Assessment of cognitive impairment and depressive signs in patients with type 2 diabetes treated with metformin from Southeast Mexico: A cross-sectional study.

Multiple factors associate diabetes with cognitive impairment and depression. Antidiabetic drugs have reported antidepressant and pro-cognitive effects in diabetic and non-diabetic subjects. Antidepressant and pro-cognitive effects of metformin are reported in various studies; however, these effects are not consistent among researches. We designed a cross-sectional study. We recruited patients with T2D diagnosis from the Diabetes Clinic of the Regional Hospital of High Specialty "Dr. Gustavo A. Rovirosa Pérez" from January 2019 to May 2022. We included 431 subjects with T2D, 374 patients with metformin treatment and 57 subjects without metformin. These patients were on intensive therapies and had not a previous diagnosis of cognitive impairment or depression. We applied Mini-Mental State Examination (MMSE) to evaluate cognitive impairment, and Hamilton Depression Rating Scale (HAM-D) to assess depressive signs. Our sample had a mean age of 53.77 ± 13.43 years. Metformin users were 374 individuals, and 57 subjects didn't use metformin. MMSE found cognitive impairment in 8.3% (n = 31) of metformin users, and 14.8% (n = 8) of patients without metformin. HAM-D scale showed that 39.5% (n = 147) of patients with metformin had depression signs, subjects without metformin and depressive signs were 44.6% (n = 25). We found no differences between groups for cognitive impairment and depression grades. We did not find associations between metformin treatment, cognitive impairment measures and depression sign measures. However, chronic metformin treatment, insulin use, glycemic control and age could influence our results.

Rabies, the cause of fatal encephalitis.

To describe the clinical progression and medical protocols applied in a 41 year old man who was bited by a bat three months before. The patient did not ask for medical care until acute tremor and pain in the right thoracic limb and hydro-phobia started. For a history of a wild animal bite associated with a unique clinical condition, we suspected of rabies encephalitis, confirming the diagnostic by pathology after his death. This case ocurred in Guadalajara, Jalisco, México, in April, 2022. The last case of human rabies reported in Jalisco secondary to bat bite was almost 30 years ago. As an uncomon disease, medical personnel and facilities should be prepared to attend this sort of cases after clinical suspicion. For the present case, the medical history was the key for diagnosis. Rabies is a disease caused by the neurotropic virus belonging to the Rhabdoviridae family whose prognosis is bleak, with mortality close to 100% and therapeutic options limited. This case emphasizes the high mortality of rabies virus infection and the importance of increasing awareness and education to the public in general, with regard to applying the vaccine as post-exposure prophylaxis.

Modelado de estructuras-3D de mutaciones raras del receptor-1-melanocortina asociadas al melanismo en el mielero / Modelling of 3d-structures of the rare melanocortin-1-receptor mutations associated to melanism in the bananaquit

ABSTRACT Melanism in plumage color is often associated to the single nucleotide polymorphism of the melanocortin-1-receptor. Despite the striking association between the substitution of a Glutamic-acid by for a Lysine at position 92 on the MC1R protein and a completely black plumage, an in-depth understanding of the effect of missense mutations on the conformational change and behavior of the MC1R in the lipid bilayer caused by the absence of a crystal structure is lacking. We examine the structural basis for receptor activation using DNA sequences from the GenBank to perform in silico protein homology-based modeling. Our tridimensional model shows that the Alanine for a 179-Threonine substitution is a structural complement of the charge-reversing effect associated to the substitution of a Glutamic-acid by for a Lysine at position 92 on the MC1R. We proposed the possibility of gradual evolution in stability and electrostatic properties of the MC1R by the sequential accumulation of these two rare substitutions. These two rare substitutions further perturb physical-chemical properties that may be necessary folding requirements of the constitutively active MC1R forms without altering of ligand binding affinity. The computational coarse-grained molecular dynamics of the MC1R binding affinities to the melanocyte-stimulating hormone predicted the disparity in ligand binding among alleles. We speculate that the disparity in structural constraints and ligand binding among the alleles within heterozygous individuals may contribute as a mechanism to the plumage color variation in the Coereba flaveola.

RESUMEN El melanismo en el color del plumaje se asocia frecuentemente al polimorfismo del receptor melanocortina-1. La ausencia de una estructura cristalográfica de la asociación entre la sustitución del Glutamato por Lisina en la posición 92 de la proteína MC1R y el plumaje completamente negro, no ha permitido tener un mejor entendimiento del efecto de mutaciones no sinónimas en la conformación y en el comportamiento en la membrana del MC1R. Examinamos la estructura asociada a la activación del receptor usando secuencias de ADN obtenidas del GenBank, para un modelamiento in silico de formas homólogas de la proteína. El modelo tridimensional muestra que la sustitución de Alanina por la Treonina en la posición 179 es un complemento estructural al efecto de reversión de carga asociado a la sustitución del Glutamato por Lisina en la posición 92 del MC1R. Proponemos la posibilidad de evolución gradual de la estabilidad y de propiedades electrostáticas del MC1R por la acumulación de estas substituciones. Estas perturban las propiedades fisicoquímicas que podrían ser necesarias para el plegamiento de las formas constitutivamente activas del MC1R sin alterar la afinidad de empalme con el ligando. La modelación computacional de la dinámica molecular de la afinidad de empalme del MC1R a la hormona estimulante de meloncitos predice la disparidad de la unión con el ligando entre alelos. Consideramos que posiblemente la disparidad entre alelos en heterocigotos en cuanto a restricciones estructurales y la unión con el ligando podría contribuir a la variación en el color del plumaje en Coereba flaveola.

Fibrin and Transforming Growth Factor Alpha Affect Prostatic Smooth Muscle Cell's Phenotype and Motility.

Smooth muscle cells (SMCs) are dynamic and transition from a contractile to a synthetic phenotype under different circumstances. Plasma factors (fibrin and transforming growth factors, TGFs) are possible components affecting SMCs differentiation and behavior. Thus, the objective of this work was to investigate how the fibrin matrix and TGFs affect SMCs differentiation and motility behavior. SMCs invaded the fibrin gel and adopted a stellate phenotype while reducing the expression of differentiation markers (Acta2, Myh11, and Smtn). At the ultrastructural level, SMCs did not assemble a basal lamina and showed numerous blebs along the entire cell surface. This transition was not associated with changes in focal adhesion kinase (FAK) content and phosphorylation status but reflected a marked change in FAK distribution in the cytoplasm. After 48 h in culture, SMCs caused an active degradation of the fibrin gel. Additionally, we tested the SMCs response to TGFs in a cell layer wound repair assay. TGFα, but not TGFß1 or TGFß3, had significantly increased motility. In conclusion, prostatic SMCs present a phenotypical transition when cultured on fibrin, adopting a micro-blebbing based motility behavior and increasing migration in response to TGFα.

Silver Enhances Hematite Nanoparticles Based Ethanol Sensor Response and Selectivity at Room Temperature.

Gas sensors are fundamental for continuous online monitoring of volatile organic compounds. Gas sensors based on semiconductor materials have demonstrated to be highly competitive, but are generally made of expensive materials and operate at high temperatures, which are drawbacks of these technologies. Herein is described a novel ethanol sensor for room temperature (25 °C) measurements based on hematite (α­Fe2O3)/silver nanoparticles. The AgNPs were shown to increase the oxide semiconductor charge carrier density, but especially to enhance the ethanol adsorption rate boosting the selectivity and sensitivity, thus allowing quantification of ethanol vapor in 2-35 mg L-1 range with an excellent linear relationship. In addition, the α-Fe2O3/Ag 3.0 wt% nanocomposite is cheap, and easy to make and process, imparting high perspectives for real applications in breath analyzers and/or sensors in food and beverage industries. This work contributes to the advance of gas sensing at ambient temperature as a competitive alternative for quantification of conventional volatile organic compounds.

Polarization, migration, and homotypical interactions among prostatic smooth muscle cells in a laminin 111-rich extracellular matrix.

Prostate cancer is a life-threatening condition worldwide. As the tumor progresses, smooth muscle cells (SMCs) become atrophic/dedifferentiated, within a series of stromal changes named stromal reaction. Here, we tested whether a laminin 111-rich extracellular matrix (Lr-ECM) could affect SMCs phenotype and differentiation status. Using time-lapse microscopy, image analyses, quantitative real-time reverse transcription polymerase chain reaction, immunohistochemistry and immunoblotting, and transmission electron microscopy, we showed that SMCs acquires a migratory behavior with a decreased expression of differentiation markers and relocation of focal adhesion kinase. SMCs set homotypic cell junctions and were active in autophagy/phagocytosis. Analysis of the migratory behavior showed that SMCs polarized and migrated toward each other, recognizing long-distance signals such as matrix tensioning. However, half of the cell population were immotile, irrespective of the nearest neighbor distance, suggesting they do not engage in productive interactions, possibly as a result of back-to-back positioning. In conclusion, the Lr-ECM, mimics the effects of the proliferating and infiltrating tumor epithelium, causing SMCs phenotypical change similar to that observed in the stromal reaction, in addition to a hitherto undescribed, stereotyped pattern of cell motility resulting from cell polarization.

Limited Renal Intravascular Lymphoma: A Case Report and Review of the Literature.

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of non-Hodgkin lymphoma. It is characterized by the proliferation of cancerous cells into the intraluminal space of the blood vessels. It has a low incidence rate of 0.095 cases per 1,000,000. The clinical presentation is insidious and unspecific, often delaying the diagnosis. IVLBCL can be diagnosed through body images and histopathology analysis. This neoplasm averages a 60% response rate to current chemotherapy treatment, favoring rituximab, and doxorubicin-based regimen if it is diagnosed in time. Here, we present the case of a 56-year-old man admitted to our hospital with a fever who was eventually diagnosed with IVLBCL. He presented to the consultation with anemia, fever, and splenomegaly. An infection panel, a bone marrow biopsy, and a PET-CT scan were performed and ruled out the possibility of infections and neoplasms. The patient later developed edematous syndrome. As a result, a renal biopsy was performed which tested positive for intravascular large B-cell lymphoma. Currently, the patient has been in complete remission for 33 months. Along with presenting this specific case, we also reviewed previously published cases of IVLBCL to illustrate the renal involvement of this pathology.

Genome sequencing of three bacteria associated to black band disease from a Colombian reef-building coral.

We announce the draft genome sequence of three Gram-negative bacteria isolated from coral tissues affected with the black band disease (BBD), identified with the NCBI's Assembly Database accession numbers: MBQF, MAYB and MBQE. These genome drafts constitute an useful tool for the characterisation of these bacteria and for the understanding of the relationship between the microbial consortia associated with the disease and the onset and progression of the pathology.

L-Type Calcium Channels Modulation by Estradiol.

Voltage-gated calcium channels are key regulators of brain function, and their dysfunction has been associated with multiple conditions and neurodegenerative diseases because they couple membrane depolarization to the influx of calcium-and other processes such as gene expression-in excitable cells. L-type calcium channels, one of the three major classes and probably the best characterized of the voltage-gated calcium channels, act as an essential calcium binding proteins with a significant biological relevance. It is well known that estradiol can activate rapidly brain signaling pathways and modulatory/regulatory proteins through non-genomic (or non-transcriptional) mechanisms, which lead to an increase of intracellular calcium that activate multiple kinases and signaling cascades, in the same way as L-type calcium channels responses. In this context, estrogens-L-type calcium channels signaling raises intracellular calcium levels and activates the same signaling cascades in the brain probably through estrogen receptor-independent modulatory mechanisms. In this review, we discuss the available literature on this area, which seems to suggest that estradiol exerts dual effects/modulation on these channels in a concentration-dependent manner (as a potentiator of these channels in pM concentrations and as an inhibitor in nM concentrations). Indeed, estradiol may orchestrate multiple neurotrophic responses, which open a new avenue for the development of novel estrogen-based therapies to alleviate different neuropathologies. We also highlight that it is essential to determine through computational and/or experimental approaches the interaction between estradiol and L-type calcium channels to assist these developments, which is an interesting area of research that deserves a closer look in future biomedical research.

Estudio de biodisponibilidad de metformina 850 mg tabletas de liberación inmediata / Bioavalability study of Metformin 850 mg immediate-release tablets

Se desarrolló un estudio de biodisponibilidad de metformina 850 mg tabletas recubiertas de liberación inmediata elaboradas por Laboratorios Coaspharma S.A., en 12 voluntarios sanos de ambos sexos, con edades entre 18 y 26 años. Para llevarlo a cabo se validó previamente un método bioanalítico para la determinación de metformina en plasma humano por cromatografía líquida de alta resolución con detector ultravioleta (HPLC-UV), el cual resultó ser selectivo, específico, lineal, exacto y preciso, por lo tanto adecuado para el análisis de las muestras. Estas fueron recolectadas periódicamente en un lapso desde 0 a 24 horas, luego de la administración por vía oral de una única dosis de metformina 850 mg. Posteriormente se determinaron los parámetros farmacocinéticos promedio de los 12 participantes, obteniendo: área bajo la curva, desde tiempo cero hasta el último tiempo de muestreo t (AUC0--->t) 6856,89 ± 2073,8 ng.h/ml, área bajo la curva desde tiempo cero hasta tiempo infinito (AUC0--->∞) 7083,74 ± 2131,52 ng.h/ml, concentración máxima (Cmaxmax) 1299,02 ± 291,90 ng/ml, tiempo máximo (t) 2,33 ± 0,47 h, tiempo de vida media (t1/2) 2,50 ± 0,84 h y constante aparente de eliminación (Ke) de 0,31 ± 0,12 h-1. Los resultados fueron similares en todos los participantes y no se produjeron reacciones adversas.

A bioavailability study was conducted in 12 healthy volunteers of both genders, aged between 18 and 26. Previous to the study, a bioanalytical method for determination of metformin in human plasma by high performance liquid chromatography with ultraviolet detector (HPLCUV) was validated, and proved to be selective, specific, linear, accurate precise, and therefore, suitable for analysis in plasma. Samples were collected from 0 to 24 hours after the oral administration of a single dose of metformin 850 mg immediate-release coated tablets, produced by Coaspharma S.A. Laboratories. Then, average pharmacokinetic parameters of the twelve volunteers were determined: area under the curve from time zero to last sampling time t (AUC0--->t) 6856.89 ± 2073.8 ng.h/mL, area under the curve from time zero to infinite time (AUC0--->∞) 7083.74 ± 2131.52 ng.h/ml, maximum concentration (Cmax) 1299.02 ± 291.90 ng/mL, maximum time (t max) 2.33 ± 0.47 h, half-life (t1/2) 2.50 ± 0.84 h and apparent elimination constant (Ke) of 0.31 ± 0.12 h-1. These results are similar between the volunteers and no adverse effect was observed. Also, the results are in agree with those reported in literature.

UV photoreceptors and UV-yellow wing pigments in Heliconius butterflies allow a color signal to serve both mimicry and intraspecific communication.

Mimetic wing coloration evolves in butterflies in the context of predator confusion. Unless butterfly eyes have adaptations for discriminating mimetic color variation, mimicry also carries a risk of confusion for the butterflies themselves. Heliconius butterfly eyes, which express recently duplicated ultraviolet (UV) opsins, have such an adaptation. To examine bird and butterfly color vision as sources of selection on butterfly coloration, we studied yellow wing pigmentation in the tribe Heliconiini. We confirmed, using reflectance and mass spectrometry, that only Heliconius use 3-hydroxy-DL-kynurenine (3-OHK), which looks yellow to humans but reflects both UV- and long-wavelength light, whereas butterflies in related genera have chemically unknown yellow pigments mostly lacking UV reflectance. Modeling of these color signals reveals that the two UV photoreceptors of Heliconius are better suited to separating 3-OHK from non-3-OHK spectra compared with the photoreceptors of related genera or birds. The co-occurrence of potentially enhanced UV vision and a UV-reflecting yellow wing pigment could allow unpalatable Heliconius private intraspecific communication in the presence of mimics. Our results are the best available evidence for the correlated evolution of a color signal and color vision. They also suggest that predator visual systems are error prone in the context of mimicry.

Evaluation of Fournier's necrosis in a high complexity hospital.

OBJECTIVES: To determine clinical characteristics of the population with Fournier's necrosis at Hospital Universitario del Valle (HUV) in Cali during the period 2003-2008. METHODS: We performed a retrospective review of patients with the diagnosis of Fournier's necrosis at HUV during the period 2003-2008. We collected information on age,personal history, duration of illness, hospitalization, surgeries performed, time to surgical treatment, isolated germs, and mortality. Univariate descriptive analysis was performed in STATA v 10.1. RESULTS: 42 patients with mean age 51 years and 12 days mean disease duration. 26% had diabetes mellitus and 21.4% urethral trauma before admission. Average time to surgical debridement was 41.4 hours. 62% required suprapubic cystostomy, 14.3% derivative colostomy, 9.5% and 2.4% orchiectomy and penectomy respectively. The average hospital stay was 23 days and 12% required ICU care. Scrotal cultures were positive in 59.5%: 64% a single germ and 36% polymicrobial. Reported mortality was 17%. CONCLUSION: Fournier's necrosis is a life-threatening clinical entity in patients with multiple comorbidities requiring multiple interventions. Broad-spectrum antimicrobial therapy, aggressive debridement of necrotic tissue and comprehensive management of these patients are the mainstays in the treatment of these severely ill patients.

Spatial components of bird diversity in the Andes of Colombia: implications for designing a regional reserve system.

Beta diversity, or the turnover in species composition among sampling sites in a region, is an important criterion for obtaining adequate representation of regional biodiversity in systems of protected areas. Recently, the additive model for partitioning regional (gamma) diversity (in opposition to the multiplicative model) has been proposed because it allows a direct measure of the contribution of beta diversity to gamma diversity. We determined avian beta diversity along latitudinal (among neighboring river drainages) and elevational axes in a 1347-km2 region on the western slope of the Central Cordillera of the Colombian Andes, where a regional system of protected areas is being designed. We then compared avian beta diversity between sites based on rapid versus long-term (>1 year) inventories and between fragmented sites versus continuous forest. Overall, beta diversity represented 63.1% of gamma diversity among 16 sites. Elevational differences in species composition accounted for 43.3% of regional diversity, whereas differences among drainages accounted for 19.8%. A complementary cluster analysis showed that sites grouped by elevational zones. Rapid inventories overestimated beta diversity because of sampling effects, but the effect was biologically small. Estimators of species richness derived from species accumulation curves provided a useful alternative to compensate for undersampling in short-term surveys. Forest fragmentation increased beta diversity because of differential local extinction of populations. Nevertheless, in our region, forest fragments contributed to gamma diversity because they contained complementary sets of species. More importantly, they contained populations of special-interest species. Although the region is relatively small, our analyses indicate that spatial differentiation of the biota is an important factor for deciding number and location of protected areas in the Andean region.

Wine distillates: practical operating recipe formulation for stills.

Consumer perceptions of flavors are associated with the chemical composition of foods. However, consumer preferences change; therefore, it is necessary for food manufacturers to be able to adapt their products. Unlike in aged spirits, the chemical composition of young spirits is determined during distillation; therefore, this is where distillers must tailor their operating recipes to the new trends. Even for an experienced distiller, the complexity of the process makes adapting the operating recipe far from straightforward. In this study, we developed a methodology for generating practical recipes that makes use of computer simulations and optimization techniques. We used Pisco Brandy, a young Muscat wine distillate from Chile and Peru as our case study. Even so, because our methodology is independent of the chemical composition of the broth, it can be applied throughout the industry. Drawing on the experience and preferences of industry enologists, we designed a preferred distillate and used our methodology to obtain the appropriate recipe. This recipe was validated in lab scale experiments, and we obtained a much closer distillate to the desired prescription than commercial products.

Effect of polymorphic colour vision for fruit detection in the spider monkey Ateles geoffroyi, and its implications for the maintenance of polymorphic colour vision in platyrrhine monkeys.

Most platyrrhine monkeys have an X-linked tri-allelic polymorphism for medium and long wavelength (M/L) sensitive cone photopigments. These pigments' sensitivity maxima (lambdamax) range from 535 to 562 nm. All animals also have an autosomally coded short-wavelength-sensitive (S) cone pigment. In populations with three M/L alleles there are six different colour vision phenotypes. Heterozygous females have trichromatic colour vision, while males and homozygous females are dichromats. The selective basis for this polymorphism is not understood, but is probably affected by the costs and benefits of trichromatic compared to dichromatic colour vision. For example, it has been suggested that trichromats are better equipped than dichromats to detect fruit against a leaf background. To investigate this possibility, we modeled fruit detection by various colour vision phenotypes present in the frugivorous spider monkey, Ateles geoffroyi. Our study population is thought to have three M/L alleles with cone pigment lambdamax values close to 535, 550 and 562 nm. The model predicted that all trichromat phenotypes had an advantage over dichromats, and the 535/562 nm phenotype was best; however, the model predicted that dichromats could detect all of the fruit species consumed by spider monkeys. We conclude that the heterozygote advantage experienced by females may be the most plausible explanation for the maintenance of this polymorphism in A. geoffroyi. Nevertheless, more studies need to evaluate social foraging behaviour and the performance of different phenotypes of other New World monkeys to determine if this is a global explanation for this phenomena or more specific to A. geofforyi.

The effect of colour vision status on the detection and selection of fruits by tamarins (Saguinus spp.).

The evolution of trichromatic colour vision by the majority of anthropoid primates has been linked to the efficient detection and selection of food, particularly ripe fruits among leaves in dappled light. Modelling of visual signals has shown that trichromats should be more efficient than dichromats at distinguishing both fruits from leaves and ripe from unripe fruits. This prediction is tested in a controlled captive setting using stimuli recreated from those actually encountered by wild tamarins (Saguinus spp.). Dietary data and reflectance spectra of Abuta fluminum fruits eaten by wild saddleback (Saguinus fuscicollis) and moustached (Saguinus mystax) tamarins and their associated leaves were collected in Peru. A. fluminum leaves, and fruits in three stages of ripeness, were reproduced and presented to captive saddleback and red-bellied tamarins (Saguinus labiatus). Trichromats were quicker to learn the task and were more efficient at selecting ripe fruits than were dichromats. This is the first time that a trichromatic foraging advantage has been demonstrated for monkeys using naturalistic stimuli with the same chromatic properties as those encountered by wild animals.