The aminoshikimic acid pathway in bacteria as source of precursors for the synthesis of antibacterial and antiviral compounds.

The aminoshikimic acid (ASA) pathway comprises a series of reactions resulting in the synthesis of 3-amino-5-hydroxybenzoic acid (AHBA), present in bacteria such as Amycolatopsis mediterranei and Streptomyces. AHBA is the precursor for synthesizing the mC7N units, the characteristic structural component of ansamycins and mitomycins antibiotics, compounds with important antimicrobial and anticancer activities. Furthermore, aminoshikimic acid, another relevant intermediate of the ASA pathway, is an attractive candidate for a precursor for oseltamivir phosphate synthesis, the most potent anti-influenza neuraminidase inhibitor treatment of both seasonal and pandemic influenza. This review discusses the relevance of the key intermediate AHBA as a scaffold molecule to synthesize diverse ansamycins and mitomycins. We describe the structure and control of the expression of the model biosynthetic cluster rif in A. mediterranei to synthesize ansamycins and review several current pharmaceutical applications of these molecules. Additionally, we discuss some relevant strategies developed for overproducing these chemicals, focusing on the relevance of the ASA pathway intermediates kanosamine, AHAB, and ASA.

Recombinant Listeria promotes tumor rejection by CD8+ T cell-dependent remodeling of the tumor microenvironment.

Agents that remodel the tumor microenvironment (TME), prime functional tumor-specific T cells, and block inhibitory signaling pathways are essential components of effective immunotherapy. We are evaluating live-attenuated, double-deleted Listeria monocytogenes expressing tumor antigens (LADD-Ag) in the clinic. Here we show in numerous mouse models that while treatment with nonrecombinant LADD induced some changes in the TME, no antitumor efficacy was observed, even when combined with immune checkpoint blockade. In contrast, LADD-Ag promoted tumor rejection by priming tumor-specific KLRG1+PD1loCD62L- CD8+ T cells. These IFNγ-producing effector CD8+ T cells infiltrated the tumor and converted the tumor from an immunosuppressive to an inflamed microenvironment that was characterized by a decrease in regulatory T cells (Treg) levels, a proinflammatory cytokine milieu, and the shift of M2 macrophages to an inducible nitric oxide synthase (iNOS)+CD206- M1 phenotype. Remarkably, these LADD-Ag-induced tumor-specific T cells persisted for more than 2 months after primary tumor challenge and rapidly controlled secondary tumor challenge. Our results indicate that the striking antitumor efficacy observed in mice with LADD-based immunotherapy stems from TME remodeling which is a direct consequence of eliciting potent, systemic tumor-specific CD8+ T cells.

Combining Adobe Forms and Dropbox to Obtain a Low-Cost Electronic Data Collection System.

BACKGROUND: The method used to collect, store, and analyze data can affect the quality of data obtained. Many studies have shown the advantages of electronic systems over paper. Numerous tools are available for this purpose; however, they tend to be implemented only in high-budget protocols as they tend to be expensive. INTRODUCTION: We report the experience of the Affective Disorders' Clinic of the National Institute of Psychiatry in Mexico City using Adobe Acrobat® Forms combined with Dropbox® as storage and distribution method for clinical protocols. MATERIALS AND METHODS: Adobe Acrobat 9 Pro® was used to create personalized forms to capture data for seven different clinical purposes. Dropbox was used to share the distributed forms with fellow researchers. Completed forms were stored in Dropbox and the main researcher kept the data collection file, from where the forms were gathered for analysis. RESULTS: Sixteen forms created for different clinical purposes had an average of 1.2% missing fields. DISCUSSION: The main drawbacks relate to remote filling and the time spent in fine-tuning complex forms. The main advantages relate to the simplicity of the implementation of the method and the fact that no software other than the one available at the Institute is required. CONCLUSIONS: Compared with other types of electronic data collection systems, the combination of these tools achieves similar goals and is low cost, requiring minimal knowledge of informatics.

The effects of NutraGen supplement on cattle growth performance, energetic efficiency, carcass characteristics, and characteristics of digestion in calf-fed Holstein steers.

Evaluation of the effects of feeding NutraGen supplement (NutraGen, NTG; Phibro Animal Health, Teaneck, NJ, USA) on growth performance, energetic efficiency, carcass characteristcs, and characteristics of digestion in calf-fed Holstein steers fed a conventional growing-finishing diet. Trial 1 evaluated growth performance, dietary energetics and carcass characteristics. Two hundred Holstein steer calves (134 ± 5 kg) were blocked by initial body weight (BW) and randomly assigned to 40 pens (5 steers/pen). Dietary treatments consisted of a steam-flaked corn-based growing-finishing diet supplemented with 0, 0.2, 0.4, or 0.6% NTG (DM basis). In trial 2, four Holstein steers (170 ±6 kg) with cannulas in the rumen and proximal duodenum were used in a 4 × 4 Latin square experiment to evaluate digestibility and ruminal characteristics using the treatments from trial 1. Compared to non-supplemented cattle, NTG increased BW (2.0%, P = 0.02) and tended to increase ADG (3.6%, P = 0.07) during the initial 56 d period. However, there were no treatment effects on overall growth performance and efficiency of dietary energy utilization after the first 56 days (P > 0.10). Supplementation of NTG increased (linear effect; P ≤ 0.03) longissimus muscle area and kidney, pelvic, and heart fat. There was no effect (P ≥ 0.05) of NTG supplementation on other carcass characteristics, liver abscess incidence, or liver abscess scars. Supplementation decreased the molar proportion of ruminal propionate (P = 0.05) and tended to increase acetate:propionate molar ratio (P = 0.09). However, there was no effect of NTG supplementation on ruminal and total tract diet digestion. NTG increased performance of Holstein steers during the first 56 d on feed in the feedlot. In addition, the steers had an increase in KPH fat and LM area, indicating that the additive induced change in metabolism of the steers.

Interaction of early metabolizable protein supplementation and virginiamycin on feedlot growth performance and carcass characteristics of calf-fed Holstein steers.

One hundred sixty-eight Holstein steer calves (133.4 ±â€…7.9 kg) were used to evaluate the influence of virginiamycin (VM) supplementation on cattle growth performance and liver abscess incidence, and the effect of feeding 100% vs. 87% of metabolizable protein (MP) requirements during the initial 112 d on growth performance, efficiency of energy utilization, and carcass characteristics. Steers were balanced by weight and assigned to 28 pens (6 steers/pen). During the initial 112-d feeding period, dietary treatments consisted of two levels of MP (100% vs. 87% of expected requirements) supplemented with or without 22.5 mg/kg VM in a 2 × 2 factorial arrangement. There were no VM × MP supplementation interactions (P ≥ 0.14) on any of the parameters measured in both experiments. Calf-fed Holstein steers supplemented with VM increased (P ≤ 0.03) overall average daily gain (ADG), feed efficiency (G:F), observed/expected net energy (NE) values for maintenance and gain, and final body weight (BW). Cattle fed VM also increased (P ≤ 0.04) carcass weight, dressing percent, and longissimus muscle area. However, there was no effect (P ≥ 0.22) of VM supplementation on any other carcass characteristics. Calf-fed Holstein steers fed 100% MP requirements during the initial 112-d feeding period had greater (P ≤ 0.02) ADG, G:F, observed/expected NE values for maintenance and gain, and live BW compared with steers fed 87% of the expected MP requirements. However, there was no effect (P ≥ 0.17) of MP supply during the initial 112-d period on overall (342 d) growth performance measurements. The incidence of liver abscesses was low (averaging 7.7%) and not affected by dietary treatments. We conclude that, independent of MP supplies, supplemental VM enhances overall growth performance and efficiency of energy utilization of calf-fed Holstein steers.

Solid bifocal pseudopapillary neoplasm of the pancreas: A case report.

INTRODUCTION: This neoplasm of the pancreas is an uncommon entity, with a frequency of 0.3-2.7% of all pancreatic tumors and even more so the finding of a synchronous lesion of the same histological lineage. For this reason, we report the atypical presentation of a SPNPs through a clinical case, review of the literature and a classification proposal, from the quantitative point of view. CASE PRESENTATION: 21-year-old patient, with incidental finding of two pancreatic tumors. Surgery included a pyloric preserving pancreatoduodenectomy with pancreatojejunostomy, distal pancreatectomy and central pancreas was preserved. The patient presents low output pancreatic fistula and nosocomial infection, treated with antibiotic therapy, being discharged 29 days after the intervention. Pathological and immunohistochemical analysis consistent with two SPNP. DISCUSSION: Its diagnosis is confirmed with the histological study and two synchronic SPNP are a rare entity and for this, or multiple lesions, an attempt should be made of a conservative resection of the parenchyma to minimize pancreatic insufficiency in a frequently young population, and always look for R0 resection, due to its uncertain behavior. CONCLUSION: Bifocal SPNP is rare and for this it is utility classify this entity -from the quantitative point of view- into unifocal, bifocal and multifocal for future medical research.

An Affordable and Feasible Technique for Minimally Invasive Tubular Lumbar Discectomy.

BACKGROUND: The benefits of minimally invasive spine surgery are attainable only if hospitals have the financial resources to acquire essential equipment. We present a surgical approach readily available to countries where unacceptably expensive materials are the main limitation for use of minimally invasive spine surgery. METHODS: This retrospective study included 30 patients who underwent minimally invasive spine surgery using syringes as dilators and retractors for posterior lumbar approaches. Inclusion criteria were lumbar radicular/back pain, degenerative disc, spondylolysis, unilateral approach, and maximum of 2 affected spine levels. Demographic characteristics, affected radicular level, diagnosis, type and length of surgery, hospital length of stay, MacNab criteria, complications, and resumption of daily activities were analyzed. RESULTS: Of 30 patients, 17 (56.6%) presented with S1 radicular pain. Pain was mainly due to posterolateral hernia (70%; n = 21) requiring 1-level discectomy. In 6 patients (20%), discectomy and an interspinous process device were required. One patient (3.33%) underwent 2-level discectomy. All surgeries were performed using syringes as dilators and retractors. Maximum syringe diameter used was 2 cm (20-mL syringes) in 29 patients (96.6%) and 3 cm (60-mL syringe) in 1 patient. Average length of surgery was 1.5 hours, and average hospital stay was 1.8 days. Based on MacNab criteria, excellent, good, and fair outcomes were achieved in 25 patients (83%), 3 patients (10%), and 2 patients (6.7%). Complications were observed in 5 patients (16.7%). CONCLUSIONS: This is a safe and feasible technique with excellent results obtained at low cost and is becoming an attractive surgical option in developing countries.

Process reengineering and patient-centered approach strengthen efficiency in specialized care.

OBJECTIVES: To improve multiple levels of utilization and efficiency in specialized outpatient consults using information technology-based systems, process reengineering, and patient-centeredness. STUDY DESIGN: Prospective research from 2008 to 2014 conducted in a hospital in Madrid, Spain. Quantitative analysis of 1,162,477 consecutive consultation requests and qualitative techniques of 72,368 surveys using a structured questionnaire. METHODS: Key performance indicators were evaluated: operational outcomes (productivity, time gap between requested consultations and performance, staffing accuracy, wait time, and underlying variability), administrative burden (downtime losses; no-show, drop-in, cancelled, and rescheduled visits), perceived quality scores, and income. Data mining, modeling seasonality in demand, process reengineering, and a patient-centered approach were incorporated as strategies to drive changes. RESULTS: Productivity increased 34% for the entire period, closing the gap between consultation request and performance from 43.7% to 8.7%. Wait time decreased from 82.7 to 7.9 days, with an 82.9% reduction in interservice variability. Staffing adjustments prevented understaffing situations; more accurate modeling reduced understaffing from 282 to 4 full-time equivalent staff. A seasonal autoregressive integrated moving average (1,0,0)(0,1,0) model explained 90.3% of forecasted data variability with an absolute percentage error between 2.4% and 8.3%. The project reduced administrative burden, inefficiency, and downtime losses by 47.3%, 53.7%, and 54.5%, respectively. Perceived quality indices improved by 19.6%, and complaints were reduced from 63 to 10 per 10,000 consultation-years. Hospital incomes rose by 49.4%. CONCLUSIONS: Improving efficiency is complex and requires a multimodal approach. Health information systems, patient feedback, and multidisciplinary teams are components that can improve clinical processes.

Pie diabetico y estilo de vida: Reporte de Caso / Diabetic foot and lifestyle: Case Report

La diabetes sigue siendo la principal causa de amputación no traumática en la mayoría de los países occidentales1, informes epidemiológicos indican que más de un millón de amputaciones se realizan en personas con diabetes cada año, esto equivale a una amputación por diabetes en algún lugar del mundo cada 30 segundos, la mayoría de estas amputaciones son precedidas por úlceras2. Presentamos un caso de un paciente varón de 39 años pluripatológico que padece de Diabetes Mellitus e Hipertensión no controlada, con complicaciones tardías, renal, anemia, retinopatía, y pie diabético isquémico y neuropático, con indicación de amputación. Se emplea estilos de vida saludables6, controlando glicemias, hipertensión, sin requerir medicación y disminuyendo la proteinuria. No se presentaron efectos adversos. Con evolución favorable desde entonces. Conclusión: El estilo de vida saludables es una intervención que entre más tempranamente sea empleada serán mayores sus beneficios, sin el riesgo de efectos adversos, ni costos innecesarios, pero aun en etapas tardías ha mostrado beneficios en el control glicémico, hipertensivo y renal.

Diabetes is still the leading cause of non-traumatic amputation in most Western countries, epidemiological reports indicate that more than a million amputations are performed in people with diabetes each year, this is equivalent to an amputation for diabetes somewhere in the world every 30 seconds, most of these amputations are preceded by ulcers. We present a case of a 39-year-old male patient suffering from diabetes mellitus and uncontrolled hypertension, with late complications, chronic kidney disease, anemia, retinopathy, and ischemic and neuropathic diabetic foot, with indication for amputation. Healthy lifestyles are used, controlling glycemia, hypertension, without requiring medication and reducing proteinuria. There were no adverse effects. With favorable evolution since then. Conclution: A healthy lifestyle is an intervention that the earlier it is used, the greater its benefits, without the risk of adverse effects or unnecessary costs, but even in late stages it has shown benefits in glycemic, hypertensive and renal control.

Bases conceptuales de la cirugía metabólica / Conceptual Bases of Metabolic Surgery

Resumen: El término de síndrome metabólico (SM) se ha utilizado desde su definición en el año 2001 por el programa nacional del colesterol (NCEP: ATP III). El concepto ha sido discutido en la literatura científica por décadas. El síndrome X y otros términos como "el cuarteto de la muerte" y el síndrome de resistencia a la insulina, han sido utilizados para describir la asociación entre factores de riesgo metabólico y cardiovascular. En México, la prevalencia de SM en la Encuesta Nacional de Salud y Nutrición (ENSANUT) fue de un 34% para el año 2000; y para el 2012, del 41%. Las modificaciones del estilo de vida junto con aumento en la actividad física, dejar de fumar y limitar el consumo de alcohol son primordiales para el manejo y la prevención debido a que juegan un rol central en las anormalidades metabólicas. Sin embargo, a pesar del impresionante armamento de medicamentos disponible para la diabetes, se ha descrito que hasta el 50% de los pacientes no alcanzan las metas adecuadas de control, definidas por la Asociación Americana de Diabetes (hemoglobina glucosilada <7%). En contraste, la cirugía bariátrica (CB) ha confirmado claramente que contribuye a mejorar la función de las células beta en pacientes con índice de masa corporal (IMC) >35 kg/m2, así como el control de la dislipidemia y otras alteraciones metabólicas.

Abstract: The term Metabolic Syndrome (MS) has been used since its introduction in 2001 by the National Cholesterol Program (NCEP: ATP III). The concept has been discussed in the scientific literature for decades. The X Syndrome and other terms such as "death quartet" and insulin resistance syndrome have been used to describe the association between metabolic and cardiovascular risk factors. In Mexico, the prevalence of MS in the National Health and Nutrition Survey (Encuesta Nacional de Salud y Nutrición, ENSANUT) was 34% in 2000 and 41% in 2012. Lifestyle modifications along with increased physical activity, quitting smoking, and limiting alcohol consumption are essential for management and prevention because they play a central role in metabolic abnormalities. However, despite the large amount of medications available for diabetes, up to 50% of patients have been reported to fail to achieve adequate control goals, as defined by the American Diabetes Association (glycosylated hemoglobin <7%). In contrast, bariatric surgery (BS) has clearly confirmed that it contributes to improved beta cell function in patients with BMI >35 kg / m2, as well as control of dyslipidemia and other metabolic disorders.

An easy approach for the purification of native TFIIH.

Transcriptional regulation depends on the appropriate set of positive and negative regulating signals in order to provide the correct gene expression. In vitro studies in eukaryotic gene expression over the last few years have provided a wealth of information about new factors involved in the regulation of genes. However, the dissection of this mechanism requires the addition of well-characterized general transcription factors; with the exception of TFIID and TFIIH, all others can easily be expressed in a recombinant form. Here we provide a simple methodology to obtain partially purified transcriptionally active TFIIH free from other general transcription factors and active in transcription.

Using History to Analyze the Learning by Observing and Pitching In Practices of Contemporary Mesoamerican Societies.

The analysis of Indigenous learning practices in Mexico and the United States typically relies on ethnography, oral history, and participant observation as the methodology for understanding the socialization processes of Mesoamerican societies. In this chapter, we consider the importance of using historical analysis as an added methodology for understanding the Indigenous learning practices by considering three case studies of Indigenous communities in Mexico, where a consideration of historical patterns have proven fruitful for understanding the contemporary Learning by Observing and Pitching In (LOPI) practices. These communities include the Nahua people of the state of Puebla, the P'urhépecha communities of the state of Michoacán, and the Nahua people of the Texcoco area to the southeast of Mexico City. We conclude that a consideration of the cultural patterns that have developed in Mesoamerican societies across time would benefit contemporary researchers as one component of their LOPI research.

Cenestesia y esquizofrenia cenestopática / Cenesthesias and cenesthopathic schizophrenia

Presentamos tres casos clínicos de pacientes con diferentes síntomas cenestésicos. En dos de ellos los síntomas cenestésicos son los principales, y en el tercer caso, los síntomas cenestésicos acompañan a los síntomas paranoides. Este tipo de síntomas descritos desde Kraepelin, hace más de cuarenta años, sigue teniendo vigencia y mayor importancia, pues se relaciona a un peor curso y pronóstico si lo comparamos con la esquizofrenia paranoide dentro de la cual se incluye en la clasificación actual.

We present three cases of patients with different cenesthopathic symptoms. In two cases the symptoms are primarily cenesthopathic, and in the third case, the cenesthopathic symptoms were accompanying paranoid symptoms. Such symptoms described since Kraepelin, over forty years ago, are still relevant and more important, as they relate to a worse course and prognosis when compared with paranoid schizophrenia within which is included in the current classification.

Sistema de instrumentación transpedicular modificado, para el tratamiento de la inestabilidad vertebral toracolumbar / Modified transpedicular instrumentation system for the treatment of thoracolumbar vertebral instability

En estudio se revisaron 189 pacientes con diagnóstico de inestabilidad vertebral toracolumbar, ocasionada por enfermedades como: espondilolistesis, inestabilidad vertebral posquirúrgica, fracturas, infecciones, tumores óseos primarios y metastásicos a nivel toracolumbar. Su estabilidad fue recuperada mediante un implante de tornillos transpediculares conectados con barras de acero inoxidable. Actualmente existen sistemas de fijación transpendicular que requieren de mucho instrumental y de tornillos que se componen de varias piezas que hacen difícil su aplicación, además el valor económico de los sistemas de importación es muy elevado y no está al alcance de la mayoría de nuestros pacientes. Esto motivó al autor del trabajo para modificar y reducir el instrumento; los tornillos se componen de dos piezas, son autoperforantes (por dos ranuras en la punta en forma de bisel). La tuerca es de caja con un perno en el centro, que evita que se unan las espigas y así no hay aflojamiento de la unión tornillo-tuerca y barra. Esto proporciona la estabilidad vertebral requerida y permite una rehabilitación temprana sin complicaciones posteriores al reposo prolongado. Todos los pacientes tenían el diagnóstico de inestabilidad vertebral, tratados con el sistema de implante transpendicular modificado, con cinco años de evolución. Como complicaciones se tuvieron; cuatro infecciones de la herida quirúrgica, una embolia pulmonar, seis rechazos del implante, tres aflojamientos del sistema (uno por ruptura del implante, tres aflojamientos del sistema (uno por ruptura de tornillos y dos por aflojamiento de las tuercas). En todos los casos se alcanzó la artrodesis, la estabilidad vertebral y no existió agravamiento de daño neurológico. En conclusión, con las modificaciones que se hicieron de otros implantes para estabilizar la columna vertebral toracolumbar, se logró que la aplicación fuera más fácil, disminuyendo el tiempo y riesgo quirúrgico, el gasto de sangre y la administración de anestésico y medicamentos en el transoperatorio, además de abatir el costo del implante