Inhibition of mitochondrial fission by Drp-1 blockade by short-term leptin and Mdivi-1 treatment improves white adipose tissue abnormalities in obesity and diabetes.

BACKGROUND: Obesity and type 2 diabetes are chronic diseases characterized by insulin resistance, mitochondrial dysfunction and morphological abnormalities. OBJECTIVE: We have investigated if dysregulation of mitochondrial dynamics and biogenesis is involved in an animal model of obesity and diabetes. METHODS: The effect of short-term leptin and mdivi-1 - a selective inhibitor of Drp-1 fission-protein - treatment on mitochondrial dynamics and biogenesis was evaluated in epididymal white adipose tissue (WAT) from male ob/ob mice. RESULTS: An increase in Drp-1 protein levels and a decrease in Mfn2 and OPA-1 protein expression were observed with enhanced and sustained mitochondrial fragmentation in ob/ob mice compared to wt C57BL/6 animals (p < 0.05). The content of mitochondrial DNA and PGC-1α mRNA expression -both parameters of mitochondrial biogenesis- were reduced in ob/ob mice (p < 0.05). Treatment with leptin and mdivi-1 significantly increased mitochondrial biogenesis, improved fusion-to-fission balance and attenuated mitochondrial dysfunction, thus inducing white-to-beige adipocyte transdifferentiation. Measurements of glucose and lipid oxidation in adipocytes revealed that both leptin and mdivi-1 increase substrates oxidation while in vivo determination of blood glucose concentration showed decreased levels by 50% in ob/ob mice, almost to the wt level. CONCLUSIONS: Pharmacological targeting of Drp-1 fission protein may be a potential novel therapeutic tool for obesity and type 2 diabetes.

Processing methods for human amniotic membrane as scaffold for tissue engineering with mesenchymal stromal human cells.

Tissue engineering is an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function. The aims of this work were to compare chemically and physically processed human Amniotic Membranes (hAM) and analyze the cytocompatibility and proliferation rate (PR) of two primary human mesenchymal stromal cell lines, from different sources and donor conditions seeded over these scaffolds. The evaluated hAM processes were: cold shock to obtain a frozen amniotic membrane (FEAM) with remaining dead epithelial cells, denudation of hAM with trypsin for 20/10 min (DEAM20/10) or treatment with sodium dodecyl sulfate to decellularized hAM (DAM). All samples were sterilized with gamma radiation. The selection of the treated hAM to then generate composites was performed by scanning and transmission electron microscopy and characterization by X-ray diffraction, selecting DEAM10 and FEAM as scaffolds for cell seeding. Two sources of primary human stromal cells were used, both developed by our researchers, human Dental Pulp Stem Cells (hDPSC) from living donors and human Mesenchymal Stromal Cells (hMSC) from bone marrow isolated from brain dead donors. This last line of cells conveys a novel source of human cells that, to our knowledge, have not been tested as part of this type of construct. We developed four in vitro constructs without cytotoxicity signs and with different PR depending on the scaffolds and cells. hDPSC and hMSC grew over both FEAM and DEAM10, but DEAM10 allowed higher PR.

Cochlear morphometry in healthy ears of a mexican population: A comparison of measurement techniques.

OBJECTIVE: This study describes the cochlear morphometry of a mexican population analysed by laterality and sex. The objective is to compare Cochlear Length (CL) evaluation between Alexiades et al. formula and manual method described by Würfel et al. PATIENTS: Hispanic patients from Mexico, with an age of 18 years or older, were included. Morphometric examination was performed retrospectively on 200 subjects who underwent previously temporal bone imaging for clinical purposes. MATERIALS AND METHODS: Horos for Mac program was used to measure CL, cochlear height, distance A, and distance B. WorkStation AW Volume Share 2 was used to obtain volume. CL was measured in 400 temporal bones (228 females, 172 males). RESULTS: The mean CL was 34.02mm±2.15mm. A significant difference was found in all variables between sex (P=≤0.05) and laterality (P=≤0.05). The Alexiades equation was used for determining CL and compared with the manual formula, with no significant differences (κ=0.71). However, the time consumption was 5 times faster with the calculated method. The Alexiades formula was demonstrated to be a reliable method measurement. CONCLUSION: Preoperative Computed Tomography evaluation of the internal ear helps to plan the Cochlear Implants (CI) surgical approach and allows to choose an appropriate electrode length for each necessity. Our findings may be useful to facilitate and adapt preoperative management of CI surgery by considering the characteristics of cochlear morphology of Latin-American populations.

Folliculotropic Mycosis Fungoides in a Latin American Hospital: Survival Analysis. / Análisis de supervivencia en pacientes con micosis fungoide foliculotropa de un centro latinoamericano.

INTRODUCTION: Folliculotropic mycosis fungoides is a variant that has poor prognosis and a variable clinical presentation. Concerns have been expressed that the current TNMB staging of this tumor may not be useful. A recently developed classification system based on clinical and histologic variables classifies this tumor as early or advanced, a distinction found to correlate with prognosis. The aim of this study was to compare survival in FMF in Colombia between patients with early versus advanced tumors. MATERIAL AND METHODS: Retrospective, observational study of clinical course and outcomes in patients with FMF treated at the National Cancer Institute of Colombia between 2008 and 2020. Survival was compared between early and advanced disease. RESULTS: Twenty-one patients (11 with early FMF and 10 with advanced FMF) were studied. Seven patients, all with advanced disease, died. Survival at 5 years was 62% overall and 40% for patients with advanced FMF. No differences were observed when survival was analyzed according to TNMB stage. CONCLUSIONS: TNMB staging is not useful in FMF. The new classification system based on clinicopathologic features appears to provide reliable information for assessing prognosis and guiding treatment decisions.

Modulation of Interfacial Hydration by Carbonyl Groups in Lipid Membranes.

The lack of carbonyl groups and the presence of ether bonds give the lipid interphase a different water organization around the phosphate groups that affects the compressibility and electrical properties of lipid membranes. Generalized polarization of 1,2-di-O-tetradecyl-sn-glycero-3-phosphocholine (14:0 diether PC) in correlation with Fourier transform infrared (FTIR) analysis indicates a higher level of polarizability of water molecules in the membrane phase around the phosphate groups both below and above Tm. This reorganization of water promotes a different response in compressibility and dipole moment of the interphase, which is related to different H bonding of water molecules with phosphates (PO) and carbonyl (CO) groups.

[The medical act in the era of telemedicine]. / El acto médico en la era de la telemedicina.

Telemedicine partially resolved inequalities in access to health care, especially in geographical areas with a low number of doctors and in places with absent or insufficient specialists. Currently, Chile has a National Telehealth Program, but there are no specific laws on digital medicine that recognize remote medical acts and it is uncertain if they really are medical acts. The goal of a medical act is the well-being of a patient, requiring a therapeutic alliance based on the doctor's knowledge of the needs, expectations and fears of such a patient. This article tries to determine if patient care by telemedicine can be considered a medical act. For this purpose, the conception of a medical act defined by P. Laín Entralgo, M. Besio and the main medical and professional associations is analyzed in depth. It is concluded that although direct physical contact between doctor and patient largely supports the therapeutic alliance, telemedicine has been successful, particularly in its synchronous modality. Taking the necessary precautions, in most cases distant medical acts can be carried out allowing a humanized and respectful care of people.

Diabetes, undernutrition, migration and indigenous communities: tuberculosis in Chiapas, Mexico.

We investigated the distribution of comorbidities among adult tuberculosis (TB) patients in Chiapas, the poorest Mexican state, with a high presence of indigenous population, and a corridor for migrants from Latin America. Secondary analysis on 5508 new adult TB patients diagnosed between 2010 and 2014 revealed that the most prevalent comorbidities were diabetes mellitus (DM; 19.1%) and undernutrition (14.4%). The prevalence of DM in these TB patients was significantly higher among middle aged (41-64 years) compared with older adults (⩾65 years) (38.6% vs. 23.2%; P < 0.0001). The prevalence of undernutrition was lower among those with DM, and higher in communities with high indigenous presence. Immigrants only comprised 2% of all TB cases, but were more likely to have unfavourable TB treatment outcomes (treatment failure, death and default) when compared with those born in Chiapas (29.5% vs. 11.1%; P < 0.05). Unfavourable TB outcomes were also more prevalent among the TB patients with undernutrition, HIV or older age, but not DM (P < 0.05). Our study in Chiapas illustrates the challenges of other regions worldwide where social (e.g. indigenous origin, poverty, migration) and host factors (DM, undernutrition, HIV, older age) are associated with TB. Further understanding of these critical factors will guide local policy makers and health providers to improve TB management.

Fiber-optic vectorial magnetic-field gradiometry by a spatiotemporal differential optical detection of magnetic resonance in nitrogen-vacancy centers in diamond.

Highly sensitive room-temperature vectorial magnetic-field gradiometry is demonstrated using optically detected magnetic resonance (ODMR) in fiber-coupled nitrogen-vacancy (NV) centers in diamond. With a bulk NV-diamond magnetometer coupled to a pair of optical fibers integrated with a microwave transmission line, the differential ODMR measurements are implemented in both space and time, with magnetic-field gradient measurements supplemented with differential ODMR signal detection in the time domain, allowing efficient noise cancellation and providing a sensitivity of magnetogradiometry at the level of 10-7 nT/(nmHz1/2).

Allosteric reversion of Haemophilus influenzae ß-carbonic anhydrase via a proline shift.

Haemophilus influenzae ß-carbonic anhydrase (HICA) has been reverse-engineered in the allosteric site region to resemble the nonallosteric Pisum sativum enzyme in order to identify critical features of allostery and intersusbunit communication. Three variants (W39V/G41A, P48S/A49P, and W39V/G41A/P48S/A49P) were identified, through a comparison with a crystal structure of nonallosteric P. sativum ß-carbonic anhydrase (PSCA, PDB 1EKJ ), to potentially revert HICA to a nonallosteric enzyme. The W39V/G41A and P48S/A49P mutations decreased the apparent kcat/Km proton dependence from 4 to 2 and 1, respectively, increasing the overall maximal kcat/Km to 16 ± 2 µM(-1) s(-1) (380% of wild type) and 17 ± 3 µM(-1) s(-1) (405% of wild type). The pKa values of the metal-bound water molecule based on the pH-rate profile kinetics (8.32 ± 0.04 for W39V/G41A and 8.3 ± 0.1 for P48S/A49P) were also slightly higher than that for the wild-type enzyme (7.74 ± 0.04). The P48S/A49P variant has lost all pH-rate cooperativity. The W39V/G41A/P48S/A49P variant's kinetics were unusual and were fit with a log-linear function with a slope 0.9 ± 0.2. The crystal structure of the W39V/G41A variant revealed an active site very similar to the T-state wild-type oligomer with bicarbonate trapped in the escort site. By contrast, the X-ray crystal structure of a proline shift variant (P48S/A49P) reveals that it has adopted an active site conformation nearly identical to that of nonallosteric ß-carbonic anhydrase (R-state) for one chain, including a tight association with the dimer-exchanged N-terminal helices; the second chain in the asymmetric unit is associated in a biologically relevant oligomer, but it adopts a T-state conformation that is not capped by dimer-exchanged N-terminal helices. The hybrid R/T nature of HICA P48S/A49P structurally recapitulates the interruption of pH-rate cooperativity observed for this variant. Comparison of the conformations of the R and T chains of P48S/A49P suggests a new hypothesis to explain HICA allosteric communication that is mediated by the N-terminal helices and anion binding at the dimer interface.

Cognition, structural brain changes and complicated grief. A population-based study.

BACKGROUND: Several psychosocial risk factors for complicated grief have been described. However, the association of complicated grief with cognitive and biological risk factors is unclear. The present study examined whether complicated grief and normal grief are related to cognitive performance or structural brain volumes in a large population-based study. METHOD: The present research comprised cross-sectional analyses embedded in the Rotterdam Study. The study included 5501 non-demented persons. Participants were classified as experiencing no grief (n = 4731), normal grief (n = 615) or complicated grief (n = 155) as assessed with the Inventory of Complicated Grief. All persons underwent cognitive testing (Mini-Mental State Examination, Letter-Digit Substitution Test, Stroop Test, Word Fluency Task, word learning test - immediate and delayed recall), and magnetic resonance imaging to measure general brain parameters (white matter, gray matter), and white matter lesions. Total brain volume was defined as the sum of gray matter plus normal white matter and white matter lesion volume. Persons with depressive disorders were excluded and analyses were adjusted for depressive symptoms. RESULTS: Compared with no-grief participants, participants with complicated grief had lower scores for the Letter-Digit Substitution Test [Z-score -0.16 v. 0.04, 95% confidence interval (CI) -0.36 to -0.04, p = 0.01] and Word Fluency Task (Z-score -0.15 v. 0.03, 95% CI -0.35 to -0.02, p = 0.02) and smaller total volumes of brain matter (933.53 ml v. 952.42 ml, 95% CI -37.6 to -0.10, p = 0.04). CONCLUSIONS: Participants with complicated grief performed poorly in cognitive tests and had a smaller total brain volume. Although the effect sizes were small, these findings suggest that there may be a neurological correlate of complicated grief, but not of normal grief, in the general population.

Leishmania infantum in wild rodents: reservoirs or just irrelevant incidental hosts?

Wild rodents constitute a very large biomass of potential reservoirs for Leishmania spp. Therefore, an epidemiological study was carried out in a well-known focus of canine leishmaniasis from southern Spain, with the objective of detecting and characterizing Leishmania infantum infection in wild rodents. Blood, liver, spleen, bone marrow, and skin from 37 rodents (24 Apodemus sylvaticus, 9 Rattus rattus, and 4 Mus musculus) were analyzed by optical microscopy, culture, and two different polymerase chain reactions. L. infantum DNA was found in 27% (10 out of 37) of the trapped rodents, in a variety of tissues: bone marrow, spleen, or healthy skin (ear lobe). High prevalences of L. infantum infection were found in the three investigated rodent species. The presence of other trypanosomatids was also evidenced. These rodent species are abundant, widely distributed in Europe, and have a long enough lifespan to overcome the low sandfly activity season. They live in a suitable habitat for sandflies and serve as blood sources for these insects, which can become infected when induced to feed on Leishmania-infected animals. Whether they are reservoirs or just irrelevant incidental hosts, it is clear that the epidemiology of L. infantum is more complex than previously thought, and so is its control. The classic epidemiological cycle dog-sandfly-human is turning into a network of animal species that collaborate with the dog in the maintenance of the parasite under natural conditions and probably showing local differences.

[Students' perceptions comparing standardized and non-standardized oral exams in internal medicine]. / Percepción de examen oral estandarizado vs no estandarizado en el internado de medicina interna.

BACKGROUND: Oral examinations are a useful tool to appraise certain medical skills compared to other examinations. However, they have some disadvantages that might be reduced with standardization. AIM: To compare students' perception comparing a standardized oral exam (SOE) versus a traditional, non-standardized oral exam (NSOE). MATERIAL AND METHODS: During the first semester of 2013 a NSOE was applied to internal medicine undergraduate students. During the second semester, a SOE was applied. An anonymous and voluntary perception questionnaire, consisting in 10 questions based on a 5-level Likert scale, was answered by these students. Statistical analysis was done using the Mann-Whitney U test. RESULTS: Among the 118 students, 50.8% were evaluated using NSOE and 49.2% using SOE. Questionnaire response rate was 84%. Among respondents, 52% took the SOE and 48%, the NSOE. Students evaluated using SOE perceived that the degree of complexity of clinical cases was similar for all examinees (p < 0.05), that exam duration was standardized (p < 0.05), and that grades obtained were less influenced by the clinical site where the exam was taken (p < 0.05). However, anxiety level remained high in both groups, as well as the overall satisfaction experience. CONCLUSIONS: Standardization of an oral examination improves the perception of medical students about levels of difficulty, duration and external influences on the final grade.

Fiber-optic magnetometry with randomly oriented spins.

We demonstrate fiber-optic magnetometry using a random ensemble of nitrogen-vacancy (NV) centers in nanodiamond coupled to a tapered optical fiber, which provides a waveguide delivery of optical fields for the initialization, polarization, and readout of the electron spin in NV centers.

The effect of vertical sleeve gastrectomy on food choice in rats.

OBJECTIVE: Diets high in fat are implicated in the development and maintenance of obesity, and obese individuals display greater preferences for high-fat foods than do their lean counterparts. Weight-reduction bariatric surgery is associated with changes in food choice. In particular, after Roux-en-Y gastric bypass (RYGB), humans and rodents select or prefer foods that are lower in fat content. We asked whether a bariatric surgical procedure limited to the stomach, vertical sleeve gastrectomy (VSG), causes a similar reduction of fat intake/preference. RESEARCH DESIGN AND METHODS: Rats received VSG or Sham surgery or remained surgically naïve, and were assessed for food preference using three diet-choice paradigms. Using progressive-ratio (PR) and conditioned taste aversion paradigms, we further asked whether surgically induced changes in food choice are secondary to changes in the reward value of food and/or to the formation of a food aversion. Finally, food choice was compared between VSG- and RYGB-operated rats. RESULTS: VSG rats decreased their intake of dietary fat, and shifted their preference toward lower caloric-density foods. This change in food choice was not associated with changes in motivated responding on a PR schedule for either a fat or a carbohydrate food reinforcer. When VSG and RYGB were compared directly, both procedures caused comparable changes in food choice. The conditioned taste aversion paradigm revealed that VSG rats form an aversion to an intra-gastric oil administration whereas RYGB rats do not. CONCLUSIONS: VSG and RYGB, two anatomically distinct bariatric procedures, produce similar changes in food choice.

Thyroid nodules in Hispanic patients with systemic lupus erythematosus.

A thyroid nodule (TN) is a discrete lesion in the thyroid gland radiologically distinct from the adjacent parenchyma, with a prevalence variable depending on the diagnostic method used and the study population. Thyroid disorders have been identified in more than 50% of patients with systemic lupus erythematosus (SLE); however, the prevalence of TN has not been frequently studied. We identified a prevalence of 27% TN in 55 SLE patients > 16 years of age. One-third of TN were >1 cm with radiological features of malignancy. The mean age of patients with TN was 39 ± 11 years, 93% women, and SLE duration 10 ± 6 years. Among patients, we reported family history of cancer in three cases (20%), thyroid disease in one (7%), and autoimmune disease in six (40%). Regarding treatment, 50% of patients with TN were treated with azathioprine vs. 23% of patients without TN (p = 0.02), with an OR of 3.94 (95% CI 1.12-13.84, p = 0.03). As a conclusion a high prevalence of TN in SLE patients was found. Prevalence of TN correlated only with history of azathioprine use. We don't know the long-term implications of our findings; however, a functional and morphological evaluation of the thyroid gland is warranted in all patients with SLE.

Auditory steady state response in sound field.

OBJECTIVE: Physiological and behavioral responses were compared in normal-hearing subjects via analyses of the auditory steady-state response (ASSR) and conventional audiometry under sound field conditions. DESIGN: The auditory stimuli, presented through a loudspeaker, consisted of four carrier tones (500, 1000, 2000, and 4000 Hz), presented singly for behavioral testing but combined (multiple frequency technique), to estimate thresholds using the ASSR. STUDY SAMPLE: Twenty normal-hearing adults were examined. RESULTS: The average differences between the physiological and behavioral thresholds were between 17 and 22 dB HL. The Spearman rank correlation between ASSR and behavioral thresholds was significant for all frequencies (p < 0.05). Significant differences were found in the ASSR amplitude among frequencies, and strong correlations between the ASSR amplitude and the stimulus level (p < 0.05). CONCLUSIONS: The ASSR in sound field testing was found to yield hearing threshold estimates deemed to be reasonably well correlated with behaviorally assessed thresholds.

Central nervous system: a modified immune surveillance circuit?

Immune surveillance in the central nervous system (CNS) was considered impossible because: (i) the brain parenchyma is separated from the blood circulation by the blood-brain barrier (BBB); (ii) the brain lacks lymphatic drainage and (iii) the brain displays low major histocompatibility complex class II (MHCII) expression. In this context, the BBB prevents entry of immune molecules and effector cells to the CNS. The absence of lymphatic vessels avoids CNS antigens from reaching the lymph nodes for lymphocyte presentation and activation. Finally, the low MHCII expression hinders effective antigen presentation and re-activation of T cells for a competent immune response. All these factors limit the effectiveness of the afferent and efferent arms necessary to carry out immune surveillance. Nevertheless, recent evidence supports that CNS is monitored by the immune system through a modified surveillance circuit; this work reviews these findings.

Epizootic myocarditis associated with encephalomyocarditis virus in a group of rhesus macaques (Macaca mulatta).

Six cases of fatal myocarditis associated with encephalomyocarditis virus occurred over a 14-month period in a group of outdoor-housed juvenile rhesus macaques. All animals were younger than 3 years of age and died or were euthanized following acute onset of dyspnea or pulmonary effusion (3 of 6) or were found dead without premonitory signs (3 of 6). Gross findings included pulmonary congestion (6 of 6), variable degrees of pleural effusion (4 of 6), multifocal pale tan foci throughout the myocardium (3 of 6), hepatomegaly and hepatic congestion (3 of 6), and pericardial effusion (1 of 6). Histologically, affected myocardium was infiltrated multifocally by lymphoplasmacytic and histiocytic inflammation admixed with necrotic and degenerate myofibers and infrequent mineralization (6 of 6). Pulmonary edema was present in all animals. Encephalomyocarditis virus was confirmed in 6 of 6 hearts by immunohistochemistry, and virus was isolated from one case by polymerase chain reaction. Sequencing of virus isolated from 1 affected animal indicated infection with a novel encephalomyocarditis virus. Encephalomyocarditis virus should be considered as a differential etiology in outbreaks of myocarditis and pulmonary edema in juvenile primates.

Morphological and reproductive variation among populations of the Pacific molly Poecilia butleri.

In viviparous organisms, pregnant females typically experience an increase in body mass and body volume. In this study, the prediction that variation in reproductive traits among populations of viviparous organisms should be related to variation among populations in body shape was tested in the Pacific molly Poecilia butleri, a viviparous fish that inhabits western Mexico and northern Central America. Variation among 10 populations in four reproductive traits was examined: brood size, individual embryo mass, total reproductive allotment and degree of maternal provisioning of nutrients to developing embryos. Variation among these populations in body shape was also examined. Significant variation among populations was observed in both brood size and reproductive allotment but not in embryo mass or degree of maternal provisioning. Significant variation among populations was also observed in body shape. After correcting for female size, however, reproductive traits and body shape were not associated among populations. This suggests that selective pressures acting on reproduction do not necessarily affect morphology and vice versa. Several factors might contribute to this unexpected lack of association between reproductive traits and morphology.