Linking the shifts in the metabolically active microbiota in a UASB and hybrid anaerobic-aerobic bioreactor for swine wastewater treatment.

Due to the high concentration of pollutants, swine wastewater needs to be treated prior to disposal. The combination of anaerobic and aerobic technologies in one hybrid system allows to obtain higher removal efficiencies compared to those achieved via conventional biological treatment, and the performance of a hybrid system depends on the microbial community in the bioreactor. Here, we evaluated the community assembly of an anaerobic-aerobic hybrid reactor for swine wastewater treatment. Sequencing of partial 16S rRNA coding genes was performed using Illumina from DNA and retrotranscribed RNA templates (cDNA) extracted from samples from both sections of the hybrid system and from a UASB bioreactor fed with the same swine wastewater influent. Proteobacteria and Firmicutes were the dominant phyla and play a key role in anaerobic fermentation, followed by Methanosaeta and Methanobacterium. Several differences were found in the relative abundances of some genera between the DNA and cDNA samples, indicating an increase in the diversity of the metabolically active community, highlighting Chlorobaculum, Cladimonas, Turicibacter and Clostridium senso stricto. Nitrifying bacteria were more abundant in the hybrid bioreactor. Beta diversity analysis revealed that the microbial community structure significantly differed among the samples (p < 0.05) and between both anaerobic treatments. The main predicted metabolic pathways were the biosynthesis of amino acids and the formation of antibiotics. Also, the metabolism of C5-branched dibasic acid, Vit B5 and CoA, exhibited an important relationship with the main nitrogen-removing microorganisms. The anaerobic-aerobic hybrid bioreactor showed a higher ammonia removal rate compared to the conventional UASB system. However, further research and adjustments are needed to completely remove nitrogen from wastewater.

Looking in a mirror, laparoscopic gastric sleeve in situs inversus patient: a case report.

Laparoscopic sleeve gastrectomy has been widely accepted and adopted as a weight loss procedure for obesity. Although technically demanding, it is feasible and can improve patients' overall health. However, any variation from normal anatomy can be challenging for any surgery, especially bariatric surgery, where a mistake could mean going from a life-saving opportunity to costing the patient's life. We present the case of an obese patient who sought medical attention and decided on bariatric surgery. During her preoperative evaluation, situs inversus totalis was discovered. After careful planning, the surgical team completed the surgery without complications, and the patient recovered completely.

Abdominal tuberculosis mimicking ovarian cancer. A case series report.

INTRODUCTION: Peritoneal tuberculosis (abdominal tuberculosis) can be confused with a malignant neoplasm. OBJECTIVE: To describe clinical and demographic characteristics of patients with abdominal tuberculosis mimicking advanced ovarian cancer, diagnosed in a national reference cancer center. METHODS: Clinical and pathological characteristics of nine patients with abdominal tuberculosis that clinically resembled advanced ovarian cancer are described. RESULTS: Median age was 47 years; the most common socioeconomic status was low (44%). Abdominal pain and weight loss occurred in 77.7%; ascites, in 55.5%; 22.2% had a positive COMBE test, and 100% had no history of pulmonary tuberculosis. CA-125 elevation was reported in 77.7%, with levels > 500 U/mL in 57.1%. Tomography reported carcinomatosis in 50% and pelvic tumor and ascites in 37.5%. All patients underwent surgery, where 62.5% were diagnosed by intraoperative pathology study as neoplastic disease. CONCLUSION: Tuberculosis is considered the great imitator, which is why abdominal tuberculosis diagnosis should be borne in mind when faced with a suspicious case, even when clinical presentation, imaging studies, and even intraoperative examination suggest ovarian cancer.

INTRODUCCIÓN: La tuberculosis peritoneal (tuberculosis abdominal) puede ser confundida con una neoplasia maligna. OBJETIVO: Describir características clínicas y demográficas de pacientes con tuberculosis abdominal que semeja cáncer de ovario avanzado, diagnosticados en un centro oncológico de referencia nacional. MÉTODOS: Se describen las características clínicas y patológicas de nueve pacientes con tuberculosis abdominal que clínicamente semejaba cáncer de ovario avanzado. RESULTADOS: La mediana de edad fue de 47 años, el estrato socioeconómico más común fue bajo (44 %). El dolor abdominal y la pérdida ponderal se presentaron en 77.7 %, ascitis en 55.5 %, prueba COMBE positiva en 22.2 % y ausencia de antecedente de tuberculosis pulmonar en 100 %. La elevación de CA-125 se reportó en 77.7 %, con > 500 U/mL en 57.1 %. La tomografía indicó carcinomatosis en 50 % y tumor pélvico y ascitis en 37.5 %. Todas las pacientes fueron sometidas a cirugía; 62.5 % fueron diagnosticadas mediante estudio patológico transoperatorio como enfermedad neoplásica. CONCLUSIÓN: La tuberculosis es considerada como la gran imitadora, por ello se debe tener en mente el diagnóstico de tuberculosis abdominal ante un caso sospechoso, aun cuando la presentación clínica, estudios de imagen e, incluso, el examen transoperatorio sugieran cáncer de ovario.

Tuberculosis abdominal que mimetiza cáncer de ovario. Reporte de una serie de casos / Abdominal tuberculosis mimicking ovarian cancer. A case series report

Resumen Introducción: La tuberculosis peritoneal (tuberculosis abdominal) puede ser confundida con una neoplasia maligna. Objetivo: Describir características clínicas y demográficas de pacientes con tuberculosis abdominal que semeja cáncer de ovario avanzado, diagnosticados en un centro oncológico de referencia nacional. Métodos: Se describen las características clínicas y patológicas de nueve pacientes con tuberculosis abdominal que clínicamente semejaba cáncer de ovario avanzado Resultados: La mediana de edad fue de 47 años, el estrato socioeconómico más común fue bajo (44 %). El dolor abdominal y la pérdida ponderal se presentaron en 77.7 %, ascitis en 55.5 %, prueba COMBE positiva en 22.2 % y ausencia de antecedente de tuberculosis pulmonar en 100 %. La elevación de CA-125 se reportó en 77.7 %, con > 500 U/mL en 57.1 %. La tomografía indicó carcinomatosis en 50 % y tumor pélvico y ascitis en 37.5 %. Todas las pacientes fueron sometidas a cirugía; 62.5 % fueron diagnosticadas mediante estudio patológico transoperatorio como enfermedad neoplásica Conclusión: La tuberculosis es considerada como la gran imitadora, por ello se debe tener en mente el diagnóstico de tuberculosis abdominal ante un caso sospechoso, aun cuando la presentación clínica, estudios de imagen e, incluso, el examen transoperatorio sugieran cáncer de ovario.

Abstract Introduction: Peritoneal tuberculosis (abdominal tuberculosis) can be confused with a malignant neoplasm. Objective: To describe clinical and demographic characteristics of patients with abdominal tuberculosis mimicking advanced ovarian cancer, diagnosed in a national reference cancer center. Methods: Clinical and pathological characteristics of nine patients with abdominal tuberculosis that clinically resembled advanced ovarian cancer are described. Results: Median age was 47 years; the most common socioeconomic status was low (44%). Abdominal pain and weight loss occurred in 77.7%; ascites, in 55.5%; 22.2% had a positive COMBE test, and 100% had no history of pulmonary tuberculosis. CA-125 elevation was reported in 77.7%, with levels > 500 U/mL in 57.1%. Tomography reported carcinomatosis in 50% and pelvic tumor and ascites in 37.5%. All patients underwent surgery, where 62.5% were diagnosed by intraoperative pathology study as neoplastic disease. Conclusion: Tuberculosis is considered the great imitator, which is why abdominal tuberculosis diagnosis should be borne in mind when faced with a suspicious case, even when clinical presentation, imaging studies, and even intraoperative examination suggest ovarian cancer.

Effect of degradation of a black mangrove forest on seasonal greenhouse gas emissions.

Mangroves play an essential role in the global carbon cycle. However, they are highly vulnerable to degradation with little-known effects on greenhouse gas (GHG) emissions. This study compared seasonal soil carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) fluxes from a black mangrove (Avicennia germinans) forest in the Tampamachoco coastal lagoon, Veracruz, Mexico, in areas subjected to different degrees of environmental degradation (full canopy, transitional and dead mangrove), caused by hydrological perturbation. Furthermore, we aimed at determining the environmental factors driving seasonal fluxes. There was a combined effect of seasonality and degradation on CH4 fluxes, highest during the rainy season in the dead mangrove (0.93 ± 0.18 mg CH4 m-2 h-1). CO2 fluxes were highest during the dry season (220 ± 23 mg CO2 m-2 h-1), with no significant differences among degradation levels. N2O fluxes did not vary among seasons or degradation levels (- 3.8 to 2.9 mg N2O m-2 h-1). The overall CO2-eq emission rate was 15.3 ± 2.7 Mg CO2-eq ha-1 year-1, with CO2 as the main gas contributing to total emissions. The main factors controlling CH4 fluxes were seasonal porewater salinity and the availability of NO2-, NO3-, and SO4-2 in the soil, favored by high water level and temperature in the absence of pneumatophores. The main determining factors controlling CO2 fluxes were water level, porewater redox potential, and soil Cl- and SO4-2 concentration. Finally, N2O fluxes were related to NO2-, NO3-, and SO4-2 soil concentrations. This study contributes to improving the knowledge of soil GHG fluxes dynamics in mangroves and the effect of degradation of these ecosystems on the coastal biogeochemical cycles, which may bring important insights for assessing accurate ways to mitigate climate change protecting and restoring these ecosystems.

Ecology and molecular targets of hypermutation in the global microbiome.

Changes in the sequence of an organism's genome, i.e., mutations, are the raw material of evolution. The frequency and location of mutations can be constrained by specific molecular mechanisms, such as diversity-generating retroelements (DGRs). DGRs have been characterized from cultivated bacteria and bacteriophages, and perform error-prone reverse transcription leading to mutations being introduced in specific target genes. DGR loci were also identified in several metagenomes, but the ecological roles and evolutionary drivers of these DGRs remain poorly understood. Here, we analyze a dataset of >30,000 DGRs from public metagenomes, establish six major lineages of DGRs including three primarily encoded by phages and seemingly used to diversify host attachment proteins, and demonstrate that DGRs are broadly active and responsible for >10% of all amino acid changes in some organisms. Overall, these results highlight the constraints under which DGRs evolve, and elucidate several distinct roles these elements play in natural communities.

Antisclerothic effect of tibolone by reducing proinflammatory cytokines expression, ROS production and LDL-ox uptake in THP-1 macrophages.

BACKGROUND: Cardiovascular disease is more frequent in menopausal women, which has been related to factor such as weight gain, altered fat distribution, and increased inflammation markers including adipokines (MCP-1, TNF-α, IL-6) and cytokines (IL-1, IL-6, TNF-α) produced by macrophages. In addition to their phagocytic activity, macrophages secrete cytokines and chemokines that induces cell recruitment, which is a process related to vascular damage that favors the formation of atheromatous plaques. Tibolone (Tb) therapy is used to reduce the symptoms of menopause as well as osteoporosis and it has been shown to decreases the risk of fractures. METHODS: To investigate the effect of tibolone in macrophage enzymatic activity, gene expression of cytokines, and its effect on foam cells formation. We use phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 cells. The cells were incubated 24 h and 48 h using pre and post-treatment schemes. We evaluated total ROS determination by NBT assay, expression of cytokines (IL-1ß, IL-6, TNF-α, NOS2, ARG1, TGFß) by RT-qPCR and foam cell formation in THP-1 differentiated macrophages stimulated with PMA. RESULTS: It was observed that the minor levels of total ROS determination were obtained with tibolone at 48 h in post-treatment scheme. Also, in a long term we found decrease the proinflammatory cytokines (IL-1ß, IL-6 and TNF-α). Finally, with treatment for 24 h with P4 y Tb we observed fewer LDL vesicles into macrophages cytoplasm. CONCLUSIONS: These results suggest that tibolone reduces the inflammatory process, also inhibits the foam cells formation; suggesting a possible role in reducing cardiovascular risk.

Asociación de factores de riesgo independientes con fracaso posextubación en pacientes desconectados de la ventilación mecánica / Association of independent risk factors with post-extubation failure in patients undergoing mechanical ventilation weaning

Resumen Introducción: Aun con adecuado protocolo de desconexión de la ventilación mecánica (DVM), el procedimiento falla en 15 a 30 % de los casos. Objetivo: Evaluar la asociación entre factores de riesgo independientes y fracaso posextubación en pacientes con DVM en una unidad de cuidados intensivos. Método: Estudio de cohorte, longitudinal, prospectivo, analítico, que incluyó pacientes sometidos a ventilación mecánica por más de 24 horas y que fueron extubados. Se obtuvieron reportes preextubación de hemoglobina, albúmina, fósforo, índice cintura-cadera y puntuación SOFA. Se definió como fracaso de extubación al reinicio de la ventilación mecánica en 48 horas o menos. Resultados: Se extubaron 123 pacientes, 74 hombres (60 %); la edad promedio fue de 50 ± 18 años. Ocurrió fracaso de extubación en 37 (30 %). Como factores de riesgo independentes se asoció hipoalbuminemia en 29 (23.8 %, RR = 1.43, IC 95 % = 1.11-1.85) e hipofosfatemia en 18 (14.6 %, RR = 2.98, IC 95 % = 1.66-5.35); se observaron dos o más factores de riesgo independientes en 22.7 % (RR = 1.51, IC 95 % = 1.14-2.00). Conclusiones: Identificar los factores de riesgo independentes antes de la DVM puede ayudar a reducir el fracaso de la extubación y la morbimortalidad asociada.

Abstract Introduction: Even with an adequate mechanical ventilation weaning (MVW) protocol, the procedure fails in 15 to 30 % of cases. Objective: To assess the association between independent risk factors (IRFs) and post-extubation failure in patients undergoing MVW in an intensive care unit. Method: Longitudinal, prospective, analytical cohort study in patients on mechanical ventilation for more than 24 hours and who were extubated. Pre-extubation reports of hemoglobin, albumin, phosphorus, waist-hip ratio and SOFA score were obtained. Extubation failure was defined as resumption of mechanical ventilation within 48 hours or less. Results: 123 patients were extubated, out of whom 74 were males (60 %); average age was 50 ± 18 years. Extubation failure occurred in 37 (30 %). Hypoalbuminemia was associated as an independent risk factor in 29 (23.8 %, RR = 1.43, 95 % CI = 1.11-1.85) and hypophosphatemia was in 18 (14.6 %, RR = 2.98, 95 % CI = 1.66-5.35); two or more IRFs were observed in 22.7 % (RR = 1.51, 95 % CI = 1.14-2.00). Conclusions: Identifying independent risk factors prior to MVW can help reduce the risk of extubation failure and associated morbidity and mortality.

Metagenomic Insight into Environmentally Challenged Methane-Fed Microbial Communities.

In this study, we aimed to investigate, through high-resolution metagenomics and metatranscriptomics, the composition and the trajectories of microbial communities originating from a natural sample, fed exclusively with methane, over 14 weeks of laboratory incubation. This study builds on our prior data, suggesting that multiple functional guilds feed on methane, likely through guild-to-guild carbon transfer, and potentially through intraguild and intraspecies interactions. We observed that, under two simulated dioxygen partial pressures-low versus high-community trajectories were different, with considerable variability among the replicates. In all microcosms, four major functional guilds were prominently present, representing Methylococcaceae (the true methanotrophs), Methylophilaceae (the nonmethanotrophic methylotrophs), Burkholderiales, and Bacteroidetes. Additional functional guilds were detected in multiple samples, such as members of Opitutae, as well as the predatory species, suggesting additional complexity for methane-oxidizing communities. Metatranscriptomic analysis suggested simultaneous expression of the two alternative types of methanol dehydrogenases in both Methylococcaceae and Methylophilaceae, while high expression of the oxidative/nitrosative stress response genes suggested competition for dioxygen among the community members. The transcriptomic analysis further suggested that Burkholderiales likely feed on acetate that is produced by Methylococcaceae under hypoxic conditions, while Bacteroidetes likely feed on biopolymers produced by both Methylococcaceae and Methylophilaceae.

Carbon stocks and greenhouse gas emissions (CH4 and N2O) in mangroves with different vegetation assemblies in the central coastal plain of Veracruz Mexico.

The aim of this study was to quantify carbon stocks and the emission of the greenhouse gases (N2O and CH4) in mangrove forests with different vegetation assemblies in coastal lagoons of Veracruz Mexico. The vegetation included: black mangrove BM, dominated by Avicennia germinans, white mangrove WM, dominated by Laguncularia. racemose, red mangrove RM, dominated by Rhizophora mangle and mixed mangrove MM, dominated by the three species. Soil C stocks ranged 187-671 Mg C ha 1 without significant (p = 0.149) differences among the mangroves with different vegetation. Significantly (p = 0.049) higher tree biomass C stock was observed in RM (127 Mg ha-1) than in MM (24.23 Mg ha-1). Methane emissions in RM (0.58-6.03 mg m-2 min-1) were significantly higher (p < 0.05) than in MM. (0.0035-0.07 mg m-2 min-1), in WM (-0.0026-0.029 mg m-2 min-1) and in BM (0.0054-0.0097 mg m-2 min-1),during rainy, windy and dry season.RM had the longest period of inundation, the highest soil carbon concentration, and the lowest salinity. CH4 emissions showed a significantly positive correlation with soils carbon concentration, water level and water pH and, negative correlation with water salinity and Cl-1 concentration in soil and water. Emissions of N2O (0.04-3.25 µg m-2 min-1) were not significantly different among the mangroves with different vegetation, but they showed seasonal variations, with higher emissions during windy and dry seasons. N2O emissions showed significantly positive correlations with soil nitrate concentration and soil temperature. Results of this research are useful for mangrove conservation and restoration strategies to maximize carbon storage and mitigate greenhouse gas emissions.

Alpha-1 Adrenergic Receptors Modulate Glutamate and GABA Neurotransmission onto Ventral Tegmental Dopamine Neurons during Cocaine Sensitization.

The ventral tegmental area (VTA) plays an important role in the reward and motivational processes that facilitate the development of drug addiction. Presynaptic α1-AR activation modulates glutamate and Gamma-aminobutyric acid (GABA) release. This work elucidates the role of VTA presynaptic α1-ARs and their modulation on glutamatergic and GABAergic neurotransmission during cocaine sensitization. Excitatory and inhibitory currents (EPSCs and IPSCs) measured by a whole cell voltage clamp show that α1-ARs activation increases EPSCs amplitude after 1 day of cocaine treatment but not after 5 days of cocaine injections. The absence of a pharmacological response to an α1-ARs agonist highlights the desensitization of the receptor after repeated cocaine administration. The desensitization of α1-ARs persists after a 7-day withdrawal period. In contrast, the modulation of α1-ARs on GABA neurotransmission, shown by decreases in IPSCs' amplitude, is not affected by acute or chronic cocaine injections. Taken together, these data suggest that α1-ARs may enhance DA neuronal excitability after repeated cocaine administration through the reduction of GABA inhibition onto VTA dopamine (DA) neurons even in the absence of α1-ARs' function on glutamate release and protein kinase C (PKC) activation. α1-AR modulatory changes in cocaine sensitization increase our knowledge of the role of the noradrenergic system in cocaine addiction and may provide possible avenues for therapeutics.

Association of independent risk factors with post-extubation failure in patients undergoing mechanical ventilation weaning.

INTRODUCTION: Even with an adequate mechanical ventilation weaning (MVW) protocol, the procedure fails in 15 to 30 % of cases. OBJECTIVE: To assess the association between independent risk factors (IRFs) and post-extubation failure in patients undergoing MVW in an intensive care unit. METHOD: Longitudinal, prospective, analytical cohort study in patients on mechanical ventilation for more than 24 hours and who were extubated. Pre-extubation reports of hemoglobin, albumin, phosphorus, waist-hip ratio and SOFA score were obtained. Extubation failure was defined as resumption of mechanical ventilation within 48 hours or less. RESULTS: 123 patients were extubated, out of whom 74 were males (60 %); average age was 50 ± 18 years. Extubation failure occurred in 37 (30 %). Hypoalbuminemia was associated as an independent risk factor in 29 (23.8 %, RR = 1.43, 95 % CI = 1.11-1.85) and hypophosphatemia was in 18 (14.6 %, RR = 2.98, 95 % CI = 1.66-5.35); two or more IRFs were observed in 22.7 % (RR = 1.51, 95 % CI = 1.14-2.00). CONCLUSIONS: Identifying independent risk factors prior to MVW can help reduce the risk of extubation failure and associated morbidity and mortality. INTRODUCCIÓN: Aun con adecuado protocolo de desconexión de la ventilación mecánica (DVM), el procedimiento falla en 15 a 30 % de los casos. OBJETIVO: Evaluar la asociación entre factores de riesgo independientes y fracaso posextubación en pacientes con DVM en una unidad de cuidados intensivos. MÉTODO: Estudio de cohorte, longitudinal, prospectivo, analítico, que incluyó pacientes sometidos a ventilación mecánica por más de 24 horas y que fueron extubados. Se obtuvieron reportes preextubación de hemoglobina, albúmina, fósforo, índice cintura-cadera y puntuación SOFA. Se definió como fracaso de extubación al reinicio de la ventilación mecánica en 48 horas o menos. RESULTADOS: Se extubaron 123 pacientes, 74 hombres (60 %); la edad promedio fue de 50 ± 18 años. Ocurrió fracaso de extubación en 37 (30 %). Como factores de riesgo independentes se asoció hipoalbuminemia en 29 (23.8 %, RR = 1.43, IC 95 % = 1.11-1.85) e hipofosfatemia en 18 (14.6 %, RR = 2.98, IC 95 % = 1.66-5.35); se observaron dos o más factores de riesgo independientes en 22.7 % (RR = 1.51, IC 95 % = 1.14-2.00). CONCLUSIONES: Identificar los factores de riesgo independentes antes de la DVM puede ayudar a reducir el fracaso de la extubación y la morbimortalidad asociada.

A Methodology Towards Mechanical Properties Optimization of Three-Component Polymers by the Gradual Variation of Feed Composition in Semi-Continuous Emulsion-Free Radical Polymerization.

In this work, a new methodology for the synthesis of three-component polymers (TCPs) was developed using a seeded, semi-continuous free-radical emulsion polymerization towards the optimization of the moduli-ultimate deformation performance and energy dissipation capacity for a styrene (S), n-butyl acrylate (BA), and 4-vinylbenzyl chloride (VBC) system. The three components were sequentially fed in pairs, varying feed composition along the conversion using S as the common monomer. To prepare a reference material, an industrial method was utilized with those monomers, using an equivalent global composition in a two-stage batch process (TS). Nanophase formation in the particles was observed by transmission electron microscopy (TEM), while the separation of the phases in the solid samples was observed by atomic force microscopy (AFM). The changes in glass transition temperature were determined by differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA). The latter was primarily used to compare mechanodynamic properties as a function of temperature for the two synthesis methods used. Thus, the higher toughness of the forced composition three-component polymeric materials was evaluated by means of their energy dissipation capacity, toughness, and stress-strain measurements at several temperatures.

F654A and K558Q Mutations in NMDA Receptor 1 Affect Ethanol-Induced Behaviors in Drosophila.

BACKGROUND: N-methyl-D-aspartate (NMDA) receptors regulate synaptic plasticity and modulate a wide variety of behaviors. Mammalian NMDA receptors are inhibited by ethanol (EtOH) even at low concentrations. In mice, the F639A mutation in transmembrane domain (TMD) 3 of the NR1 subunit reduces EtOH sensitivity of the receptor and, in some paradigms, reduces behavioral EtOH sensitivity and increases EtOH consumption. We tested the fly equivalent of the F639A and K544Q mutations for effects on EtOH sensitivity. Drosophila shows a high degree of behavioral and mechanistic conservation in its responses to EtOH. METHODS: Homologous recombination and CRISPR/Cas9 genome editing were used to generate amino acid changes in the Drosophila NMDAR1 gene, yielding F654A and K558Q alleles. Animals were tested for the degree of EtOH sensitivity, the ability to acquire tolerance to EtOH, EtOH drinking preference, circadian rhythmicity, learning, and locomotor defects. RESULTS: We observed that mutating the NMDAR1 channel also reduces EtOH sensitivity in adult flies. However, in flies, it was the K558Q mutation (orthologous to K544Q in mice) that reduces EtOH sensitivity in a recovery-from-sedation assay. The effects of the F654A mutation (orthologous to F639A in mice) were substantially different in flies than in mammals. In flies, F654A mutation produces phenotypes opposite those in mammals. In flies, the mutant allele is homozygous viable, does not seem to affect health, and increases EtOH sensitivity. Both mutations increased feeding but did not alter the animal's preference for 5% EtOH food. F654A depressed circadian rhythmicity and the capacity of males to court, but it did not depress the capacity for associative learning. K554Q, on the other hand, has little effect on circadian rhythmicity, only slightly suppresses male courtship, and is a strong learning mutant. CONCLUSIONS: Mutations in TMD 3 and in the extracellular-vestibule calcium-binding site of the NR1 NMDA subunit affect EtOH sensitivity in Drosophila.

Effectiveness of a Dietary Supplement Containing Hydrolyzed Collagen, Chondroitin Sulfate, and Glucosamine in Pain Reduction and Functional Capacity in Osteoarthritis Patients.

This observational, open, multicenter clinical trial with a single treatment group aimed to evaluate the effectiveness of a dietary supplement whose main ingredients are hydrolyzed gelatin, chondroitin sulfate, glucosamine sulfate, and devil's claw and bamboo extracts for pain reduction and improvement of functional capacities in patients with osteoarthritis (OA) of the knee and/or hip (REDART study). In all, 130 patients with OA recruited from Spanish hospitals received the dietary supplement for 6 months. The primary outcome was the patients' global assessment of pain in the affected joint as measured with a visual analogue scale (VAS). Other outcome measurements included the Lequesne Functional Index (subindexes for pain/discomfort, distance walked, and daily living) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC; subindexes for pain, stiffness, and physical function). Scores were taken at months 3 and 6 of the treatment. Patients (N = 78) showed a reduction of pain of 3.77 ± 1.77 points after 6 months (p < .0001) in the VAS. The total reduction in the Lequesne Functional Index was 6.30 ± 4.08 points after 6 months (p < .0001), with significant reductions in all subindexes of the scale. A similar pattern was found for the WOMAC index, with an overall reduction of 22.49 ± 14.03 points after 6 months (p < .0001) and significant reductions in all subindexes. No major adverse events were noted during the treatment. This exploratory study shows that treatment with the dietary supplement significantly reduces pain and improves locomotor function in patients with OA of the knee and/or hip.

aPKC-Mediated Persistent Increase in AMPA/NMDA Ratio in the VTA Participates in the Neuroadaptive Signal Necessary to Induce NAc Synaptic Plasticity After Cocaine Administration.

Chronic cocaine exposure produces enduring neuroadaptations in the brain's reward system. Persistence of early cocaine-evoked neuroadaptations in the ventral tegmental area (VTA) is necessary for later synaptic alterations in the nucleus accumbens (NAc), suggesting a temporal sequence of neuroplastic changes between these two areas. However, the molecular nature of the signal that mediates this sequential event is unknown. Here we used the behavioral sensitization model and the aPKC inhibitor of late-phase LTP maintenance, ZIP, to investigate if a persistent increase in AMPA/NMDA ratio plays a role in the molecular mechanism that allows VTA neuroadaptations to induce changes in the NAc. Results showed that intra-VTA ZIP microinfusion successfully blocked cocaine-evoked synaptic enhancement in the VTA and the expected AMPA/NMDA ratio decrease in the NAc following cocaine sensitization. ZIP microinfusions also blocked the expected AMPA/NMDA ratio increase in the NAc following cocaine withdrawal. These results suggest that a persistent increase in AMPA/NMDA ratio, mediated by aPKCs, could be the molecular signal that enables the VTA to elicit synaptic alterations in the NAc following cocaine administration.

Matrix metalloproteinase and heparin-stimulated serine proteinase activities in post-prostate massage urine of men with prostate cancer.

Proteinases secreted by the prostate gland have a reproductive function in cleaving proteins in the ejaculate and in the female reproductive tract, but some may have a fundamental role in disease and pathological processes including cancer. The purpose of this study was to determine if there were differences in proteinase activities in urine samples collected following prostate massage of men positive (CaP) or negative (no evidence of malignancy, NEM) for biopsy determined prostate cancer. Matrix metalloproteinase (MMP) and serine proteinase activities were detected using protein substrate zymography. There were no differences in activities of MMP-2, proMMP-9, and MMP-9/NGAL (neutrophil gelatinase associated lipocalin) complex (gelatin substrate) in men with detected prostate cancer, although the latter two were somewhat diminished. A caseinolytic activity of about 75kDa inhibited by calcium did not differ between the NEM and CaP groups. Heparin stimulated calcium sensitive gelatinolytic activities of approximately 22, 42, and 60kDa, but did not affect activities of MMP-2, MMP-9, or the 75kDa caseinolytic activity. The 22, 42, and 60kDa activities appear to be serine proteinases since they were inhibited by benzamidine. There was a significant decrease in the 22kDa heparin-stimulated serine proteinase activity in urines of men with cancer. Proteinase expression and activities, perhaps in combination with other potential markers, may prove useful in urine for detection and evaluation of prostate cancer.

The Effects of Ketamine on Cognitive Function in Elderly Patients Undergoing Ophthalmic Surgery: A Pilot Study.

BACKGROUND: Acute postoperative cognitive dysfunction is characterized by neurocognitive dysfunction and confusion. In this study, we compared the cognitive status of a geriatric population undergoing ophthalmic surgery, as assessed by the Short Portable Mental Status Questionnaire (SPMSQ) before and after ketamine administration. METHODS: Eighty patients were enrolled and randomly assigned in a double-blind study to receive either ketamine (0.3 mg/kg dose) or physiologic solution (control group). Sixty-five (control, n = 32; ketamine, n = 33) patients completed the trial. Cognitive performance was assessed with an abbreviated version of the SPMSQ. Measurements of analgesia, sedation, intraocular pressure, and hemodynamic variables were recorded. RESULTS: With respect to cognitive performance, the baseline evaluation was similar for the control and ketamine groups. Postoperative evaluation showed an improvement only in the ketamine group. No increase in intraocular pressure or a secondary nystagmus was observed. The average dose of midazolam was higher in the control group, but the difference was not clinically significant. After surgery, analgesic behavior was better in the ketamine group than in the control group. There were no differences between groups in the sedation scale or in hemodynamic variables. CONCLUSIONS: The administration of 0.3 mg/kg ketamine during ophthalmic surgery in geriatric patients changed their cognitive status as assessed by the SPMSQ, decreased the required dose of anesthetics, and produced no increase in intraocular pressure or in hemodynamic variables. However, because the evaluation only analyzed the immediate effects of the administered drug, further research will be required to examine the impact of ketamine on the postoperative cognitive performance of geriatric patients before the drug can be formally recommended for this purpose.

MicroRNA miR-182 cluster mediated modulation of RECK without changes in cell surface membrane type-1 matrix metalloproteinase (MT1-MMP).

Cell surface localized membrane type 1-matrix metalloproteinase (MT1-MMP) plays an important role in physiological and pathological processes and its function can be regulated by proteins such as RECK. We examined the ability of miR-182 (one of the miR-183 cluster miRNAs), which can target RECK, to control cell surface MT1-MMP activity. Expression of RECK mRNA and protein was increased with anti-miRs to miR-182, miR-183 or miR-96 in HT1080 fibrosarcoma cells, but, decreased RECK mRNA and increased its protein in the benign prostatic hyperplasia cell line BPH-1. Treatment of BPH-1 and HT-1080 cells with the anti-miRs did not change the level of cell surface MT1-MMP activity, nor their rate of migration in an in vitro wound-healing assay. Trichostatin A (TSA) did not increase the level of RECK, but blocked cell surface MT1-MMP activity and decreased cell motility. Anti-miRs mediated increased RECK levels did not interfere with cell surface MT1-MMP function, and TSA may block cell surface localization of MT1-MMP by a mechanism independent of RECK.