Effects of web-based adapted physical activity on hippocampal plasticity, cardiorespiratory fitness, symptoms, and cardiometabolic markers in patients with schizophrenia: a randomized, controlled study.

Among the lifestyle interventions, the physical activity (PA) has emerged as an adjuvant non-pharmacological treatment improving mental and physical health in patients with schizophrenia (SZPs) and increasing the hippocampus (HCP) volume. Previously investigated PA programs have been face-to-face, and not necessary adapted to patients' physiological fitness. We propose an innovative 16-week adapted PA program delivered by real-time videoconferencing (e-APA), allowing SZPs to interact with a coach and to manage their physical condition. The primary goal was to demonstrate a greater increase of total HCP volumes in SZPs receiving e-APA compared to that observed in a controlled group. The secondary objectives were to demonstrate the greater effects of e-APA compared to a controlled group on HCP subfields, cardiorespiratory fitness, clinical symptoms, cognitive functions, and lipidic profile. Thirty-five SZPs were randomized to either e-APA or a controlled group receiving a health education program under the same conditions (e-HE). Variables were assessed at pre- and post-intervention time-points. The dropout rate was 11.4%. Compared to the e-HE group, the e-APA group did not have any effect on the HCP total volumes but increased the left subiculum volume. Also, the e-APA group significantly increased cardiorespiratory fitness (VO2max), improved lipidic profile and negative symptoms but not cognitive functions. This study demonstrated the high feasibility and multiple benefits of a remote e-APA program for SZPs. e-APA may increase brain plasticity and improve health outcomes in SZPs, supporting that PA should be an add-on therapeutic intervention. ClinicalTrial.gov on 25 august 2017 (NCT03261817).

Evaluation of stress response in black-tailed prairie dogs (Cynomys ludovicianus) in arid regions from colonies in Chihuahua Mexico.

Among all the regulatory homeostatic networks in vertebrates, the activation of the hypothalamic-pituitaryadrenal axis during the stress response, has gained considerable attention, and the measurement of fecal glucocorticoids (FGC) has become an invaluable tool to assess adrenocortical activity related to stressful events in wild and captive animals. However, the use of FGC requires the validation of measurement techniques and the proper selection of the specific hormone according to the study species. The main objective of this study was to identify the dominant glucocorticoid (GC) hormone in the stress response of black-tailed prairie dogs (Cynomys ludovicianus) in an arid grassland of Chihuahua, Mexico. A capture stress challenge in the field was developed to determine if the levels of glucocorticoids (cortisol and corticosterone) both in serum and fecal samples could be attributed to stress in Cynomys ludovicianus. The samples were analysed with the technique of liquid phase radioimmunoassay , and this study showed that both cortisol and corticosterone are present at measurable levels in serum and fecal samples of black-tailed prairie dogs. We found that both GCs were present in similar concentrations in serum, however, corticosterone concentration in fecal samples was higher than cortisol. Likewise, biochemical validations performed in this study to test the assay reached acceptable levels of reliability. Therefore, we confirm that fecal analysis can be implemented as a method to measure stress responses in wild prairie dogs.

Mandibular Dysmorphology and Clinical Presentation in Treacher Collins Syndrome.

INTRODUCTION: Treacher Collins syndrome is a rare congenital disease characterized by the multiple craniofacial malformations. Although the deformities affecting patients with Treacher Collins syndrome have been well characterized, the effects of these malformations to clinical severity of the syndrome are not well understood. OBJECTIVE: To determine the association of specific Treacher Collins mandibular malformations with clinical severity. DESIGN: A retrospective radiographic observational study. SETTING: Study conducted at a single institution, a quaternary craniofacial care center. PATIENTS: 54 patients with Treacher Collins syndrome. INTERVENTIONS: Computed tomography (CT), clinical photographs and medical history were included in this analysis. Mandibles were isolated from CT data and reconstructed in three dimensions using Mimics software. Cephalometric measurements were performed on CT data. Clinical severity was determined by Teber and Vincent scores. Association of craniofacial dysmorphology to clinical severity was determined by Spearman rank coefficient. MAIN OUTCOME MEASURES: The main results obtained were the measurements of the mandibles and the quantification of the malformations of the evaluated patients. RESULTS: Among the most frequent findings in the sample are hypoplasia of the zygomatic complex, descending palpebral cleft and mandibular hypoplasia. Patients with a lower ramus/corpus ratio had a higher (more severe) Teber and Vincent classification. CONCLUSION: Patients with the most compromised mandible are also the patients with the highest number of malformations, thus, the most severe patients.

Pentoxifylline and tocopherol for the treatment of osteoradionecrosis of the jaws. A systematic review.

BACKGROUND: Osteoradionecrosis of the jaws (ORNJ) is a severe and challenging complication of head and neck radiation therapy. Despite its aggressiveness and controversy respect to its efficacy, surgical intervention remains the main treatment modality. Nevertheless, due to advances in the understanding of ORNJ physiopathology, new treatment alternatives such as the combination of pentoxifylline with tocopherol (PENTO) have emerged. The aim of this systematic review was to assess the reported efficacy of PENTO for the treatment of ORNJ.  Material and Methods: Studies were search using Pubmed, The Cochrane Library, Scopus, and Web of Science data bases following the PRISMA guidelines. Inclusion criteria were cohort, case series, randomized or non-randomized clinical studies published in English including human subjects who received PENTO as treatment for ORN of the jaws.  Results: Eleven articles met the inclusion criteria and were included for data analysis. All studies reported patients with complete mucosal coverage with no exposed bone (considered healthy) after PENTO treatment, ranging from 16.6% to 100% of the patients, depending on the study. Clinical improvement or disease stabilization was reported between 7.6% and 66.6% of studied individuals, while disease progression was seen in only 5 studies involving 7.6 - 32% of patients. CONCLUSIONS: PENTO treatment achieved a complete disease control in a significant number of patients in all studies. However, there is no standardized protocol for administering the therapy. It is necessary to determine the pharmacological doses and to evaluate the benefits of adding antibiotics and clodronate. Good quality clinical trials are needed to develop a successful algorithm for the management of ORN of the jaws.

Perineural invasion predicts poor survival and cervical lymph node metastasis in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) usually invades peripheral nerves through a process known as perineural invasion (PNI), recognized as an adverse factor considered for the administration of postoperative adjuvant therapy. The aim of this study was to assess the impact of PNI on survival and cervical lymph node metastasis in a cohort of OSCC patients. MATERIAL AND METHODS: Presence, location and extension of PNI were assessed in a cohort of 57 paraffin-embedded OSCC resections. Clinico-pathological variables were obtained from each case. Five-year overall survival (OS) and 5-year disease-specific survival (DSS) curves were constructed according to the Kaplan-Meier method and compared with log-rank test. The Cox proportional hazard model was used to assess the role of PNI as an independent risk factor related to poor survival, and a binary logistic regression was performed to estimate the predictive value of PNI for regional lymph node metastasis. RESULTS: PNI was observed in 49.1% of the cases, affecting only small nerves. Peritumoral PNI was the most common location, and multifocal PNI the most frequent extent. Most PNI positive cases had cervical metastasis (p=0.001), and PNI was more frequent in stages III-IV than in I-II (p=0.02). The five-year OS and the 5-year DSS decreased in PNI positive and peritumoral PNI cases. PNI was an independent risk factor for poor 5-year OS and poor 5-year DSS. The odds for cervical lymph node metastasis were of 6.076 (p=0.006) and 10.257 (p=0.007) for PNI and Tumor budding (TB) positive cases, respectively. CONCLUSIONS: PNI is a frequent finding in OSCC and an independent risk factor for poor OS and DSS. PNI and TB are both risk factors associated to an increased likelihood for the development of lymph node metastasis. Therefore, we suggest further investigations to test the combined PNI-TB scoring system in risk stratification models for OSCC.

Functional properties of cream from dairy cows with experimentally altered milk fat composition.

Modification of milk fat composition might be a desirable method to alter manufacturing characteristics or produce dairy products low in saturated fat that more closely meet consumer dietary preferences. The aim of this research was to evaluate functional properties of cream obtained from milks with fat composition modified by altering the profile of long-chain fatty acids (FA) absorbed from the intestine. A control and 5 mixtures of long-chain free FA were infused into the abomasum of lactating dairy cows in a 6 × 6 Latin square design with 21-d periods. Treatments were as follows: (1) control (no FA infused), (2) mostly saturated FA (C16:C18 = 0.74), (3) low linoleic palm FA (C16:C18 = 0.73), (4) palm FA (C16:C18 = 0.73), (5) soy FA (C16:C18 = 0.10), and (6) high palmitic soy FA (C16:C18 = 0.73). All treatments included meat solubles and Tween 80 as emulsifiers. Viscosity, overrun, whipping time, foam firmness, and foam stability were evaluated in creams (33% fat). Cream from cows infused with soy FA (treatment 5) had the longest whipping time and lowest overrun, foam stability, viscosity, melting point, firmness, and solid fat content at 5 and 20°C because the fat had the highest unsaturated FA content. Increasing palmitic acid content of soy FA (treatment 6) improved functional variables in cream relative to soy FA alone. Differences among treatments 1 to 4 were less pronounced because of the effect of C18:1 trans in treatments 3 and 4 on milk fat yield and composition. Milk fat from cows infused with palm FA (treatment 4) exhibited comparable or better functionality than control cream. Increased polyunsaturated FA in milk fat resulted in increased amounts of triglyceride (TG) fractions with 28, 30, 38, and 40 carbon numbers, increased oleic acid resulted in increased 50-carbon TG, and higher palmitic and myristic acids resulted in greater 44, 46, and 48 carbon number TG. These TG groups consistently correlated with functional properties of creams from different treatments. Our results indicated that optimal functionality of cream is dependent more on its content of palmitic acid than on unsaturated FA. However, an optimal composition of milk fat for cream functional characteristics might be obtained through nutritional manipulation of diets for dairy cows to deliver an optimal profile of FA.

Whey protein addition and its increased light absorption and tinctorial strength of model solutions colored with anthocyanins.

Anthocyanins (ACN) are pigments with vivid colors, but their application as food colorants is restricted by their limited stability and color expression. Anthocyanins exhibit higher stability in dairy systems than in buffers at similar pH, suggesting that pigments may be able to interact with dairy components such as proteins, resulting in improved performance as colorants. Our objective was to determine the type of interaction between whey proteins (WP) and ACN leading to color enhancements and to determine the role of the ACN chemical structure in this interaction. Model solutions colored with semipurified pigments from sources with different ACN profiles (Berberis boliviana, grape skin, purple corn, black carrot, and red cabbage) were mixed with different concentrations of whey protein isolate (WPI) in pH 3 buffer. Absorption spectra of these solutions were acquired using an absorbance microplate reader, and color parameters were calculated from spectral data. Isolated ACN 3-glucosides were used to determine the role of the aglycone structure in the WP-ACN interaction using visible and fluorescence spectroscopy. In silico modeling was used to visualize potential differences in the interaction between ß-lactoglobulin and ACN. Addition of WPI resulted in hyperchromic shifts at the wavelength of maximum absorption in the visible range (λvis-max) of up to 19%, and a significant increase in tinctorial strength for all ACN sources (ΔE > 5). Moreover, ACN acylation did not seem to play a significant role in the WP-ACN interaction. When using isolated ACN, WPI addition resulted in hyperchromic shifts at the λvis-max only for methoxylated ACN such as petunidin-3-glucoside (up to 24%), and malvidin-3-glucoside (up to 97%). The bimolecular quenching constant values (Kq > 1010M-1s-1) strongly suggested that the predominant type of quenching interaction was static. Analysis of enthalpy, entropy, and Gibbs free energy showed that this binding was spontaneous; depending on the chemical structure of the ACN, the predominant binding forces could be hydrophobic interactions or hydrogen bonding. Modeling suggested that methoxylations in the B ring of the aglycon structure promoted interactions with electron acceptor amino acids. Overall, WP could be used to enhance the tinctorial strength of select ACN depending on their structural characteristics. Therefore, ACN source selection may play a key role for specific applications in dairy products.

The prognostic value of quantitating and localizing F-18 FDG uptake in cardiac sarcoidosis.

BACKGROUND: There is no identified level of FDG uptake in cardiac sarcoidosis (CS) associated with increased risk of arrhythmias, conduction disease, heart failure, or death. We aim to utilize standardized uptake value (SUV) quantitation and localization to identify patients at increased risk of cardiac events. METHODS AND RESULTS: F18-FDG PET/CT with MPI was used in CS diagnosis (N = 67). Mean and max SUV were measured and grouped as basal, mid, and apical disease. Post-scan ventricular tachycardia, AICD placement, complete heart block, pacemaker placement, atrial fibrillation, heart failure, and cardiac-related hospital admissions were recorded (mean follow up 2.98 ± 2 years). Poisson regression analysis revealed that max SUV, mean SUV, as well as mean basal SUV, and LVEF were significantly associated with total cardiac events. Max SUV odds ratio (OR) = 1.068 (95% CI 1.024-1.114, P = 0.002), mean SUV OR = 1.059 (95% CI 1.008-1.113, P = 0.023), mean SUV OR = 1.061 (95% CI 1.012-1.112, P = 0.014), scan LVEF OR = 0.731 (95% CI 0.664-0.805, P < 0.001). CONCLUSIONS: SUV at time of CS diagnosis has significant associations with future cardiac events. Patients with higher SUV, particularly in basal segments, are at increased risk of events. Further studies are needed to identify treatment methods utilizing risk stratification of CS.

Survival outcome in severe left-sided congenital diaphragmatic hernia with and without fetal endoscopic tracheal occlusion in a country with suboptimal neonatal management.

OBJECTIVE: To evaluate the impact of fetal endoscopic tracheal occlusion (FETO) on improving survival of fetuses with severe left-sided congenital diaphragmatic hernia (CDH), as compared with contemporaneous cases managed expectantly during pregnancy, in a country with suboptimal neonatal management. METHODS: In this prospective cohort study, consecutive fetuses with isolated left-sided CDH, normal karyotype and severe pulmonary hypoplasia (defined as liver herniation and observed/expected lung-to-head circumference ratio below 26%) were selected for FETO at less than 32 weeks of gestation in a single tertiary referral center in Queretaro, Mexico. Postnatal outcome (survival up to 28 days after birth) was compared between fetuses treated with FETO and contemporaneous cases with similar lung size managed expectantly during pregnancy. RESULTS: Twenty-five fetuses with isolated severe left-sided CDH treated with FETO were matched individually with 25 cases managed expectantly during pregnancy. Endotracheal placement of the balloon was performed successfully on the first attempt in all cases. The median gestational age (GA) at balloon placement was 29.1 (range, 25.6-31.8) weeks and 34.1 (range, 30.0-36.1) weeks at balloon removal. There were no technical problems with the introduction or removal of the balloon in any cases. The median GA at delivery was significantly lower in the group treated with FETO than in those managed expectantly (35.3 vs 37.7 weeks; P = 0.04). The survival rate was significantly higher in the group treated with FETO than in those without fetal intervention (32% vs 0%; P < 0.001). CONCLUSION: In settings with suboptimal neonatal management, FETO was associated with improved neonatal survival in fetuses with isolated left-sided CDH and severe pulmonary hypoplasia. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Resultado de supervivencia en una hernia diafragmática congénita grave del lado izquierdo, con y sin oclusión traqueal endoscópica fetal en un país con un tratamiento neonatal subóptimo OBJETIVO: Evaluar el impacto de la oclusión traqueal endoscópica fetal (OTEF) en la mejora de la supervivencia de los fetos con hernia diafragmática congénita (HDC) grave del lado izquierdo, en comparación con los casos actuales tratados como embarazo gestante, en un país con un tratamiento neonatal subóptimo. MÉTODOS: En este estudio prospectivo de cohortes, se seleccionaron fetos consecutivos con HDC aislada del lado izquierdo, cariotipo normal e hipoplasia pulmonar grave (definida como hernia hepática y una proporción observada/esperada de la circunferencia pulmonar-cabeza inferior al 26%) para una OTEF antes de las 32 semanas de gestación, en un único centro de medicina especializada terciaria en Querétaro (México). El resultado postnatal (supervivencia hasta los 28 días después del nacimiento) se comparó entre fetos tratados con OTEF y los casos contemporáneos con tamaño pulmonar similar, tratados como embarazo gestante. RESULTADOS: Veinticinco fetos con HDC grave aislada del lado izquierdo que habían sido tratados con OTEF fueron emparejados individualmente con 25 casos tratados como embarazo gestante. La colocación endotraqueal del globo se realizó con éxito en el primer intento en todos los casos. La mediana de la edad gestacional (EG) en el momento de la colocación del globo fue de 29,1 (rango, 25,6-31,8) semanas y 34,1 (rango, 30,0-36,1) semanas cuando se retiró el globo. En ningún caso hubo problemas técnicos con la introducción o la retirada del globo. La mediana de la EG en el momento del parto fue significativamente menor en el grupo tratado con OTEF que en el grupo tratado como gestante (35,3 vs 37,7 semanas; P=0,04). La tasa de supervivencia fue significativamente más alta en el grupo tratado con OTEF que en los casos sin intervención fetal (32% vs 0%; P<0,001). CONCLUSIÓN: En los entornos con un tratamiento neonatal subóptimo, la OTEF se asoció con una mejora de la supervivencia neonatal en los fetos con HDC aislada del lado izquierdo y con hipoplasia pulmonar grave. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Influence of nanoholes array geometrical parameters on magnetic properties of Dy-Fe antidot thin films.

Nanoscale artificially engineered spintronic materials could be used to enlarge the storage density of magnetic recording media. For this purpose, magnetic nanostructures such as antidot arrays exhibiting high uniaxial magnetic anisotropy are new contestants in the field of ultrahigh density magnetic data storage devices. In this context, we focus on the synthesis of nanostructured magnetic materials consisting of Dy-Fe alloyed antidot thin films, deposited onto the surface of nanoporous alumina membranes served as patterned templates. Noticeable variations of in the in-plane magnetic anisotropy have been observed by modifying the layer thickness at both microscopic and macroscopic scales. The microscopic magnetic properties have been locally studied by Nano-MOKE magnetometry. For thinner antidot samples with 15, 20 and 25 nm in thickness, a tri-axial in-plane magnetic anisotropy has been detected. Meanwhile, for thicker antidot samples (40-60 nm of layer thickness), an in-plane uniaxial magnetic anisotropy has been noted. We attribute these changes in the magnetic anisotropy to the strong correlation between the edge-to-edge distance among adjacent nanoholes, W, and the local magnetic anisotropy of antidot samples. The effective magnetic anisotropy exhibits an unexpected crossover from the in-plane to out-of-plane direction due to the increasing of the effective perpendicular magnetic anisotropy with varying the layer thickness of antidot thin films. Therefore, we detected a critical layer thickness, t = 25 nm for the Dy-Fe alloy antidot arrays, at which the appearance of the perpendicular magnetization is observed. Furthermore, an enhancement in the Curie temperature of the antidot arrays compared to the continuous thin films has been obtained. We attribute these effects to the complex magnetization reversal processes and the high thermal stability of the hexagonal structure of antidot arrays. These findings can be of high interest for the development of novel magnetic sensors and for thermo-magnetic recording patterned media based on template-assisted deposition techniques.

Direct visualization of the native structure of viroid RNAs at single-molecule resolution by atomic force microscopy.

Viroids are small infectious, non-protein-coding circular RNAs that replicate independently and, in some cases, incite diseases in plants. They are classified into two families: Pospiviroidae, composed of species that have a central conserved region (CCR) and replicate in the cell nucleus, and Avsunviroidae, containing species that lack a CCR and whose multimeric replicative intermediates of either polarity generated in plastids self-cleave through hammerhead ribozymes. The compact, rod-like or branched, secondary structures of viroid RNAs have been predicted by RNA folding algorithms and further examined using different in vitro and in vivo experimental techniques. However, direct data about their native tertiary structure remain scarce. Here we have applied atomic force microscopy (AFM) to image at single-molecule resolution different variant RNAs of three representative viroids: potato spindle tuber viroid (PSTVd, family Pospiviroidae), peach latent mosaic viroid and eggplant latent viroid (PLMVd and ELVd, family Avsunviroidae). Our results provide a direct visualization of their native, three-dimensional conformations at 0 and 4 mM Mg2+ and highlight the role that some elements of tertiary structure play in their stabilization. The AFM images show that addition of 4 mM Mg2+ to the folding buffer results in a size contraction in PSTVd and ELVd, as well as in PLMVd when the kissing-loop interaction that stabilizes its 3D structure is preserved.

Increased phagocytosis and growth inhibition of Encephalitozoon cuniculi by LPS-activated J774A.1 murine macrophages.

Encephalitozoon cuniculi is an obligate macrophage parasite of vertebrates that commonly infects rodents, monkeys, dogs, birds, and humans. In the present study, we aimed to assess the phagocytosis and intracellular survival of E. cuniculi spores using untreated and lipopolysaccharide (LPS)-activated J774A.1 murine macrophages and assess the macrophage viability. The experimental groups comprised untreated spores, spores killed by heat treatment at 90 °C, and spores killed by treatment with 10% formalin. LPS-activated macrophages significantly increased the phagocytosis of spores and reduced their intracellular growth after 24 and 48 h (P < 0.01); however, after 72 h, we observed an increase in spore replication but no detectable microbicidal activity. These results indicate that LPS activation enhanced E. cuniculi phagocytosis between 24 and 48 h of treatment, but the effect was lost after 72 h, enabling parasitic growth. This study contributes to the understanding of the phagocytosis and survival of E. cuniculi in murine macrophages.

Prospective comparison among three intrarectal anesthetic treatments combined with periprostatic nerve block during transrectal ultrasonography-guided prostate biopsy.

BACKGROUND: Recent trends in prostate biopsy analgesia suggest a combination anesthetic to provide better pain relief than periprostatic nerve block (PPNB) alone. This study aimed to demonstrate the efficacy and safety of three intrarectal local anesthesia (IRLA) combined with PPNB in patients undergoing transrectal ultrasonography (TRUS)-guided prostate biopsy. METHODS: In this prospective, randomized study, 120 prostate biopsy patients were equally divided into four IRLA groups: group 1 (placebo) received simple lubrication; group 2 received 2% lidocaine gel; group 3 received 100 mg indomethacin suppository and group 4 received 5% prilocaine/lidocaine (EMLA) cream. PPNB with 2% lidocaine was applied in all groups. A ten-point visual analog scale evaluated both pain associated with the probe insertion and pain associated with prostate sampling. Adverse effects or complications due to anesthesia during and after the procedure were documented. RESULTS: Compared with group 1, groups 3 and 4 had significantly lower pain scores at both probe insertion and prostate sampling while group 2 showed no significant differences at both pain scores. Moreover, group 4 showed significantly lower pain scores at probe insertion compared to group 3, while no significant difference was observed at prostate sampling. Mild complications were observed in all groups with no significant difference in the incidence of complications between groups. CONCLUSION: Intrarectal application of EMLA cream is a more efficient pain reduction than either 2% lidocaine gel or 100 mg indomethacin suppository when applied combined with PPNB. This combination represents an effective option of pain relief for patients undergoing TRUS-guided prostate biopsy.

Prevalence of human papillomavirus types in North and Central regions of Mexico.

Human papillomavirus (HPV) is a DNA virus linked to mucosal and cutaneous carcinogenesis. More than 200 different HPV types exist. We carried out a transversal study to investigate the prevalence of HPV types in two regions of Mexico. A total of 724 genital and non-genital samples from women (F) and men (M) were studied; 241 (33%) from North-Eastern (NE) and 483 (66%) from South-Central (SC) Mexico. The overall prevalence was 87%. In genital lesions from females, the NE group showed a prevalence of HPV types 16 (37%), 6 (13%), 59 (6%), 11, 18 and 66 (5.4% each); and the SC group showed types 6 (17%), 16 (15%), 11 (14.5%), 18 (12%) and 53 (6%). In the genital lesions from males, NE group showed types 16 (38%), 6 (21%), 11 (13%) and 59 plus 31 (7.5%) and the SC group showed types 6 (25%), 11 (22%), 18 (17%) and 16 (11.5%). When the two regions were compared, a higher prevalence of low-risk HPV 6 and 11 was found in the SC region and of high-risk HPV 59, 31 and 66 (the latter can also be present in benign lesions) in the NE region. Our findings complement efforts to understand HPV demographics as a prerequisite to guide and assess the impact of preventive interventions.

MiR-138 indirectly regulates the MDR1 promoter by NF-κB/p65 silencing.

MicroRNAs (miRNAs) are known to mediate post-transcriptional gene silencing in the cytoplasm and recent evidence indicates that may also possess nuclear roles in regulating gene expression. A previous study showed that miR-138 is involved in the multidrug resistance of leukemia cells through down-regulation of the drug efflux pump P-glycoprotein (P-gp), the protein encoded by the human multidrug-resistant ABCB1/MDR1 gene. However, the transcriptional regulatory mechanisms responsible remain to be elucidated. To deepen the description of the mechanism of transcriptional gene silencing on the MDR1 promoter, we initially performed a bioinformatics search for potential miR-138 binding sites in the MDR1 gene promoter sequence. Interestingly, we did not find miR-138 binding sites in this region, suggesting an indirect regulation. From six representative transcriptional factors involved in MDR1 gene regulation, an in silico analysis revealed that NF-κB/p65 has a specific binding site for miR-138. The results of luciferase reporter assay, western blot and flow cytometry shown here suggest that miR-138 might modulate the human MDR1 expression by inhibiting NF-κB/p65 as an indirect mechanism of MDR1 regulation. Furthermore, employing the human macrophage-like cell line U937 we observed comparable results with NF-κB/p65 down-regulation and we also observed a significant reduction in the IL-6 and TNF-α mRNA, as well as in their secreted pro-inflammatory cytokines following miR-138 expression, suggesting that canonical NF-κB target genes might also be potential targets for miR-138 in leukemia cells.

The influence of benign prostatic hyperplasia on sperm morphological features and sperm DNA integrity in dogs.

Benign prostatic hyperplasia (BPH) has a high incidence in older intact dogs. Due to the increased prostatic oxidative stress and hormonal imbalance of BPH, sperm damage can arise, such as sperm morphological alterations and DNA fragmentation. This study aimed to compare the reproductive potential of healthy dogs and those affected by benign prostatic hyperplasia. Ten dogs were assigned to two experimental groups: dogs without BPH (control; n = 5) and dogs diagnosed with BPH (n = 5), based on clinical signs and ultrasonographic findings. Three semen collections were performed from each dog within one month and analysed using computer-assisted sperm analysis (CASA) and functional tests. Control group showed higher percentage of sperm DNA integrity (95 ± 1.8%) compared to the BPH group (79.2 ± 6.4%). On the other hand, the percentage of minor sperm defects, amplitude of lateral sperm head displacement of the spermatozoa and medium sperm mitochondrial activity were higher in the BPH group. In conclusion, BPH decreases sperm DNA integrity, increases mitochondrial activity, as well as modifies sperm movement pattern. Therefore, a careful sperm analysis of aged dogs with BPH is required before a reproductive programme can be established for such patients.

Leishmania mexicana: promastigotes and amastigotes secrete protein phosphatases and this correlates with the production of inflammatory cytokines in macrophages.

Phosphatase activity of Leishmania spp. has been shown to deregulate the signalling pathways of the host cell. We here show that Leishmania mexicana promastigotes and amastigotes secrete proteins with phosphatase activity to the culture medium, which was higher in the Promastigote Secretion Medium (PSM) as compared with the Amastigote Secretion Medium (ASM) and was not due to cell lysis, since parasite viability was not affected by the secretion process. The biochemical characterization showed that the phosphatase activity present in PSM was higher in dephosphorylating the peptide END (pY) INASL as compared with the peptide RRA (pT)VA. In contrast, the phosphatase activity in ASM showed little dephosphorylating capacity for both peptides. Inhibition assays demonstrated that the phosphatase activity of both PSM and ASM was sensible only to protein tyrosine phosphatases inhibitors. An antibody against a protein phosphatase 2C (PP2C) of Leishmania major cross-reacted with a 44·9 kDa molecule in different cellular fractions of L. mexicana promastigotes and amastigotes, however, in PSM and ASM, the antibody recognized a protein about 70 kDa. By electron microscopy, the PP2C was localized in the flagellar pocket of amastigotes. PSM and ASM induced the production of tumor necrosis factor alpha, IL-1ß, IL-12p70 and IL-10 in human macrophages.

[Subsequent reoperation obstetric hysterectomy and selective ligation of hypogastric arteries]. / Reintervención posterior a histerectomía obstétrica y ligadura selectiva de arterias hipogástricas.

Background: Bleeding in pregnancy, childbirth or postpartum period is an emergency. Selective internal iliac (hypogastric) arteries ligation is a surgical therapy in selected cases of obstetric massive hemorrhage. It had proven to be safe. Objetive: To evaluate the risk for re-intervention for post-operatory bleeding in patients with obstetric hysterectomy and selective hypogastric arteries ligation. Material and method: Cross-sectional study including women diagnosed with obstetric hysterectomy with and without selective arterial ligation as a factor to assess the risk of re-intervention, from December 2013 to December 2014, at High Specialty Medical Unit 23 of Gynaecology and Obstetrics, in Monterrey, which is a tertiary care medical center. Those patients with 28 weeks of gestation or more were selected. The postoperative blood loss was quantified by open drainage system (Penrose). Results: We performed 88 hysterectomies in the study period. We included 45 women according to selection criteria. The average was 31.9 ± 5.48 years old. Performing a selective hypogastric arteries ligation may be a protective factor (p<0.05) for re-intervention as a consequence of postoperative bleeding. Conclusion: Selective arterial ligation is a factor that could help to prevent a re-intervention. A continuous training of physicians and residents of Gynecology and Obstetrics is essential to ensure the reduction in morbidity and maternal mortality.