Prolactin is an Endogenous Antioxidant Factor in Astrocytes That Limits Oxidative Stress-Induced Astrocytic Cell Death via the STAT3/NRF2 Signaling Pathway.

Oxidative stress-induced death of neurons and astrocytes contributes to the pathogenesis of numerous neurodegenerative diseases. While significant progress has been made in identifying neuroprotective molecules against neuronal oxidative damage, little is known about their counterparts for astrocytes. Prolactin (PRL), a hormone known to stimulate astroglial proliferation, viability, and cytokine expression, exhibits antioxidant effects in neurons. However, its role in protecting astrocytes from oxidative stress remains unexplored. Here, we investigated the effect of PRL against hydrogen peroxide (H2O2)-induced oxidative insult in primary cortical astrocyte cultures. Incubation of astrocytes with PRL led to increased enzymatic activity of superoxide dismutase (SOD) and glutathione peroxidase (GPX), resulting in higher total antioxidant capacity. Concomitantly, PRL prevented H2O2-induced cell death, reactive oxygen species accumulation, and protein and lipid oxidation. The protective effect of PRL upon H2O2-induced cell death can be explained by the activation of both signal transducer and activator of transcription 3 (STAT3) and NFE2 like bZIP transcription factor 2 (NRF2) transduction cascades. We demonstrated that PRL induced nuclear translocation and transcriptional upregulation of Nrf2, concurrently with the transcriptional upregulation of the NRF2-dependent genes heme oxygenase 1, Sod1, Sod2, and Gpx1. Pharmacological blockade of STAT3 suppressed PRL-induced transcriptional upregulation of Nrf2, Sod1 and Gpx1 mRNA, and SOD and GPX activities. Furthermore, genetic ablation of the PRL receptor increased astroglial susceptibility to H2O2-induced cell death and superoxide accumulation, while diminishing their intrinsic antioxidant capacity. Overall, these findings unveil PRL as a potent antioxidant hormone that protects astrocytes from oxidative insult, which may contribute to brain neuroprotection.

Prolactin Inhibits or Stimulates the Inflammatory Response of Joint Tissues in a Cytokine-dependent Manner.

The close association between rheumatoid arthritis (RA), sex, reproductive state, and stress has long linked prolactin (PRL) to disease progression. PRL has both proinflammatory and anti-inflammatory outcomes in RA, but responsible mechanisms are not understood. Here, we show that PRL modifies in an opposite manner the proinflammatory actions of IL-1ß and TNF-α in mouse synovial fibroblasts in culture. Both IL-1ß and TNF-α upregulated the metabolic activity and the expression of proinflammatory factors (Il1b, Inos, and Il6) via the activation of the nuclear factor-κB (NF-κB) signaling pathway. However, IL-1ß increased and TNF-α decreased the levels of the long PRL receptor isoform in association with dual actions of PRL on synovial fibroblast inflammatory response. PRL reduced the proinflammatory effect and activation of NF-κB by IL-1ß but increased TNF-α-induced inflammation and NF-κB signaling. The double-faceted role of PRL against the 2 cytokines manifested also in vivo. IL-1ß or TNF-α with or without PRL were injected into the knee joints of healthy mice, and joint inflammation was monitored after 24 hours. IL-1ß and TNF-α increased the joint expression of proinflammatory factors and the infiltration of immune cells. PRL prevented the actions of IL-1ß but was either inactive or further increased the proinflammatory effect of TNF-α. We conclude that PRL exerts opposite actions on joint inflammation in males and females that depend on specific proinflammatory cytokines, the level of the PRL receptor, and the activation of NF-κB signaling. Dual actions of PRL may help balance joint inflammation in RA and provide insights for development of new treatments.

Latin American Origin Is Not Associated with Worse Outcomes among Hospitalized Patients with COVID-19 in a Public Healthcare System.

Exploring differences in clinical outcomes based on race and origin among patients hospitalized for COVID-19 is a controversial issue. The ALC COVID-19 Registry includes all confirmed COVID-19 patients admitted to hospital from 3 March 2020 to 17 December 2020. The data were obtained from electronic health records in order to evaluate the differences in the clinical features and outcomes among European and Latin American patients. The follow-ups occurred after 156 days. A propensity score weighting (PSW) logistic regression model was used to estimate the odds ratio (OR, 95% CI) for Latin American origin and outcome associations. Of the 696 patients included, 46.7% were women, with a median age of 65 (IQR 53-67) years, 614 (88.2%) were European, and 82 (11.8%) were Latin American. Latin American patients were younger, with fewer comorbidities, and a higher incidence of extensive pneumonia. After adjusting for residual confounders, Latin American origin was not associated with an increased risk of death (PSW OR 0.85 (0.23-3.14)) or with the need for invasive mechanical ventilation (PSW OR 0.35 (0.12-1.03)). Latin American origin was associated with a shorter hospital stay, but without differences in how long the patient remained on mechanical ventilation. In a public healthcare system, the rates of death or mechanical ventilation in severe COVID-19 cases were found to be comparable between patients of European and Latin American origins.

Efficient anchoring of nanostructured cadmium selenide on different kinds of carbon nanotubes.

We report a method for the efficient anchoring of cadmium selenide (CdSe) nanoparticles on the surface of different types of multi-walled carbon nanotubes (purified, N-doped, O-doped and exfoliated). Characterization using different types of electron microscopies (SEM, STEM, and TEM), energy dispersive spectroscopy (EDS) and x-ray diffraction showed well anchored CdSe nanoparticles (NP) on the nanotube surfaces, NP shapes and sizes varied with temperature and other synthesis conditions, and formed with good yields. The method here reported does not require previous activation of the carbon nanotube surface by chemical functionalization, nor the use of organic solvents, and the reaction proceeded in aqueous solutions, making this process simpler and more environmentally friendly than others.

Vasoinhibin generation and effect on neuronal apoptosis in the hippocampus of late mouse embryos.

Morphological and behavioral evidence suggests that vasoinhibin is present in the central nervous system (CNS), triggering neuroendocrine and behavioral responses to stress. Moreover, vasoinhibin reduces neuronal survival and differentiation of primary sensory neurons of the peripheral nervous system. To address the functional role played by vasoinhibin at the CNS, and to better understand the underlying mechanisms involved in its actions, we treated primary cultured hippocampal neurons obtained from embryonic day 16 (E16) mice with a human recombinant vasoinhibin. We examined the resulting cellular changes, focusing on neuronal cell death, and explored the local generation of vasoinhibin within the hippocampus. Our results show that vasoinhibin significantly reduced neuronal cell density and increased immunoreactive activated caspase-3 and TUNEL-positive staining at 72, 16, and 24 h, respectively. Furthermore, vasoinhibin increased the expression of proapoptotic genes BAX, BAD, BIM, and PUMA and decreased that of the antiapoptotic gene BCL-2 at 24 h, as assessed by quantitative real-time reverse transcription-polymerase chain reaction. Vasoinhibin effects were blocked by coincubation with a vasoinhibin antibody or with prolactin. Immunoreactive bands consistent with vasoinhibin were observed in hippocampal extracts by Western blot analysis, and a prolactin standard was cleaved to vasoinhibin by a hippocampal lysate in a heat- and cathepsin D inhibitor pepstatin A-dependent fashion. Taken together, these data support the notion that vasoinhibin is locally produced by cathepsin D within the embryonic mouse hippocampus, a brain region that plays a critical role in emotional regulation, resulting in decreased neuronal cell viability via the activation of the intrinsic apoptosis pathway.

Morphological and functional changes of chronic pancreatitis in patients with dyspepsia: A prospective, observational, cross-sectional study.

OBJECTIVE: Whether chronic pancreatitis (CP) may present with dyspepsia is controversial. We aimed at evaluating the frequency and risk factors of changes of CP in patients presenting with epigastric pain syndrome (EPS)-like symptoms. DESIGN: A prospective, observational, cross-sectional study was carried out in patients with EPS-like symptoms. Patients underwent endoscopic ultrasound (EUS) evaluation of the pancreas, and changes of CP were defined as the presence of five or more EUS criteria of the disease. In patients with 3 or 4 EUS criteria, magnetic resonance dynamic evaluation of the pancreas (MRI/sMRCP) and endoscopic pancreatic function test (ePFT) were carried out to confirm or exclude the presence of changes of CP. A multivariate logistic regression analysis was performed to evaluate factors associated with CP findings, and results are shown as odds ratio (OR) and 95% confidence interval (CI). RESULTS: 213 patients were included. Changes of CP were confirmed by EUS (≥5 criteria) in 18 patients (8.4%). Thirty-four patients had 3-4 EUS criteria, and changes of CP were confirmed in 27 of them by MRI/sMRCP and ePFT (12.7%). Morphological and functional findings of CP were then present in 45 patients (21.1%). Male gender (OR 2.97; 95%CI 1.39-6.37) and alcohol and tobacco consumption (OR 6.56; 95%CI 1.97-21.85) were associated with the presence of changes of CP. CONCLUSION: Morphological and functional changes of CP are frequent in patients with EPS-like symptoms. Whether these pancreatic changes explain EPS-like symptoms requires further investigation.

In Situ Production of Graphene-Fiber Hybrid Structures.

We report a scalable method to obtain a new material where large graphene sheets form webs linking carbon fibers. Film-fiber hybrid nonwoven mats are formed during fiber processing and converted to carbon structures after a simple thermal treatment. This contrasts with multistep methods that attempt to mix previously prepared graphene and fibers, or require complicated and costly processes for deposition of graphene over carbon fibers. The developed graphene-fiber hybrid structures have seamless connections between graphene and fibers, and in fact the graphene "veils" extend directly from one fiber into another forming a continuous surface. The graphene-fiber hybrid structures are produced in situ from aqueous poly(vinyl alcohol) solutions. The solutions were subjected to centrifugal spinning to produce fine nanofiber mats. The addition of salt to the polymer solution stimulated a capillarity effect that promoted the formation of thin veils, which become graphene sheets upon dehydration by sulfuric acid vapor followed by carbonization (at relatively low temperatures, below 800 °C). These veils extend over several micrometers within the pores of the fiber network, and consist of crystalline graphene layers that cross-link the fibers to form a highly interconnected hybrid network. The surface area and pore diameter of the hybrid structures were measured to be 521 m2g-1 and 10 nm, respectively. The resulting structure shows high electrical conductivity, 550 S/m, and promising shielding of electromagnetic interference, making it an attractive system for a broad range of electronic applications.

Experience in real clinical practice with new direct acting antivirals in chronic hepatitis C. / Experiencia en práctica clínica real con los nuevos antivirales de acción directa en hepatitis crónica C.

INTRODUCTION AND OBJECTIVE: Inclusion of direct-acting antivirals into clinical practice in patients with chronic HCV (CHC) has been a milestone in medicine. PATIENTS AND METHODS: Analytical, prospective study, involving 126 patients with chronic HCV treated with direct-acting antivirals. Efficacy and safety of treatment and factors associated with failure treatment were evaluated. RESULTS: Age 54±10. Male (70%). Cirrhosis (60%). Distribution according to genotypes: G1a (31%), G1b (42%); G3 (14%); G4 (13%). Child-Pugh B and C (n=15). Naïve (56%). SVR rate was (87.3%): Child-A (91%), Child-B (75%) and Child-C (60%). The best cure rates were achieved with a 3D/2D±ribavirin (SVR=97.4%;n=39) and sofosbuvir/ledipasvir±ribavirin (RVS=93.1%; n=29) combination. An SVR rate of <90% was achieved with sofosbuvir+simeprevir±ribavirin (SVR=88%, n=25), simeprevir+daclatasvir±ribavirin 73%, n=15). The association of ribavirin to these last three therapeutic options (n=19) improved cure rates (SVR=94.7%, 18/19) compared to its absence (n=39;SVR=77%). Improvement in MELD (40%). Output transplant list (20%). Substitutions associated with resistors NS3: G1a (positions 80K; n=5); G1b and G4 (position 168 and 36; n=4), while for NS5a: G1a (position 30; n=2) and G1b and G3 (position 93; n=3). Variables associated with failure in multivariate analysis (p<0.05): presence of ascites, G3 and ribavirin dosage<600mg/day. DISCUSSION: The presence of genotype 3, ascites or dosage of ribavirin<600mg/day were associated with higher failure rates. The use of ribavirin>600mg/day in cirrhotic G1 or G3, who will be treated with sofosbuvir+simeprevir or daclatasvir is recommended where no baseline resistance test is available.

[Lipid kinetics during dual antiviral therapy in patients with chronic hepatitis C]. / Cinética lipídica en el tratamiento antiviral dual en pacientes con hepatitis crónica C.

BACKGROUND AND OBJECTIVE: We analyzed baseline and kinetic characteristics of lipid metabolism during the first month of bitherapy in patients with chronic hepatitis C genotype 1 (CHC-1). PATIENTS AND METHODS: A longitudinal, prospective study including 99 naïve CHC-1 patients with liver biopsy who were treated with bitherapy. Our patients were assigned to one of 5 different "degrees of lipid requirement" that we established depending on the degree of liver fibrosis, baseline viral load and infectivity ratio (ratio between the median level of triglycerides and high densitity lipoproteins-cholesterol during the first month). The goal was to achieve "a favorable lipid metabolism" (FLM) by establishing a necessary minimum level of low density lipoproteins (LDL)-cholesterol during this period for each one of them. We also analyzed the relationship with the rate of sustained virological response. RESULTS: Patients with liver fibrosis F3-F4 who had higher baseline levels of LDL-cholesterol achieved higher rates of sustained virological response. Those patients who had a lower value of infectivity ratio and median levels of LDL-cholesterol during the first month of bitherapy also achieved higher rates of sustained virological response: SVR group 100 (23) mg/dl against non-SVR group: 89 (28) mg/dl; odds ratio 1.1; 95% confidence interval (1.0-1.2); P<.05, these differences being more significant for genotype IL-28B-CC (P=.013). Patients with sustained virological response had higher rates of FLM. CONCLUSIONS: Not every patient with CHC-1 has the same lipid kinetics during the first month of bitherapy, and it is necessary to achieve a sustained virological response and/or a FLM to keep higher plasma levels of LDL-cholesterol during this period. Those subjects without FLM could benefit from statins.

Long-term complications of rattlesnake bites: a telephone survey from Central California.

OBJECTIVE: The purpose of this institutional review board-approved, cross-sectional study was to identify residual symptoms and signs of envenomation reported by snakebite survivors via a telephone survey. METHODS: Victims of rattlesnake bite who were treated at a single hospital center during a 10-year period were contacted through a telephone survey. Study subjects were included through a diagnosis-based retrospective chart review of snakebite victims, and excluded if they did not receive rattlesnake antivenom. Data collection was done using a standardized form that included sections about residual, recurrent, or new pain, weakness, paresthesias, or other limitations of the bitten limb. RESULTS: We identified 46 snakebite cases including 5 of 46 "dry" bites. The remaining cases (41 of 46) all received Crofab. Interviews were completed for 31% of these patients (13 of 41), and the remainder were lost to follow-up. Most bites occurred in men (12 cases, 92% males) and on the arms (9 cases, 69%). Six of the 13 respondents (46%) reported residual symptoms from the bite. Persistent symptoms described included localized pain at the bite site (3 cases), numbness or paresthesias (2 cases), abnormal skin peeling and discoloration at the bite site (2 cases), and persistent weakness of the bitten extremity (1 case). Among patients reporting persistent symptoms, the bite-to-survey interval ranged from 7 months to 12 years, with a median interval of 4 years. CONCLUSIONS: Our study population demonstrated a notable incidence (43%) of self-reported persistent symptoms related to their rattlesnake bites, although the overall level of disability from these injuries seems low.

Snakebite Survivors Club: retrospective review of rattlesnake bites in Central California.

OBJECTIVE: We investigated clinical patterns of crotaline envenomation presenting to a tertiary-care academic hospital in Central California over a 10-year period. METHODS: An IRB-approved, retrospective chart review was conducted on all patients diagnosed with snakebite from December 2000 to December 2010. Data abstracted: demographics, anatomic location of bite, comorbid conditions and intoxicants, length of stay, antivenom dose, laboratory results, and complications or procedures. RESULTS: There were 46 snakebite cases admitted over the study period. Five were "dry bites"; the remaining cases (41/46) received antivenom. There was a male predominance (83% male victims). Upper extremity bites were more common (32/41 upper vs 10/42 lower extremity). One victim sustained bilateral bites to the hands. Thirty-five patients (85%) were admitted, with an average length of stay 2.12 days. The longest hospitalization was 15 days. There were no fatalities. The average time from bite to ED presentation was 2 h 44 min. Bites occurred during every month except November, with the majority occurring during spring and summer months and peaking in June (12/42 cases). Most bites occurred in the hours between noon and 8 pm. The amount of antivenom given ranged from 2 to 35 vials (average, 9 vials). Interfacility transfers were common in our study population: thirteen (32%) patients were transferred into our emergency department for a higher level of care, and 3 (7%) were transferred out (two because of insurance requirements, and one for higher level of Pediatric ICU care). There were no surgical interventions in our study group. Intoxication did not appear to play a major role in this population as only 3 patients (7%) were found to be acutely intoxicated: one with cannabis and amphetamines, 1 with alcohol, and 1 with opioids. CONCLUSIONS: In Central California, crotaline envenomations occurred mainly in adult males. Dry bites, or bites not requiring antivenom administration, were uncommon, comprising only 10% of bites in this study population. Contrary to popular and clinical beliefs, substance abuse and/or alcohol intoxication did not appear to play a role in the majority of patients in this study. Care providers and snakebite specialists should be aware that snakebite patients are often transferred between facilities, a finding that may be useful in designing future first aid protocols and research. We hope these findings add concrete data and help correct some common misconceptions about snakebites in Central California.

Ex-MWNTs: graphene sheets and ribbons produced by lithium intercalation and exfoliation of carbon nanotubes.

We found that multiwalled carbon nanotubes (MWNTs) can be opened longitudinally by intercalation of lithium and ammonia followed by exfoliation. Intercalation of open-ended tubes and exfoliation with acid treatment and abrupt heating provided the best results. The resulting material consists of: (i) multilayered flat graphitic structures (nanoribbons), (ii) partially open MWNTs, and (iii) graphene flakes. We called the completely unwrapped nanotubes ex-MWNTs, and their large number of edge atoms makes them attractive for many applications.

Sindrome de friccion de la banda iliotibial / Iliotibial band friction syndrome

El objetivo del trabajo es presentar nuestra experiencia en el tratamiento del Síndrome de fricción de la banda iliotibial (SFBIT). El SFBIT es una lesión por sobreuso, producida por la fricción en exceso entre la banda iliotibial (BIT) y el epicóndilo femoral externo.Fueron tratados 16 pacientes, 5 de los cuales demandaron tratamiento quirúrgico. En todos los casos realizamos el aplanamiento del epicóndilo externo con resultados satisfactorios y sin recurrencias en la patología.

Activation, proliferation and commitment of endogenous stem/progenitor cells to the oligodendrocyte lineage by TS1 in a rat model of dysmyelination.

Wild-type and myelin-deficient rats received a single intraparenchymal injection of TS1, a specific combination of IGF-1 and transferrin (Tf), into their corpus callosum at postnatal day 4. The fate of endogenous stem cells in the brain was examined by the expression of the stem cell marker nestin, together with Tf, neurofilaments and glial fibrillary acidic protein from 2 to 14 days after injection. Treated mutants lacked nestin expression in the ventricular wall and had an increase in nestin-labeled radial cell processes in the subventricular regions, and extended into the parenchyma. The subventricular zone was populated by healthy new oligodendrocytes (OLs). BrdU incorporation showed that these cells originated by proliferation and were identified as OLs based upon Tf expression. Thus, TS1 is an effective treatment to promote endogenous subventricular zone progenitor proliferation, migration and OL lineage specification. This strategy offers for the first time the possibility of myelin restoration to treat myelin disorders.

Análisis económico del uso de agua de atajados con la utilización de sistemas de riego por aspersión (Municipio de Santivañez-Capinota)

El trabajo se llevó a cabo con el objetivo de establecer la factibilidad técnica y económica del método de riego por aspersión en los cultivos de papa y cebolla mediante el uso como fuente de agua de atajados basandose en indicadores económicos y productivos. Este trabajo se llevó a cabo en las comunidades de Catachilla y Villa Nueva del Municipio de Santivañez. Se llegó a producir con el agua de los atajados los cultivos de papa (época de lluvias) y de cebolla (a secano) y se logró cubrir la inversión realizada, pero existen notables diferencias en los costos en el manejo de un equipo de bombeo a gasolina (Villa Nueva) y a energía eléctrica Catachilla, la segunda presenta más ventajas en términos económicos alargando la vida útil del proyecto y disminuyendo los costos de operación. En la producción de cebolla se presentaron pérdidas en la comunidad de Catachilla por los bajo precios del mercado y menor rendimiento por las condiciones del terreno. esta situación se ve compensada por la producción de papa durante la época de lluvias, donde los ingresos lograron cubrir la inversión. La relación del Beneficio/costo en los dos casos estudiado es de 1. En Catachilla los valores del VAN llegan a $Us. 1244.57 a 13

de interés y el TIR de 21.79

. En Villa Nueva se tuvo que el valor del VAN alcanza a $Us.1194.- y el TIR es del 24.9

. Los costos por servicio de agua se incrementa por el uso de gasolina a $Us. 022/m3, y por el uso de la energía eléctrica se tiene un costo de $Us. 0.13

Drenaje percutáneo de absceso hepático amibiano guiado por medio de ultrasonido. Resultados preliminares / Percutaneous drainage of amebic hepatic abscess by guided ultrasound. Preliminary results

El absceso hepático amibiano (AHA) es la más frecuente complicación extraintestinal de la amibiasis. A través del tiempo, su tratamiento ha sufrido algunos cambios, actualmente es a base de antiamibianos y en algunos casos el drenaje percutáneo. El objetivo de este trabajo es presentar nuestra experiencia en el tratamiento mediante el drenaje percutáneo, guiado por ultrasonido en pacientes con AHA. Se Incluyeron en este trabajo 170 pacientes que ingresaron al Servicio de Gastroenterología del Hospital General de Zona No 1 del Instituto Mexicano del Seguro Social, durante un periodo de ocho años (1990-1997), quienes reunieron de los siguientes criterios de inclusión: falla terapéutica clínica, AHA mayor a ocho centímetros por ultrasonido, de material netamente líquido, riesgo de ruptura, incapacidad prolongada sin datos de toxico-infección, ruta de drenaje accesible, disponibilidad de quirófano ante el riesgo de complicación, pruebas de coagulación normales. Dichos criterios se proponen a la comunidad médica. Se utilizó la técnica de Seldinger modificada.En 131 pacientes se realizó una sola punción, puesto que tenían absceso único, en 39 pacientes se requirió de una segunda evacuación por presentar dos abscesos, y en cuatro casos se requirió de una tercera evacuación, puesto que existía la presencia de tres abscesos o más y sólo en un caso se requirió procedimiento quirúrgico urgente por ruptura de absceso residual a pleural; sufrieron complicaciones solamente cinco pacientes, incluyéndose este último, los otros cuatro tuvieron resolución espontánea de sus complicaciones. Los pacientes fueron egresados a las 24 h ulteriores al procedimiento y ningún paciente requirió rehospitalización, por lo que se considera que es un procedimiento que en manos expertas de radiólogos intervencionistas, tiene cada vez menor morbilidad y mortalidad. Se pretende llevar este trabajo a 10 años