Fracture in Irradiated Rat Femur: A Description of an Experimental Model and Evaluation of its Effectiveness / Fratura em fêmur irradiado de rato: Descrição de um modelo experimental e avaliação de sua eficácia

Abstract Objective We aim to describe an experimental model for studying femoral fractures in rats after exposure to ionizing radiation, demonstrating a way to apply a substance for analysis, the method for patterning fracture and irradiation, and how to evaluate its effectiveness based on radiographic studies. Methods We used 24 rats divided into 2 groups of 12 animals each. The STUDY group was exposed to ionizing radiation and treated with saline solution, and the CONTROL group was not exposed to radiation and was treated with saline solution. All animals were subjected to standardized fracture of the right femur that was fixed with intramedullary wire. The efficiency of the bone union was assessed by radiographic exam. Results Fracture healing was more efficient in bones not exposed to ionizing radiation (p = 0.012). All fractures met the criteria of being simple, diaphyseal, transverse or short oblique. Conclusion The experimental model presented is an efficient alternative for the study of fractures in irradiated bones in rats.

Resumo Objetivo Nosso objetivo é descrever um modelo experimental para estudo de fraturas de fêmur em ratos após exposição a radiação ionizante, demonstrando uma forma de aplicação de uma substância para análise, o método de padronização de fratura e irradiação e a forma de avaliação de sua eficácia com base em estudos radiográficos. Métodos Utilizamos 24 ratos divididos em dois grupos de 12 animais cada. O grupo ESTUDO foi exposto à radiação ionizante e tratado com soro fisiológico, enquanto o grupo CONTROLE não foi exposto à radiação e foi tratado com soro fisiológico. Todos os animais foram submetidos à fratura padronizada do fêmur direito e sua fixação com fio intramedular. A eficácia da consolidação óssea foi determinada por exame radiográfico. Resultados A cicatrização de fraturas foi mais eficiente em ossos não expostos à radiação ionizante (p = 0,012). Todas as fraturas atenderam aos critérios de serem simples, diafisárias, transversas ou oblíquas curtas. Conclusão O modelo experimental apresentado é uma boa alternativa para o estudo de fraturas em ossos irradiados em ratos.

Development of nomogram and discussion of radiotherapy effect for osteosarcoma survival.

This study aimed to develop a predictive system for prognostic evaluation of osteosarcoma patients. We obtained osteosarcoma sample data from 1998 to 2016 using SEER*Stat software version 8.3.8, and established a multivariable Cox regression model using R-4.0.3 software. Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The diagnosis of the model was completed through influential cases, proportionality, and multicollinearity. The predictive ability of the model was tested using area under the curve (AUC), calibration curves, and Brier scores. Finally, the bootstrap method was used to internally verify the model. In total, data from 3566 patients with osteosarcoma were included in this study. The multivariate Cox regression model was used to determine the independent prognostic variables. A nomogram and Kaplan-Meier survival curve were established. The AUC and Brier scores indicated that the model had a good predictive calibration. In addition, we found that the radiotherapy appears to be a risk factor of patients with osteosarcoma and made a discussion. We developed a prognostic evaluation system for patients with osteosarcoma for 1-, 3-, and 5-year overall survival with good predictive ability using sample data extracted from the SEER database. This has important clinical significance for the early identification and treatment of high-risk groups of osteosarcoma patients.

Investigation of Developmental Stage/Age, Gamma Irradiation Dose, and Temperature in Sterilization of Male Aedes aegypti (Diptera: Culicidae) in a Sterile Insect Technique Program.

The sterilization process using gamma irradiation is a crucial component in a program using sterile insect technique (SIT) to control Aedes aegypti. Unfortunately, there is no efficient standard protocol for sterilizing mosquitoes that can produce a high level of sterility while maintaining mating ability and longevity. Therefore, we conducted a study of the critical factors necessary to develop such a standard protocol. In this study, male Ae. aegypti pupae, as well as adults aged 1 d and 3 d, were irradiated using a Gamma-cell 220 irradiator doses of 0, 20, 40, 60, 70, 80, and 100 Gray (Gy). In addition, male Ae. aegypti in the pupal and adult stage aged 1 d were irradiated at a dose of 70 Gy at various temperatures. Changes in emergence rates, longevity, sterility, and mating competitiveness were recorded for each combination of parameters. Results showed that an increase of irradiation dose leads to a rise of induced sterility at all developmental stages, while simultaneously reducing emergence rate, survival, and mating competitiveness. Higher temperatures resulted in increased levels of sterility, reduced longevity, and did not affect the ability to mate. This study found that an irradiation dose of 70 Gy at a temperature between 20.00 and 22.30°C administered in the pupal stage induced a high level of sterility (around 98%), while maintaining mating competitiveness and longevity.

Caracterización clínico-epidemiológica de pacientes con daño actínico crónico. Cochabamba, Bolivia / Clinical-epidemiological characterization of patients with chronic actinic damage. Cochabamba, Bolivia

RESUMEN Introducción: el daño actínico crónico es un grupo de alteraciones en la estructura, función y apariencia de la piel como resultado de la exposición no controlada a las radiaciones ultravioletas. Puede provocar el cáncer de piel. Objetivo: caracterizar a los pacientes con daño actínico crónico, atendidos en la consulta de Dermatología del Hospital Comunitario Valle Hermoso, en el departamento de Cochabamba, Bolivia. Materiales y métodos: se realizó un estudio clínico descriptivo, prospectivo, en un universo de 1 833 pacientes diagnosticados con daño actínico crónico, atendidos en la consulta de Dermatología del Hospital Comunitario Valle Hermoso, en Cochabamba, entre septiembre de 2017 y septiembre de 2018. Se evaluaron las variables edad, sexo, color y fototipo de piel, ocupación, uso de medios de protección solar, exposición a otro tipo de radiaciones, manifestaciones clínicas de fotodaño y altitud del lugar de residencia. Resultados: predominaron el grupo de edad de 25 a 59 años, el sexo femenino, el color de piel mestizo (77,08 %), el fototipo de piel IV (76,98 %) y la ocupación comerciante (72,56 %). La mayoría de los pacientes (82,7 %) no utilizaron medios de protección solar, y el 99,8 % no tuvieron exposición a otro tipo de radiaciones. Las lesiones por fotodaño que prevalecieron fueron melasma (83,03 %) y lentigos (12,22 %). El 99,29 % vivían en zonas de gran altitud. Conclusiones: se caracterizaron los pacientes con daño actínico crónico, obteniendo en algunas variables estudiadas resultados similares a los mencionados por otros investigadores (AU).

ABSTRACT Introduction: chronic actinic damage is a group of alterations in the structure, function, and appearance of the skin as a result of uncontrolled exposure to ultraviolet radiation. It can cause skin cancer. Objective: to characterize the patients with chronic actinic damage, treated at the Dermatology consultation of Valle Hermoso Community Hospital, in the department of Cochabamba, Bolivia. Materials and methods: a descriptive, prospective clinical study was conducted in a universe of 1,833 patients diagnosed with chronic actinic damage, treated at the Dermatology clinic of the Valle Hermoso Community Hospital, Cochabamba, between September 2017 and September 2018. The variables age, sex, skin color, skin phototype, occupation, use of sun protectors, exposure to other types of radiation, clinical manifestations of photodamage and altitude of the place of residence were evaluated. Results: the age group from 25 to 59 years, the female sex, mestizo skin color (77.08 %), the IV skin phototype (76.98 %) and merchant occupation (72.56 %) predominated. Most patients (82.7 %) did not use sun protection means, and 99.8 % had no other radiation exposure. The prevailing photodamage lesions were melasma (83.03 %) and lentigo (12.22 %). 99.29 % lived in high altitude areas. Conclusions: the patients with chronic actinic damage were characterized, obtaining in some variables studied results similar to those mentioned by other researchers (AU).

Actividad fotoprotectora de una crema con extracto acuoso liofilizado de Lepidium meyenii (MACA) frente a la irradiación ultravioleta en piel de ratones / Photoprotective activity of a cream containing lyophilized aqueous extract of Lepidium meyenii (MACA) against ultraviolet irradiation on mouse skin

RESUMEN Objetivos: Evaluar la actividad fotoprotectora de una crema con extracto acuoso liofilizado de maca (ELM) frente a la irradiación ultravioleta (UV) en la piel de ratones. Materiales y métodos: Se realizó un estudio experimental en 35ratones BALB/c. Los tratamientos fueron aplicados por vía tópica en el dorso de los animales y posteriormente irradiados con rayos ultravioleta B, para luego medir el grosor en micras (µm) de muestras histológicas de la piel de los ratones. Se asignaron siete grupos divididos en no irradiado: blanco (G1) e irradiados con luz UV: sin tratamiento (G2); con protector solar comercial con factor de protección solar (FPS) 30 (G3); crema (placebo) (G4); ELM al 15% en agua (G5); ELM al 5% en crema (G6); y ELM al 15% en crema (G7). Se determinó el FPS in vitro, mediante el método de Mansur. Se realizaron las lecturas de las absorbancias en un espectrofotómetro ultravioleta-visible (UV-VIS) y se determinaron los FPS para las siguientes formulaciones: ELM al 5% en crema, benzofenona-4 (BZF-4) y bloqueador solar comercial FPS 30. Resultados: El grosor de piel de ratón en micras (µm) fue de 27,28 en G2; 18,31 en G3; 27,33 en G4; 19,51 en G5 y 18,04 en G6; no hubo diferencia significativa entre el grupo no expuesto a la radiación (G1) y el grupo ELM al 15% en crema (G7), ambos presentaron los menores grosores (12,76 y 14,20 µm, respectivamente). El FPS de ELM al 15% en crema fue 5,480 ± 0,020. Conclusiones: La formulación con ELM en crema presentó actividad fotoprotectora frente a la irradiación UV, los alcaloides fueron los componentes fitoquímicos mayormente encontrados y la formulación fue compatible con el activo (ELM).

ABSTRACT Objectives: To evaluate the photoprotective activity of a cream with lyophilized aqueous extract of maca (LEM) against ultraviolet (UV) irradiation in the skin of mice. Materials and methods: An experimental study was carried out on 35 BALB/c mice. Treatment was applied topically on the dorsum of the animals, which were subsequently irradiated with ultraviolet B rays, and then we measured the thickness in microns (μm) of histological samples of the skin of the mice. Seven groups were assigned, divided into non-irradiated: Blank (G1) and irradiated with UV light: no treatment (G2); with commercial sunscreen with sun protection factor (SPF) 30 (G3); cream (placebo) (G4); LEM at 15% in water (G5); LEM cream at 5% (G6); and LEM cream at 15% (G7). In vitro SPF was determined using the Mansur method. Absorbance readings were taken in an ultraviolet- visible spectrophotometer (UV-VIS) and SPFs were determined for the following formulations: LEM cream at 5%, benzophenone-4 (BZF-4) and commercial sunscreen SPF 30. Results: Mouse skin thickness in microns (μm) was 27.28 in G2; 18.31 in G3; 27.33 in G4; 19.51 in G5 and 18.04 in G6. There was no significant difference between the group not exposed to radiation (G1) and the 15% LEM cream group (G7), both had the lowest thicknesses (12.76 and 14.20 μm, respectively). The SPF of LEM cream at 15% was 5.480 ± 0.020. Conclusions: The formulation with LEM cream showed photoprotective activity against UV irradiation, alkaloids were the phytochemical components mostly found and the formulation was compatible with the active principle (LEM).

Quantifying the inovation of cosmetic formulations that contains phenolic rich fruit extracts as fotoprotective bioactives / Quantificando a inovação de formulações cosméticas que contêm extratos de frutas ricas em substâncias fenólicas como bioativos fotoprotetivos

Introduction: sunscreen is a cosmetic used to protect human skin from the deleterious effects of UV radiation and thus minimize the risks of developing skin cancer. Extracts produced from fruits, such as Abiu, Guava, Rambutan and Grape, have significant concentrations of chromophores and phenolic substances that have the ability to absorb UV light and neutralize free radicals. The production of cosmetics from naturally occurring substances with such activities will be of great importance for Brazilian industry and could reduce the cost of production, given the large existing biodiversity in the country. Objectives: carry out a patent search for formulations and cosmetic products that contains phenolic rich fruit extracts as photoprotective and antioxidant bioactives. Methodology: a survey of patents was carried out in the database of the National Institute of Intellectual Property (INPI) and the European Patent Office (EPO), covering a time period between 2008 and 2018, using a combination of keywords related to herbal cosmetics and sunscreens. Results: this research identifies a significant number of patents related to plant extract in association with sunscreen product, however, no patent filings were identified for cosmetic products containing extracts of the evaluated fruits, either alone or in combination, for photoprotective and antioxidant purposes. Conclusion: the Brazilian and international market for sun care products moves millions to billions of dollars annually and have a significant annual growth prospect. Considering the great biodiversity existing in the country, the production of cosmetics from naturally occurring substances with such activities will be of great importance for the Brazilian industrial sector.

Introdução: os filtros solares são cosméticos usados para proteger a pele humana dos efeitos deletérios da radiação UV e assim, minimizar os riscos de desenvolvimento de câncer de pele. Extratos produzidos a partir de frutos, como Abiu, Goiaba, Rambutan e Uva, têm concentrações significativas de cromóforos e substâncias fenólicas que têm a capacidade de absorver a radiação UV e neutralizar os radicais livres. A produção de cosméticos a partir de substâncias naturais com essas atividades será de grande importância para a indústria brasileira e poderá reduzir o custo de produção, dada a grande biodiversidade existente no país. Objetivos: realizar uma busca de registros de patentes de formulações e produtos cosméticos que contêm extratos de frutos ricos em fenólicos como bioativos fotoprotetores e antioxidantes. Metodologia: foi realizado um levantamento de patentes no banco de dados do Instituto Nacional de Propriedade Intelectual (INPI) e do Escritório Europeu de Patentes (EPO), abrangendo um período de tempo entre 2008 e 2018, utilizando uma combinação de palavras-chave relacionadas a cosméticos à base de plantas e protetores solares. Resultados: esta pesquisa identificou um número significativo de patentes relacionadas ao extrato de plantas em associação ao produto protetor solar, no entanto, não foram identificados pedidos de patente para produtos cosméticos que contenham extratos das frutas avaliadas, isoladamente ou em combinação, para fins fotoprotetores e antioxidantes. Conclusão: o mercado brasileiro e internacional de produtos de proteção solar movimenta milhões a bilhões de dólares anualmente e tem a perspectiva de crescimento anual significativa. Considerando a grande biodiversidade existente no país, a produção de cosméticos a partir de substâncias naturais com essas atividades será de grande importância para o setor industrial brasileiro.

Radiation effects on atherosclerosis in atomic bomb survivors: a cross-sectional study using structural equation modeling.

Past reports indicated that total-body irradiation at low to moderate doses could be responsible for cardiovascular disease risks, but the mechanism remains unclear. The purpose of this study was to investigate the association between radiation exposure and atherosclerosis, an underlying pathology of cardiovascular diseases, in the Japanese atomic bomb survivors. We performed a cross-sectional study measuring 14 clinical-physiological atherosclerosis indicators during clinical exams from 2010 to 2014 in 3274 participants of the Adult Health Study cohort. Multivariable analyses were performed by using a structural equation model with latent factors representing underlying atherosclerotic pathologies: (1) arterial stiffness, (2) calcification, and (3) plaque　as measured with indicators chosen a priori on the basis of clinical-physiological knowledge. Radiation was linearly associated with calcification (standardized coefficient per Gy 0.15, 95 % confidence interval: CI [0.070, 0.23]) and plaque (0.11, 95 % CI [0.029, 0.20]), small associations that were comparable to about 2 years of aging per Gy of radiation exposure, but not with arterial stiffness (0.036, 95 % CI [- 0.025, 0.095]). The model fitted better and had narrower confidence intervals than separate ordinary regression models explaining individual indicators independently. The associations were less evident when the dose range was restricted to a maximum of 2 or 1 Gy. By combining individual clinical-physiological indicators that are correlated because of common, underlying atherosclerotic pathologies, we found a small, but significant association of radiation with atherosclerosis.

Weekly radiotherapy in elderly breast cancer patients: a comparison between two hypofractionation schedules

Purpose Weekly irradiation in breast cancer in elderly patients is a treatment option, whose tolerance may be influenced by the fractionation used. The objective of this study is to compare the tolerance and long-term side effects of two different fractionations. Materials and methods 47 elderly patients were recruited after conservative or radical treatment that also received irradiation with a dose per fraction of 6.25 Gy or 5 Gy for one session per week, 6 sessions in total. The long-term tolerance results are compared by assessing toxicity using CTCAE version 5.0 scales for dermatitis, telangectasia, fibrosis and pain of the irradiated breast. In addition, objective parameters of skin status (erythema, hyperpigmentation, elasticity and hydration) by a multi-probe MultiSkin Test-Center system were obtained and compared between groups. Results After an average follow-up of 5 years, all patients were free of disease and with complete local control. A total of 20 patients with 6.25 Gy fractionation and 27 patients with 5 Gy fractionation have been included. Patients treated with lower fractionation had a lower incidence of dermatitis, telangectasia, fibrosis, or local pain. The decrease in elasticity measured by the multi-probe system was smaller with the fractionation of 5 Gy. No differences were observed in the other objective parameters. Conclusion Weekly irradiation with 5 Gy fractionation is better tolerated than with higher fractionation (AU)

Effect of Interleukin-7 on Radiation-Induced Lymphopenia and Its Antitumor Effects in a Mouse Model.

PURPOSE: Local ionizing radiation (IR) can lead to systemic lymphocyte depletion, which is associated with poor survival outcomes in patients with cancer. Interleukin-7 (IL-7) plays an important role in lymphocyte homeostasis; however, its role in alleviating radiation-induced lymphopenia remains unclear. Hence, we established a radiation-induced lymphopenia animal model and evaluated the effect of exogenous IL-7 administration. METHODS: C3H/HeN mice underwent x-ray irradiation of 30 Gy in 10 fractions at the right hind limbs. Next, 10 mg/kg of IL-7 was injected subcutaneously, and the lymphocyte count in blood was measured. Murine hepatocellular carcinoma (HCa-1) cells were inoculated subcutaneously into the right thighs of tumor model mice, which underwent the same treatment. RESULTS: In the naïve mouse model, the decreased CD45+ cell count after irradiation gradually recovered to the initial level over 3 weeks in the IR group, whereas it markedly increased to 373% of the initial level in 1 week in the IR+IL-7 group. Similar trends were observed for the CD3+, CD8+, CD4+, regulatory T cells, and CD19+ B cell counts. Similar findings were observed in the tumor mouse model. CD8+ and CD4+ T cell infiltration in tumor specimens was higher in the IL-7 and IR+IL-7 groups than in the nontreated and IR groups. Tumor growth was significantly more suppressed in the IR+IL-7 group than in the IR group. The median survival time was significantly longer in the IR+IL-7 group (not reached) than in the IR (56 days; P = .0382), IL-7 (36 days; P = .0004), or nontreated groups (36 days; P < .0001). CONCLUSIONS: Administration of exogenous IL-7 after IR not only restored lymphocyte counts but also enhanced the antitumor effect. Exogenous IL-7 can be beneficial in overcoming radiation-induced lymphopenia and in enhancing the treatment outcome in combination with radiation therapy, which needs validation through future clinical studies.

Evaluation of perfusion MRI value for tumor progression assessment after glioma radiotherapy: A systematic review and meta-analysis.

OBJECTIVES: This study aimed to evaluate the diagnostic performance of magnetic resonance perfusion-weighted imaging (PWI) as a noninvasive method to assess post-treatment radiation effect and tumor progression in patients with glioma. METHODS: A systematic literature search was performed in the PubMed, Cochrane Library, and Embase databases up to March 2020. The quality of the included studies was assessed by the quality assessment of diagnostic accuracy studies 2. Data were extracted to calculate sensitivity, specificity, and diagnostic odds ratio (DOR), 95% Confidence interval (CI) and analyze the heterogeneity of the studies (Spearman correlation coefficient, I2 test). We performed meta-regression and subgroup analyses to identify the impact of study heterogeneity. RESULTS: Twenty studies were included, with available data for analysis on 939 patients and 968 lesions. All included studies used dynamic susceptibility contrast (DSC) PWI, four also used dynamic contrast-enhanced PWI, and three also used arterial spin marker imaging PWI. When DSC was considered, the pooled sensitivity and specificity were 0.83 (95% CI, 0.79 to 0.86) and 0.83 (95% CI, 0.78 to 0.87), respectively; pooled DOR, 21.31 (95% CI, 13.07 to 34.73); area under the curve (AUC), 0.887; Q∗, 0.8176. In studies using dynamic contrast-enhanced, the pooled sensitivity and specificity were 0.73 (95% CI, 0.66 to 0.80) and 0.80 (95% CI, 0.69 to 0.88), respectively; pooled DOR, 10.83 (95% CI, 2.01 to 58.43); AUC, 0.9416; Q∗, 0.8795. In studies using arterial spin labeling, the pooled sensitivity and specificity were 0.79 (95% CI, 0.69 to 0.87) and 0.78 (95% CI, 0.67 to 0.87), respectively; pooled DOR, 15.63 (95% CI, 4.61 to 53.02); AUC, 0.8786; Q∗, 0.809. CONCLUSIONS: Perfusion magnetic resonance imaging displays moderate overall accuracy in identifying post-treatment radiation effect and tumor progression in patients with glioma. Based on the current evidence, DSC-PWI is a relatively reliable option for assessing tumor progression after glioma radiotherapy.

El ocaso del modelo lineal sin umbral / The downfall of the linear non-threshold model

El modelo lineal sin umbral (MLSU) es una función dosis-respuesta teórica obtenida de extrapolar los efectos tardíos debidos a la exposición a altas dosis de radiación ionizante al rango de las bajas dosis, pero existen grandes incertidumbres respecto a su validez. La aceptación del MLSU como modelo probabilístico preponderante ha sobrevivido hasta nuestros días y constituye la piedra angular que sostiene las políticas actuales de protección radiológica. En las últimas décadas, los avances en biología molecular y evolutiva, en la inmunología del cáncer, así como los resultados obtenidos de los estudios epidemiológicos y en modelos animales, han puesto en entredicho la fiabilidad del MLSU en favor de otras alternativas, como la teoría hormética. A la vista de las evidencias, se hace necesario un debate entre las sociedades científicas implicadas y los organismos reguladores que aborde una redefinición de las bases de la protección radiológica, cuya importancia sería capital en el ámbito médico

The linear non-threshold model (LNTM) is a theoretical dose-response function as a result of extrapolating the late effects of high-dose exposure to ionizing radiation to the low-dose range, but there is great uncertainty about its validity. The acceptance of LNTM as the dominant probabilistic model have survived to the present day and it is actually the cornerstone of current radiation protection policies. In the last decades, advances in molecular and evolutive biology, cancer immunology, and many epidemiological and animal studies have cast serious doubts about the reliability of the NLTM, as well as suggesting alternative models, like the hormetic theory. Considering the given evidences, a discussion between the involved scientific societies and the regulatory commissions is promtly required in order to to reach a redefiniton of theradiation protection basis, as it would be specially crucial in the medical field

Hair loss due to scalp ringworm irradiation in childhood: health and psychosocial risks for women.

BACKGROUND: Until 1960, hundreds of thousands of children worldwide had been treated for scalp ringworm by epilation via irradiation. The discovery of late health effects in adulthood prompted investigation of the medical aspects of irradiation in childhood and led to the establishment of strict protocols for the use of X-ray irradiation. These studies ignored alopecia, which affects some individuals who underwent irradiation for scalp ringworm as children. This study examined the impact of alopecia due to irradiation for scalp ringworm on the health and psychosocial status of affected women. METHODS: We analysed a random sample of 130 medical files of women recognised by Israel's state committees as suffering from permanent hair loss as a result of scalp ringworm irradiation in childhood. The coded medical data included demographic variables, self-reported mental health conditions, self-reported physical health conditions, self-reported social conditions, and spousal relationship. RESULTS: Compared with the general population of women in Israel, research participants reported significantly higher rates of depression, anti-depressant and/or anti-anxiety drug use, psychotherapy or psychiatric hospitalisation, attempted suicide, migraines, cancer, and divorce. Many described humiliating social experiences due to their appearance, both in childhood and adulthood, that led them to curtail their social interactions. The participants also reported that alopecia negatively affected their spousal relationships. CONCLUSIONS: Life with hair loss from scalp ringworm irradiation in childhood has a negative impact on women's health status and psychosocial state. Health policy-makers must broaden their approach to women who underwent scalp ringworm irradiation by addressing the effects of their hair loss in addition to the effects of the radiation treatment per se. This may be achieved by guiding physicians who provide medical services to these women to take into account the psychosocial and health risks related to hair loss in their diagnosis and treatment as well as by creating a cadre of specially trained mental health professionals who can address their unique psychosocial needs. They must also consider including the specialized mental health services tailored for these women's unique needs in the Healthcare Basket.

How Precision Medicine Might Better Serve Downwinders.

Despite the advances in developing nuclear weapons and other technologies, not much is known about the long-term effects of radiation on human health. In a world where nuclear energy could help curb carbon emissions, it almost seems paradoxical that its possible long-term risks and impacts to human health are still poorly understood. While researchers have investigated the effects of acute radiation in the aftermath of nuclear incidents such as Chernobyl, Hiroshima, Nagasaki, and Fukushima, more needs to be done to understand the impacts of long-term and low-dose nuclear radiation. Studying the downwinders from the Nevada Test Site could offer one window to investigate those myriad effects.

Uso do laser de baixa intensidade nas radiodermites: revisão sistemática / Uso de láser de baja intensidad en radiodermitis: revisión sistemática / Low intensity laser use in radiotherapy lesions: systematic review

Objetivo: analisar e categorizar o método de uso e benefícios e principais considerações sobre uso do laser em lesões induzidas por radiação. Método: revisão sistemática desenvolvidas em Public Medline, Literatura Latino-Americana do Caribe em Ciências da Saúde, Cumulative Index to Nursing and Allied Health Literature, SCOPUS e Biblioteca Virtual de Saúde. Resultados: analisou-se sete estudos. Observou-se em 86% (6) desses estudos uma conclusão positiva à terapêutica de laser de baixa intensidade, relatando: 43% (3) diminuição significativa e regressão da dor; 29% (2) redução significativa na duração e gravidade da mucosite e 29% (2) redução da inflamação e cicatrização. Conclusão: evidenciou-se melhora da cicatrização, da dor local e da capacidade anti-inflamatória. É necessário realizar mais pesquisas com amostras robustas que comparem os tipos de lasers, o comprimento das ondas e sua intensidade, para o seu uso como terapêutica.(AU)

Objective: to analyze and categorize the method of use and benefits and main considerations on the use of laser in radiation-induced injuries. Method: systematic review developed in the databases Public Medline, Latin American Caribbean Literature in Health Sciences, Cumulative Index to Nursing and Allied Health Literature, SCOPUS and Virtual Health Library. Results: seven studies were analyzed. A positive conclusion to low-level laser therapy was observed in 86% (6) of these studies, reporting: 43% (3) significant decrease and regression of pain; 29% (2) significant reduction in the duration and severity of mucositis and 29% (2) reduction in inflammation and healing. Conclusion: there was an improvement in healing, local pain and anti-inflammatory capacity. More research is needed with robust samples that compare the types of lasers, the length of the waves and their intensity, for their use as therapy.(AU)

Objetivo: analizar y clasificar el método de uso y los beneficios y las principales consideraciones sobre el uso del láser en lesiones inducidas por radiación. Método: revisión sistemática desarrollada en Public Medline, Literatura Latinoamericana del Caribe en Ciencias de la Salud, Índice acumulativo de literatura de enfermería y salud aliada, SCOPUS y Biblioteca Virtual en Salud. Resultados: se analizaron siete estudios. Se observó una conclusión positiva de la terapia con láser de bajo nivel en el 86% (6) de estos estudios: 43% (3) disminución significativa y regresión del dolor; 29% (2) reducción significativa en la duración y gravedad de la mucositis y 29% (2) reducción en la inflamación y la curación. Conclusión: hubo una mejora en la curación, dolor local y capacidad antiinflamatoria. Se necesita investigación con muestras robustas que comparen los tipos de láser, la longitud de las ondas y su intensidad, para su uso como terapia.(AU)

Characteristics of induced mutations in offspring derived from irradiated mouse spermatogonia and mature oocytes.

The exposure of germ cells to radiation introduces mutations in the genomes of offspring, and a previous whole-genome sequencing study indicated that the irradiation of mouse sperm induces insertions/deletions (indels) and multisite mutations (clustered single nucleotide variants and indels). However, the current knowledge on the mutation spectra is limited, and the effects of radiation exposure on germ cells at stages other than the sperm stage remain unknown. Here, we performed whole-genome sequencing experiments to investigate the exposure of spermatogonia and mature oocytes. We compared de novo mutations in a total of 24 F1 mice conceived before and after the irradiation of their parents. The results indicated that radiation exposure, 4 Gy of gamma rays, induced 9.6 indels and 2.5 multisite mutations in spermatogonia and 4.7 indels and 3.1 multisite mutations in mature oocytes in the autosomal regions of each F1 individual. Notably, we found two types of deletions, namely, small deletions (mainly 1~12 nucleotides) in non-repeat sequences, many of which showed microhomology at the breakpoint junction, and single-nucleotide deletions in mononucleotide repeat sequences. The results suggest that these deletions and multisite mutations could be a typical signature of mutations induced by parental irradiation in mammals.

Nonmicrobial Activation of TLRs Controls Intestinal Growth, Wound Repair, and Radioprotection.

TLRs, key components of the innate immune system, recognize microbial molecules. However, TLRs also recognize some nonmicrobial molecules. In particular, TLR2 and TLR4 recognize hyaluronic acid, a glycosaminoglycan in the extracellular matrix. In neonatal mice endogenous hyaluronic acid binding to TLR4 drives normal intestinal growth. Hyaluronic acid binding to TLR4 in pericryptal macrophages results in cyclooxygenase2- dependent PGE2 production, which transactivates EGFR in LGR5+ crypt epithelial stem cells leading to increased proliferation. The expanded population of LGR5+ stem cells leads to crypt fission and lengthening of the intestine and colon. Blocking this pathway at any point (TLR4 activation, PGE2 production, EGFR transactivation) results in diminished intestinal and colonic growth. A similar pathway leads to epithelial proliferation in wound repair. The repair phase of dextran sodium sulfate colitis is marked by increased epithelial proliferation. In this model, TLR2 and TLR4 in pericryptal macrophages are activated by microbial products or by host hyaluronic acid, resulting in production of CXCL12, a chemokine. CXCL12 induces the migration of cyclooxygenase2-expressing mesenchymal stem cells from the lamina propria of the upper colonic crypts to a site adjacent to LGR5+ epithelial stem cells. PGE2 released by these mesenchymal stem cells transactivates EGFR in LGR5+ epithelial stem cells leading to increased proliferation. Several TLR2 and TLR4 agonists, including hyaluronic acid, are radioprotective in the intestine through the inhibition of radiation-induced apoptosis in LGR5+ epithelial stem cells. Administration of exogenous TLR2 or TLR4 agonists activates TLR2/TLR4 on pericryptal macrophages inducing CXCL12 production with migration of cyclooxygenase2-expressing mesenchymal stem cells from the lamina propria of the villi to a site adjacent to LGR5+ epithelial stem cells. PGE2 produced by these mesenchymal stem cells, blocks radiation-induced apoptosis in LGR5+ epithelial stem cells by an EGFR mediated pathway.

Photothermal Effect-based Cytotoxic Ability of Melanin from Shells to Heal Wounds Infected with Drug-resistant Bacteria / 生物医学与环境科学（英文）

Objective@#Owing to antibiotic abuse and the subsequent development of antibiotic resistance, bacterial infection has become one of the most persistent unresolved problems. New antibacterial agents, especially those that are environmental-friendly, are urgently needed.@*Methods@#Melanin extracted by filtration centrifugation and acid and proteolytic hydrolysis was characterized using UV, FTIR, TEM, and XPS. Photothermal conversion was calculated, and the bacteriostatic effects, and , were assessed by plate counting and ratios (%) of wound areas.@*Results@#Natural melanin hydrolyzed by trypsin had good photothermal conversion effects, which resulted in superior bacteriostatic activities. The extracted melanin along with laser NIR irradiation at 808 nm promoted the healing of wounds infected by drug-resistant bacteria and was biocompatible according to toxicity tests and .@*Conclusion@#The present findings indicated a safe and efficient method of developing natural antibacterial agents.