Fertility preservation in hematological cancer patients.

Among adolescents and young adults, hematological malignancies are the most common malignancies. Although the survival rate of hematological malignancies in young patients has been dramatically improved, due to the continuous improvement and development of tumor diagnosis and treatment options, cytotoxic therapies can significantly reduce a patient's reproductive capacity and cause irreversible infertility. The most two established solutions are embryo cryopreservation and oocyte cryopreservation which can be considered in single female. Sperm or testicular tissue cryopreservation in adult male are feasible approaches that must be considered before gonadotoxic therapy. A comprehensive consultation with reproductive specialists when once diagnosed is a significantly issue which would help those survivors who want to have children. In this article, we review germ cell toxicity, which happens during the treatment of hematological malignancies, and aims to propose safety, efficacy fertility preservation methods in younger patients with hematological malignancies.

Assessing cell chimerism in an acute graft-versus-host disease model established in TLR4 knockout mice.

BACKGROUND: Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation. OBJECTIVE: To elucidate the role of Toll-like receptor 4 (TLR4), the major receptor for bacterial lipopolysaccharide, in the development of GVHD, we constructed a GVHD model in TLR4 knockout (TLR4-/-) mice and monitored the cell chimerism. METHODS: In this study, we used polymerase chain reaction to identify whether TLR4 knockout (TLR4-/-) mice were established. Before transplantation, we pretreated mice with irradiation so as to obtain an appropriate irradiation dose. Flow cytometry was applied to measure the chimerism status, the distributions of antigen-presenting cells (APCs), and T-cells in TLR4+/+ and TLR4-/- recipient mice. RESULTS: The general condition of TLR4-/- recipients was better than that of TLR4+/+ recipients, and the TLR4-/- recipient mice showed less severe GVHD manifestations than the TLR4+/+ recipient mice. Most of the APCs and T-cells in the host mouse spleen were derived from donor cells, and CD4+ T-cells, including memory T-cells, were in the majority in host mice. CONCLUSION: In general, our data show that TLR4 deletion attenuated GVHD development, which suggests that TLR4 could be used as a novel target and therapeutic paradigm in GVHD therapies.

ANTECEDENTES: La enfermedad de injerto contra huésped (EICH) es una complicación importante después del trasplante alogénico de células madre hematopoyéticas. OBJETIVOS: Para dilucidar el papel de TLR4, el principal receptor de LPS bacteriano, en el desarrollo de GVHD, construimos un modelo de GVHD en ratones knockout para TLR4 (TLR4-/-) y monitoreamos el quimerismo celular. MÉTODOS: En este estudio, usamos PCR para identificar si se establecieron ratones knockout para TLR4 (TLR4-/-). Antes del trasplante, pretratamos a los ratones con irradiación para obtener la dosis de irradiación adecuada. Se aplicó citometría de flujo para medir el estado de quimerismo, las distribuciones de APC y células T en ratones receptores TLR4+/+ y TLR4-/-. RESULTADOS: El estado general de los receptores de TLR4-/- fue mejor que el de los receptores de TLR4+/+, y los ratones receptores de TLR4-/- mostraron manifestaciones de GVHD menos graves que los ratones receptores de TLR4+/+. La mayoría de las APC y las células T en el bazo del ratón huésped se derivaron de las células del donante, y las células T CD4+, incluidas las células T de memoria, se encontraban en su mayoría en los ratones huéspedes. CONCLUSIÓN: En general, nuestros datos muestran que la eliminación de TLR4 atenuó el desarrollo de GVHD, lo que sugiere que TLR4 podría usarse como un nuevo objetivo y paradigma terapéutico en las terapias de GVHD.

The long-term outcomes of posterior nasal neurectomy with or without pharyngeal neurectomy in patients with allergic rhinitis: a randomized controlled trial.

INTRODUCTION: Allergic rhinitis is a form of IgE mediated inflammation of the nasal mucosa in response to specific allergens, resulting in typical symptoms. OBJECTIVES: This study was designed with the primary goal of comparing the clinical efficacy of posterior nasal neurectomy with or without pharyngeal neurectomy for the treatment of moderate-to-severe perennial allergic rhinitis. Secondary study aims included a comparison of the severity of comorbidities, including chronic cough and asthma, between patients in these two surgical treatment groups. METHODS: A total of 52 patients were enrolled in this randomized controlled trial and were assigned to either the control group (posterior nasal neurectomy) or the experimental group (posterior nasal neurectomy + pharyngeal neurectomy). The visual analog scale and rhinoconjunctivitis quality of life questionnaire were used to compare the differences in patient symptoms between baseline and 6-, 12-, and 24-months post-treatment. In addition, patient cough and asthma symptoms were monitored during follow-up via visual analog scale and asthma control test respectively. RESULTS: No significant differences in preoperative scores were evident between groups (p > 0.05). At 6-months post-treatment, there were significant differences in visual analog scale, rhinoconjunctivitis quality of life questionnaire, and asthma control test scores relative to baseline values in experimental group and control group patients (p < 0.05), and this remained true upon 12- and 24-month follow-up. No significant differences in visual analog scale, rhinoconjunctivitis quality of life questionnaire, or asthma control test scores were observed between the two treatment groups at any postoperative follow-up time point (p > 0.05), while coughing severity was found to be significantly reduced in the experimental group relative to the control group (p < 0.05). CONCLUSION: posterior nasal neurectomy can be safely implemented with or without pharyngeal neurectomy in order to effectively treat allergic rhinitis. Combined posterior nasal neurectomy and pharyngeal neurectomy treatment may offer greater value than posterior nasal neurectomy alone for the treatment of allergic rhinitis patients with chronic cough.

The long-term outcomes of posterior nasal neurectomy with or without pharyngeal neurectomy in patients with allergic rhinitis: a randomized controlled trial / Os resultados no longo prazo da neurectomia nasal posterior com ou sem neurectomia faríngea em pacientes com rinite alérgica: um ensaio clínico randomizado

Abstract Introduction Allergic rhinitis is a form of IgE mediated inflammation of the nasal mucosa in response to specific allergens, resulting in typical symptoms. Objectives This study was designed with the primary goal of comparing the clinical efficacy of posterior nasal neurectomy with or without pharyngeal neurectomy for the treatment of moderate-to-severe perennial allergic rhinitis. Secondary study aims included a comparison of the severity of comorbidities, including chronic cough and asthma, between patients in these two surgical treatment groups. Methods A total of 52 patients were enrolled in this randomized controlled trial and were assigned to either the control group (posterior nasal neurectomy) or the experimental group (posterior nasal neurectomy + pharyngeal neurectomy). The visual analog scale and rhinoconjunctivitis quality of life questionnaire were used to compare the differences in patient symptoms between baseline and 6-, 12-, and 24-months post-treatment. In addition, patient cough and asthma symptoms were monitored during follow-up via visual analog scale and asthma control test respectively. Results No significant differences in preoperative scores were evident between groups (p> 0.05). At 6-months post-treatment, there were significant differences in visual analog scale, rhinoconjunctivitis quality of life questionnaire, and asthma control test scores relative to baseline values in experimental group and control group patients (p< 0.05), and this remained true upon 12- and 24-month follow-up. No significant differences in visual analog scale, rhinoconjunctivitis quality of life questionnaire, or asthma control test scores were observed between the two treatment groups at any postoperative follow-up time point (p> 0.05), while coughing severity was found to be significantly reduced in the experimental group relative to the control group (p< 0.05). Conclusion posterior nasal neurectomy can be safely implemented with or without pharyngeal neurectomy in order to effectively treat allergic rhinitis. Combined posterior nasal neurectomy and pharyngeal neurectomy treatment may offer greater value than posterior nasal neurectomy alone for the treatment of allergic rhinitis patients with chronic cough.

Resumo Introdução A rinite alérgica é uma forma de inflamação da mucosa nasal mediada por IgE em resposta a alérgenos específicos, resulta em sintomas típicos. Objetivos Comparar a eficácia clínica da neurectomia nasal posterior com ou sem neurectomia faríngea para o tratamento da rinite alérgica perene de moderada a grave. Além disso, comparar a gravidade das comorbidades, inclusive tosse crônica e asma, entre os pacientes nesses dois grupos de tratamento cirúrgico. Método Foram incluidos neste ensaio clínico randomizado e designados para o grupo controle (neurectomia nasal posterior) ou para o grupo experimental (neurectomia nasal posterior + neurectomia faríngea) 52 pacientes. A escala visual analógica e o questionário de qualidade de vida na rinoconjuntivite (rhinoconjunctivitis quality of life questionnaire) foram usados para comparar as diferenças nos sintomas dos pacientes entre o período inicial e 6, 12 e 24 meses após o tratamento. Além disso, a tosse e os sintomas de asma dos pacientes foram monitorados durante o acompanhamento por meio da escala visual analógica e do teste de controle da asma (asthma control test ), respectivamente. Resultados Nenhuma diferença significante nos escores pré‐operatórios foi evidenciada entre os grupos (p > 0,05). Aos seis meses pós‐tratamento, houve diferenças significantes nos escores da escala visual analógica, no questionário de qualidade de vida na rinoconjuntivite e no teste de controle de asma em relação aos valores basais dos pacientes no grupo experimental e no grupo controle (p < 0,05), o que permaneceu verdadeiro após 12 e 24 meses de acompanhamento. Não foram observadas diferenças significantes nos escores da escala visual analógica e nem no questionário de qualidade de vida para conjuntivite ou no teste de controle da asma entre os dois grupos de tratamento em qualquer momento do acompanhamento pós‐operatório (p > 0,05), enquanto a gravidade da tosse foi significantemente reduzida no grupo experimental em relação ao grupo controle (p < 0,05). Conclusão A neurectomia nasal posterior pôde ser feita com segurança com ou sem neurectomia faríngea para o tratamento eficaz da rinite alérgica. O tratamento combinado com neurectomia nasal posterior e neurectomia faríngea pode oferecer mais benefício do que a neurectomia nasal posterior isolada para o tratamento de pacientes com rinite alérgica e tosse crônica.

Tumor cells generate astrocyte-like cells that contribute to SHH-driven medulloblastoma relapse.

Astrocytes, a major glial cell type in the brain, play a critical role in supporting the progression of medulloblastoma (MB), the most common malignant pediatric brain tumor. Through lineage tracing analyses and single-cell RNA sequencing, we demonstrate that astrocytes are predominantly derived from the transdifferentiation of tumor cells in relapsed MB (but not in primary MB), although MB cells are generally believed to be neuronal-lineage committed. Such transdifferentiation of MB cells relies on Sox9, a transcription factor critical for gliogenesis. Our studies further reveal that bone morphogenetic proteins (BMPs) stimulate the transdifferentiation of MB cells by inducing the phosphorylation of Sox9. Pharmacological inhibition of BMP signaling represses MB cell transdifferentiation into astrocytes and suppresses tumor relapse. Our studies establish the distinct cellular sources of astrocytes in primary and relapsed MB and provide an avenue to prevent and treat MB relapse by targeting tumor cell transdifferentiation.

Repeatability and Reproducibility of Photoreceptor Density Measurement in the Macula Using the Spectralis High Magnification Module.

PURPOSE: To evaluate the repeatability and reproducibility of photoreceptor density assessment with manual cell counting in healthy participants imaged with the Heidelberg Spectralis High Magnification Module (HMM). DESIGN: Precision study, evaluation of diagnostic test or technology. PARTICIPANTS: Eleven eyes of 8 participants. METHODS: Images were acquired using the Spectralis HMM by a single operator during 2 separate imaging sessions. The 3 highest-quality images of each eye from each session were selected for analysis and coregistered. For a subset of participants, a second operator acquired images in 1 session, and images with the best quality were selected for analysis. Photoreceptor densities were obtained by manual counts in squares of 0.0625 mm2 located in the parafovea. Repeatability (intragrader and intrasession) and reproducibility (interoperator, intergrader, and intersession) were assessed by calculating the intraclass correlation coefficient (ICC) from linear mixed effects models. Bland-Altman plots, coefficients of repeatability, and Pearson correlation results were reported. MAIN OUTCOME MEASURES: Intragrader, intrasession, intersession, interoperator, and intergrader ICC estimates and their 95% confidence intervals for photoreceptor density measurements in the parafovea. RESULTS: Twenty-four eyes of 13 healthy participants were imaged initially. Of these, 11 eyes (45.83%) of 8 participants that had at least 3 acceptable images in each session were included in this study. Mean parafoveal photoreceptor density was 14 988 cells/mm2 (standard deviation, 1403.15 cells/mm2). Intragrader ICC was 0.84 (95% confidence interval, 0.57-0.95), intrasession ICC was 0.69 (95% confidence interval, 0.17-0.86), intersession ICC was 0.88 (95% confidence interval, 0.53-0.96), interoperator ICC was 0.70 (95% confidence interval, 0-0.95), and intergrader ICC was 0.22 (95% confidence interval, 0-0.71). CONCLUSIONS: Images obtained with the HMM allow for photoreceptor mosaic visualization in the macular area, mainly in the parafovea. Although densities obtained are in accordance with other reported methods in the literature, variability within and between images of the apparent cell mosaic were observed, and this study did not demonstrate high repeatability or reproducibility for quantitative assessments using the manual counting method.

Complementary feeding and childhood adiposity in preschool-aged children in a large Chinese cohort.

OBJECTIVE: To examine the association between the timing and type of complementary feeding and childhood adiposity in Mainland China. STUDY DESIGN: During 1999-2009, 97 424 singletons were enrolled in the Jiaxing Birth Cohort, a population-based prospective cohort study in Southeast China. Of these children, 43 848 children provided complementary diet information and other anthropometric measurements at 1, 3, and 6 months of age and were followed up until 4-5 years of age. Obesity and overweight were identified as body mass index (BMI)-for-age z-score (SD) ≥2 and between 1 and 2, respectively. RESULTS: Among 40 510 children in the statistical analysis, 3.18% were overweight and 64.8% were fed complementary food before 3 months of age. Early introduction of complementary foods was associated with greater BMI z-score (P-trend < .001) and higher risk of overweight (P-trend = .033). Compared with introduction of complementary foods between 4-6 months of age, before 3 months of age of introduction was associated with 11% greater risk of overweight (OR 1.11, 95% CI 1.03-1.19). No significant association between timing of complementary feeding and obesity was observed. Fish liver oil was the major type of complementary food associated with adiposity. Early introduction of fish liver oil was associated with greater BMI z-score (P < .001) and greater risk of overweight (P-trend = .004). CONCLUSIONS: Early introduction of fish liver oil is associated with greater childhood BMI and risk of overweight in Chinese children at 4-5 years of age.

High-level expression of modified gene encoding human adiponectin in transgenic rice.

Adiponectin is a polypeptide specifically secreted from human adipocytes, and its deficiency is closely linked to increased obesity and type II diabetes. There is an urgent demand for large-scale production of human adiponectin for pharmaceutical applications. Here, we report that we have successfully obtained a high-level of expression of modified genes encoding human adiponectin in transgenic rice. The 735 bp cDNA of the native human sequence was adopted to rice codon usage, fused to the translation initiation sequence in the N terminus and to the KDEL signal sequence in the C terminus. An amplification promoting sequence acting as an enhancer of transcription was also introduced to enhance gene expression. The presence of the transgene and mRNA transcripts was confirmed by PCR, Southern blot and RT-PCR. Western blot analysis revealed that a protein of approximately 30 kDa was produced in rice leaves. ELISA analysis was used to determine the amount of recombinant adiponectin in transformants with the modified gene in up to 0.32% of total soluble leaf protein. Our results establish the feasibility of high-level expression of recombinant human adiponectin in transgenic rice.

High-level expression of modified gene encoding human adiponectin in transgenic rice

Adiponectin is a polypeptide specifically secreted from human adipocytes, and its deficiency is closely linked to increased obesity and type II diabetes. There is an urgent demand for large-scale production of human adiponectin for pharmaceutical applications. Here, we report that we have successfully obtained a high-level of expression of modified genes encoding human adiponectin in transgenic rice. The 735 bp cDNA of the native human sequence was adopted to rice codon usage, fused to the translation initiation sequence in the N terminus and to the KDEL signal sequence in the C terminus. An amplification promoting sequence acting as an enhancer of transcription was also introduced to enhance gene expression. The presence of the transgene and mRNA transcripts was confirmed by PCR, Southern blot and RT-PCR. Western blot analysis revealed that a protein of approximately 30 kDa was produced in rice leaves. ELISA analysis was used to determine the amount of recombinant adiponectin in transformants with the modified gene in up to 0.32% of total soluble leaf protein. Our results establish the feasibility of high-level expression of recombinant human adiponectin in transgenic rice.