynamics simulations were carried out. Finally, as a proof of concept, we tested the LdNDT/dFAdo system in human cervical cancer (HeLa) cells. Interestingly, LdNDT/dFAdo showed a pronounced reduction in cellular viability with inhibitory concentrations in the low micromolar range. These results open up future opportunities for the clinical implementation of nucleoside 2'-deoxyribosyltransferases (NDTs) in cancer treatment.
Subject(s)
Genes, Transgenic, Suicide , Nucleosides/pharmacology , Pentosyltransferases/metabolism , Prodrugs/pharmacology , Deoxyadenosines/metabolism , Fluorouracil/chemistry , Fluorouracil/pharmacology , Glycoside Hydrolases/metabolism , Glycosylation/drug effects , HeLa Cells , Humans , Lactobacillus/enzymology , Molecular Dynamics Simulation , Nucleosides/chemistry , Prodrugs/chemistryABSTRACT
Nucleoside-2'-deoxyribosyl-transferases (NDTs) catalyze a transglycosylation reaction consisting of the exchange of the 2'-deoxyribose moiety between a purine and/or pyrimidine nucleoside and a purine and/or pyrimidine base. Because NDTs are highly specific for 2'-deoxyribonucleosides they generally display poor activity on modified C2' and C3' nucleosides and this limitation hampers their applicability as biocatalysts for the synthesis of modified nucleosides. We now report the production and purification of a novel NDT from Archaeoglobus veneficus that is endowed with native ribosyltransferase activity and hence it is more properly classified as an N-ribosyltransferase (AvNRT). Biophysical and biochemical characterization revealed that AvNRT is a homotetramer that displays maximum activity at 80°C and pH 6 and shows remarkably high stability at high temperatures (60-80°C). In addition, the activity of AvNRT was found to increase up to 2-fold in 4 M NaCl aqueous solution and to be retained in the presence of several water-miscible organic solvents. For completeness, and as a proof of concept for possible industrial applications, this thermophilic and halotolerant biocatalyst was successfully employed in the synthesis of different purine ribonucleoside analogs.
ABSTRACT
In our search for novel biocatalysts for the synthesis of nucleic acid derivatives, we found a good candidate in a putative dual-domain hypoxanthine-guanine phosphoribosyltransferase (HGPRT)/adenylate kinase (AMPK) from Zobellia galactanivorans (ZgHGPRT/AMPK). In this respect, we report for the first time the recombinant expression, production, and characterization of a bifunctional HGPRT/AMPK. Biochemical characterization of the recombinant protein indicates that the enzyme is a homodimer, with high activity in the pH range 6-7 and in a temperature interval from 30 to 80°C. Thermal denaturation experiments revealed that ZgHGPRT/AMPK exhibits an apparent unfolding temperature (Tm) of 45°C and a retained activity of around 80% when incubated at 40°C for 240 min. This bifunctional enzyme shows a dependence on divalent cations, with a remarkable preference for Mg2+ and Co2+ as cofactors. More interestingly, substrate specificity studies revealed ZgHGPRT/AMPK as a bifunctional enzyme, which acts as phosphoribosyltransferase or adenylate kinase depending upon the nature of the substrate. Finally, to assess the potential of ZgHGPRT/AMPK as biocatalyst for the synthesis of nucleoside-5'-mono, di- and triphosphates, the kinetic analysis of both activities (phosphoribosyltransferase and adenylate kinase) and the effect of water-miscible solvents on enzyme activity were studied.
ABSTRACT
La fractura de clavícula representa 35 a 45 % de las fracturas de la cintura escapular, y de ellas el 15-25% comprometen el extremo distal de ella. El objetivo de esta publicación es describir nuestra técnica de reconstrucción artroscópica de las fracturas del extremo distal de clavícula con sistema AC TigthRope o sistema DogBone con sutura fibertape. La reconstrucción y estabilización artroscópica de las fracturas inestables del extremo distal de la clavícula con sistema AC TigthRope o sistema Dogbone ambos con sutura FiberTape mas la estabilización del fragmento distal de la fractura mediante suturas transósea permite una fijación estable para la consolidación de la misma. La técnica descripta permite rápida recuperación funcional y el retorno a las actividades de la vida diaria. Tipo de Trabajo: Técnica Quirúrgica. Nivel de Evidencia: V.
Fractures of the clavicle represent between 35 to 45% of all the fractures of the shoulder girdle, and 15 to 25% of these are of the distal clavicle. The purpose of this study is to describe our arthroscopic reconstruction technique of the distal clavicle using the AC Tightrope or DogBone Systems with fibertape. The arthroscopic reconstruction and stabilization of ustable distal clavicle fractures with the AC TightRope or DogBone Systems both with Fibertape with stabilization of the unstable bone fragments with trans oseous sutures allow a stable fixation until it consolidates. The technique described allows a fast recovery and retour to the activities of daily living. Type of Study: Surgical Technique. Level of Evidence: V.
Subject(s)
Arthroscopy/methods , Clavicle/injuries , Clavicle/surgery , Fractures, Bone/surgery , Plastic Surgery Procedures/methods , Shoulder Joint/surgery , Treatment OutcomeABSTRACT
Objetivo: revisar sistemáticamente la bibliografía que reporten resultados de la reconstrucción artroscópica de las lesiones aisladas del tendón del subescapular con anclajes con súper-suturas; reportar el manejo del tendón del bíceps y la coracoides y evaluar la cicatrización del tendón al hueso mediante RNM. Material y Método: Realizamos una búsqueda sistemática de la literatura en ingles y español en las bases de datos de PubMed MEDLINE, EMBASE y LILACS mediante los términos de: Lesiones Aisladas del Subescapular y Reparación Artroscópica. Incluimos solo estudios que evalúan técnicas, resultados funcionales e imagenológico de lesiones aisladas del subescapular. Realizamos un análisis descriptivo de la bibliografía incluida. Resultados: Incluimos 7 artículos que cumplieron con los criterios de inclusión y exclusión. Los estudios incluidos se realizaron entre el 2003 y el 2013, con un total de 207 pacientes, 51 años de edad promedio. Las evaluaciones funcionales mejoraron significativamente al comparar los resultados pre y postoperatorios. La evaluación por RNM demostró alto índice de cicatrización con un bajo índice de re-ruptura. Las complicaciones fueron infrecuentes. Conclusión: Nuestra revisión sistemática demuestra que la reconstrucción artroscópica de las lesiones aisladas del tendón del subescapular es una buena opción de tratamiento con buenos resultados clínicos funcionales, buena integridad del tendón al hueso y un bajo índice de complicaciones. El bajo nivel de evidencia científica de la bibliografía demuestra la necesidad de realizar estudios prospectivos comparativos para obtener resultados de mayor poder estadístico. Nivel de Evidencia: IV. Tipo de estudio: Revisión sistemática de estudios
Purpose: to systematically review the literature to identify all studies reporting outcomes of arthroscopically repaired isolated subscapular tendon tears, the frequency and management of associated long head of biceps pathology, and the MRI integrity of subscapular tendon reconstruction. Methods: A systematic literature review in spanish and english language using the PubMed MEDLINE, EMBASE y LILACS databases with the term of: "Arthroscopic reconstruction of isolated subscapular tendon tears". Only studies evaluating the techniques, outcomes and MRI integrity of the reconstruction of isolated subscapularis repair were included. Descriptive analysis was provided for the available literature. Results: Seven studies were included in this review. The studies were done in between 2003 to 2013, 207 patients with 51 mean age. Uniformly, improvements in patient-reported outcome scores were substantial after arthroscopic subscapularis repair. Excellent MRI tendon to bone to integrity with very low complication rate. Conclusions: Arthroscopic subscapularis repair is a reasonable option to treat isolated tears of the subscapularis tendon to obtain successful functional outcomes. We need future prospective comparative studies. Level of Evidence: IV. Type of study: Systematic review of studies
Subject(s)
Humans , Arthroscopy/methods , Rotator Cuff/surgery , Shoulder Joint/surgery , Tendon Injuries/surgery , Treatment OutcomeABSTRACT
Las infección odontogénica es aquella que tiene su origen en el propio diente o en los tejidos que los rodean íntimamente, progresa a lo largo del periodonto hasta el ápice, afectando al hueso periapical y desde esta zona se disemina a través del hueso y del periostio hacia estructuras vecinas o más lejanas. Su importancia radica en que puede ser origen de infecciones que comprometan estructuras vecinas (cortical, periotio) o más alejadas que pueden producir infecciones intracraneales, retrofaringea, hematogeneas que ocasionen problemas reumatológicos o depósito sobre válvulas cardíacas (endocarditis). Los condicionantes o factores que influyen en la propagación de las infecciones dependen del balance entre las condiciones del paciente y microorganismo. El objetivo de esta revisión de las infecciones odontogénicas, es por la gran frecuencia o incidencia con la que aparece en la práctica diaria. El propósito es ser útil como material de consulta para colegas y estudiantes de cómo abordaremos las características clínicas de su manifestación así como los tratamientos para remitir dicha infección. El tratamiento de la infección odontogénica se basa, en general, en terapéuticas conbinadas (farmacológicas/ odontológica/Quirúrgica) donde la antimicrobiana no siempre es necesaria ni suficiente, el tratamiento oportuno de las infecciones odontogénicas para detener la diseminación de una infección hacia las estructuras ayacentes.
Subject(s)
Humans , Abscess , Cellulite , Surgery, Oral , Drainage , Infections , DentistryABSTRACT
El síndrome de Moebius conocido también como diplejia facial congénita o agenesia nuclear, es una enfermedad neurológica congénita poco frecuente en la que se ven afectados los núcleos de origen de los pares craneales VI y VII, impidiendo su total desarrollo. Aunque su etiología es idiopática se asocia al uso de sustancias teratógenas, tales como cocaína, talidomida, misoprostol, etc. Se describe el caso clínico de un paciente de 11 meses de edad cuya madre usó tabletas de misoprostol por vía vaginal (400 mcg),durante el primer trimestre de gestación, con fines abortivos, presentando al nacimiento defectos congénitos. El misoprostol es un análogo de la prostaglandina E1 y fue creado para el tratamiento de la úlcera gástrica, pero, además posee acción uterotónica y tiene capacidad de maduración del cuello uterino. Si se lo usa al final de la gestación colabora como buen inductor del parto, no siendo así en el primer trimestre de gestación, donde los efectos son devastadores provocando un aborto, o en su defecto, genera déficit en la irrigación sanguínea, afectando el desarrollo embriológico del nuevo ser. En países donde el aborto no es legal, el misoprostol se emplea para la interrupción del embarazo, sin embargo la infrecuente supervisión profesional, llevan a que algunos de los embarazos continúen produciendo exposición prenatal al misoprostol, lo cual está asociado con la ocurrencia de anomalías congénitas. El presente trabajo demuestra la injerencia del misoprostol como agente teratógeno durante el primer trimestre de embarazo y posible inductor al desarrollo del síndrome de Moebius.
The Moebius syndrome, also known as congenital facial diplegia or nuclear agenesis, is a rare congenital neurological disorder which affects the nuclei of origin of cranial nerves VI and VII, preventing their full development. Although etiology is idiopathic, it is associated with the use of teratogenic substances such as cocaine, thalidomide, misoprostol, etc. The clinical case of an 11-month old patient is described, whose mother used misoprostol tablets vaginally (400 mcg) during the first trimester of pregnancy with abortive purposes, presenting birth defects. Misoprostol is a prostalglandin E1 analogue and was created for the treatment of gastric ulcer, but also has an uterotonic action and the capacity to ripen the cervix. If it is used at the end of the pregnancy, it works as a good inducer of birth, not so in the first trimester of pregnancy, where the effects are devastating causing an abortion, or otherwise, creating deficits in blood supply, affecting the embryological development of the new being. In countries where abortion is illegal, misoprostol is used for the termination of pregnancy, but the lack of professional supervision causes some of the pregnancies to continue, producing prenatal exposure to misoprostol, which is associated with the occurrence of congenital anomalies. This study demonstrates the interference of misoprostol as a teratogen in the first trimester of pregnancy and as thepossible inducer of the development of the Moebius syndrome
Subject(s)
Male , Infant , Abnormalities, Drug-Induced , Abortifacient Agents, Nonsteroidal , Misoprostol , Mobius Syndrome , Congenital Abnormalities , Facial Paralysis , Muscle HypotoniaABSTRACT
OBJECTIVE: To evaluate the effect of tobacco smoking, respiratory symptoms, and asthma on lung function among Mexican adults who were evaluated during a medical exam in a private health clinic. MATERIAL AND METHODS: Reference prediction equations were generated for spirometry parameters [forced vital capacity (FVC), forced expired volume in one second (FEV1) and FEV1/FVC] based on multiple linear regression models. The effect of tobacco smoking, respiratory symptoms and asthma on these equations were explored. RESULTS: Spirometry tests were performed on 919 subjects from 14 to 86 years of age. Asthma decreased FVC and FEV1 in men with a R2 change <1%. Respiratory symptoms decreased the FEV1/FVC ratio in both sexes. Tobacco smoking was associated with a significant reduction in FEV in women. CONCLUSIONS: Asthma lightly reduced lung function in males while tobacco smoking decreased FEV, particularly in females.
Subject(s)
Asthma/physiopathology , Forced Expiratory Volume , Smoking/adverse effects , Vital Capacity , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Mexico , Middle Aged , Respiratory Function Tests , Retrospective Studies , Spirometry , Urban PopulationABSTRACT
OBJETIVO: Evaluar el efecto del tabaquismo, los síntomas respiratorios y el asma sobre la función pulmonar espirométrica en población adulta mexicana. MATERIAL Y MÉTODOS: Se generaron ecuaciones de predicción basadas en modelos de regresión lineal múltiple para la capacidad vital forzada (FVC), el vollumen espiratorio forzado al primer segundo (FEV1) y FEV1/FVC de espirometrías obtenidas de adultos que acuden a evaluación de salud y se determinó el efecto del tabaquismo, los síntomas respiratorios y el asma sobre los modelos de estos parámetros. RESULTADOS: Se estudiaron 919 sujetos de entre 14 y 86 años de edad. El asma disminuye la FVC y el FEV1 en hombres con un cambio en la R² <1 por ciento. Los síntomas respiratorios reducen FEV1/FVC en ambos sexos. El tabaquismo disminuye significativamente el FEV1 en las mujeres. CONCLUSIONES: El antecedente de asma disminuyó discretamente la función pulmonar en hombres, mientras que la historia de tabaquismo redujo el FEV1, particularmente en las mujeres de la población que se estudió.
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Asthma/physiopathology , Forced Expiratory Volume , Smoking/adverse effects , Vital Capacity , Mexico , Respiratory Function Tests , Retrospective Studies , Spirometry , Urban PopulationABSTRACT
Noroviruses are human enteric caliciviruses for which no cell culture is available. Consequently, the mechanisms and factors involved in their replication have been difficult to study. In an attempt to analyze the cis- and trans-acting factors that could have a role in NV replication, the 3(')-untranslated region of the genome was studied. Use of Zuker's mfold-2 software predicted that NV 3(')UTR contains a stem-loop structure of 47 nts. Proteins from HeLa cell extracts, such as La and PTB, form stable complexes with this region. The addition of a poly(A) tail (24 nts) to the 3(')UTR permits the specific binding of the poly(A) binding protein (PABP) present in HeLa cell extracts, as well as the recombinant PABP. Since La, PTB, and PABP are important trans-acting factors required for viral translation and replication, these RNA-protein interactions may play a role in NV replication or translation.
Subject(s)
Bacterial Proteins/chemistry , Carrier Proteins/chemistry , Norwalk virus/genetics , Polypyrimidine Tract-Binding Protein/chemistry , RNA/genetics , Ribonucleoproteins/chemistry , 3' Untranslated Regions , Autoantigens , Base Sequence , HeLa Cells , Humans , Intracellular Signaling Peptides and Proteins , Molecular Sequence Data , Nucleic Acid Conformation , Poly A , Precipitin Tests , Protein Binding , Protein Biosynthesis , RNA/metabolism , Recombinant Proteins/metabolism , Transcription, Genetic , Ultraviolet Rays , SS-B AntigenABSTRACT
En este estudio se identificaron posibles beneficios en el subsistema volitivo, habituacional y de desempeño propios del modelo de la ocupación humana que trae consigo la intervención terapéutica asistida con perros, en comparación con la centrada en la relación terapeuta usuario. Esta investigación se realizó con adolecentes (entre 12 y 18 años) con deficiencia mental (autismo o retardo mental leve moderado). Con este propósito se seleccionaron dos instituciones, una que ofrece terapia asistida con perros, y otra, centrada en la en la relación terapeuta usuario, escogiendo 3 participantes por institución con características ocupacionales similares. Fue un estudio observacional con diseño expostfacto, con 2 grupos diferenciados en la terapia. Se pudo establecer que la intervención asistida con perros con un buen manejo de la actividad, se constituye en una alternativa de intervención en el modelo de la ocupación humana, ya que el perro sirve e incide motivacionalmente a nivel de subsistema volitivo, para generar cambios en los otros dos subsistemas: habituacional y de desempeño.
Subject(s)
Animals , Adolescent , Animal Use Alternatives , Dogs , TherapeuticsABSTRACT
El objetivo de este trabajo es el de evaluar la hipótesis de que, tal y como fue definido por sus creadores, el enfoque de la reingeniería de procesos para la mejora de los niveles de eficiencia y de productividad no puede ser implantado con éxito en los hospitales públicos españoles y que, en realidad, las experiencias así denominadas no obedecen a los preceptos de dicho enfoque. La técnica de estudio consistió, por una parte, en una revisión y contrastación teórica fundamentada en la bibliografía relacionada con la materia y, por otra, en la experimentación mediante un caso de estudio efectuado en un hospital público con el que evaluar la hipótesis planteada. En la revisión y contrastación bibliográfica se detectó que la técnica de mejora de la eficiencia en el trabajo según los conceptos teóricos del enfoque de la reingeniería de procesos no es adaptable a los hospitales públicos españoles. En el caso de estudio se confirmó este extremo, advirtiéndose además que para proponer cambios relativamente importantes en los procesos de trabajo en los hospitales públicos es necesario tomar en consideración una serie de factores organizativos y humanos, que deben ser elementos siempre presentes independientemente del enfoque metodológico adoptado. La incorporación indiscriminada de tendencias de moda en el campo de la gestión de empresas en la administración de los hospitales públicos puede traer consigo efectos contraproducentes si no se evalúan en detalle previamente a su incorporación. Es necesario valorar antes su idoneidad para el propósito que se persigue (AU)