Metformin Reduces Tumor Growth in a Murine Flank Schwannoma Model.

HYPOTHESIS: Metformin and aspirin reduce vestibular schwannoma (VS) growth. BACKGROUND: There have been reported associations between patients with VS prescribed metformin and decreased tumor volumetric growth. Aspirin has also been associated with decreased VS growth in animal studies. METHODS: Rat schwannoma cell lines were grown and implanted into 50 athymic nude mice. Tumors were grown to 5 mm, and then mice were injected with either low- or high-dose metformin, aspirin, or saline daily. Tumors were measured until 14 days elapsed or mice demonstrated symptoms such as ulceration, inability to walk, or passed away. RESULTS: There were no significant differences in day 0 tumor sizes between the control and the treatment groups ( p = 0.73). In the low-dose, but not high-dose groups, day 7 volumes were significantly different for both metformin ( p = 0.04) and aspirin ( p = 0.02) compared with placebo. Mean tumor growth rates were 126.6 ± 65.6 mm 3 /day for saline compared with 73.7 ± 29.5 mm 3 /day for low-dose metformin ( p = 0.03) and 68.7 ± 34.8 mm 3 /day for low-dose aspirin ( p = 0.016). There were no significant differences in tumor sizes ( p = 0.59) or growth rates ( p = 0.75) between low-dose metformin and aspirin groups. Low-dose groups had treatment stopped at 14 days, with continued monitoring demonstrating significant increases in tumor growth off treatment for both aspirin ( p = 0.006) and metformin ( p = 0.048). CONCLUSIONS: Metformin treatment significantly reduced VS growth to a similar level as aspirin. Furthermore, when removing both metformin and aspirin treatment, tumor growth significantly increased.

Cardiometabolic risk factors and antithrombotic treatment in a Mexican population with atrial fibrillation and heart failure with reduced ejection fraction.

INTRODUCTION: Heart failure in patients with non-valvular atrial fibrillation (NVAF) is two to three times more common than in individuals without NVAF. OBJECTIVE: To identify cardiometabolic risk factors (CMRF) and antithrombotic treatment in patients with NVAF and heart failure with reduced ejection fraction (HFrEF), and to determine if there were differences according to gender. METHODS: CMRF, pro-thrombotic risk, bleeding risk, and antithrombotic therapy were globally analyzed and according to gender. RESULTS: Out of 1,423 patients with NVAF, 336 had HFrEF. On average, females were older than males. There was no difference between genders with regard to the type of NVAF or direct oral anticoagulants use. Hypertension was more common in women. History of transient ischemic attack was reported in 3.6% of the patients and cerebrovascular event in 10%, without differences in terms of gender. The percentage of men with elevated embolic risk was higher, but without antithrombotic treatment, in comparison with women. CONCLUSIONS: Significant differences were found according to gender in patients with NVAF and HFrEF, both in CMRF and some comorbidities, as well as in antithrombotic treatment according to embolic and bleeding risk.

INTRODUCCIÓN: La insuficiencia cardiaca en pacientes con fibrilación auricular no valvular (FANV) es de dos a tres veces más frecuente que en individuos sin FANV. OBJETIVO: Identificar los factores de riesgo cardiometabólico (FRCM) y el tratamiento antitrombótico de pacientes con FANV e insuficiencia cardiaca con fracción de expulsión reducida (IC-FEr), y determinar si existen diferencias conforme al sexo. MÉTODOS: En forma global y de acuerdo con el sexo se analizaron FRCM, riesgo protrombótico, riesgo de sangrado y terapia antitrombótica. RESULTADOS: De 1423 pacientes con FANV, 336 tuvieron IC-FEr. Las mujeres promediaron mayor edad que los hombres. No hubo diferencia entre los sexos respecto al tipo de FANV o uso de anticoagulantes orales directos. La hipertensión arterial sistémica fue más frecuente en mujeres. Un 3.6 % de los pacientes reportó antecedente de ataque isquémico transitorio y 10 % de evento vascular cerebral, sin diferencias en cuanto al sexo. El porcentaje de hombres con riesgo embólico elevado fue mayor, pero sin tratamiento antitrombótico, en comparación con las mujeres. CONCLUSIONES: Se encontraron diferencias significativas de acuerdo con el sexo en pacientes con FANV e IC-FEr, tanto en FRCM y algunas comorbilidades, como en el tratamiento antitrombótico de acuerdo con el riesgo embólico y de sangrado.

Factores de riesgo cardiometabólico y tratamiento antitrombótico en población mexicana con fibrilación auricular e insuficiencia cardiaca con fracción de expulsión reducida / Cardiometabolic risk factors and antithrombotic treatment in a Mexican population with atrial fibrillation and heart failure with reduced ejection fraction

Resumen Introducción: La insuficiencia cardiaca en pacientes con fibrilación auricular no valvular (FANV) es de dos a tres veces más frecuente que en individuos sin FANV. Objetivo: Identificar los factores de riesgo cardiometabólico (FRCM) y el tratamiento antitrombótico de pacientes con FANV e insuficiencia cardiaca con fracción de expulsión reducida (IC-FEr), y determinar si existen diferencias conforme al sexo. Métodos: En forma global y de acuerdo con el sexo se analizaron FRCM, riesgo protrombótico, riesgo de sangrado y terapia antitrombótica. Resultados: De 1423 pacientes con FANV, 336 tuvieron IC-FEr. Las mujeres promediaron mayor edad que los hombres. No hubo diferencia entre los sexos respecto al tipo de FANV o uso de anticoagulantes orales directos. La hipertensión arterial sistémica fue más frecuente en mujeres. Un 3.6 % de los pacientes reportó antecedente de ataque isquémico transitorio y 10 % de evento vascular cerebral, sin diferencias en cuanto al sexo. El porcentaje de hombres con riesgo embólico elevado fue mayor, pero sin tratamiento antitrombótico, en comparación con las mujeres. Conclusiones: Se encontraron diferencias significativas de acuerdo con el sexo en pacientes con FANV e IC-FEr, tanto en FRCM y algunas comorbilidades, como en el tratamiento antitrombótico de acuerdo con el riesgo embólico y de sangrado.

Abstract Introduction: Heart failure in patients with non-valvular atrial fibrillation (NVAF) is two to three times more common than in individuals without NVAF. Objective: To identify cardiometabolic risk factors (CMRF) and antithrombotic treatment in patients with NVAF and heart failure with reduced ejection fraction (HFrEF), and to determine if there were differences according to gender. Methods: CMRF, pro-thrombotic risk, bleeding risk, and antithrombotic therapy were globally analyzed and according to gender. Results: Out of 1,423 patients with NVAF, 336 had HFrEF. On average, females were older than males. There was no difference between genders with regard to the type of NVAF or direct oral anticoagulants use. Hypertension was more common in women. History of transient ischemic attack was reported in 3.6% of the patients and cerebrovascular event in 10%, without differences in terms of gender. The percentage of men with elevated embolic risk was higher, but without antithrombotic treatment, in comparison with women. Conclusions: Significant differences were found according to gender in patients with NVAF and HFrEF, both in CMRF and some comorbidities, as well as in antithrombotic treatment according to embolic and bleeding risk.

Bienestar psicológico y ansiedad en adultos mayores con osteoartrosis de rodilla / Psychological well-being and anxiety in older adults with knee osteoarthritis

Introducción: El envejecimiento poblacional en Cuba ha incrementado los casos de osteoartrosis de rodilla. Como alternativa terapéutica se utiliza el plasma rico en plaquetas autólogo, en aras de potenciar el bienestar físico y psicológico de los pacientes. Objetivo: Caracterizar la relación entre el bienestar psicológico y la ansiedad de los adultos mayores con osteoartrosis de rodilla tratados con plasma rico en plaquetas autólogo. Métodos: Se utilizó un enfoque cuantitativo, con un alcance descriptivo-correlacional, y un diseño expost-facto retrospectivo simple. El muestreo fue intencional, no probabilístico, y quedó conformado por 300 pacientes. Se aplicó la Adaptación de la Escala de Bienestar Psicológico de Ryff y el Inventario de Ansiedad Rasgo-Estado. Para el análisis de los datos se realizaron tres cortes: antes del tratamiento regenerativo y a los tres y seis meses de evolución. Resultados: Hubo cambios de niveles medio-bajo a niveles altos de bienestar psicológico. Disminuyeron los niveles de ansiedad estado, pero no los de ansiedad rasgo. El bienestar psicológico no se correlacionó con la ansiedad rasgo y la relación estadística positiva fue muy débil con la ansiedad estado. Conclusiones: Se identificaron cambios favorables del bienestar psicológico y de la ansiedad estado, con persistencia de niveles altos de ansiedad rasgo(AU)

Introduction: The population aging in Cuba has caused the increase of osteoarthrosis of the knee in the elderly. As a therapeutic alternative, it was used the clinical use of autologous platelet-rich plasma, in order to promote well-being, not only physical, but also psychological. Objective: To characterize the relationship between psychological well-being and anxiety state and feature of elderly adults with osteoarthrosis of the knee, who are subjected to regenerative treatment with autologous platelet-rich plasma. Methods: A quantitative research approach was used, with a descriptive-correlational scope, and a simple retrospective expost-fact design. Sampling was intentional, non-probabilistic and consisted of 300 older adults. The Adaptation of the Ryff Psychological Well-Being Scale and the Trait-State Anxiety Inventory were applied. For the analysis of the data, three cuts were made: before the regenerative treatment, and after three and six months of evolution. Results: There were changes from medium-low levels to high levels of psychological well-being. Levels of state anxiety decreased, but trait anxiety did not. Psychological well-being did not correlate with trait anxiety and there was a weak positive statistical relationship with state anxiety. Conclusions: Changes were identified that favor psychological well-being and trait anxiety, with persistent high levels of trait anxiety(AU)

Quistes óseos aneurismáticos. Terapia celular con células mononucleares y seguimiento imagenológico en dos pacientes adolescentes / Aneurysmal bone cysts. Mononuclear cell therapy and imaging follow-up in two adolescent patients

RESUMEN Los quistes óseos aneurismáticos son frecuentes en la edad pediátrica. Para su determinación se cuenta con diversos estudios imagenológicos como la radiografía y la tomografía axial computarizada que pueden colaborar al diagnóstico diferencial con otras lesiones. Existen disímiles opciones terapéuticas, el uso de factores de crecimiento autólogos se ha considerado como alternativa eficaz. Se presentan dos pacientes consultados en el servicio de Ortopedia del Hospital Provincial Pediátrico Universitario «José Luis Miranda¼, de Villa Clara, con diagnóstico clínico e imagenológico de quiste óseo aneurismático que recibieron tratamiento mediante terapia celular con células mononucleares con buena evolución clínica y radiográfica. Esta técnica es aplicable en nuestro medio ya que no requiere de estimables recursos materiales lo que constituye una fortaleza para su implementación. Las radiografías permiten reconocer la evolución posterior al tratamiento.

ABSTRACT Aneurysmal bone cysts are common in children. For its determination, various imaging studies are available, such as radiography and computerized axial tomography, which can collaborate in the differential diagnosis with other lesions. There are dissimilar therapeutic options, the use of autologous growth factors has been considered as an effective alternative. We present two patients seen in the Orthopedics service at "José Luis Miranda" University Pediatric Hospital in Villa Clara, with a clinical and imaging diagnosis of aneurysmal bone cyst who received treatment with mononuclear cell therapy having a good clinical and radiographic evolution. This technique is applicable in our environment since it does not require considerable material resources, which constitutes a strength for its implementation. X-rays allow us to recognize the evolution after treatment.

Territorial scent-marking effects on vigilance behavior, space use, and stress in female Columbian ground squirrels.

Social environments can profoundly affect the behavior and stress physiology of group-living animals. In many territorial species, territory owners advertise territorial boundaries to conspecifics by scent marking. Several studies have investigated the information that scent marks convey about donors' characteristics (e.g., dominance, age, sex, reproductive status), but less is known about whether scents affect the behavior and stress of recipients. We experimentally tested the hypothesis that scent marking may be a potent source of social stress in territorial species. We tested this hypothesis for Columbian ground squirrels (Urocitellus columbianus) during lactation, when territorial females defend individual nest-burrows against conspecifics. We exposed lactating females, on their territory, to the scent of other lactating females. Scents were either from unfamiliar females, kin relatives (a mother, daughter, or sister), or their own scent (control condition). We expected females to react strongly to novel scents from other females on their territory, displaying increased vigilance, and higher cortisol levels, indicative of behavioral and physiological stress. We further expected females to be more sensitive to unfamiliar female scents than to kin scents, given the matrilineal social structure of this species and known fitness benefits of co-breeding in female kin groups. Females were highly sensitive to intruder (both unfamiliar and kin) scents, but not to their own scent. Surprisingly, females reacted more strongly to the scent of close kin than to the scent of unfamiliar females. Vigilance behavior increased sharply in the presence of scents; this increase was more marked for kin than unfamiliar female scents, and was mirrored by a marked 131% increase in free plasma cortisol levels in the presence of kin (but not unfamiliar female) scents. Among kin scents, lactating females were more vigilant to the scent of sisters of equal age, but showed a marked 318% increase in plasma free cortisol levels in response to the scent of older and more dominant mothers. These results suggest that scent marks convey detailed information on the identity of intruders, directly affecting the stress axis of territory holders.

The Paris System "atypical urothelial cells" category: can the current criteria be improved?

INTRODUCTION: The Paris System (TPS) for reporting urine cytology was developed for standardization of diagnosis focusing on the detection of high-grade urothelial carcinoma (HGUC). Probably the most challenging task for TPS is to provide criteria for the atypical urothelial cell (AUC) category. The TPS criteria for AUC include increased nuclear/cytoplasmic (N/C) ratio (>0.5) and 1 of the 3 minor criteria including nuclear hyperchromasia (NH), coarse chromatin (CC) and irregular nuclear membrane (INM). We evaluated TPS-AUC diagnostic value and investigated whether other morphologic parameters can improve its criteria. MATERIALS AND METHODS: Urine samples with diagnoses of AUC collected during a 6-month period were re-reviewed. Data captured included N/C ratio >0.5, NH, CC, INM, and 2 additional criteria including enlarged nuclear size (ENS) and the presence of nucleolus (N). ENS was considered when the nucleus was 2 times larger than the urothelial cell or 3 times larger than lymphocyte. RESULTS: By applying the TPS-AUC criteria, the rate of atypia diagnosis reduced in comparison to Pre-TPS (9% versus 13%, P = 0.02). Among the AUC minor criteria, NH was the best criterion with the highest interobserver agreement (IOA) and correlation with HGUC (k = 0.342, r = 0.61, P < 0.001) and strong PPV (93.6%). ENS had the highest PPV (95.8%) and, after NH, had the highest IOA and correlation with HGUC (k = 0.29, r = 0.52, P < 0.001). CONCLUSION: TPS improves the diagnostic value of urine cytology, particularly in cases with atypia. ENS is a strong criterion for increasing the diagnostic value of AUC and potentially can improve TPS performance as a minor criterion.

Anticoagulation Therapy by Age and Embolic Risk for Nonvalvular Atrial Fibrillation in Mexico, an Upper-Middle-Income Country: The CARMEN-AF Registry.

Background: Documenting the patterns of oral anticoagulation therapy (OAT) is essential to prevent thromboembolic complications of nonvalvular atrial fibrillation (NVAF). Objective: To report the patterns of OAT according to age and thromboembolic risk in patients included in CARMEN-AF, a nationwide registry of NVAF in Mexico, an upper middle-income country. Material and methods: There were 1,423 consecutive patients ≥18 years old and with at least one thromboembolic risk factor enrolled in the CARMEN-AF Registry at their regular clinical visit during a three-year period. They were analyzed according to 1) age, 2) AF type, and 3) CHA2DS2-VASc score. Results: Overall, 16.4% of patients did not receive antithrombotic treatment, 19.4% received antiplatelet drugs (APD), 29.2% vitamin K antagonists (VKA), and 34.6% direct oral anticoagulants (DOAC). With increasing age, the proportion of subjects treated with VKA decreased significantly from 36.2% in subjects <65 years to 22.5% in those ≥75 years old (P <0.0001). Concomitantly, an increase in both APD and no antithrombotic treatment was observed with increasing age. DOAC were prescribed equally among all age groups (34.2% in <65, 36.0% in 65-74, and 33.9% in ≥75). According to the type of AF, VKA use was more common in patients with permanent AF (32.7%). A lower use of DOAC was observed in high thromboembolic risk subjects (33.6% in CHA2DS2-VASc ≥2) compared with the moderate risk group (41% in CHA2DS2-VASc = 1). Conclusions: VKA use for NVAF in Mexico decreased in relation to increasing age. The proportion of DOAC therapy was the same in all age groups. Nevertheless, elderly patients with high thromboembolic risk received a suboptimal thromboprophylaxis. These data could help to improve gaps in the implementation of global guidelines. Clinical trial registration: http://www.clinicaltrials.gov. Unique identifier: NCT02334852. Highlights: CARMEN-AF is a nationwide multi-centric registry seeking to bridge the data gap on anticoagulation therapy for NVAF in Mexico.Elderly patients are more prone to receive suboptimal OAT for NVAF.DOAC were less frequently used in high thromboembolic risk patients (CHA2DS2-VASc ≥2).

Purpureocillium lilacinum as unusual cause of pulmonary infection in immunocompromised hosts.

Purpureocillium lilacinum (P. lilacinum) is an emergent pathogenic mold that presents more commonly as an ocular infection, cutaneous and/or subcutaneous infections in patients that are usually immunocompromised. A pulmonary presentation is rare, the clinical presentation is fever and cough with radiographic presentation as pleural effusion, single-lung consolidation, and cavitary pulmonary disease. We present a case of a patient with hematologic malignancy with febrile neutropenia; after receiving chemotherapy, the patient developed a pulmonary infection with multiple bilateral consolidations shown in the thoracic computed tomography scan. Fever persisted in spite of the use of wide-spectrum antibiotics and amphotericin. Bronchoalveolar lavage was performed and the samples were cultured, isolating in the Sabouraud Dextrous Agar a filamentous fungi growth with purple colonies that were identified morphologically as P. lilacinum and later it was confirmed by molecular methods. Once the infectious agent was identified, we continued amphotericin and oral voriconazole was added to the treatment with complete resolution of the infection. The report aims to create awareness of this emerging infectious disease, as there is little information concerning the treatment and the prognosis of patients infected by P. lilacinum with a pulmonary presentation.

Giant cell tumor of bone at the proximal epiphysis of humerus in a skeletally immature patient: A case report.

INTRODUCTION: Giant cell tumor of bone (GCTB) in skeletally immature (SI) patients are rare benign lesions that have locally aggressive growth pattern and high risk of recurrence. The presence of GCTB at the proximal epiphysis of humerus in SI patients has never been described in literature. PRESENTATION OF CASE: This report shows the case of a 10-year-old SI male who presented with a GCTB at the proximal epiphysis of humerus that was treated with curettage, cement and adjuvant therapy. DISCUSSION: The presence of a lytic growing lesion at the proximal humerus in a SI patient should alert clinicians to consider GCTB in their differential diagnosis. The management of GCTB in SI patients is challenging for orthopaedic surgeons. Tumor resection with cementation and adjuvant therapy has been described as a method rationale to prevent the recurrence and preserve the joint function in SI patients with GCTB at the proximal epiphysis of humerus. Clinicians should continue to monitor these patients with radiographic imaging for possible recurrence, metastasis or growth plate injury. CONCLUSION: Tumor resection with cementation and adjuvant therapy offers a treatment alternative to prevent the recurrence and preserve the joint function in SI patients with GCTB at the proximal epiphysis of humerus. The use of a prothesis in a SI patient should avoided if possible, to prevent implant-related complications and damage to the growth plate.

Abdominal Surgical Site Infection Incidence and Risk Factors in a Mexican Population.

OBJECTIVE: To investigate possible predictors and prevalence of surgical site infections (SSIs) in a group of Mexican patients who underwent open abdominal surgery. METHODS: This retrospective study included all patients (N = 755) who underwent elective or emergency open abdominal surgeries from October 2011 to March 2012. MAIN OUTCOME MEASURE: Sociodemographic and clinical characteristics were collected through preoperative and postoperative examinations by the infection surveillance team. The relationship among variables (age, gender, body mass index, comorbidities, smoking habit, antimicrobial prophylaxis, hair removal, American Society of Anesthesiologists classification, type of operation, duration of operation, and SSI classification) was analyzed by odds ratio and χ tests. MAIN RESULTS: Of the 755 patients, 91 (12%) suffered from SSI. Several variables were associated with SSI: American Society of Anesthesiologists classification (P = .001) and receiving preoperative prophylactic antimicrobials (P < .0001), among other factors. Isolated pathogens were mostly enterobacteria (60%). CONCLUSIONS: Surveillance plays an important role in the control and prevention of SSI. Providers must implement appropriate procedures to reduce SSI after abdominal surgery.

Gender differences and management of stroke risk of nonvalvular atrial fibrillation in an upper middle-income country: Insights from the CARMEN-AF registry.

BACKGROUND: Atrial Fibrillation (AF) is associated with an increased risk of stroke and systemic embolism. Several studies have suggested that female AF patients could have a greater risk for stroke. There is scarce information about clinical characteristics and use of antithrombotic therapies in Latin American patients with nonvalvular AF. OBJECTIVE: To describe the gender differences in clinical characteristics, thromboembolic risk, and antithrombotic therapy of patients with nonvalvular AF recruited in Mexico, an upper middle-income country, into the prospective national CARMEN-AF Registry. METHODS: A total of 1423 consecutive patients, with at least one thromboembolic risk factor were enrolled in CARMEN-AF Registry during a three-year period (2014-2017). They were categorized according to Gender. RESULTS: Overall, 48.6% were women, mean age 70 ±â€¯12 years. Diabetes, smoking, alcoholism, non-ischemic cardiomyopathy, coronary artery disease, and obstructive sleep apnea were higher in men. Most women were found with paroxysmal AF (40.6%), and most men with permanent AF (44.0%). No gender differences were found in the use of vitamin K antagonists (VKA) (30.5% in women vs. 28.0% in men). No gender differences were found in the use of direct oral anticoagulants (DOAC) (33.8% women vs 35.4% men). CONCLUSIONS: CARMEN-AF Registry demonstrates that in Mexico, regardless of gender, a large proportion of patients remain undertreated. No gender differences were found in the use of VKA or DOAC.

Open source platform for collaborative construction of wearable sensor datasets for human motion analysis and an application for gait analysis.

Nearly every practical improvement in modeling human motion is well founded in a properly designed collection of data or datasets. These datasets must be made publicly available for the community could validate and accept them. It is reasonable to concede that a collective, guided enterprise could serve to devise solid and substantial datasets, as a result of a collaborative effort, in the same sense as the open software community does. In this way datasets could be complemented, extended and expanded in size with, for example, more individuals, samples and human actions. For this to be possible some commitments must be made by the collaborators, being one of them sharing the same data acquisition platform. In this paper, we offer an affordable open source hardware and software platform based on inertial wearable sensors in a way that several groups could cooperate in the construction of datasets through common software suitable for collaboration. Some experimental results about the throughput of the overall system are reported showing the feasibility of acquiring data from up to 6 sensors with a sampling frequency no less than 118Hz. Also, a proof-of-concept dataset is provided comprising sampled data from 12 subjects suitable for gait analysis.

Signature of microRNA expression during osteogenic differentiation of bone marrow MSCs reveals a putative role of miR-335-5p in osteoarthritis.

BACKGROUND: The aim of this study was to evaluate, the existence of a signature of differentially expressed microRNAs (miRNAs) during osteogenic differentiation of bone marrow MSCs from OA and healthy donors and to describe their possible implication in joint regeneration through modulation of molecular mechanisms involved in homeostatic control in OA pathophysiology. METHODS: Following phenotypic assessment of BM-MSCs obtained from OA diagnosed patients (n = 10) and non-OA (n = 10), total small RNA was isolated after osteogenic induction for 1, 10 and 21 days, miRNA profiles were generated using a commercial expression array of 754 well-characterized miRNAs. MiRNAs, with consistent differential expression were selected for further validation by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis. RESULTS: A total of 246 miRNAs were differentially expressed (fold change ≥ ± 2, P ≤0.05) between OA and non-OA BM-MSC samples; these miRNAs showed variable interactions depending on the cell and differentiation status. Two miRNAs, hsa-miR-210 and hsa-miR-335-5p out of 21 used for validation showed a significant downregulated expression during induced osteogenesis. In particular hsa-miR-335-5p, a critical regulator in bone homeostasis, was further studied. hsa-miR-335-5p downregulation in OA-MSCs, as well as their host coding gene, MEST, were also assessed. CONCLUSIONS: To our knowledge, this study represents the most comprehensive assessment to date of miRNA expression profiling in BM-MSCs from OA patients and their role during osteogenic differentiation. We describe the existence of a correlation between miR-335-5p expression and OA indicating the putative role of this miRNA in OA features. These findings, may contribute to our understanding of the molecular mechanisms involved in MSCs mediated homeostatic control in OA pathophysiology that could be applicable in future therapeutic approaches.

HIV, STI and Behavioral Risk Among Men Who have Sex with Men in a Setting of Elevated HIV Prevalence Along Ecuador's Pacific Coast.

We assessed HIV and STI prevalence, risk behaviors and factors associated with HIV infection in men who have sex with men (MSM) in Guayaquil, Ecuador. Respondent-driven sampling was used to recruit 400 MSM in 2011-2012. Participants completed a computer-assisted self-interview and provided blood samples. Statistical analysis accounted for differential probability of selection and for recruitment patterns. HIV prevalence was 11.3 %, HSV-2 30.2 %, active syphilis 6.9 % and hepatitis B 1.2 %. In the previous 12 months, 84 % of MSM reported casual male sex partners and 25 % sex work. Only 48 % of MSM consistently used condoms with male partners and 54 % had ever been tested for HIV. Of 17 % of MSM reporting a female partner, consistent condom use was 6 %. HIV infection was associated with age 25 or older, active syphilis and homosexual self-identification. Findings suggest continuing HIV risk and a need to strengthen prevention and testing among MSM.

Relationship between epicardial adipose tissue, coronary artery disease and adiponectin in a Mexican population.

BACKGROUND: The amount of epicardial adipose tissue (EAT) around the heart has been identified as an independent predictor of coronary artery disease (CAD), potentially through local release of inflammatory cytokines. Ethnic differences have been observed, but no studies have investigated this relationship in the Mexican population. The objective of the present study was to evaluate whether a relationship exist between EAT thickness assessed via echocardiography with CAD and adiponectin levels in a Mexican population. METHODS: We studied 153 consecutive patients who underwent coronary angiography and transthoracic echocardiography (TTE). EAT thickness on the free wall of the right ventricle was measured at the end of systole from parasternal long and short axis views of three consecutive cardiac cycles. Coronary angiograms were analyzed for the presence, extent and severity of CAD. Serum adiponectin, lipids, glucose, C-reactive protein and fibrinogen were determined. RESULTS: EAT thickness was greater in patients with CAD than in those without CAD from both parasternal long (5.39 ± 1.75 mm vs 4.00 ± 1.67 mm p<0.0001) and short-axis views (5.23 ± 1.67 vs 4.12 ± 1.77, p=0.001). EAT thickness measured from parasternal long and short-axis showed a statistically significant positive correlation with age (r=0.354, p<0.001; r=0.286, p<0.001 respectively), and waist circumference (r=0.189, p=0.019; r=0.217, p=0.007 respectively). A significant negative correlation between EAT thickness from the parasternal long axis with cholesterol-HDL was observed (r=-0.163, p=0.045). No significant correlation was found between epicardial fat thickness and serum adiponectin or with the severity of CAD. CONCLUSIONS: EAT thickness was greater in patients with CAD. However, no correlation was observed with the severity of the disease or with serum adiponectin levels. EAT thickness measured by echocardiography might provide additional information for risk assessment and prediction of CAD.

Polµ deficiency increases resistance to oxidative damage and delays liver aging.

Polµ is an error-prone PolX polymerase that contributes to classical NHEJ DNA repair. Mice lacking Polµ (Polµ(-/-)) show altered hematopoiesis homeostasis and DSB repair and a more pronounced nucleolytic resection of some V(D)J junctions. We previously showed that Polµ(-/-) mice have increased learning capacity at old ages, suggesting delayed brain aging. Here we investigated the effect of Polµ(-/-) deficiency on liver aging. We found that old Polµ(-/-) mice (>20 month) have greater liver regenerative capacity compared with wt animals. Old Polµ(-/-) liver showed reduced genomic instability and increased apoptosis resistance. However, Polµ(-/-) mice did not show an extended life span and other organs (e.g., heart) aged normally. Our results suggest that Polµ deficiency activates transcriptional networks that reduce constitutive apoptosis, leading to enhanced liver repair at old age.

miR-335 correlates with senescence/aging in human mesenchymal stem cells and inhibits their therapeutic actions through inhibition of AP-1 activity.

MicroRNAs, small noncoding RNAs, regulate gene expression primarily at the posttranscriptional level. We previously found that miR-335 is critically involved in the regulation and differentiation capacity of human mesenchymal stem cells (hMSCs) in vitro. In this study, we investigated the significance of miR-335 for the therapeutic potential of hMSCs. Analysis of hMSCs in ex vivo culture demonstrated a significant and progressive increase in miR-335 that is prevented by telomerase. Expression levels of miR-335 were also positively correlated with donor age of hMSCs, and were increased by stimuli that induce cell senescence, such as γ-irradiation and standard O2 concentration. Forced expression of miR-335 resulted in early senescence-like alterations in hMSCs, including: increased SA-ß-gal activity and cell size, reduced cell proliferation capacity, augmented levels of p16 protein, and the development of a senescence-associated secretory phenotype. Furthermore, overexpression of miR-335 abolished the in vivo chondro-osseous potential of hMSCs, and disabled their immunomodulatory capacity in a murine experimental model of lethal endotoxemia. These effects were accompanied by a severely reduced capacity for cell migration in response to proinflammatory signals and a marked reduction in Protein Kinase D1 phosphorylation, resulting in a pronounced decrease of AP-1 activity. Our results demonstrate that miR-335 plays a key role in the regulation of reparative activities of hMSCs and suggests that it might be considered a marker for the therapeutic potency of these cells in clinical applications.

Cell senescence abrogates the therapeutic potential of human mesenchymal stem cells in the lethal endotoxemia model.

Mesenchymal stem cells (MSCs) possess unique paracrine and immunosuppressive properties, which make them useful candidates for cellular therapy. Here, we address how cellular senescence influences the therapeutic potential of human MSCs (hMSCs). Senescence was induced in bone marrow-derived hMSC cultures with gamma irradiation. Control and senescent cells were tested for their immunoregulatory activity in vitro and in vivo, and an extensive molecular characterization of the phenotypic changes induced by senescence was performed. We also compared the gene expression profiles of senescent hMSCs with a collection of hMSCs used in an ongoing clinical study of Graft Versus Host disease (GVHD). Our results show that senescence induces extensive phenotypic changes in hMSCs and abrogates their protective activity in a murine model of LPS-induced lethal endotoxemia. Although senescent hMSCs retain an ability to regulate the inflammatory response on macrophages in vitro, and, in part retain their capacity to significantly inhibit lymphocyte proliferation, they have a severely impaired migratory capacity in response to proinflammatory signals, which is associated with an inhibition of the AP-1 pathway. Additionally, expression analysis identified PLEC, C8orf48, TRPC4, and ZNF14, as differentially regulated genes in senescent hMSCs that were similarly regulated in those hMSCs which failed to produce a therapeutic effect in a GVHD trial. All the observed phenotypic alterations were confirmed in replicative-senescent hMSCs. In conclusion, this study highlights important changes in the immunomodulatory phenotype of senescent hMSCs and provides candidate gene signatures which may be useful to evaluate the therapeutic potential of hMSCs used in future clinical studies.