Strain Improvement Program of Streptomyces roseosporus for Daptomycin Production.

Daptomycin is a cyclic lipopeptide antibiotic with potent activity against gram-positive bacteria. It has a calcium-dependent mechanism of action that disrupts multiple features of the bacterial membrane function. This antibiotic is highly demanded due to its effectiveness against to microorganisms resistant to other antibiotics, including vancomycin-resistant Staphylococcus aureus (VRSA) and methicillin-resistant S. aureus (MRSA). Daptomycin is produced by fermentation of Streptomyces roseosporus, currently identified as Streptomyces filamentosus. However, low fermentation yields and high production costs are reported. This chapter describes a method of strain improvement involving random mutagenesis, rational screening by bioassay, and flask fermentation. The ultimate objective is to select mutants of S. roseosporus overproducing daptomycin in order to design a more cost-effective daptomycin production.

Fentanyl is used in Mexico's northern border: current challenges for drug health policies.

BACKGROUND AND AIMS: Results from a recent study among 750 heroin users in three Mexico's northern border cities revealed an increase in white powder availability (also known as China white) and preference for this product among heroin users, as well as a general perception of increased overdose cases among this population. Here, we questioned whether those findings reflect an increased presence of heroin laced with fentanyl, which is associated with greater risks of overdose but that, until now, has not been described in Mexico. DESIGN: We tested fentanyl using highly sensitive test strips in syringe plungers, metal cookers and drug wrappings associated with heroin use. SETTING: Three injection sites in Tijuana, Baja California, México. PARTICIPANTS: Eighty-nine heroin users who interchanged paraphernalia for new syringes. MEASUREMENTS: We tested 59 residues of 'pure' white powder. The rest were white powder with black tar (n = 5) or white powder with crystal meth (n = 9), black tar with crystal meth (n = 1), black tar only (n = 13) and crystal meth only (n = 2). FINDINGS: Users believed that they consumed either white powder heroin, white powder heroin with crystal meth, white powder with black tar heroin or black tar heroin only. Analyses revealed that 93% (n = 55) of the 'pure' white powder samples had fentanyl. All (n = 9) the white powder samples mixed with crystal meth and 40% (n = 2) of the white powder with black tar were also laced with fentanyl. CONCLUSIONS: In a sample of 89 heroin users in Mexico, most white powder heroin users were unknowingly exposed to fentanyl, with fentanyl detected in 93% of white powder samples.

Immunogenicity, transplacental transfer of pertussis antibodies and safety following pertussis immunization during pregnancy: Evidence from a randomized, placebo-controlled trial.

BACKGROUND: Pertussis immunization during pregnancy is recommended in many countries. Data from large randomized controlled trials are needed to assess the immunogenicity, reactogenicity and safety of this approach. METHODS: This phase IV, observer-blind, randomized, placebo-controlled, multicenter trial assessed immunogenicity, transplacental transfer of maternal pertussis antibodies, reactogenicity and safety of a reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap) during pregnancy. Women received Tdap or placebo at 27-36 weeks' gestation with crossover ≤ 72-hour-postpartum immunization. Immune responses were assessed before the pregnancy dose and 1 month after, and from the umbilical cord at delivery. Superiority (primary objective) was reached if the lower limits of the 95% confidence intervals (CIs) of the pertussis geometric mean concentration (GMC) ratios (Tdap/control) in cord blood were ≥ 1.5. Solicited and unsolicited adverse events (AEs) and pregnancy-/neonate-related AEs of interest were recorded. RESULTS: 687 pregnant women were vaccinated (Tdap: N = 341 control: N = 346). Superiority of the pertussis immune response (maternally transferred pertussis antibodies in cord blood) was demonstrated by the GMC ratios (Tdap/control): 16.1 (95% CI: 13.5-19.2) for anti-filamentous hemagglutinin, 20.7 (15.9-26.9) for anti-pertactin and 8.5 (7.0-10.2) for anti-pertussis toxoid. Rates of pregnancy-/neonate-related AEs of interest, solicited general and unsolicited AEs were similar between groups. None of the serious AEs reported throughout the study were considered related to maternal Tdap vaccination. CONCLUSIONS: Tdap vaccination during pregnancy resulted in high levels of pertussis antibodies in cord blood, was well tolerated and had an acceptable safety profile. This supports the recommendation of Tdap vaccination during pregnancy to prevent early-infant pertussis disease. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02377349.

The Equivalence between Virtual and Real Feared Stimuli in a Phobic Adult Sample: A Neuroimaging Study.

The clinical use of virtual reality (VR) has proven its efficacy, especially when used as an exposure technique. A prominent property of VR's utility is its equivalence with the reality it represents. In this study, we explored this equivalence in a clinical context using neuroimaging. A sample of 32 adults with specific phobias (i.e., to cockroaches, spiders, or lizards) was divided into two groups: One was exposed to phobic stimuli using VR and the other was exposed to real phobic images (RI). We used brain activations as a dependent measure, focusing specifically on brain areas usually associated with fear processing. Whole-brain analysis detected higher activations for RI in the hippocampus, occipital, and calcarine areas. A specific analysis of the amygdala and insula also detected higher activations and extensions in response to RI, but VR stimuli also activated those areas in a significant manner. These results suggest that even in those cases where RI stimuli activate all of the brain's fear-processing circuits, VR stimuli do so as well. This implies that VR can be useful as an exposure technique similar to RI and applied as more than a mere training mechanism.

Percepción de los ginecólogos sobre la situación actual de los dispositivos intrauterinos durante el consejo contraceptivo en España para distintos perfiles de usuaria / Perception of gynecologists on the current situation of intrauterine devices during contraceptive advice in Spain for different user profiles

Objetivo: comunicar las percepciones de ginecólogos españoles sobre el uso del dispositivo intrauterino en distintos perfiles de usuaria. Materiales y métodos: estudio transversal descriptivo. 94 ginecólogos de diferentes regiones de España cumplimentaron un cuestionario sobre la situación del dispositivo intrauterino durante el consejo contraceptivo. Las valoraciones fueron consensuadas en una reunión nacional. Resultados: un 73% de los ginecólogos se manifestaron de acuerdo en recomendar los dispositivos intrauterinos en mujeres nulíparas. Sin embargo, solo un 52% declaró prescribirlo en ese perfil con frecuencia. Asimismo, un 93% de los participantes mostró acuerdo para afirmar la existencia de ideas preconcebidas sobre el dispositivo intrauterino y un 79% para afirmar que una mayor accesibilidad aumentaría su recomendación. Conclusiones: se sugiere incluir los distintos tipos de dispositivos intrauterinos durante el consejo contraceptivo según el perfil de cada usuaria, independientemente de edad o paridad, y preferiblemente los hormonales en mujeres candidatas (AU)

Objective: To communicate the perceptions of Spanish gynecologists about the use of intrauterine devices in different user profiles. Materials and methods: Cross-sectional descriptive study. 94 gynecologists answered a questionnaire related to the current situation of intrauterine devices in contraceptive counseling. Answers and considerations were validated in a national meeting. Results: 73% of gynecologists showed their agreement to recommend intrauterine devices to nulliparous women. However, only 52% declared to often prescribe these methods to these users. In addition, 93% of participants agreed to describe the existence of preconceived notions about intrauterine devices, and 79% agreed to declare that better accessibility would increase intrauterine devices prescription rates. Conclusions: Considering all intrauterine devices types during contraceptive counseling was advised, giving preference to hormone-based methods in the appropriate women. Acknowledging the different user profiles was also recommended, regardless of age and parity (AU)

Assessment of the potential for gene flow from transgenic maize (Zea mays L.) to eastern gamagrass (Tripsacum dactyloides L.).

Eastern gamagrass (Tripsacum dactyloides L.) belongs to the same tribe of the Poaceae family as maize (Zea mays L.) and grows naturally in the same region where maize is commercially produced in the USA. Although no evidence exists of gene flow from maize to eastern gamagrass in nature, experimental crosses between the two species were produced using specific techniques. As part of environmental risk assessment, the possibility of transgene flow from maize to eastern gamagrass populations in nature was evaluated with the objectives: (1) to assess the seeds of eastern gamagrass populations naturally growing near commercial maize fields for the presence of a transgenic glyphosate-tolerance gene (cp4 epsps) that would indicate cross-pollination between the two species, and (2) to evaluate the possibility of interspecific hybridization between transgenic maize used as male parent and eastern gamagrass used as female parent. A total of 46,643 seeds from 54 eastern gamagrass populations collected in proximity of maize fields in Illinois, USA were planted in a field in 2014 and 2015. Emerged seedlings were treated with glyphosate herbicide and assessed for survival. An additional 48,000 seeds from the same 54 eastern gamagrass populations were tested for the presence of the cp4 epsps transgene markers using TaqMan® PCR method. The results from these trials showed that no seedlings survived the herbicide treatment and no seed indicated presence of the herbicide tolerant cp4 epsps transgene, even though these eastern gamagrass populations were exposed to glyphosate-tolerant maize pollen for years. Furthermore, no interspecific hybrid seeds were produced from 135 hand-pollination attempts involving 1529 eastern gamagrass spikelets exposed to maize pollen. Together, these results indicate that there is no evidence of gene flow from maize to eastern gamagrass in natural habitats. The outcome of this study should be taken in consideration when assessing for environmental risks regarding the consequence of gene flow from transgenic maize to its wild relatives.

Mycobacterium smegmatis is a suitable cell factory for the production of steroidic synthons.

A number of pharmaceutical steroid synthons are currently produced through the microbial side-chain cleavage of natural sterols as an alternative to multi-step chemical synthesis. Industrially, these synthons have been usually produced through fermentative processes using environmental isolated microorganisms or their conventional mutants. Mycobacterium smegmatis mc2 155 is a model organism for tuberculosis studies which uses cholesterol as the sole carbon and energy source for growth, as other mycobacterial strains. Nevertheless, this property has not been exploited for the industrial production of steroidic synthons. Taking advantage of our knowledge on the cholesterol degradation pathway of M. smegmatis mc2 155 we have demonstrated that the MSMEG_6039 (kshB1) and MSMEG_5941 (kstD1) genes encoding a reductase component of the 3-ketosteroid 9α-hydroxylase (KshAB) and a ketosteroid Δ1 -dehydrogenase (KstD), respectively, are indispensable enzymes for the central metabolism of cholesterol. Therefore, we have constructed a MSMEG_6039 (kshB1) gene deletion mutant of M. smegmatis MS6039 that transforms efficiently natural sterols (e.g. cholesterol and phytosterols) into 1,4-androstadiene-3,17-dione. In addition, we have demonstrated that a double deletion mutant M. smegmatis MS6039-5941 [ΔMSMEG_6039 (ΔkshB1) and ΔMSMEG_5941 (ΔkstD1)] transforms natural sterols into 4-androstene-3,17-dione with high yields. These findings suggest that the catabolism of cholesterol in M. smegmatis mc2 155 is easy to handle and equally efficient for sterol transformation than other industrial strains, paving the way for valuating this strain as a suitable industrial cell factory to develop à la carte metabolic engineering strategies for the industrial production of pharmaceutical steroids.

Sarcoid-like reaction in a patient with uveitis and underlying cancer.

PURPOSE: Sarcoidosis is a granulomatous disease of unknown etiology. Occasionally, triggering causes are identified, such as neoplasms, and they are termed sarcoid-like reactions, which may appear in any sarcoidotic target tissue. Choroidal metastases appear as part of widespread metastatic disease or as the first suggestion of neoplastic disease. They can also be a part of the differential diagnosis of a spectrum of inflammatory eye diseases. We present a case in which a lung carcinoma, pulmonary and eye sarcoid-like reactions, and choroidal metastasis take place in the same patient. CASE REPORT: A 60-year-old male with a past history of pulmonary sarcoidosis and associated anterior uveitis was diagnosed with a lung carcinoma with no regional lymph nodes extension, so that the resection surgery was performed without additional systemic treatment. At the same time, he complained of visual acuity loss and pain in his right eye. An intense ocular inflammatory reaction and a choroidal mass compatible with metastasis were identified. A vitrectomy with an accompanied histological exam of the lesion was deemed inconclusive. Ocular symptoms progressively worsened showing mass growth, and as a result, an enucleation was performed and the histological study subsequently revealed metastasis from his lung carcinoma. CONCLUSION: Sarcoid-like reactions may be due to incipient malignancies. Any diagnosis of sarcoidosis requires ruling out other diseases that can produce secondary sarcoid-like reactions. In addition, any choroidal mass suggestive of metastasis requires exclusion of metastatic disease even in the absence of clinical signs indicating tumor extension.

[The National Medical Arbitration Commission: 20 years]. / La Comisión Nacional de Arbitraje Médico: 20 años.

Cuando la Secretaría de Salud todavía tenía el logotipo azul que decía SSA, corrían tiempos difíciles porque no había dinero y la idea de crear nuevas instituciones era recibida con reservas, no sólo por el Presidente Zedillo, siempre generoso y atento a las necesidades de salud de la población, sino también, como ya es costumbre, por el secretario de Hacienda, responsable de cuidar el erario público. Y es que la idea de hacer crecer el gasto corriente del gobierno se percibía, no sin razón, como un acto que podía infligir el riesgo de fomentar estructuras administrativas ineficaces y obesas. No ha sido el caso de la Comisión Nacional de Arbitraje Médico (CONAMED), pues sus aproximadamente 200 trabajadores siguen realizando una labor inmensa con una estructura ligera.

The combined use of virtual reality exposure in the treatment of agoraphobia.

INTRODUCTION: This study compares the differential efficacy of three groups of treatments for agoraphobia: paroxetine combined with cognitive-behavioral therapy, paroxetine combined with cognitive-behavioral therapy and virtual reality exposure, and a group with only paroxetine. METHODOLOGY: 99 patients with agoraphobia were finally selected. Both combined treatment groups received 11 sessions of cognitive-behavioral therapy, and one of the groups was also exposed to 4 sessions of virtual reality treatment. Treatments were applied in individual sessions once a week for 3 months. RESULTS: The three treatment groups showed statistically significant improvements. In some measures, combined treatment groups showed greater improvements. The virtual reality exposure group showed greater improvement confronting phobic stimuli. CONCLUSIONS: Treatments combining psychopharmacological and psychological therapy showed greater efficacy. Although the use of new technologies led to greater improvement, treatment adherence problems still remain.

[The impact of globalization on mental health]. / Impactos de la globalización en la salud mental.

Psychosis, dementias, anxiety, depression, suicide and suicide attempts, as well as psychiatric disorders associated to violence and poverty have increased the global burden of disease. Other related problems associated to special diets, body image, compulsive use of computers and mobile phones, and those frequently observed in migrants subjected to intense distress are reviewed as well. Information and communication technologies may have undesirable side effects affecting some individuals in their conduct and social interactions.

Metabolic engineering of Mucor circinelloides for zeaxanthin production.

Mucor circinelloides is a ß-carotene producing zygomycete amenable to metabolic engineering using molecular tools. The crtS gene of the heterobasidiomycetous yeast Xanthophyllomyces dendrorhous encodes the enzymatic activities ß-carotene hydroxylase and ketolase, allowing this yeast to produce the xanthophyll called astaxanthin. Here we describe the fermentation of X. dendrorhous in astaxanthin producing conditions to purify mRNA for the cloning of the cDNA from the crtS gene by RT-PCR. Further construction of an expression plasmid and transformation of M. circinelloides protoplasts allow the heterologous expression of the crtS cDNA in M. circinelloides to obtain ß-cryptoxanthin and zeaxanthin overproducing transformants. These two xanthophylls are hydroxylated compounds from ß-carotene. These results show that the crtS gene is involved in the conversion of ß-carotene into xanthophylls, being potentially useful to engineer carotenoid pathways.

Selection and taxonomic identification of carotenoid-producing marine actinomycetes.

Carotenoids are important pigments produced by plants and many microorganisms, including fungi, microalgae, cyanobacteria, and bacteria. Marine actinomycetes are a group of bacteria that produce a variety of metabolites with economic potential. Here, we describe a general method of selecting marine actinomycetes as carotenoids' producers. The screening is carried out at two levels: the first one involves a quick selection of strains by visual color inspection, and the second consists in the analysis of the extracts by HPLC. The taxonomic analysis of the producing strains gives us an overview of the groups of actinomycetes in which carotenoids can be found.

Assessing the ecological risks from the persistence and spread of feral populations of insect-resistant transgenic maize.

One source of potential harm from the cultivation of transgenic crops is their dispersal, persistence and spread in non-agricultural land. Ecological damage may result from such spread if the abundance of valued species is reduced. The ability of a plant to spread in non-agricultural habitats is called its invasiveness potential. The risks posed by the invasiveness potential of transgenic crops are assessed by comparing in agronomic field trials the phenotypes of the crops with the phenotypes of genetically similar non-transgenic crops known to have low invasiveness potential. If the transgenic and non-transgenic crops are similar in traits believed to control invasiveness potential, it may be concluded that the transgenic crop has low invasiveness potential and poses negligible ecological risk via persistence and spread in non-agricultural habitats. If the phenotype of the transgenic crop is outside the range of the non-transgenic comparators for the traits controlling invasiveness potential, or if the comparative approach is regarded as inadequate for reasons of risk perception or risk communication, experiments that simulate the dispersal of the crop into non-agricultural habitats may be necessary. We describe such an experiment for several commercial insect-resistant transgenic maize events in conditions similar to those found in maize-growing regions of Mexico. As expected from comparative risk assessments, the transgenic maize was found to behave similarly to non-transgenic maize and to be non-invasive. The value of this experiment in assessing and communicating the negligible ecological risk posed by the low invasiveness potential of insect-resistant transgenic maize in Mexico is discussed.

[Local impact of health global problems. Introduction]. / Problemas globales de salud de impacto local. Introducción.

During the last 3 years the National Academy of Medicine, the School of Medicine and the Ministry of Health have analyzed several global health issues with local impact. The group of articles presented in this symposium is focused on the health systems. The Mexican health system has evolved through the years facing different challenges and showing its strengths as well as several inconsistencies, flaws and limitations. The subjects analyzed deal with several alternatives to face the health challenges. All health systems are under constant change and financial resources as well as conceptual clarity, human resources, coordination, and leadership are needed.