Integrase strand transfer inhibitors resistance-associated mutations in HIV-infected pregnant women.

OBJECTIVE: To date, no data exist regarding the prevalence of integrase inhibitor (INSTI) resistance-associated mutations (HIVDRM) in HIV-infected pregnant women (HPW) in Latin America. We describe the prevalence and transmissibility of integrase HIVDRM in a historical cohort of INSTI-naïve HPW from Argentina (n=56) with Next Generation Sequencing (NGS). METHODS: Bioinformatics analysis was performed by HyDRA software for 20%, 10%, 5%, 2%, and 1% sensitivity thresholds. We calculated the mutational viral load for each INSTI-HIVDRM, considering those with >1000 c/mL as of high risk of transmissibility. RESULTS: The predominant HIV subtype was BF (78.5%). Major HIVDRM were not detected with the population sequencing 20% filter. With a 1% threshold, the prevalence increased to 8.9%; Y143C/S, E92G, E138K, and T66I mutations were found. The median (range) mutational load (expressed in c/mL) was: 355 (50.2-11705); with only 1 case >1000 c/mL Accessory mutations (G163R/K, T97A) were detected mostly with a 20% sensitivity threshold with an overall prevalence of 23.2%; the median (IQR) mutational load was: 23929 (4009-63158) c/mL; all of them above 1000 c/mL. CONCLUSIONS: Our results show evidence of the presence of major INSTI-HIVDRM as aleatory mutations and a high frequency of accessory mutations with potential transmissibility in HPW.

[Validity and reliability of the Tardieu scale for assessing upper limb spasticity in adults with cerebrovascular disease. Systematic review]. / Validez y fiabilidad de la escala de Tardieu para evaluar la espasticidad en miembro superior en adultos con enfermedad cerebrovascular. Revisión sistemática.

INTRODUCTION: The increase in the number of people with upper limb spasticity as a sequela of cerebrovascular disease, which negatively impacts their autonomy, functional independence and participation, and affects their quality of life, calls for the application of precise and objective instruments for its measurement and evaluation. OBJECTIVE: To assess the validity and reliability of the Tardieu scale in the evaluation of upper extremity spasticity in adults with cerebrovascular disease. MATERIALS AND METHODS: The search strategy was implemented in eight databases; the systematic review protocol was registered beforehand in INPLASY (with registration no. 2023110076). The evidence was synthesised in three phases: a tabular presentation of results, an evaluation of the quality of the articles, and a narrative synthesis of the findings. RESULTS: Only three of the 33 articles identified fulfilled the variables that enable the validity and reliability of the Tardieu scale to be established. The measurements of angles and velocities R1, R2 and R2-R1 were analysed. Student's t-test to assess the reliability between the measurements of R1 and R2; and angles R2 and R2-R1 showed statistical significance, which confirmed the reliability of the scale. CONCLUSIONS: The Tardieu scale proved robust. It is important to note that the sample size, the time of evolution of the disease and the age of the patients may influence the results of the scale.

TITLE: Validez y fiabilidad de la escala de Tardieu para evaluar la espasticidad en miembro superior en adultos con enfermedad cerebrovascular. Revisión sistemática.Introducción. El incremento en el número de personas con espasticidad en los miembros superiores como secuela de una enfermedad cerebrovascular, que impacta negativamente en la autonomía, la independencia funcional y la participación, y afecta a la calidad de vida de las personas, demanda la aplicación de herramientas clínicas precisas y objetivas para su medición y evaluación. Objetivo. Evaluar la validez y la fiabilidad de la escala de Tardieu en la evaluación de la espasticidad en las extremidades superiores de adultos con enfermedad cerebrovascular. Materiales y métodos. La estrategia de búsqueda se implementó en ocho bases de datos; el protocolo de revisión sistemática se registró previamente en INPLASY (registro n.o 2023110076). La síntesis de la evidencia se llevó a cabo en tres fases: presentación tabular de resultados, evaluación de la calidad de los artículos y síntesis narrativa de los hallazgos. Resultados. De los 33 artículos identificados, sólo tres cumplieron con las variables que permiten establecer la validez y la fiabilidad de la escala de Tardieu. Se analizaron las medidas de los ángulos y velocidades R1, R2 y R2-R1. La prueba de la t de Student para evaluar la fiabilidad entre las medidas de R1 y R2; los ángulos R2 y R2-R1 mostraron significancia estadística, lo que confirmó la confiabilidad de la escala. Conclusiones. La escala de Tardieu demostró robustez. Es importante considerar que el tamaño de la muestra, el tiempo de evolución de la enfermedad y la edad de los pacientes pueden influir en los resultados de la escala.

Adolescent alcohol exposure persistently alters orbitofrontal cortical encoding of Pavlovian conditional stimulus components in female rats.

Exposure to alcohol during adolescence impacts cortical and limbic brain regions undergoing maturation. In rodent models, long-term effects on behavior and neurophysiology have been described after adolescent intermittent ethanol (AIE), especially in males. We hypothesized that AIE in female rats increases conditional approach to a reward-predictive cue and corresponding neuronal activity in the orbitofrontal cortex (OFC) and nucleus accumbens (NAc). We evaluated behavior and neuronal firing after AIE (5 g/kg intragastric) or water (CON) in adult female rats. Both AIE and CON groups expressed a ST phenotype, and AIE marginally increased sign-tracking (ST) and decreased goal-tracking (GT) metrics. NAc neurons exhibited phasic firing patterns to the conditional stimulus (CS), with no differences between groups. In contrast, neuronal firing in the OFC of AIE animals was greater at CS onset and offset than in CON animals. During reward omission, OFC responses to CS offset normalized to CON levels, but enhanced OFC firing to CS onset persisted in AIE. We suggest that the enhanced OFC neural activity observed in AIE rats to the CS could contribute to behavioral inflexibility. Ultimately, AIE persistently impacts the neurocircuitry of reward-motivated behavior in female rats.

[The origin of a scientific article: the research question (second part)]. / El origen de un artículo científico: la pregunta de investigación (segunda parte).

No Abstract available.

[The origin of a scientific article: the research question (first part)]. / El origen de un artículo científico: la pregunta de investigación (primera parte).

No Abstract available.

Plasma rich in growth factors membrane as a macular hole treatment in a vitrectomized patient due to rhegmatogenous retinal detachment.

The formation of a macular hole after vitrectomy due to rhegmatogenous retinal detachment is a rare complication. Although there are different surgical options in the treatment of these macular holes with favorable outcomes, it has been shown that the history of macula-off retinal detachment is the most important risk factor related to the need for multiple interventions to close these macular holes, therefore special attention should be paid in the management of these patients. We present the case of a patient with macula-off rhegmatogenous retinal detachment who required treatment with cataract surgery with intraocular lens implant and pars plana vitrectomy. Four years after the primary surgery, she presented a large macular hole, and was treated with membrane of plasm rich in growth factors with closure of the macular hole and visual improvement without recurrence 12 months after surgery.

[The Mexican Orthopedic Act on its 72nd anniversary]. / El Acta Ortopédica Mexicana a sus 72 años.

No Abstract available.

Behavioral effects of environmental enrichment on male and female wistar rats with early life stress experiences.

Exposure to adverse childhood experiences or early life stress experiences (ELSs) increase the risk of non-adaptive behaviors and psychopathology in adulthood. Environmental enrichment (EE) has been proposed to minimize these effects. The vast number of methodological variations in animal studies underscores the lack of systematicity in the studies and the need for a detailed understanding of how enrichment interacts with other variables. Here we evaluate the effects of environmental enrichment in male and female Wistar rats exposed to adverse early life experiences (prenatal, postnatal, and combined) on emotional (elevated plus maze), social (social interaction chamber), memory (Morris water maze) and flexibility tasks. Our results-collected from PND 51 to 64-confirmed: 1) the positive effect of environmental enrichment (PND 28-49) on anxiety-like behaviors in animals submitted to ELSs. These effects depended on type of experience and type of enrichment: foraging enrichment reduced anxiety-like behaviors in animals with prenatal and postnatal stress but increased them in animals without ELSs. This effect was sex-dependent: females showed lower anxiety compared to males. Our data also indicated that females exposed to prenatal and postnatal stress had lower anxious responses than males in the same conditions; 2) no differences were found for social interactions; 3) concerning memory, there was a significant interaction between the three factors: A significant interaction for males with prenatal stress was observed for foraging enrichment, while physical enrichment was positive for males with postnatal stress; d) regarding cognitive flexibility, a positive effect of EE was found in animals exposed to adverse ELSs: animals with combined stress and exposed to physical enrichment showed a higher index of cognitive flexibility than those not exposed to enrichment. Yet, within animals with no EE, those exposed to combined stress showed lower flexibility than those exposed to both prenatal stress and no stress. On the other hand, animals with prenatal stress and exposed to foraging-type enrichment showed lower cognitive flexibility than those with no EE. The prenatal stress-inducing conditions used here 5) did not induced fetal or maternal problems and 6) did not induced changes in the volume of the dentate gyrus of the hippocampus.

Procuramiento y uso de aloinjertos cutáneos de piel total criopreservados obtenidos de pacientes sometidas a abdominoplastía / Procurement and use of cryopreserved whole skin cutaneous allografts obtained from patients undergoing abdominoplasty

Resumen Introducción: Los aloinjerto cutáneos (AC) son excelentes sustitutos cutáneos temporales, sin embargo, la donación y procura de piel cadavérica, fuente habitual de AC, es baja. Objetivo: Evaluar la factibilidad de utilizar la piel proveniente de abdominoplastías como fuente de AC y su eficacia clínica. Materiales y Método: Entre el 17 de agosto de 2020 al 28 de febrero de 2021 se analizó una cohorte prospectiva de 14 pacientes femeninas sometidas a abdominoplastía por motivos estéticos, que aceptaron donar la piel del colgajo cutáneo abdominal redundante, la cual fue criopreservada. Se utilizaron los AC de piel total criopreservados (ACPTC) en 10 pacientes con diagnósticos de: pie diabético (4), laparostomía contenida (2) herida compleja extremidad inferior (2), sarcoma de cuero cabelludo recidivado (1) y melanoma (1). Resultados: Se obtuvieron 14 colgajos de piel total, los cuales fueron procesados obteniendo una superficie promedio de 302 cm2 y 8,3 láminas de distintos tamaños de utilidad clínica por paciente. En todos los pacientes en que se utilizó ACPTC hubo un prendimiento inicial del AC para posteriormente, en promedio 21 días, presentar una escara necrótica que al ser retirada presentaba un tejido vital adherido al receptor rico en fibroblastos, siendo algunos pacientes auto injertados y otros manejados con cicatrización por segunda intención como tratamiento definitivo. Discusión: Los ACPTC proporcionan una cobertura intermedia, pues una parte se integra en forma definitiva, actuando como un andamiaje biológico para la formación de una interfase sobre la cual se puede autoinjertar o dejar evolucionar con cicatrización por segunda intención y una parte es rechazada. Conclusión: La procura de piel de donante vivo, en pacientes sometidos a cirugías de contorno corporal es un proceso factible, fuente de ACPTC, los cuales permiten una nueva cobertura intermedia con múltiples aplicaciones clínicas.

Introduction: Skin allografts (SA) are outstanding temporary skin substitutes; however, cadaveric skin donation and procurement, a common source of SA, remains low. Aim: To evaluate the feasibility and clinical efficacy of using skin from abdominoplasties as a source of SA. Materials and Method: A prospective cohort was analyzed from August 17th, 2020 and February 28th, 2021, with 14 female patients submitted to abdominoplasty surgeries for aesthetic motives, who authorized skin donation from the redundant abdominal flap which was posteriorly cryopreserved. Cryopreserved total skin allografts (CTSA) was used in 10 patients with the following diagnoses: diabetic foot (4), contained laparostomy (2) complex wound of the lower limb (2), relapsing sarcoma of the scalp (1), and melanoma (1). Results: 14 CTSA were obtained, which were processed, obtaining an average area of 302 cm2 and 8.3 sheets of different sizes and clinical applications from each patient. In all patients who received CTSA, an initial attachment was observed, followed by the appearance of a necrotic scar in an average of21 days. The peeling of the latter revealed a vital tissue tightly adhered to the receptor and rich in fibroblasts. Some of the patients received autografts, and others were managed with secondary intention scarring as a definite treatment. Discussion: CTSA provide an intermediate coverage since one part is definitely adhered to, acting as a biologic scaffolding for the formation of an interface that can be autografted or left for a secondary intention scarring, and the host rejects the other portion. Conclusión: skin procurement from a living donor in patients submitted to body contour surgeries is a feasible process and significant source of CTSA, which permits a new intermediate coverage with multiple clinical uses.

[Editorial]. / Editorial.

No Abstract available.

[Four years follow up in congenital talipes equino varus patients managed with Ponseti method]. / Seguimiento por cuatro años de pacientes con pie equinovaro aducto congénito manejados con método Ponseti.

INTRODUCTION: Congenital talipes equino varus (club foot) is a frequent congenital deformity of the foot. The Ponseti method is the gold standard for treatment. It consists of foot manipulation with weekly serial cast, minimally invasive surgery and Dennis-Brown bar up to five years. OBJECTIVE: To describe the follow-up of patients with PEVAC treated using the Ponseti method. MATERIAL AND METHODS: Descriptive, longitudinal study, during 2013-2019, in patients with PEVAC managed with Ponseti method. We included patients with uni- or bilateral club foot, under two years of age, without prior surgery, whose parents signed informed consent. Patients with other malformations were excluded. Serial weekly cast was placed for 4-8 weeks, a tenotomy of the Achilles tendon was performed, and cast for three more weeks; then reverse footwear with Dennis-Brown bar. The revisions were recorded at day zero, at eight weeks and every three months up to five years of age. Correction of deformity and pain on walking was assessed. RESULTS: There were 22 patients; 17 (77.3%) corrected more than 90% of the deformity, with adequate functionality and 86.3% without pain on gait, mean follow-up 3.9 years (1-7 years); six patients relapsed (27.27%) due to poor attachment, one re-treated with cast, and five with anterior tibial transfer, all successfully. CONCLUSIONS: The club foot managed with Ponseti method corrects more than 90% of the deformity and without or minimal pain with good adherence to treatment. We had a 27.27% recurrence in our series.

INTRODUCCIÓN: El pie equinovaro aducto congénito (PEVAC) es una deformidad congénita frecuente del pie. El método Ponseti es el estándar de oro para el tratamiento. Consiste en la manipulación del pie con yesos seriados semanales, una cirugía mínimamente invasiva y barra Dennis-Brown hasta los cinco años. OBJETIVO: Describir el seguimiento de los pacientes con PEVAC tratados mediante método Ponseti. MATERIAL Y MÉTODOS: Estudio descriptivo, longitudinal, durante 2013-2019, en pacientes con PEVAC manejados con método Ponseti. Se incluyeron pacientes con PEVAC uni- o bilateral, menores de dos años, sin cirugía previa, cuyos padres firmaron consentimiento informado. Se excluyeron pacientes con otras malformaciones. Se colocó yeso semanal seriado por cuatro a ocho semanas, se realizó tenotomía del tendón de Aquiles y yeso por tres semanas más; luego calzado de horma inversa con barra Dennis-Brown. Se registraron las revisiones al día cero, a las ocho semanas y cada tres meses hasta los cinco años de edad. Se valoró la corrección de la deformidad y el dolor a la marcha. RESULTADOS: Fueron 22 pacientes; 17 (77.3%) corrigieron más de 90% de la deformidad, con adecuada funcionalidad y 86.3% sin dolor a la marcha, seguimiento medio de 3.9 años (uno a siete años); seis pacientes tuvieron recidiva (27.27%) por mal apego, uno retratado con yesos y cinco con transferencia de tibial anterior, todos con éxito. CONCLUSIONES: El PEVAC manejado con método Ponseti corrige más de 90% de la deformidad y sin o mínimo dolor con buen apego al tratamiento. Tuvimos una recidiva de 27.27% en nuestra serie.

Reverse transcriptase and protease inhibitors mutational viral load in HIV infected pregnant women with transmitted drug resistance in Argentina.

OBJECTIVE: Argentina has reported high levels of transmitted drug resistance (TDR), in HIV-infected pregnant women by population sequencing. We aimed to describe, in patients with TDR, the percentage of quasispecies harboring resistance mutations (RAMs) and mutational load (ML). METHODS: Retrospective study in a cohort of 40 naïve HIV-infected pregnant women, whose pretreatment samples had been genotyped by TRUGENE (period 2008-2014). Samples were re-sequenced with Ultra-deep Sequencing and ML was calculated considering baseline HIV-1 RNA load multiplied by the frequency of quasispecies harboring RAMs. RESULTS: TDR for NNRTIs, NRTIs and PIs was 17.5% (n=7 patients), 10% (n=4), 12.5% (n=5) respectively. Predominant NNRTI RAMs were K103N (n=4; 10%) and G190A/E/S (n=3; 7.5%). For NNRTIs, 78% of RAMs were present in >93.5% of viral population and ML was >1000 copies/mL (c/mL) for 89%, with a median (IQR) of 8330 c/ml (7738-29796). The following NRTI RAMs were described (per patient: % of quasispecies, ML): T215I (99.7%, 11014 c/ml); D67G (1.28%, 502 c/mL); M41L (79.8%, 88578 c/mL) and M184I (1.02%, 173 c/mL). Most frequent PI-RAMs were I85V, M46I, I50V and L90M (n=2, 5% each). For PIs, quasispecies with RAMs were <2.3% of viral population and ML was <350 c/mL for 77.8% of them. CONCLUSIONS: NNRTI-RAMs are predominant within the viral population, usually exceeding the threshold of 1000 c/mL, indicating potential higher risk of perinatal transmission. Conversely, PI mutations appear mostly as minority variants, with potential lower risk of transmission. Among NRTI, quasispecies harboring RAMs and ML values were variable.

Diabetes is a major cause of influenza-associated mortality in Mexico.

BACKGROUND: Influenza is a major cause of mortality worldwide. Most influenza-associated deaths are associated with cardiovascular or respiratory disorders. However, a large proportion of influenza-associated deaths do not have respiratory or cardiovascular disorders declared as the underlying cause of death. Diabetic individuals are at increased risk for influenza-mortality. In this study, we assessed the contribution of diabetes to influenza-associated mortality in Mexico. METHODS: Diabetes influenza-associated mortality was estimated for the Mexican population using National Mortality Databases from the Mexican Ministry of Health from 1998 through 2015. Diabetes influenza-associated mortality was calculated applying Serfling cyclical regression models to weekly mortality rates for persons 20-59 years, 60 and more years, and all ages, and by sex. RESULTS: There was a high correlation between weekly pneumonia and influenza mortality and diabetes-related mortality. Yearly influenza-associated diabetes mortality rates varied between 2.0 and 5.9/100,000. Up until the 2005-2006 season, diabetes-associated mortality rates were higher in females, while after that season rates were higher in males. Yearly influenza-associated diabetes mortality rates for adults 20-59 years of age ranged between 1.7 and 3.4/100,000, while estimates for adults 60 years and older ranged between 16.3 and 46.1/100,000. Approximately one third of estimated diabetes influenza-associated deaths occurred in adults 20-59 years of age. On average, diabetes deaths accounted for 19.6% of estimated influenza-associated all-cause mortality. CONCLUSION: Diabetes is a major cause of estimated influenza-associated mortality in Mexico. Health-care authorities and professionals in countries with high diabetes prevalence should be aware of the potential impact of influenza in individuals with this condition.

Clinical Factors Associated with High Glycemic Variability Defined by Coefficient of Variation in Patients with Type 2 Diabetes.

BACKGROUND: High glycemic Variability (HGV) has become a stronger predictor of hypoglycemia. However, clinical factors associate with HGV still are unknown. OBJECTIVE: To determine clinical variables that were associated with a coefficient of variation (CV) above 36% evaluated by continuous glucose monitoring (CGM) in a group of patients with diabetes mellitus. METHODS: A cohort of patients with type 2 diabetes (T2D) was evaluated. Demographic variables, HbA1c, glomerular filtration rate (GFR) and treatment regimen were assessed. A bivariate analysis was performed, to evaluate the association between the outcome variable (CV> 36%) and each of the independent variables. A multivariate model was constructed to evaluate associations after controlling for confounding variables. RESULTS: CGM data from 274 patients were analyzed. CV> 36% was present in 56 patients (20.4%). In the bivariate analysis, demographic and clinical variables were included, such as time since diagnosis, hypoglycemia history, A1c, GFR and treatment established. In the multivariate analysis, GFR <45 mL/min (OR 2.81; CI 1.27,6.23; p:0.01), A1c > 9% (OR 2.81; CI 1.05,7.51; p:0.04) and hypoglycemia history (OR 2.09; CI 1.02,4.32; p:0.04) were associated with HGV. Treatment with iDPP4 (OR 0.39; CI 0.19,0.82; p:0.01) and AGLP1 (OR 0.08; CI 0.01,0.68; p:0.02) was inversely associated with GV. CONCLUSION: Clinical variables such as GFR <45 mL/min, HbA1C>9% and a history of hypoglycemia are associated with a high GV. Our data suggest that the use of technology and treatments able to reduce glycemic variability could be useful in this population to reduce the risk of hypoglycemia and to improve glycemic control.

Efecto del Programa de Prevención de Lesiones en Seleccionados Masculinos de Hockey sobre Césped / Effect of the Injury Prevention Program on Selected Men's Field Hockey Teams

Introducción: La implementación de programas de prevención de lesiones en deportistas es fundamental para evitar las consecuencias físicas, de rendimiento y salud que puede provocar una lesión. No obstante, en hockey sobre césped la evidencia es escasa y poco transferible a jugadores masculinos de élite, existiendo así la necesidad de desarrollar estudios en esta población específica. Objetivos: Determinar el efecto de un programa de prevención de lesiones en seleccionados masculinos de hockey sobre césped en relación a la cantidad de lesiones en extremidades inferiores y zona lumbar presentadas por los jugadores en los Juegos Panamericanos. Métodos: Se analizó a 30 jugadores realizando una comparación mediante un análisis estadístico de las lesiones registradas en seleccionados nacionales de hockey sobre césped durante los Juegos Panamericanos del año 2015 (grupo control, sin programa de prevención de lesiones) y durante los Juegos Panamericanos del año 2019 (grupo intervenido con programa de prevención de lesiones). Resultados: No se encontró diferencia estadísticamente significativa en cuanto a cantidad de lesiones presentadas por los jugadores comparando los años 2015 y 2019 (p=0,068). Se encontró diferencia estadísticamente significativa en cuanto a cantidad de jugadores lesionados comparando los años 2015 y 2019 (p= 0.04). Conclusión: Se evidencia una reducción significativa en la cantidad de jugadores lesionados, en el grupo de jugadores que realizó el programa de prevención de lesiones previo a los Juegos Panamericanos de Lima 2019.

Introduction: The implementation of injury prevention programs in athletes is essential to avoid the physical, performance and health consequences that an injury can cause. However, the evidence in field hockey is scarce and not very transferable to elite male athletes, thus there is a need to carry out studies in this specific population. Objectives: To determine the effect of an injury prevention program in national selected male field hockey players in relation to the amount of injuries in the lower extremities (LES) and lumbar area presented by the players in the Pan American Games. Methods: 30 players were analyzed by making a comparison through a statistical analysis of the injuries registered in selected national field hockey players during the Pan American Games of 2015 (control group, without injury prevention program) and during the Pan American Games of 2019 (group intervened with injury prevention program). Results: No statistically significant difference was found in terms of the amount of injuries presented by the players comparing the years 2015 and 2019 (p = 0.068). A statistically significant difference was found in terms of the number of injured players comparing the years 2015 and 2019 (p = 0.04). Conclusion: A significant reduction in the number of injured players is evidenced in the group of players that carried out the injury prevention program prior to the Lima 2019 Pan American Games.

H2A.Z overexpression suppresses senescence and chemosensitivity in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most intractable and devastating malignant tumors. Epigenetic modifications such as DNA methylation and histone modification regulate tumor initiation and progression. However, the contribution of histone variants in PDAC is unknown. Here, we demonstrated that the histone variant H2A.Z is highly expressed in PDAC cell lines and PDAC patients and that its overexpression correlates with poor prognosis. Moreover, all three H2A.Z isoforms (H2A.Z.1, H2A.Z.2.1, and H2A.Z.2.2) are highly expressed in PDAC cell lines and PDAC patients. Knockdown of these H2A.Z isoforms in PDAC cell lines induces a senescent phenotype, cell cycle arrest in phase G2/M, increased expression of cyclin-dependent kinase inhibitor CDKN2A/p16, SA-ß-galactosidase activity and interleukin 8 production. Transcriptome analysis of H2A.Z-depleted PDAC cells showed altered gene expression in fatty acid biosynthesis pathways and those that regulate cell cycle and DNA damage repair. Importantly, depletion of H2A.Z isoforms reduces the tumor size in a mouse xenograft model in vivo and sensitizes PDAC cells to gemcitabine. Overexpression of H2A.Z.1 and H2A.Z.2.1 more than H2A.Z.2.2 partially restores the oncogenic phenotype. Therefore, our data suggest that overexpression of H2A.Z isoforms enables cells to overcome the oncoprotective barrier associated with senescence, favoring PDAC tumor grow and chemoresistance. These results make H2A.Z a potential candidate as a diagnostic biomarker and therapeutic target for PDAC.

Use of coumarins as complementary medicine with an integrative approach against cervical cancer: background and mechanisms of action.

Cervical cancer is characterized by the cellular transformation caused by Human Papillomavirus (HPV), favoring cell proliferation, migration, invasion, and metastasis. Cervical cancer is conventionally treated with radiation therapy, and chemotherapy focused on the destruction of tumor cells. However, chemoresistance and low selectivity between tumor and non-tumor cells have been reported, causing side effects in patients. Metabolites of natural origin have shown selectivity against tumor cells, suggesting their use for reducing the side effects caused by drugs used in conventional therapy. Among these compounds, several natural coumarins stand out, such as auraptene, scopoletin, osthole, and praeruptorin, of which antiproliferative, anti-migratory, and anti-invasive activity have been reported. Auraptene, scopoletin, osthole, and praeruptorin show a cytotoxic or antiproliferative effect on cervical tumor cells, arresting the cell cycle by inducing the overexpression of negative regulators of the cell cycle, or inducing cell death by increasing the expression of pro-apoptotic proteins and decreasing that of anti-apoptotic proteins. On the other hand, auraptene, scopoletin, and praeruptorin inhibit the capacity for migration, invasion, and metastasis of cervical tumor cells, mainly by inhibiting the expression and activity of matrix metalloproteinase-2 and -9. The PI3K/Akt signal pathway appears to be central to the anti-tumor activity of the coumarins analyzed in this review. In addition, auraptene, osthole, and praeruptorin are useful in sensitizing tumor cells to radiotherapy or chemotherapeutic molecules, such as FOLFOX, cisplatin, or DOX. Coumarins offer an excellent possibility for developing new drugs as complementary medicine with an integrative approach against cervical cancer.

Augmenting Global Coherence in EEG Signals with Binaural or Monaural Noises.

Internal stochastic resonance (internal SR) is a phenomenon of non-linear systems in which the addition of a non-zero level of noise produces an enhancement in the coherence between two or more signals. In a previous study, we found that the simultaneous administration of multisensory visual and auditory noise augments global coherence in electroencephalographic (EEG) signals via this phenomenon. Here, we examined whether such global coherence can also be augmented with at least one noisy acoustic source. We performed experiments on healthy subjects and applied the following binaural and monaural noise-stimulation protocols. First, we administered to the left ear Gaussian noise of fixed intensity, while we delivered to the right ear a second Gaussian noise of variable intensity levels (binaural protocol). Second, we applied the Gaussian noise of the same variable intensity levels but only to one ear (monaural protocol). We performed a permutation test analysis, finding that during both noise protocols there was a significant enhancement in the global coherence in EEG signals via the occurrence of internal SR within central pathways of the auditory system.