Therapeutic efficacy of rituximab combined with cyclosporin A on B-cell dysregulation in chronic graft-versus-host disease.

OBJECTIVE: Chronic graft-versus-host disease (cGVHD) is a significant complication following allogenic hematopoietic stem cell transplantation, often necessitating therapeutic interventions such as rituximab (RTX) and cyclosporin A (CsA). This study aims to elucidate the mechanisms by which RTX and CsA jointly address B-cell dysregulation in cGVHD, providing a theoretical foundation and scientific rationale for the treatment and prognostic evaluation of this condition. METHODS: A total of 30 cGVHD mouse models were established by subjecting recipient mice to total body irradiation followed by injection of a mixed suspension of bone marrow cells and splenocytes from donor mice. From Day 2 to Day 29 post-model establishment, the mice received subcutaneous administration of RTX and CsA. Throughout the study, body weight, clinical cGVHD scores, and survival rates were monitored. Blood samples were collected via the orbital venous plexus. Serum levels of B-cell activating factor (BAFF) and pro-inflammatory factors were measured using enzyme-linked immunosorbent assay (ELISA), and the ratio of regulatory B cells (Bregs) in the blood sample was assessed via flow cytometry. RESULTS: Mice with cGVHD exhibited a 14.5% decrease in body weight, elevated clinical scores, and more severe symptoms compared to the control group. Notably, all mice in both the cGVHD and control groups survived until the conclusion of the study. Induction of cGVHD resulted in B-cell dysregulation, evidenced by elevated serum BAFF levels and a decreased proportion of Bregs. However, treatment with RTX combined with CsA ameliorated B-cell dysregulation and significantly reduced serum levels of pro-inflammatory factors in cGVHD mice, with decreases of 39.78% in TNF-α and 37.89% in IL-6. CONCLUSION: The combination of RTX and CsA effectively mitigates B-cell dysregulation in cGVHD, thereby reducing the severity and progression of the disease.

Selection of a novel cell-internalizing RNA aptamer specific for CD22 antigen in B cell acute lymphoblastic leukemia.

Despite improvements in B cell acute lymphoblastic leukemia (B-ALL) treatment, a significant number of patients experience relapse of the disease, resulting in poor prognosis and high mortality. One of the drawbacks of current B-ALL treatments is the high toxicity associated with the non-specificity of chemotherapeutic drugs. Targeted therapy is an appealing strategy to treat B-ALL to mitigate these toxic off-target effects. One such target is the B cell surface protein CD22. The restricted expression of CD22 on the B-cell lineage and its ligand-induced internalizing properties make it an attractive target in cases of B cell malignancies. To target B-ALL and the CD22 protein, we performed cell internalization SELEX (Systematic Evolution of Ligands by EXponential enrichment) followed by molecular docking to identify internalizing aptamers specific for B-ALL cells that bind the CD22 cell-surface receptor. We identified two RNA aptamers, B-ALL1 and B-ALL2, that target human malignant B cells, with B-ALL1 the first documented RNA aptamer interacting with the CD22 antigen. These B-ALL-specific aptamers represent an important first step toward developing novel targeted therapies for B cell malignancy treatments.

Analysis of home gymnastics during covid-19 / Análise da ginástica doméstica durante a covid-19 / Análisis de la gimnasia doméstica durante el covid-19

ABSTRACT Introduction Gymnastics has become a viral sport thanks to home isolation and low requirements for sports venues and equipment. However, evidence is still lacking that home gymnastics can maintain physical and psychological function stability, even if performed correctly. Objective Analyze the effects of home gymnastics during covid-19 restrictions. Methods This experiment adopts the intragroup control method, five times a week for four weeks. Before and after the experiment, relevant data such as baseline physical quality, body shape, body composition, and exercise indexes are collected. The data are compared and analyzed statistically. Results Home gymnastics can effectively improve the body composition of its practitioners, improve basal metabolism, improve their body shape, improve cardiopulmonary function, and make athletes maintain good exercise ability, good lifestyle habits, and a healthy mentality. Conclusion It is recommended that teachers and interested departments actively organize students at home to perform corresponding gymnastics and use sports to ward off bad lifestyle habits and anxiety, promoting good physical and psychological function during home isolation. Level of evidence II; Therapeutic studies - investigating treatment outcomes.

RESUMO Introdução A ginástica tornou-se um esporte viral graças ao isolamento doméstico e devido a suas baixas exigências para locais e equipamentos esportivos. Porém ainda faltam evidências de que a ginástica em casa possa manter a estabilidade da função física e psicológica, ainda que executada corretamente. Objetivo Analisar os efeitos da ginástica doméstica durante as restrições da covid-19. Métodos Este experimento adota o método de controle intragrupo, cinco vezes por semana durante quatro semanas. Antes e depois do experimento, os dados relevantes como qualidade física basal, forma corporal, composição corporal e índices de exercício são coletados. Os dados são comparados e analisados estatisticamente. Resultados A ginástica em casa pode efetivamente melhorar a composição corporal dos seus praticantes, melhorar o metabolismo basal, melhorar sua forma corporal, melhorar a função cardiopulmonar, e fazer com que os esportistas mantenham boa capacidade de exercício, bons hábitos de vida e mentalidade saudável. Conclusão Recomenda-se aos professores e departamentos interessados a organizarem ativamente os estudantes em casa para realizar a ginástica correspondente e usar o esporte para afastar os maus hábitos de vida e a ansiedade, promovendo uma boa função física e psicológica durante o isolamento doméstico. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción La gimnasia se ha convertido en un deporte viral gracias al aislamiento doméstico y a sus escasas necesidades de instalaciones y equipamiento deportivo. Sin embargo, todavía no hay pruebas de que la gimnasia doméstica pueda mantener la estabilidad de la función física y psicológica, incluso si se realiza correctamente. Objetivo Analizar los efectos de la gimnasia domiciliaria durante las restricciones de covid-19. Métodos Este experimento adopta el método de control intragrupo, cinco veces por semana durante cuatro semanas. Antes y después del experimento, se recogen datos relevantes como la calidad física de referencia, la forma corporal, la composición corporal y los índices de ejercicio. Los datos se comparan y se analizan estadísticamente. Resultados La gimnasia en casa puede mejorar eficazmente la composición corporal de sus practicantes, mejorar el metabolismo basal, mejorar su forma corporal, mejorar la función cardiopulmonar y hacer que los deportistas mantengan una buena capacidad de ejercicio, buenos hábitos de vida y una mentalidad saludable. Conclusión Se recomienda a los profesores y a los departamentos interesados que organicen activamente a los alumnos en casa para que realicen la gimnasia correspondiente y utilicen el deporte para alejar los malos hábitos de vida y la ansiedad, promoviendo un buen funcionamiento físico y psicológico durante el aislamiento en casa. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Antibiofilm and immunomodulatory resorbable nanofibrous filing for dental pulp regenerative procedures.

Multifunctional scaffolds with host defense peptides designed for regenerative endodontics are desirable nanobiotechnological tools for dentistry. Here, different scaffolds were tested for use during the pulp revascularization process, including poly(vinyl alcohol)-PVA hydrogels or resins, collagen hydrogels and poly(vinyl alcohol) PVA/Chitosan (PVA/CS) nanofibers. Based on time to degradation (21 days), nanofibers were chosen to be incorporated with ciprofloxacin and IDR-1002 (each at 50 mg/g). Nanofibers containing ciprofloxacin and IDR-1002 had anti-biofilm activity against Enterococcus faecalis, Staphylococcus aureus and a multispecies oral biofilm, besides anti-inflammatory activities. The in vivo subcutaneous tissue response to tooth fragments filled with nanofibers demonstrated a pulp-like tissue formation, when compared to empty teeth fragments. Thus, we designed a strong antimicrobial, immunomodulatory and regenerative candidate for pulp revascularization and regeneration procedures.

Assessment of knowledge, attitudes, and practices towards Zika virus among healthcare workers in St. Kitts.

BACKGROUND: Healthcare workers are usually the first responders during outbreaks and are instrumental in educating the populace about the prevention of different diseases and illnesses. The aim of this study was to assess the association between healthcare workers' characteristics and knowledge, attitudes and practices toward Zika virus. METHODS: This was a cross-sectional study that collected data from healthcare workers at 3 medical facilities using a validated self-administered questionnaire between July 2017 - September 2017. Logistic regression models were used to examine the association between sociodemographic and knowledge, attitudes, and practices. RESULTS: A total of 190 healthcare workers were analyzed. Of these, 60, 72.6 and 64.7% had good knowledge, positive attitudes, and good practices toward Zika virus, respectively. Healthcare workers without a formal degree were less likely to have good knowledge of Zika virus (adjusted odds ratio (AOR) = 0:49; 95% confidence interval (CI) = 0.24-0.99) compared to those with a formal degree. Reduced odds for positive attitude towards Zika virus were observed in healthcare workers with low income as compared to those with high income (AOR = 0.31; 95% CI =0.13-0.75). Being younger than 40 years old was associated with poor Zika virus practices (AOR = 0:34; 95% CI = 0.15-0.79). CONCLUSIONS: Significant association between healthcare workers' sociodemographic characteristics and Zika virus knowledge, attitudes and practices were observed. Public health interventions that seek to increase Zika virus awareness should aim to train healthcare workers who are younger, without formal degree and those earning low income.

A severe COVID-19 case with schizophrenia as well as other chronic diseases.

The prognosis of COVID-19 (coronavirus disease 2019) is usually poor when it occurs in aged adults or in patients with chronic diseases, which brought a great challenge to clinical practice. Furthermore, widespread depression, anxiety, and panic related to SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2) infection affected treatment compliance and recovery. Here we report the successful treatment of a 57-year-old male with severe COVID-19, schizophrenia, hypertension, and type 2 diabetes. The patient's negative emotions (such as tension, panic, and anxiety), particularly his aggression and paranoia, seriously hindered treatment, leading to a deteriorating condition. Psychological counseling and supportive psychotherapy were given but the effect was weak. To improve adherence, risperidone and quetiapine fumarate were replaced by olanzapine for anti-schizophrenic treatment to reduce insomnia and anxiety side effects, associated with sedative-hypnotic drugs as well as psychological counseling. The treatment compliance of the patient improved significantly. The patient's serum alanine aminotransferase increased abnormally in the late stage of hospitalization, suggesting potential liver damage after complex medication strategies. We also monitored the changes of lymphocyte subsets and retrospectively analyzed the virus-specific antibody response. The results suggested that dynamic monitoring of lymphocyte subsets and virus-specific antibody response could facilitate disease progression evaluation and timely treatment plan adjustments. An effective psychotropic drug intervention associated with psychological counselling and psychotherapy are essential for the successful adherence, treatment, and rehabilitation of psychiatric disorders in COVID-19 patients.

A severe COVID-19 case with schizophrenia as well as other chronic diseases

The prognosis of COVID-19 (coronavirus disease 2019) is usually poor when it occurs in aged adults or in patients with chronic diseases, which brought a great challenge to clinical practice. Furthermore, widespread depression, anxiety, and panic related to SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2) infection affected treatment compliance and recovery. Here we report the successful treatment of a 57-year-old male with severe COVID-19, schizophrenia, hypertension, and type 2 diabetes. The patient's negative emotions (such as tension, panic, and anxiety), particularly his aggression and paranoia, seriously hindered treatment, leading to a deteriorating condition. Psychological counseling and supportive psychotherapy were given but the effect was weak. To improve adherence, risperidone and quetiapine fumarate were replaced by olanzapine for anti-schizophrenic treatment to reduce insomnia and anxiety side effects, associated with sedative-hypnotic drugs as well as psychological counseling. The treatment compliance of the patient improved significantly. The patient's serum alanine aminotransferase increased abnormally in the late stage of hospitalization, suggesting potential liver damage after complex medication strategies. We also monitored the changes of lymphocyte subsets and retrospectively analyzed the virus-specific antibody response. The results suggested that dynamic monitoring of lymphocyte subsets and virus-specific antibody response could facilitate disease progression evaluation and timely treatment plan adjustments. An effective psychotropic drug intervention associated with psychological counselling and psychotherapy are essential for the successful adherence, treatment, and rehabilitation of psychiatric disorders in COVID-19 patients.

Profiling epigenetic changes in human cell line induced by atrazine exposure.

How environmental chemicals can affect and exert their toxic effect at a molecular level has gained significant interest in recent years, not only for understanding their immediate health implications over exposed individuals, but also for their subsequent progeny. Atrazine (ATZ) is a commonly used herbicide in the U.S. and a long-suspected endocrine disrupting chemical. The molecular mechanism conferring long-term adverse health outcomes, however, remain elusive. Here, we explored changes in epigenetic marks that arise after exposure to ATZ at selected doses using image-based analysis coupled with data clustering. Significant decreases in methylated CpG (meCpG) and histone 3 lysine 9 tri-methylated (H3K9me3) were observed in the selected human cell line with a clear spatial preference. Treating cells with ATZ leads to the loss of a subpopulation of cells with high meCpG levels as identified in our clustering and histogram analysis. A similar trend was observed in H3K9me3 potentially attributing to the cross-talking between meCpG and H3K9me3. Changes in meCpG are likely to be associated with alterations in epigenetic enzyme expression levels regulating meCpG and persist after the removal of ATZ source which collectively provide a plausible mechanism for long-term ATZ-induced toxicity.

Diet and Nutritional Interventions with the Special Role of Myo-Inositol in Gestational Diabetes Mellitus Management. An Evidence-Based Critical Appraisal.

BACKGROUND: Gestational Diabetes Mellitus (GDM), defined as glucose intolerance with onset or first recognition during pregnancy, represents one of the most common maternal-fetal complications during pregnancy and it is associated with poor perinatal outcomes. To date, GDM is a rising condition over the last decades coinciding with the ongoing epidemic of obesity and Type 2 Diabetes Mellitus (T2DM). OBJECTIVE: The aim of this review is to discuss the role of diet and nutritional interventions in preventing GDM with the explanation of the special role of myo-inositol (MI) in this matter. METHODS: We performed an overview of the most recent literature data on the subject with particular attention to the effectiveness of diet and nutritional interventions in the prevention of GDM with the special role of MI. RESULTS: Nutritional intervention and physical activity before and during pregnancy are mandatory in women affected by GDM. Moreover, the availability of insulin-sensitizers such as different forms of inositol has dramatically changed the scenario, allowing the treatment of several metabolic diseases, such as those related to glucose dysbalance. Although the optimal dose, frequency, and form of MI administration need to be further investigated, diet supplementation with MI appears to be an attractive alternative for the GDM prevention as well as for the reduction of GDM-related complications. CONCLUSIONS: More studies should be conducted to prove the most effective nutritional intervention in GDM. Regarding the potential effectiveness of MI, further evidence in multicenter, randomized controlled trials is needed to draw firm conclusions.

Influence of facial threading on various physiological parameters of the skin: non-randomized trial involving adult women in Taiwan

Abstract: Background: Facial threading involves the removal of hairs to restore facial skin smoothness. However, its effectiveness has not been rigorously evaluated. Objective: To evaluate effects of facial threading on skin roughness, hydration, melanin index, and vellus hair on the face, complemented by a subjective evaluation of the tactile feel of the skin and improvement in skin color. Method: Participants who had not used exfoliators for two weeks before the experiment were included. Each participant underwent one session of facial threading every 21 days, for a total of 3 sessions. A three-dimensional skin roughness instrument and a multifunctional skin testing system were used to evaluate changes in roughness, hydration, and pigmentation on the forehead, cheeks, and corners of the mouth. A photomicrographic camera was used to record changes in vellus hair. Subjective reports of skin smoothness and color were recorded. Result: Eighteen participants completed the study. Facial threading produced a significant decrease in skin roughness on the forehead (22.42%, p = .013), right cheek (77%, p = .02), and left corner of the mouth (33.02%, p = .001). Subjective improvement in tactile feel of the skin and coloring were reported. Study Limitations: The study did not include randomization, with further limitations of a small sample size and a single site. Conclusion: Facial threading reduced skin roughness by 26.74% after three threading sessions, with improved subjective assessment of tactile feel and coloring. Future research should include a comparison with other cosmetic products with similar beautifying effects or a control group.

Influence of facial threading on various physiological parameters of the skin: non-randomized trial involving adult women in Taiwan.

BACKGROUND: Facial threading involves the removal of hairs to restore facial skin smoothness. However, its effectiveness has not been rigorously evaluated. OBJECTIVE: To evaluate effects of facial threading on skin roughness, hydration, melanin index, and vellus hair on the face, complemented by a subjective evaluation of the tactile feel of the skin and improvement in skin color. METHOD: Participants who had not used exfoliators for two weeks before the experiment were included. Each participant underwent one session of facial threading every 21 days, for a total of 3 sessions. A three-dimensional skin roughness instrument and a multifunctional skin testing system were used to evaluate changes in roughness, hydration, and pigmentation on the forehead, cheeks, and corners of the mouth. A photomicrographic camera was used to record changes in vellus hair. Subjective reports of skin smoothness and color were recorded. RESULT: Eighteen participants completed the study. Facial threading produced a significant decrease in skin roughness on the forehead (22.42%, p = .013), right cheek (77%, p = .02), and left corner of the mouth (33.02%, p = .001). Subjective improvement in tactile feel of the skin and coloring were reported. STUDY LIMITATIONS: The study did not include randomization, with further limitations of a small sample size and a single site. CONCLUSION: Facial threading reduced skin roughness by 26.74% after three threading sessions, with improved subjective assessment of tactile feel and coloring. Future research should include a comparison with other cosmetic products with similar beautifying effects or a control group.

Epidemiological characterization and prognostic factors in patients with confirmed cerebral cryptococcosis in central Taiwan

Background Cryptococcal meningitis is a deadly fungal infection. This study aimed to characterize the epidemiology of cerebral cryptococcosis and to define its prognostic factors. Methods This cross-sectional study collected clinical information from cryptococcal meningitis patients with confirmed cerebral cryptococcosis from 2006 to 2012 at the Changhua Christian Healthcare System to access prognostic factors. Result Fifty-nine adult cryptococcal meningitis patients were studied. The incidence at Changhua Christian Healthcare System was approximately 170 episodes per 100,000 patients within the studied period. Forty-one of 59 cryptococcal meningitis patients developed complications. Overall, 12 of 59 patients died, for a three-month mortality rate of 20.3 %. Prognostic factors positively associated with the three-month mortality included age (>55 years), patient delay, prolonged delay by the doctor in administering antifungal agent therapy, duration of intensive care unit stay, chronic lung disease, cryptococcemia, headache, altered mental status, positive blood cultures, and high cerebrospinal fluid opening pressure (>250 mm H2O). Conclusions We strongly recommend early administration of an antifungal agent to each suspected cryptococcal meningitis patient to decrease both the delay by doctors in administering therapy and the mortality risk. Aggressive and supportive care for severe cryptococcal meningitis patients is critical to decrease overall mortality from this infection.(AU)

Epidemiological characterization and prognostic factors in patients with confirmed cerebral cryptococcosis in central Taiwan.

BACKGROUND: Cryptococcal meningitis is a deadly fungal infection. This study aimed to characterize the epidemiology of cerebral cryptococcosis and to define its prognostic factors. METHODS: This cross-sectional study collected clinical information from cryptococcal meningitis patients with confirmed cerebral cryptococcosis from 2006 to 2012 at the Changhua Christian Healthcare System to access prognostic factors. RESULTS: Fifty-nine adult cryptococcal meningitis patients were studied. The incidence at Changhua Christian Healthcare System was approximately 170 episodes per 100,000 patients within the studied period. Forty-one of 59 cryptococcal meningitis patients developed complications. Overall, 12 of 59 patients died, for a three-month mortality rate of 20.3 %. Prognostic factors positively associated with the three-month mortality included age (>55 years), patient delay, prolonged delay by the doctor in administering antifungal agent therapy, duration of intensive care unit stay, chronic lung disease, cryptococcemia, headache, altered mental status, positive blood cultures, and high cerebrospinal fluid opening pressure (≥250 mm H2O). CONCLUSIONS: We strongly recommend early administration of an antifungal agent to each suspected cryptococcal meningitis patient to decrease both the delay by doctors in administering therapy and the mortality risk. Aggressive and supportive care for severe cryptococcal meningitis patients is critical to decrease overall mortality from this infection.

Epidemiological characterization and prognostic factors in patients with confirmed cerebral cryptococcosis in central Taiwan

BackgroundCryptococcal meningitis is a deadly fungal infection. This study aimed to characterize the epidemiology of cerebral cryptococcosis and to define its prognostic factors.MethodsThis cross-sectional study collected clinical information from cryptococcal meningitis patients with confirmed cerebral cryptococcosis from 2006 to 2012 at the Changhua Christian Healthcare System to access prognostic factors.ResultsFifty-nine adult cryptococcal meningitis patients were studied. The incidence at Changhua Christian Healthcare System was approximately 170 episodes per 100,000 patients within the studied period. Forty-one of 59 cryptococcal meningitis patients developed complications. Overall, 12 of 59 patients died, for a three-month mortality rate of 20.3 %. Prognostic factors positively associated with the three-month mortality included age (>55 years), patient delay, prolonged delay by the doctor in administering antifungal agent therapy, duration of intensive care unit stay, chronic lung disease, cryptococcemia, headache, altered mental status, positive blood cultures, and high cerebrospinal fluid opening pressure (>250 mm H2O).ConclusionsWe strongly recommend early administration of an antifungal agent to each suspected cryptococcal meningitis patient to decrease both the delay by doctors in administering therapy and the mortality risk. Aggressive and supportive care for severe cryptococcal meningitis patients is critical to decrease overall mortality from this infection.(AU)

Epidemiological characterization and prognostic factors in patients with confirmed cerebral cryptococcosis in central Taiwan

Background Cryptococcal meningitis is a deadly fungal infection. This study aimed to characterize the epidemiology of cerebral cryptococcosis and to define its prognostic factors. Methods This cross-sectional study collected clinical information from cryptococcal meningitis patients with confirmed cerebral cryptococcosis from 2006 to 2012 at the Changhua Christian Healthcare System to access prognostic factors. Result Fifty-nine adult cryptococcal meningitis patients were studied. The incidence at Changhua Christian Healthcare System was approximately 170 episodes per 100,000 patients within the studied period. Forty-one of 59 cryptococcal meningitis patients developed complications. Overall, 12 of 59 patients died, for a three-month mortality rate of 20.3 %. Prognostic factors positively associated with the three-month mortality included age (>55 years), patient delay, prolonged delay by the doctor in administering antifungal agent therapy, duration of intensive care unit stay, chronic lung disease, cryptococcemia, headache, altered mental status, positive blood cultures, and high cerebrospinal fluid opening pressure (>250 mm H2O). Conclusions We strongly recommend early administration of an antifungal agent to each suspected cryptococcal meningitis patient to decrease both the delay by doctors in administering therapy and the mortality risk. Aggressive and supportive care for severe cryptococcal meningitis patients is critical to decrease overall mortality from this infection.

La ketamina mejora la supervivencia en lesión por quemadura severa en ratas, a través de la expresión de la proteina de choque 70 / Ketamine improves survival in severe burn injury in rats via the expression of heat shock protein 70

Se ha demostrado que la ketamina, una anestésico general, produce una respuesta de choque térmico (HSR) en algunos animales experimentales. Examinamos si la ketamina mejora la supervivencia en lesión por quemadura severa en ratas, a través de la expresión de la proteína de choque 70. Un total de 124 ratas Wistar machos se dividieron aleatoriamente en 3 grupos: un grupo de control (grupo C, n = 20), un grupo quemado (grupo B, n = 52) y un grupo quemado + ketamina (grupo K, n = 52). Las ratas de los grupos B y K presentaban quemaduras de espesor completo en el 30% del total de su superficie corporal. Las ratas del grupo K se trataron con ketamina (40mg/kg, i.m.) a los 15min después de la lesión y las del grupo B se inyectaron con igual volumen de solución salina. Luego de practicar la eutanasia a las ratas, se examinó la expresión de HSP70 en muestras del miocardio y del cerebro con análisis Western blot. En las ratas que no se sacrificaron se evaluó el estado de supervivencia. Luego de 10 días, la tasa de supervivencia en las ratas del grupo K era superior a las del grupo B (70% versus 30%). Los análisis Western blot mostraron que la expresión de proteína HSP70 en el miocardio en respuesta a la administración de ketamina es más fuerte que en respuesta a la administración de solución salina a las 3 h (158% versus 65%) y a las 6h (165% versus 68%). En comparación con el grupo B, la ketamina aumentó marcadamente el nivel de expresión de la proteína HSP70 en tejido cerebral a las 3h y a las 6 h (79% versus 51% a las 3 h; 123% versus 98% a las 6 h). Concluimos que el tratamiento con ketamina mejora la supervivencia en lesión por quemadura severa, mediante la expresión de la proteína de choque 70 en los tejidos del miocardio y del cerebro.

Ketamine, a general anesthetic, has been shown to elicit the heat-shock response (HSR) in some of the animal models. We examined whether ketamine improves survival in severe burn injury in rats via the expression of heat shock protein 70. 124 male Wistar rats were randomly divided into three groups: a control group (group C, n = 20), burned group (group B, n = 52), and burned + ketamine group (group K, n = 52). The rats in groups B and K had full-thickness burns of 30% of their total body surface. The rats in group K were treated with ketamine (40 mg/kg, i.m.) 15 min after injury, and those in group B were injected with saline at the same volume. After the rats were euthanized, HSP70 expression in myocardium and brain samples was examined by Western blot analysis. Survival status was evaluated for the rats not euthanized. After 10 days, survival rate of rats in group K was higher than that of group B (70% versus 30%). Western blot analyses revealed that HSP70 protein expression in myocardium in response to ketamine administration is stronger than that in response to saline administration at 3 h (158% versus 65%) and 6 h (165% versus 68%). Compared with that in group B, ketamine strongly increased HSP70 protein expression level in cerebral tissue at 3 h and 6 h (79% versus 51%, at 3 h; 123% versus 98%, at 6 h). We concluded that ketamine therapy improves survival in severe burn injury via the expression of heat shock protein 70 in myocardial and cerebral tissues.

Biodiversity of the oleaginous microorganisms in Tibetan Plateau

Microbial lipids, which are also known as single cell oils (SCO), are produced by oleaginous microorganisms including oleaginous bacteria, yeast, fungus and algae through converting carbohydrates into lipids under certain conditions. Due to its unique environment having extremely low temperature and anoxia, the Tibetan Plateau is amongst the regions with numerous rare ecotypes such as arid desert, salt marsh, alpine permafrost, hot spring, and lawn. By using a rapid, convenient screening method, we identified 31 strains of oleaginous microorganisms from different habitats in the Tibetan Plateau, which include wetlands, lawn, hot spring, alpine permafrost, and saline-alkali soil. Molecular identity analysis showed that they belong to 15 different species, 7 of which are reported for the first time as lipid-producing microorganisms, that is, Cladosporium sp., Gibberella fujikuro, Ochrobactrum sp., Plectosphaerella sp., Tilletiopsis albescens, Backusella ctenidia, and Davidiella tassiana. The distribution of the oleaginous microorganisms varies with habitats. 11 strains were found in hot spring (35.5%), 10 in farmland (32.3%), 6 in lawn (19.4%), 2 in sand (6.4%), 1 in wetland (3.2%), and 1 in permafrost (3.2%). Carbon utilization analysis indicated that most of these filamentous fungi can use xylose and carboxymethyl cellulose (CMC) as carbon source, where Backusella ctenidia, Fusarium sp. and Gibberella fujikuroi have the strongest capability.

Preclinical modeling of combined phosphatidylinositol-3-kinase inhibition with endocrine therapy for estrogen receptor-positive breast cancer.

INTRODUCTION: Inhibition of phosphatidylinositol-3-kinase (PI3K) induces apoptosis when combined with estrogen deprivation in estrogen receptor (ER)-positive breast cancer. The aims of the present study were to identify effective PI3K pathway inhibitor and endocrine therapy combinations, to evaluate the effect of PI3K pathway mutations and estrogen dependency on tumor response, and to determine the relevance of PIK3CA mutation in recurrent disease. METHODS: The PI3K catalytic subunit inhibitor BKM120, the mammalian target of rapamycin (mTOR) inhibitor RAD001 and the dual PI3K/mTOR inhibitor BGT226 were tested against ER-positive breast cancer cell lines before and after long-term estrogen deprivation (LTED). The impact of estradiol deprivation and the ER downregulator fulvestrant on PI3K pathway inhibitor-induced apoptosis was assessed. PIK3CA hotspot mutation analysis was performed in 51 recurrent or metastatic breast cancers and correlated with ER status and survival. RESULTS: Drug-induced apoptosis was most marked in short-term estrogen-deprived cells with PIK3CA mutation and phosphatase and tensin homolog loss. Apoptosis was most highly induced by BGT226, followed by BKM120, and then RAD001. Estradiol antagonized PI3K inhibitor-induced apoptosis following short-term estrogen deprivation, emphasizing a role for estrogen-deprivation therapy in promoting PI3K inhibitor activity in the first-line setting. ER-positive MCF7 LTED cells exhibited relative resistance to PI3K pathway inhibition that was reversed by fulvestrant. In contrast, T47D LTED cells exhibited ER loss and ER-independent PI3K agent sensitivity. PIK3CA mutation was prevalent in relapsed ER-positive disease (48%) and was associated with persistent ER positivity and a late relapse pattern. CONCLUSIONS: Estrogen deprivation increased the apoptotic effects of PI3K and dual PI3K/mTOR inhibitors in ER-positive disease, providing a rationale for PI3K/aromatase inhibitor combinations as first-line therapy. In LTED cells, differential effects on ER expression may be a relevant consideration. When ER was persistently expressed, fulvestrant strongly promoted PI3K drug activity. When ER was lost, PI3K inhibitor monotherapy was sufficient to induce high-level apoptosis. Although tumors with PIK3CA mutation had a late recurrence pattern, these mutations were common in metastatic disease and were most often associated with persistent ER expression. Targeting PIK3CA mutant tumors with a PI3K pathway inhibitor and fulvestrant is therefore a feasible strategy for aromatase-inhibitor-resistant ER-positive relapsed breast cancer.

Education changes Mexican nurses' knowledge and attitudes regarding pediatric pain.

This study explored the effectiveness of a pain education intervention on Mexican nurses' knowledge and attitudes toward pediatric pain. A convenience sample of 106 registered nurses from three hospitals in Mexico City was recruited. A Pediatric Pain Education Program (PPEP) was developed, implemented, and evaluated by a nurse researcher, clinical nurse specialist, and a child life specialist. The 4-hour program, which was translated into Spanish, consisted of pain assessment, physiology, and management, including pharmacology and nonpharmacology. The effects of PPEP were measured in a one-group pretest-posttest design using a translated Spanish version of the Pediatric Nurses' Knowledge and Attitudes Survey (PNKAS). A total of 79 nurses completed both tests. A paired t test indicated significant differences between pre- and posttest results (p < .0001) on the PNKAS. The hospital site and years of nursing experience were significantly related to nurses' pre- and post-PNKAS scores. One test item on children's ability to reliably report their pain had a significantly lower score after the intervention (p = .016). The intervention was effective in improving Mexican pediatric nurses' knowledge and attitudes. However, it is not known how long this effect was maintained. Health care professionals can share a common vision for pain management by increasing international collaborative efforts and by advancing pediatric pain knowledge.

A retrospective study of trauma-associated oral and maxillofacial lesions in a population from southern Taiwan.

OBJECTIVE: The aim of this retrospective analysis was to determine the age, gender, frequency and distribution of trauma-associated hard tissue and soft tissue lesions of the oral and maxillofacial region in a population from southern Taiwan. PATIENTS AND METHODS: Approximately 10% of the 27,995 biopsy records of patients with history of trauma resulting in lesions who were treated at our institution between 1991 and 2006 were examined for this study. RESULTS: In the included records, there were 2,762 soft tissue and 26 hard tissue lesions. Mucocele was the most frequent trauma-associated soft tissue lesion (955 cases). The youngest patients were those who presented with mucocele (mean age = 27.3 years), while the oldest patients were those with peripheral giant cell granuloma (58 years). The lower lip was the most frequent site of occurrence of mucocele (676, 64.5%) and was also the predominant site of occurrence of all soft tissue lesions (815, 29.5%), followed by the buccal mucosa (654, 23.4%) and the tongue (392, 14.2%). Trauma-associated hard tissue lesions included only osteoradionecrosis (24 cases) and traumatic bone cysts (2 cases). CONCLUSION: As little data of this nature have been reported from populations of Asian developing countries, the findings of this retrospective analysis is valuable for epidemiological documentation of type of traumatic oral lesions as well as for informing the professionals and the layman about the importance of this category of oral lesions.