In the case of girls, the pubertal stage was also a CMRI predictive factor. In conclusion, BMI was an important indicator of cardiovascular risk in both sexes. Pubertal stage was associated with cardiovascular risk only in the girls.This study explored the association between pubertal stage and anthropometric and cardiometabolic risk factors in youth. A cross-sectional study was conducted in 2877 Colombian children and adolescents (9–17.9 years of age). Weight, height, and waist circumference were measured and body mass index (BMI) was calculated. A biochemical study was performed to determine the cardiometabolic risk index (CMRI). Blood pressure was evaluated and pubertal stage was assessed with the Tanner criteria. Hierarchical multiple regression analyses were performed. The most significant variable ( During puberty, boys and girls develop their secondary sexual characteristics and their reproductive competence, which is triggered by the secretion of the gonadotropin-releasing hormone (GnRH) . Among oEvidence has shown that precocious puberty is associated with a higher adult body mass index (BMI), fasting insulin, diastolic blood pressure (DBP), and decreased High-density lipoprotein (HDL) cholesterol in both sexes, as well as with higher total serum cholesterol, Low-density lipoprotein (LDL) cholesterol, and triglycerides in males . ConversOther studies found that excess fat (BMI and skinfold thickness) was associated with pubertal stage and with early maturation in boys and girls, though the associations were in opposite directions. Compared with their counterparts, early maturing boys had thinner skinfolds, whereas early maturing girls had thicker ones . These rThe objective of this study was to explore the association between pubertal stage and biochemical and anthropometric factors in Colombian children and adolescents.n = 2877) of healthy Colombian children and adolescents, 9–17.9 years of age. Data were collected from 2013 to 2016 and the analysis was conducted in 2016. The exclusion criteria included having a clinical diagnosis of cardiovascular disease, having type 1 or type 2 diabetes mellitus, being pregnant, using alcohol or drugs, and not having lived in Bogota for at least one school year. Exclusion from the study was made effective a posteriori, without the students being aware of their exclusion, to avoid any undesired situations.Schoolchildren included in this secondary analysis are part of The Fuprecol Study  carried out in Bogotá, Colombia. A detailed description of Fuprecol design, methods, and primary outcomes for our current cohort can be seen elsewhere ,11. The ® Model BF689, Tokyo, Japan) with a low technical error of measurement (TEM = 0.510). Body height was measured to the nearest 0.1 cm in bare or stocking feet with the adolescent standing upright against a portable stadiometer . Then, BMI was calculated as body weight in kilograms divided by the square of height in meters. BMI was classified as underweight, normal weight, overweight, or obese using the International Obesity Task Force (IOTF) criteria [® 8004-MA, Parsippany, NJ, USA).Data on the variables were collected at the same time in the morning (between 7:00 a.m. and 10:00 a.m.). Body weight was measured to the nearest 0.10 kg with the participant lightly dressed using a portable electronic weight scale  according to the protocol of Ramírez-Vélez et al. [In all measures, we found almost excellent test-retest reliability , height (ICC = 0.973), BMI (ICC = 0.897), and WC (ICC = 0.967)). To classify WC, we used criterion-referenced health-related cut-off points derived from de Ferranti et al.  because z et al. . The meaz et al. .Blood samples were obtained from each subject early in the morning, following a 10-h overnight fast by venipuncture from the antecubital vein. Before the samples were taken, the fasting condition was confirmed by the child and the parents. Blood samples were obtained from an antecubital vein, and analyses were subsequently completed within one day of collection. The cholesterol linked to high-density lipoproteins (HDL-C), glucose, triglycerides (TG), and total cholesterol were measured using colorimetric enzymatic methods with a Cardiocheck analyzer. The fraction of cholesterol linked to low-density lipoproteins (LDL-C) was calculated with the Friedewald formula . The preAfter the tests and blood draw, diastolic blood pressure (DBP) and systolic blood pressure (SBP) were determined as the average of two measurements separated by a five-minute interval, with the child resting for at least five minutes before the first measurement. Participants were seated in a quiet, calm environment with their right arm in a semi-flexed position at heart level. Blood pressure was measured using a Dynamap vital signs monitors . High resting blood pressure for pediatric is defined as a SBP ≥ 90th centile or DBP ≥ 90th centile. All centile-based threshold limits were sex- and age-specific and selected on the basis of the De Ferranti et al.  definitiParticipants self-assessed their pubertal stage of secondary sex characteristics , according to the criteria of Tanner and Whitehouse . The rouThe Fuprecol Study was conducted in accordance with the Helsinki Declaration for Human Studies and approved by the Colombian Data Protection Authority  and the Review Committee for Research on Human Subjects at the University of Rosario (Code No. CEI-ABN026-000262). All participants were informed of the study’s goals, and written informed consent was obtained from participants and their parents or legal guardians.n (%). The normality of the variables was verified using histograms and Q-Q plots (“Q” stands for quantile). Differences were analyzed with the Student t-test or chi-square test (χ2) in order to explore differences between sex and pubertal stage groups. The ANCOVA model was used to assess mean differences in CMRI among the categories of pubertal stage, controlling for age.The morphological component, physical fitness, and cardiometabolic risk factors of the study sample are presented as mean values, standard deviation (SD), or relative frequencies F-test was used to assess the significance of the additional terms in comparison to the preceding model. The interaction effect of the pubertal stage was indicated by the significance of the interaction terms added to the regression model. All models were adjusted for age. We used SPSS V. 21.0 software for Windows . Statistical significance was set at p < 0.05.Each of the component variables of the risk score was regressed with age (and with body height for SBP and DBP) separately for boys and girls. The standardized residuals were retained to represent the z-score of age-adjusted values for each of the component variables. All the statistical analyses were conducted separately for boys and girls. In parallel, a CMRI without the central obesity component  was also calculated for comparison. Hierarchical multiple regression analyses were applied to examine the interaction effect of pubertal stage on the association between CMRI and BMI. The z-score of the unadjusted BMI (ZBMI) was first entered into the regression model with the CMRI score as the dependent variable. Then, pubertal stage was recoded as a categorical variable  and entered into the regression. Finally, the interaction terms of the pubertal stages and ZBMI were entered into the regression model. The p = 0.067). As can be observed in p = 0.001), with a higher prevalence of overweight (23.1%) in the girls. When the amount of body fat was analyzed, the results showed that the girls had an average of 24.9% whereas the boys had an average of 16.6%. These differences were statistically significant (p = 0.013).The sample population was composed of 2877 participants, 54.5% of whom were female. No statistically significant gender-based differences were found (p = 0.157).Regarding stages of pubertal stage, there were no significant differences between boys and girls (p < 0.05) were high systolic blood pressure, overweight/obese and obese in both sexes. Moreover, in the case of the boys, there were statistically significant differences in the variables of low HDL-C (p = 0.001) and CMRI (p = 0.003). As can be observed, in the post-pubertal stage, CMRI values were positive in both sexes.R2) in CMRI in both boys (20.0%) and girls (20.5%). Pubertal stage was entered in Model 2 and accounted for a significant increase in variance explained in both sexes, (boys R2 = 22.0% and girls R2 = 21.0%). When the interaction-term of ZBMI and puberty was entered in Model 3, there was a further significant increase of the variance explained in both sexes, (boys R2 = 23.0% and girls R2 = 23.0%) (a). On the other hand, hierarchical regression results for the CMRI without the central obesity component , shown a lower proportion of variance explained in each model.Summary risk scores to quantify the cardiovascular risk were used to examine the interaction effect of pubertal stages on the association of cardiovascular risk factors by BMI in the analyses. When sex-specific characteristics for the CMRI, the ZBMI explained a significant proportion of the variance (= 23.0%) , CMRI a.a). Such an interaction effect of pubertal stage was, however, reversed in boys; the marginal effect of increasing 1 unit of ZBMI on the CMRI was decreased by an average of 0.050 and 0.011 units in the pubertal stage and post-pubertal stage, respectively (b).In particular, the marginal effect of increasing 1 unit of ZBMI on the CMRI would be further increased by an average of 0.016 and 0.009 units to the score for girls in the pubertal stage and post-pubertal stage, respectively , CMR1 a.ectively . A similectively , CMRI b.This study explored the association between pubertal stage and anthropometric and cardiometabolic risk factors in 2877 Colombian children and adolescents (9–17.9 years old). Our findings show significant gender-based differences in the nutritional status of the participants with a higher prevalence of overweight among the girls (23%). This finding agrees with Briceño et al. , who stuPrevious studies have shown that the timing of pubertal development affects body composition in girls  and in bAccording to Prenkert and Ehnfors , these dIn regard to pubertal stage and cardiovascular risk factors, puberty was significantly associated with some cardiovascular risk factors, such as high systolic blood pressure, overweight/obesity, and obesity. This suggests that the simple and inexpensive measure of BMI can be as clinically important or even more important than total adiposity measures assessed by accurate, complex, and expensive methods . NonetheOne of the major issues at puberty is the difference in the percentage of body fat between sexes. Consequently, for girls, the physiological pattern of body fat, running parallel to age and pubertal development , could be associated with increased early cardiovascular risk . As for We explored the association between pubertal stages and individual cardiometabolic risk factors to examine whether pubertal stage was associated with CMRI, whereas the other studies looked into the changes of metabolic profile that occur in different pubertal stages by sex. Additionally, the association of CMRI is statistically more demanding than CMRI, as it removes the WC component from the risk score. The results of our study as well as those of other studies suggest that it would be appropriate to include the evaluation of pubertal development stage in clinical screening, given its association with cardiovascular risk. However, similar to the findings of the Chan et al.  in Hong This study had some limitations. First, all participants were from the same region in Colombia. Consequently, any inferences for all Colombian children and adolescents should be made with caution. Second, this research did not consider the potential impact of determinants such as socioeconomic, dietary and physical activity patterns, and ethnic factors, all of which can modulate growth and levels of adiposity. However, such limitations do not compromise the interest of the results obtained. One of the strong points of the study is its large sample size. Another positive aspect is that the children and adolescents in the sample attended public schools, which were located in different districts of Bogotá, therefore including a mix of locally-born residents and those arriving from other regions, and so it is racially and culturally diverse.Our findings suggest that there may be an interaction effect of pubertal stage on the association of cardiometabolic risk by BMI. Nevertheless, further research is required to analyze in greater depth the association between different pubertal stages and risk factors such as obesity at early ages. These results can be used as a baseline for long-term health surveillance. A longitudinal study is needed to further examine any moderation effect.


Serum levels of melatonin, 4-hydroxynonenal (HNE), adiponectin, omentin-1, leptin, and resistin, as well as erythrocytic malondialdehyde (MDA) concentration and Zn/Cu-superoxide dismutase, catalase, and glutathione peroxidase (GPx) activities, were measured at baseline and after supplementation. Significant body weight reduction was observed only in the melatonin group. After melatonin supplementation, the adiponectin and omentin-1 levels and GPx activities statistically increased, whereas the MDA concentrations were reduced. In the placebo group, a significant rise in the HNE and a drop in the melatonin concentrations were found. The results show evidence of increased oxidative stress accompanying calorie restriction. Melatonin supplementation facilitated body weight reduction, improved the antioxidant defense, and regulated adipokine secretion. The findings strongly suggest that melatonin should be considered in obesity management. This trial is registered with CTRI/2017/07/009093.Obesity is one of the major global health problems. Melatonin deficiency has been demonstrated to correlate with obesity. The aim of the study was to estimate the effect of melatonin on oxidative stress and adipokine levels in obese patients on a calorie-restricted diet. Thirty obese patients were supplemented with a daily dose of 10 mg of melatonin ( A bodf cancer . The prof cancer , 2. The Excessive adiposity is a multifactorial disorder, generally resulting from the interaction of high dietary energy intake, low physical activity, genetic factors, eating disorders, environmental and socioeconomic factors, and societal influence . AdiposeChronic inflammation, tissue dysfunction, increased plasma levels of glucose and lipids, hyperleptinemia, and decreased antioxidant defense belong to the factors disturbing the oxidant-antioxidant balance in the obese state. During obesity, the generation of reactive oxygen species (ROS) is induced via various biochemical mechanisms, including activation of NADPH oxidases and protein kinase C, oxidative phosphorylation, glyceraldehyde auto-oxidation, and polyol and hexosamine pathways , 14. MorAn optimal candidate to diminish the deleterious consequences of excessive adiposity would be an agent that simultaneously exhibits anti-inflammatory and antioxidant properties, as well as having an impact on the adipokine secretion. A molecule which meets these conditions is melatonin (N-acetyl-5-methoxytryptamine). This indoleamine, secreted mainly by pinealocytes, is a derivative of tryptophan. Its synthesis/secretion is highest during the dark phase of the light/dark cycle . MelatonObesity has been related to the chronic sleep disruption, another epidemic of the industrialized world –30. The 2 were included in the study. The participants were evaluated by a standard physical examination and routine clinical laboratory tests. According to the International Classification of Diseases, 10th revision [Thirty volunteers with BMI ≥ 30 kg/mrevision , all subrevision , addictiThe eligible participants with obesity class I or class II  were ranThe anthropometric measurements were performed twice, at baseline and after 30 days of melatonin/placebo supplementation. Body weight and height of the subjects were measured using a medical weighing scale with a height rod. The accuracy of measurements was 0.1 kg and 0.5 cm, respectively. The weight in kg was divided by the square of the height in m to obtain the BMI value. Waist and hip circumferences were recorded using an anthropometric tape accurate to 0.5 cm. The waist circumference was measured in the horizontal plane directly above the umbilicus, whereas the hip circumference was measured at the largest part of the hips. The waist-hip ratio was calculated as the waist circumference divided by the hip circumference.g for 10 min at 4°C). The serum and plasma were separated and stored at −80°C for further analysis. Subsequently, the erythrocytes were washed three times with a phosphate-buffered saline (PBS) solution at a ratio of 1 : 3 with a simultaneous centrifugation of the sample after each wash . The washed red blood cells were mixed with a PBS solution to obtain erythrocytic suspension with a 50% hematocrit index. The suspension was used to determine the parameters of oxidative stress.Blood samples were collected in the morning (08 : 00 hr) after overnight fasting from the median cubital vein into polypropylene tubes (6 mL) without anticoagulant to obtain serum or in EDTA-containing tubes (9 mL) to obtain plasma and erythrocytes at baseline and after 30 days of melatonin/placebo treatment. All samples were centrifuged , 4-hydroxynonenal (HNE) , adiponectin , leptin , resistin , and omentin-1 , according to the manufacturers' instructions.2O2 decomposition at 240 nm. The principle of the method for GPx activity measurement was based on recording the decrease in absorbance of NADPH at 340 nm using H2O2 and reduced glutathione as substrates, in the presence of yeast glutathione reductase and NaN3 to inhibit the pseudoperoxidase activity of Hb. The Hb concentration was estimated at 540 nm according to the method of Drabkin [Erythrocytic malondialdehyde (MDA) concentration and the activities of Zn/Cu-superoxide dismutase , catalase , and cytosolic glutathione peroxidase  were assayed according to the methods of Buege and Aust  in the m Drabkin .t-test for the comparison of the MEL and PL groups and a paired t-test for the comparison of the same group before and after supplementation. The hypothesis of normal distribution was assessed by the Shapiro-Wilk test. In turn, the homogeneity of variances was verified using the Levene's test. Pearson's correlation coefficient was used to quantify the relationship between the parameters measured. The level of significance was set at P < 0.05.All results are expressed as the means ± S.E.M. Statistical analysis included Student's Demographic, anthropometric, and clinical characteristics of the study participants are presented in The results of biochemical measurements at baseline and after 30 days of calorie-restricted diet subjects with the melatonin or placebo supplementation are summarized in r = −0.393; P < 0.05), BMI and adiponectin , and leptin and omentin-1 . Significant positive correlation was found between BMI and leptin . MDA concentration was negatively correlated with GPx activity , but surprisingly, it was positively correlated with SOD-1  and CAT  activities.When data from all subjects were pooled, the interesting correlations were revealed. Statistically significant negative correlations were noted between body weight and adiponectin  on redox status and circulating adipokines in obese human subjects on a calorie-restricted diet. As mentioned, there exist only a few reports related to the impact of exogenous melatonin on obesity in humans. Koziróg et al.  investigA 30-day calorie-restricted diet combined with melatonin supplementation resulted in a statistically significant weight loss, whereas a low-calorie diet per se yielded only a slight reduction in body weight. This is in accordance with the results of many animal studies –34, 36. Obesity is associated with an altered redox state, including both enhanced reactive oxygen species (ROS) generation and inadequate antioxidant defense . These cThe results of the present study indicate that exogenous melatonin may prevent the rise in oxidative stress in the initial stage of weight loss. When melatonin was supplemented to the subjects, there were no changes in the HNE and melatonin concentrations after 30 days of a low-calorie diet. Exogenous melatonin could be used to counteract the increased oxidative stress accompanying the weight loss. HNE is a major product of nonenzymatic peroxidation of polyunsaturated fatty acids . HNE is Positive correlations between erythrocytic MDA concentration and the activities of SOD-1 and CAT are important observations in the present study. In the early stages of obesity, compensatory mechanisms stimulate the activities of antioxidant enzymes to counteract the augmented synthesis of ROS, but they are insufficient to prevent oxidative damage , 49. TheExcessive adiposity is a condition characterized by a severe dysfunction of WAT, including the alterations of tissue composition and the modifications of its endocrine function . The disAdiponectin is a hormone strongly involved in the regulation of lipid and glucose metabolism. It improves insulin sensitivity, regulates appetite and energy expenditure, and exerts anti-inflammatory, antiproliferative, and antiapoptotic actions . AdiponeIn the present study, a 30-day low-calorie diet resulted in no change of the circulating morning levels of adiponectin, whereas the supplementation of melatonin significantly increased the concentration of this adipokine. Gonciarz et al.  also fouOmentin-1 is another insulin-sensitizing and anti-inflammatory adipokine , 74. It Both adiponectin and omentin-1 were found to improve insulin sensitivity , 76. IncLeptin- and resistin-exhibited elevated levels are positively correlated with obesity and its complications , 12, 88.ob/ob) mice. The links between resistin and obesity need further investigations.Similar results were obtained in the case of resistin. Resistin is a proinflammatory adipokine, which is associated with the development of insulin resistance , 101. ThThe positive impact of exogenous melatonin on weight reduction, observed in the present study, strongly supports that administration of this agent may be a useful adjunct in obesity treatment. In addition, melatonin significantly reduced oxidative stress and regulated the circulating adipokines beneficial for energy homeostasis in obese subjects on a low-calorie diet. Thus, exogenous melatonin may facilitate the health improvement during obesity management. These results confirm that melatonin supplementation, mimicking the conditions of normal sleep, could have a desirable effect in humans during dietary weight loss.The present study has some limitations. The small number of participants is a limiting factor; thus, it may be treated as a pilot study. However, to the best of the authors' knowledge, it is the first report related to the effects of melatonin supplementation on human obesity with such large doses of the hormone. Another limitation is the study design—the blood samples were taken only once a day, in the morning. It was sufficient to observe the changes in the circulating levels of the selected adipokines. Nevertheless, in the case of adipokines with the circadian pattern of secretion, it would be interesting to examine their maximum release after melatonin supplementation. Undoubtedly, the results of the present study are very promising but raised new questions requiring further research.


Finally, for the entire population, combined hormonal contraceptives demonstrated to do not increase breast cancer risk. The results of our study suggest that women at high familial risk and mutation carries develop tumors with different clinical-pathological characteristics and, consequently, are influenced by different protective and risk factors.Reproductive history and exogenous hormonal exposures are acknowledged risk factors for breast cancer in the general population. In women at increased breast cancer risk for genetic predisposition or positive family history, data regarding these risk factors are limited or conflicting, and recommendations for these categories are unclear. We evaluated the characteristics of reproductive life in 2522 women at increased genetic or familial breast cancer risk attending our Family Cancer Center. Breast cancers in BRCA mutation carriers were more likely to be hormone receptor negative, diagnosed at 35 years or before and multiple during the lifetime than tumors in women at increased familial risk, while the distribution of invasive cancers and HER2 positive tumors was similar in the different risk groups. At least one full-term pregnancy (HR 0.27; 95% CI 0.12–0.58;  Breast cancer (BC) represents the most common form of cancer and the leading cause of cancer death among women worldwide, with an estimated 1.7 million cases and 521,900 deaths in 2012. BC alone accounts for 25% of all cancer cases and 15% of all cancer deaths among females [In the general population, acknowledged risk factors for BC are aging, white race, reproductive history , exposures  or hormone replacement therapy), alcohol, tobacco smoking, overweight and obesity, lack of exercise, dense breast tissue, previous chest radiation, precancerous lesions, personal history of BC, family history and mutations in BC predisposition genes  .These risk factors have also been investigated in the high-risk population of BRCA mutation carriers in a variety of studies. Particularly, a recent meta-analysis  showed tIn conclusion, it results unclear the extent to which these modifiers of risk influence BC risk in BRCA mutation carriers and in women with a family history of BC. Nonetheless, an accurate risk assessment in these high-risk populations remains fundamental, in order to establish personalized strategies for risk control .We collected the main reproductive factors through the revision of the medical records of 2527 women attending the MFCC between May 2010 and January 2016. One woman with a MLH1 mutation and 4 women who underwent bilateral prophylactic mastectomy have been subsequently excluded, thus 2522 women were finally analyzed. Characteristics of the entire population divided by subgroups and the distribution of reproductive variables are presented in Table The mean age ± SD of the entire population at the end of the period was 52 ± 13 years, ranging from 17 years to 92 years. Among these women, 113 (5%) had a pathogenic mutation in one of the BRCA genes (VHR Group). The mean age for the mutation carriers at the end of the period was 51 ± 14, years and they were 64 BRCA1 and 49 BRCA2. In addition, 1541 (61%) were at High Risk (HR) with a mean age of 52 ± 13 years and 868 (34%) women were at Intermediate Risk (IR) with a mean age of 52 ± 12 years, according to the Modena criteria. Fourteen women with a BRCA variant of unknown significance (VUS) have been classified according to their family history (2 at Intermediate Risk and 12 at High Risk).p < 0.001) . One hundred and sixty-three of these women developed BC before the first access at the MCFF. The Modena Criteria correctly identified 3 different categories at increasing cumulative BC risk (p = 0.024), diagnosed at 35 years or before (p = 0.002) and multiple during the lifetime (p = 0.017). Consequently, age at diagnosis was significantly lower in VHR compared to HR and IR  (p = 0.007). On the contrary, the distribution of invasive BC (p = 0.338) and HER2 positive tumors (p = 0.545) was similar in the three groups of patients. Nevertheless, it should be noted that BRCA1-related BC were significantly more likely to be hormone receptor negative than BRCA2-related tumors (p = 0.036). Moreover, somewhat surprisingly, we found a higher rate of HER2-negative tumors than that seen in the general population for all the three groups at increasing risk .The characteristics of tumors developed by each group are summarized in Table The cumulative risks at 60 years according to the characteristics of reproductive life and CHCs use for each risk category are presented in Table p = 0.001). In order to avoid the potential bias due to BC detected before pregnancy, in this analysis we included women that developed cancer before getting pregnant in the group of nulliparous. Notably, among parous women, an increasing number of full-term pregnancies seem to be associated with a decrease in BC risk . Interestingly, only in HR group, age at first live birth ≤ 30 showed to significantly reduce risk for BC (p = 0.048).Among BRCA mutation carriers, women with at least one full-term pregnancy compared with nulliparous women had a lower risk of BC (p = 0.005) or more (p = 0.022) than one year showed to significantly reduce the risk for BC.We observed no association between ever having breast-fed and BC risk, among women at increased familial risk (HR and IR groups). In these two groups, there was also no statistically significant association between duration of breastfeeding (more or less than 12 months) and BC risk. Interestingly, only in VHR group, breastfeeding either less (p = 0.384) and for the HR group (p = 0.987). Conversely, in the IR group a miscarriage or an abortion seems to have increased the risk of BC (p = 0.018).We found no association between having a miscarriage or abortion and the risk of BC for the VHR group (p = 0.004). For the analysis of menopausal age, we’ve considered only women diagnosed after their menopause. Interestingly, late menopause (> 50 years) seems to be even protective in BRCA mutation carriers (p = 0.033).In HR women, a late age at menarche (> 12 years) showed to significantly reduce risk for BC . In previous literature, age at first full-term pregnancy demonstrated to be a powerful denominator of future BC risk in the general population, as it determines the length of time the undifferentiated breast tissue remains particularly vulnerable –21. Intep < 0.0001) for every 12 months of breastfeeding [After pregnancy, an extended period of breastfeeding contributes to the functional ripening of the glandular tissue. On these bases, the duration of breastfeeding is believed to have an influence on BC risk. Particularly, the Collaborative Group on Hormonal Factors in Breast Cancer found that the RR for BC decreased by 4.3%  for every year younger at menarche, and independently by a smaller amount , for every year older at menopause. Particularly, exposure to endogenous ovarian hormones are more relevant for estrogen receptor positive disease than for estrogen receptor negative disease and for lobular than for ductal tumors [Several studies have found that women using oral contraceptives have a slightly greater risk of BC than women who have never used them. This risk seems to go back to normal over time once the pills are stopped. Nevertheless, these studies mostly refer to CHC used before 1975 and may be the result of exposure to higher dosages of estrogens , 32. MorOne of the main limitations of our study consists in the lack of data, because several medical records have not been entirely filled. As regards tumor characteristics, the immune-histochemical features were available only for women with invasive carcinomas, diagnosed or treated in the province of Modena in the last 20 years, or for women who provided their past documentation. Moreover, the systematic evaluation of HER2 status became available in our Institution only in 2006, when Trastuzumab has been approved in the adjuvant setting. Another limitation of our study is the non-availability of information regarding start age for CHC, breastfeeding and abortion, which showed in previous literature to play a role in the modulation of BC risk.Somewhat unexpectedly, we found different risk and protective factors between HR and IR women . These results may have three possible explanations. Firstly, the IR group is smaller and with fewer events than the HR group, and this might have affected the statistical power of the analyses. Secondly, we do not have any information regarding the presence of other possible pathogenic mutations in other susceptibility genes in this population of women. It is likely that a part of these women with positive family history, especially in the HR group, may carry an inherited mutation other than BRCA, which may have contributed to modify their risk of developing BC, irrespectively of the characteristics of reproductive life. Finally, women belonging to the IR group might have a lower risk perception compared to HR risk women, because of their slighter familiarity and less intensive surveillance program. Therefore, IR women might have worked less hard in order to change their modifiable risk factors, such as alcohol assumption, tobacco smoking, dietary habits and physical exercise. Overall, these missing genetic and lifestyle factors represent possible confounders in our analysis.Overall, in our study at least one full-term pregnancy, breastfeeding and late age (> 50 years) at menopause represent the principal protective factors in BRCA mutation carriers, while in women at increased familial risk early age at first full-term pregnancy and late menarche represent the principal protective factors. These data are relevant in particular for BRCA mutation carriers, which in our sample got fewer pregnancies than other women, maybe because of the concern of mutation inheritance. These results confirm that pregnancies and the reproductive lifespan play crucial roles in the definition of BC risk in women at increased familial and genetic risk. Moreover, women at high familial risk and mutation carries develop tumors with different clinical-pathological features and, consequently, are influenced by different protective and risk factors. Nevertheless, it is noteworthy that in our sample as well as in literature, hormone receptor negative tumors are mainly associated with BRCA1-mutation carriers, while patients with a BRCA2 mutation seem to develop tumors with histopathological profile more similar to that of tumors affecting the general population , 34. TheSince 1995, the MFCC classifies women with a family history of breast and/or ovarian cancer according to the Modena criteria , 18 and,Criterion 1: At least three relatives with BC in two different generations, regardless of family structure. Alternatively, two relatives with BC and one with OC or one with BC and two with OC in two different generations.Criterion 2: At least two family members affected by BC with a first-degree relationship. Alternatively, one relative with BC and one with OC. In the case of male interposition, a relationship of different degree (second or third) is allowed.Criterion 3: At least one BC diagnosed before 40 years of age or bilateral.The Modena criteria used to classify families are the following:According to these criteria, families are divided into main clusters Table : HereditTogether with these basic clusters, some further criteria have been added Table : Early OThe characteristics of reproductive life were obtained through the revision of the medical records of 2527 women that started their surveillance program at the MFCC between May 2010 and January 2016. Particularly, we evaluated number of pregnancies, age at first full-term pregnancy, breastfeeding, abortions, menarche, menopause, and use of combined hormonal contraceptives (CHC). Also women with a previous diagnosis of breast cancer are admitted to the Center and have been included in the present study. The aim of our study was to analyze the impact of reproductive history and exogenous hormonal exposures in the development of BC in a population of BRCA mutation carriers and in women with family history of breast and/or ovarian cancer.At first, women were divided according to a combination of the Modena Criteria and the Tyrer-Cuzick model in the following three groups:women with a recognized BRCA1/2 mutation at the genetic testing.women not tested for BRCA genes or with a non-informative result, with a 3-fold increased lifetime risk of developing BC according to the Tyrer-Cuzick model or belonging to HBC/HBOC, SHBC/SHBOC, BOC, HOC, and EOBC families according to the Modena criteria.women not tested for BRCA genes or with a non-informative result, not belonging to the High Risk Group, with a 2-fold increased lifetime risk of developing BC according to the Tyrer-Cuzick model or belonging to FBC/FBOC, SFBC/SFBOC, SFBC+/SFBOC+ and MBC families according to the Modena criteria.Women already diagnosed with BC at the time of the first access were classified according to the Modena Criteria, since the Tyrer-Cuzick model should not be applied to affected women.Interestingly, the combined classification did not show to correctly stratify the cumulative risk at 60 years of these women Figure  and HR wwomen with a recognized BRCA1/2 mutation at the genetic testing.women not tested for BRCA genes or with a non-informative result, belonging to HBC/HBOC, SHBC/SHBOC, BOC, HOC, and EOBC families.women not tested for BRCA genes or with a non-informative result, belonging to FBC/FBOC, SFBC/SFBOC, SFBC+/SFBOC+ and MBC families.Notably, women with a BRCA variant of unknown significance (VUS) have been classified according to their family history, as current Guidelines recommend. One woman with a MLH1 mutation and 3 women who underwent bilateral prophylactic mastectomy have been excluded from the analyses.Since the median age of these women was quite low, we decided to evaluate the cumulative risk at 60 years according to the characteristics of their reproductive life. Analyses were conducted separately for subjects with mutations and women with a family history of BC according to the three risk categories. Unknown data  has been excluded from the analyses.p-value < 0.05 were considered significant.In the descriptive analysis, the continuous variables were summarized by means of mean and standard deviation (SD), and the categorical variables were reported as absolute and percent values. Distributions of continuous covariates by group were compared using one-way ANOVA . The comparison of categorical variables between groups was performed using the Chi2 test or Fisher's exact test, when appropriate. The cumulative risk to develop BC was calculated from the age of menarche to the age of diagnosis of BC, or age of the last control for censored patients. The cumulative hazard rate was calculated and graphically reported by means of Nelson-Aalen estimator . The cum


The study was designed to examine if baroreflex sensitivity (BRS) could predict the short-term outcome of postural tachycardia syndrome (POTS) in children.Seventy-seven children subjects were included in the study. Among them, 45 children were in the POTS group and another 32 healthy children were in the control group. A ninety-day clinical follow-up was conducted and the symptom score before and after the follow-up was calculated for POTS patients by using POTS score system. Hemodynamics and continuous BRS monitoring were recorded by Finapres Medical System-FMS . According to the symptom score change during follow-up period, POTS patients were further divided into subgroup A (n = 24) with symptom score decreased by at least two points and subgroup B (n = 21) with symptom score decreased by less than two points. The predictive value of BRS in the short-term outcome of POTS in children was analyzed using receiver-operating characteristic (ROC) curve.BRS of POTS children was significantly higher than that of the healthy children . It was higher in subgroup B than that of subgroup A . BRS was positively correlated with HR change in POTS Group . Area under curve (AUC) was 0.855 , and BRS of 17.01 ms/mmHg as a cut-off value yielded the predictive sensitivity of 85.7% and specificity of 87.5%.BRS is a useful index to predict the short-term outcome of POTS in children. Its symptoms had significant associations with postural change. Main hemodynamic characteristics of POTS was a significant increase in heart rate at upright position compared with supine position, and the increase amplitude of heart rate is ≥40 heart beats/min, or the maximum heart rate is ≥120 heart beats/min . Studies/100,000 , while o/100,000 . Therefoet al. showed that POTS children had abnormality of autonomic nervous function [et al. showed that sympathetic activity of POTS patients increased abnormally, and the abnormality of autonomic nervous activity was involved in pathogenesis of POTS [Generally speaking, the POTS prognosis is related with its pathogenesis . The prefunction . Furlan, of POTS . Therefoet al. showed that the reduction of BRS was closely related to the occurrence of hypertension [BRS comprises basic mechanistic elements of regulating blood pressure. Carotid sinus and aorta arch sense the traction of vascular wall by blood pressure change, transmitting to cardiovascular regulatory center of medulla and hypothalamus, thus to regulate the activity of autonomic nervous system. Thus, BRS plays an important role in keeping the stability of cardiovascular function, especially the regulation of upright blood pressure change. Harrington, rtension . HoweverThis research included 45 POTS children, all of whom were admitted to the Department of Pediatrics of Peking University First Hospital because of orthostatic intolerance symptom from November 2013 to August 2015. They were diagnosed as POTS according to the clinical pictures and upright tilt test [Medical records and samples were obtained from November 2013 to August 2015. Authors had access to information that could identify individual participants during data collection. All the selected subjects had no history of fever and medication within two weeks. This research protocol was approved by Ethics Committee of Peking University First Hospital, Beijing, China and the informed consent was obtained from parents and guardians of all study subjects. We obtained informed written consent from the next of kin, caretakers, or guardians on behalf of the children enrolled in the study. The Ethics Committee of Peking University First Hospital for Clinical Study approved this consent procedure.(1) mainly elder children; (2) with orthostatic intolerance, such as dizziness and headache, amaurosis, palpitation, nausea, blurred vision and even syncope in severe cases, with orthostatic intolerance symptoms lasting for at least three months; 3) positive head-up tilt test (HUTT) with an increase in heart rate ≥ 40 heart beats/min or a maximum heart rate ≥120 heart beats/min when upright or tilt within 10 min, accompanied with orthostatic intolerance symptoms including dizziness and headache, amaurosis, palpitation and nausea, and blurred vision, and syncope might be cause in severe condition; (4) in addition, other diseases that could cause orthostatic intolerance symptoms including cerebral vascular diseases and organic heart disease were excluded [ positiveThe protocol for HUTT was according to the previously published literatures , 20. ChiFMS  with a finger sensor was used for continuously monitoring and collecting hemodynamic data generated beat-by-beat. HR, BP and BRS were measured using a model flow method. With a finger cuff, arterial blood pressure was obtained continuously and noninvasively by using the system and beatscope software with the volume-clamp technique maintaining the diameter of the artery under an inflated finger cuff at a set point, thereby determining arterial pressure with time changes. Diodes were located in the finger cuff, on either side of the finger, to detect changes in artery diameter and change the inflation of the cuff to remain the diameter at the set point. The cuff is inflated or deflated via an air bladder connected to an air hose and pump. The software, using a mathematical model, generates an aortic pulse waveform from the finger arterial pressure wave. This computation takes into account changes in the pulse pressure and waveform shape as the pressure pulse is transmitted down the brachial arteries to the finger arteries. With the Finapres finger cuff, together with beatscope software, left ventricular stroke volume was calculated and together with HR and BRS were calculated. The BRS was calculated at rest and in supine position. Parameters such as age, sex, body height and weight were also included in the computation for each individual subject –23. The Symptom scoring was applied to evaluate the effect of conventional therapy. Score was calculated according to occurrence frequency of clinical symptom of subjects to carry out respective score of clinical symptom when diagnosed and at follow-up of patients; symptom score when diagnosed was recorded as baseline score, and symptom score at follow-up was recorded as the end score. Score calculation was also applied to control subjects. Subjects were instructed to rate their symptoms for at least 3 months prior to completion of questionnaire by parent or subjects. Score included the following clinical symptoms: syncope, dizziness, chest tightness, nausea, palpitation, headache, blurred vision, hand shaking and cold sweat. The score calculation standard was provided below: 0 score, no symptoms; 1 score, symptoms less than once on average per month; 2 scores, 2–4 times on average per month; 3 scores, 2–7 times on average per week; and 4 scores, over once on average per day. All the scores were the sum of each symptom-based score. After children were diagnosed as POTS, baseline symptom scores were recorded, and scores were recorded again at follow-up according to symptom score system. Those whose end scores at follow-up decreased by more than 2 scores compared with baseline scores were assigned into subgroup A; while those whose end scores increased or decreased less than 2 scores compared with baseline scores were assigned into subgroup B –27.The conventional therapy was used for each POTS child in this research after diagnosis, including oral rehydration saline (ORS), exercise of autonomic nervous function and health education. The dosage of ORS was 1 bag/day. One bag of ORS contained 0.65 g of sodium chloride, 0.725 g of sodium citrate, and 0.375 g of potassium chloride. The exercise of autonomic nervous function used in this research mainly included upright training. The method of upright training was to stand against a wall , once a day, for 5–20 min. The training time was gradually extended according to the tolerance degree of upright position. In case of syncope aura or other disorders occurred, the training was terminated immediately –29. HealThe analysis was carried out with SPSS 16.0 software, and measurement data are expressed in mean ± standard deviation. Independent sample t-test was used for comparison of BRS between two groups, and variance of analysis was used for comparison among three groups. Pearson correlation analysis was used for correlation analysis, and chi-square test was used for comparison of rates. ROC curve was used to analyze BRS on prediction of the prognosis of POTS children, and area under curve indicated the value of the index on prediction of the result; area under curve between 0.5–0.7 indicated a relatively small predictive value, area under curve between 0.7–0.9 indicated a medium predictive value, and area under curve above 0.9 indicated a relatively high diagnostic value. Ninety-five percent of confidence interval of the curve area (not including 0.5 or p<0.05) indicated that the index had a value on prediction of the research result. P<0.05 indicated there was statistical difference.The POTS group included 25 males and 20 females, at the age of 12.5±2.5 years old. Control group consisted of 19 males and 13 females, at the age of 11.8±3 years old. Two groups had no statistical difference (p>0.05) in gender ratio, age, height, weight, systolic pressure at supine position, and diastolic pressure at supine position. The heart rate of POTS children at supine position, however, was lower than that of children in control group (p<0.05), and BRS value of POTS group was higher than that of children in control group (p<0.01) .The end symptom score at follow-up was lower than the baseline symptom score when diagnosed (p<0.01) in POTS group . The basNo statistical difference were found in gender ratio, age, height, weight, heart rate, systolic pressure at supine position, and diastolic pressure at supine position between the subgroup A and subgroup B (p>0.05) . There wBRS of POTS children was significantly higher than that of the healthy children . It was higher in subgroup B than that of subgroup A  .Correlation analysis of BRS and HR in POTS group: Heart rate change from supine to upright was positively correlated with BRS in POTS group .ROC curve of the predictive value of BRS for short-term outcome of POTS: The ROC curve showed that the area under the curve was 0.855 (95%CI 0.735–0.975). With BRS value of 17.01 ms/mmHg as a cutoff value, the predicted sensitivity was 85.7%, and specificity 87.5% .et al. showed that POTS patients were characterized by intolerance to movement and physical labor in addition to orthostatic intolerance [POTS has a relatively high incidence among school-aged children, with the proportion of girls higher than boys . In Chinolerance . TherefoThe pathogenesis of POTS mainly involved autonomic nervous dysfunction . BRS plaet al. showed that low blood volume might cause increase in BRS [et al [et al [The present study showed that BRS of children with POTS was significantly higher than that of control subjects . Convertino, e in BRS . In adulS [et al  and Fu, l [et al . While, l [et al . But in The present follow-up study showed that BRS of POTS in subgroup A was significantly lower than that in subgroup B . It was speculated that abnormal increase in BRS might affect disease prognosis. POTS patients with high BRS had a low threshold of blood pressure decrease caused by position change, and slight change in pressure might reflectively cause over activation of sympathetic nerve of children cases, resulting in a greater adverse impact on the prognosis if the increase value of heart rate was increased. As such, the present study suggested that baseline BRS might be a good index of predicating the prognosis of children with POTS, and the area under curve was 0.855, with a BRS value of 17.01 ms/mmHg as a cutoff value yielding the predicted sensitivity of 85.7% and specificity of 87.5%. Hence, detection of BRS could well predict the disease outcome of POTS patients, and the advantage of the detection was convenient, inexpensive, easy to perform and noninvasive in the prediction.The accuracy of the finger monitoring method of hemodynamics used in present study has been proved in previous studies and it can well reflect the real hemodynamics –50. HoweIn conclusion, BRS value is a useful index to predict the short-term outcome of POTS in children.


Background: Discrimination is a common experience for Blacks across various developmental periods. Although much is known about the effect of discrimination on suicidal ideation of adults, less is known about the same association in Black youth. Aim: We examined the association between discrimination and suicidal ideation in a national sample of Black youth. We also explored gender and ethnic differences in this association. Methods: We used data from the National Survey of American Life-Adolescents (NSAL-A), 2003–2004. In total, 1170 Black adolescents entered the study. This number was composed of 810 African American and 360 Caribbean Black youth (aged 13 to 17 years). Demographic and socioeconomic factors were controls, perceived discrimination was the predictor, and lifetime suicidal ideation was the outcome. Logistic regression was used to test the association between perceived discrimination and suicidal ideation in the pooled sample, as well as based on ethnicity and gender. Results: In the pooled sample of Black youth, higher perceived discrimination was associated with higher odds of suicidal ideation (Odds Ratio (OR) = 1.09; 95% Confidence Interval (CI) = 1.02−1.17). This association was significant net of age, ethnicity, gender, and socioeconomic status. We did not find interactions between perceived discrimination and ethnicity or gender on suicidal ideation. Perceived discrimination was associated with suicidal ideation in African Americans  and Caribbean Blacks , males , and females . Conclusion: Discrimination jeopardizes the mental health of Black youth. In a universal pattern, discrimination is associated with suicidal ideation in Black youth. More research is needed on this topic. The harmful effects of discrimination on the mental health of Black populations are well established ,2,3. HowDiscrimination is defined as differential and unjust treatment of individuals because of particular identities such as race, ethnicity, age, gender . In the Although the negative effect of discrimination on the mental health of adults is well documented ,11,14,15Black youth may become more aware of their identities during their transition to adolescence and adulthood, and therefore may be sensitive to discriminatory experiences that relate to their racial and general identities ,22. As aGibbons et al.  showed tDiscrimination, however, may not have similar effects across all groups of Blacks. Hudson et al.  have shoThis study investigated the effects of discrimination, ethnicity, gender, and SES on suicidal ideation in a national sample of Black youth. We also tested gender and ethnic differences in this regard. We hypothesized that discrimination will be associated with more suicidal ideation for all groups of Black youth.This is a cross-sectional study. We used data from the National Survey of American Life-Adolescent Supplement (NSAL-A), 2003 ,36. The The University of Michigan Institute Review Board approved the NSAL study. Adolescents’ legal guardians provided informed written consent. All adolescents provided assent themselves. Respondents received $50 as financial compensation. The study was funded by the National Institute of Mental Health (NIMH) and was conducted by the University of Michigan, Ann Arbor, MI, USA.The study enrolled 1170 Black adolescents, including 810 African Americans and 360 Caribbean Blacks. Participating youth ranged in age from 13 to 17 years. At the time of the study, all participants resided in the United States. More detailed information on the sampling strategy is available elsewhere ,38.The NSAL-Adolescent sample was drawn from the NSAL, a national probability sample of adult Blacks in the United States. The NSAL-adult sample was screened for African American and Caribbean Black households with eligible adolescents living in the households. Adolescents living in households were randomly selected for participation. If more than one eligible adolescent lived in a household, two adolescents were selected based on the gender of the first eligible adolescent. This strategy resulted in non-independence for adolescent samples. In response to this lack of independence, the adolescent supplement data were weighted to adjust for non-independence of the selection probabilities and non-response at the household and individual levels. The weighted data were then post-stratified to represent national estimates based on gender, age, and ethnicity ,10.All interviews were conducted in English. Interviews lasted 100 minutes on average. The overall response rate was 80.6%. The response rate was slightly higher for Caribbean Black youth (83.5%) than for African American youth (80.4%).For the majority (82%) of the interviews, data collection occurred during in-person interviews conducted in the adolescents’ homes. The remaining 18% of interviews were conducted entirely or partially by telephone. All in-person interviews used computer-assisted personal interviews (CAPIs). With CAPI, computers are used by trained interviewers to conduct the interviews. CAPI is the preferred method of interviewing for long and complex questionnaires.Sociodemographics: The study included demographic factors, such as age, gender, and ethnicity. Socioeconomic status (SES) was also measured. For SES, we used the poverty index, defined as the income-to-needs ratio from the 2001 United States Census. The poverty index was calculated by dividing household income by the poverty threshold [hreshold . Higher Ethnicity: Ethnicity was the self-identified ethnicity of the family household in which the adolescent lived. Participants self-identified as either African Americans or Caribbean Blacks. African American was defined as Black without having ancestral ties to the Caribbean. Caribbean Black was defined as Black having ancestral ties to a country included on a list of Caribbean countries provided by the interviewer, or that the particpant’s parents or grandparents were born in a Caribbean country. Caribbean countries included Antigua and Barbuda, Barbados, Bahamas, Cuba, Dominican Republic, Dominica, Grenada, Haiti, Jamaica, Saint Vincent and the Grenadines, Trinidad and Tobago, Saint Lucia, and Saint Kitts and Nevis.Discrimination: NSAL-A used a 13-item modified version of the Everyday Discrimination Scale (EDS) to measure discrimination. These items assess chronic, routine, and less overt discriminatory experiences that have occurred over the past year [ast year . Althougast year ,40,41. RSuicidal ideation: Lifetime serious suicidal ideation was asked using the following single-item measure: Did the following experience ever happen to you? “You seriously thought about killing yourself”. Single-item measures of suicidal ideation have been frequently used in large-scale national epidemiological studies [ studies ,42,43,44 studies .To accommodate the complex design of the NSAL-A, Stata 13.0  was used for data analysis. Adjusted odds ratios (ORs) and their 95% confidence intervals were reported.We used the Taylor expansion approximation technique to re-calculate the complex design-based estimates of variance. Standard errors reflect the weights due to the complex sampling design. All percentages reported in this study are weighted. As the Caribbean Black sample is more clustered than the African American sample, the standard errors are systematically larger for Caribbean Black than that for African American youth. As a result, findings are more conservative for Caribbean Black youth.We used survey logistic regression for multivariable analysis. In our model, discrimination was the main predictor, lifetime suicidal ideation was the main outcome, and age, gender, ethnicity, and the poverty index were covariates. We fit multiple logistic regression models to determine the role of discrimination on suicidal ideation in the pooled sample as the subgroups. In the first step, the association of interest was estimated in the pooled sample. In the next step, we added the interaction terms (between discrimination and ethnicity or gender) to the model. Finally, we ran models specific to ethnicity and gender.p values less than 0.05 were considered statistically significant. Missing data was not imputed. We used complete case analysis for our regression models.From logistic regressions, we reported Odds Ratios (ORs) and associated 95% Confidence Intervals (CIs). n = 563, 48%) and girls . The mean age of the participants was 15 years (SD = 1.42). Of the sample, 40% were between the ages of 13 and 14 years (n = 477), 41% were between the ages 15 and 16 years (n = 441), and 19% were age 17 years (n = 252). Most (96%) participants were enrolled in high school. The median family income was US$28,000, with a range from 0 to US$520,000.The sample was evenly composed of boys (p < 0.001). Caribbean Blacks were also older than African Americans (p < 0.05). The proportion of girls was marginally higher for Caribbean Blacks than African Americans (p < 0.1). African Americans and Caribbean Blacks reported similar levels of discrimination. However, boys reported significantly higher levels of discrimination compared to girls (p < 0.05). African Americans and Caribbean Blacks did not differ in suicidal ideation (p = 0.586). Suicidal ideation was more common among girls than boys   had a higher median income than African Americans  (= 0.045) .Model 1 only included the main effects. In Model 2, we included an interaction term between ethnicity and discrimination. Model 3 included an interaction term between gender and discrimination. Model 4 included both interaction terms . This association was significant above and beyond age, ethnicity, gender, and socioeconomic status. Models 2 to 4 did not find any interactions between ethnicity or gender with perceived discrimination on suicidal ideation , study setting , or developmental age . It is not clear whether gender differences in suicidal ideation become more significant during emerging adulthood or not. It is also likely that gender differences are more pronounced for mental health outcomes rather than suicidal ideation.Our study showed gender differences in exposure to discrimination, with males reporting more discrimination than females. There are other studies showing that among Blacks, males report higher rates of perceived discrimination compared to females ,50. SuchThe current study did not find any ethnic differences in the effects of discrimination on suicidal ideation among Black male and female youth. These results are different from the previous studies that have shown ethnic differences in mental health effects of discrimination among Blacks. In the first study, Seaton et al.  reportedAlthough we found that females reported more suicidal ideation than males and males reported more discrimination than females in the current study, we did not find the same ethnicity by gender differences in the effects of discrimination on suicidal ideation as other studies with different mental health outcomes. This finding suggests that the nature of suicidal ideation in the face of discrimination is equally harmful for all groups of Black youth.This study had a few limitations. First, given the cross-sectional design of the study, the associations reported here should not be interpreted as causation. Second, the sample size was not identical across gender and ethnic groups. Third, the main outcome was evaluated using a single-item measure. Although this is a common approach in studying suicidal ideation in large-scale national studies ,42,43,44Future research might delineate ways to focus on protective factors as well as effective interventions that can undo racism and discrimination. Additional research is needed with a more comprehensive set of control variables. A host of variables may contribute to the observed association between experiences of discrimination and suicidal ideation. For example, negative affectivity, neuroticism, or vigilance could be third variables that contribute to both perceived discrimination and suicidal ideation. There is also a need for studies that delve into mechanisms that link perceived discrimination to suicidal ideation. Furthermore, there is a need to study higher levels and structural factors that shape the mental health of Black youth. Research should also test whether interventions are similarly effective for different gender and ethnic groups.In summary, in line with the literature that shows that discrimination jeopardizes other mental health outcomes, we found that discrimination was associated with suicidal ideation in Black youth. This association was found to be universal regardless of the ethnicity or gender of the youth.


Infertility and its treatment can have a considerable effect on a person’squality of life (QoL). The Fertility QoL (FertiQoL) questionnaire is currently the mostfrequently used instrument to measure QoL in people with fertility problems. This studyaims to examine the reliability and validity of the FertiQoL in infertile Iranian women.This cross-sectional study included 155 women with fertility problemsin a referral fertility clinic in Tehran, Iran from January to March 2014. A battery of instrumentswas used: FertiQoL, Satisfaction with Life Scale (SWLS), Hospital Anxiety and DepressionScale (HADS), and a demographic questionnaire. Construct validity of the scale was evaluatedusing confirmatory factor analysis (CFA). We assessed internal consistency with Cronbach’s alphaand convergent validity was examined by correlating the FertiQoL with SWLS and HADS.The results of the CFA generally supported the four-factor model of CoreFertiQoL and two-factor model of Treatment FertiQoL. Both FertiQoL modules and theirsubscales revealed acceptable internal consistency that ranged from 0.643 to 0.911.However, the FertiQoL might be improved if Q15 and T2 items were removed from thescale. These items had low loadings on the Relational and Environment factors whichdecreased their internal consistency. The FertiQoL and their subscales significantly correlated with both SWLS and HADS, which confirmed convergent validity.The Persian version of the FertiQoL is a valid, reliable instrument to measureQoL in infertile women and seems to perform as well as the original English Version. Infertility is a global public health issue that affectsapproximately 10-15% of reproductive-agedcouples worldwide -4. GrowiThe World Health Organization (WHO) has definedQoL as ‘an individual's perception of their positionin life in the context of the culture and value systemsin which they live and in relation to their goals,expectations, standards and concerns’ . QoL canThe FertiQoL tool consists of two modules: Core FertiQoL and Treatment FertiQoL. The Core FertiQoL module assesses the impact of infertility in diverse life areas such as general health, self-esteem, emotions, partnership, family and social relationships, work life, and future life plans. The optional Treatment FertiQoL module assesses the burden or tolerability of fertility treatment. The FertiQoL has been used in various cultures and populations, and has been translated into 26 languages. However, few studies examined the psychometric properties of the FertiQoL. Initial psychometric properties of the FertiQoL were evaluated by Boivin et al.  in the UTo the best of our knowledge, no studies evaluated the psychometric properties of the Persian version of the FertiQoL. Therefore, the present study aimed to examine the reliability and validity of the FertiQoL in infertile Iranian women.We conducted this cross-sectional study at Royan Institute, Tehran, Iran from January 2014 to March 2014. The Infertility Clinic of Royan Institute is a referral infertility center which provides comprehensive treatment, including assisted reproduction techniques (ART). The inclusion criteria for this study were as follows: i. Women aged 18-45 years; ii. Diagnosed with couple infertility; and iii. Ability to read and write in Persian. Participants were selected through convenient sampling from infertile women in the embryo transfer stage of ART cycles at Royan Institute. The sample size was calculated at 120 patients, considering that 5 patients were necessary for each item (subject-to-item ratio: 5:1). As a rule of thumb, a minimum sample size of 100 would be enough for a psychometric study  is a short 5-item instrument designed to measure global cognitive judgments of satisfaction with one’s life. Each item was scored on a 7-point Likert scale that ranged from 1 (strongly disagree) to 7 (strongly agree). Scale scores range from 5-35, with higher scores indicative of greater life satisfaction . The PerThe Hospital Anxiety and Depression Scale (HADS) is a 14-item self-report inventory composed of two subscales: Anxiety (HADS-A) and Depression (HADS-D). Both subscales of HADS consist of 7 items with each item scored on a 4-point Likert scale that ranges from 0 to 3. Subscale scores range from 0-21, with higher scores indicating higher level of anxiety and depression, respectively. We have used the Persian version of HADS in the present study. This version has previously been shown to have satisfactory reliability and validity (The factor structure of the Core FertiQoL and Treatment FertiQoL were examined by CFA. These models were tested using covariance matrices and the maximum likelihood estimation method. Goodness of fit of models were assessed using the chi-square (χ2), relative chi-square (χ2/df), the comparative fit index (CFI), the root mean square error of approximation (RMSEA), and the standardized root mean square residual (SRMR). The χ2 statistic is the classical measure for evaluating model fitness, but it is highly sensitive to sample size . TherefoAll data analyses were performed using SPSS version 16.0 , except for the CFAs, which were performed using Lisrel 8.80 . All statistical tests were two-tailed and a P value of less than 0.05 was considered statistically significant.The demographic and fertility characteristics of the women are presented in We used the CFAs to determine the goodness of fit for the four-factor model of Core FertiQoL and two-factor model of Treatment FertiQoL. Although the χ2 value of the Core FertiQoL model was not satisfactory , the relative chi-square (χ2/df=1.63) was satisfactory. Examination of other goodness of fit indices indicated that the model provided an acceptable fit to the data, with CFI=0.96, RMSEA=0.064, and SRMR=0.067. All factor loadings were significant, except for Q15 (0.16), which ranged from 0.36 to 0.97 .The CFA for two-factor model of Treatment FertiQoL showed a significant χ2 value . The relative chi-square was 1.89, which indicated that the model was an acceptable fit to data. The other fit indices were CFI=0.91, RMSEA=0.076, and SRMR=0.071. All factor loadings were significant, except for T2 (0.02), which ranged from 0.35 to 0.74 .In order to examine the convergent validity of the FertiQoL, we calculated Pearson correlation coefficients between FertiQoL, SWLS, and HADS . As expeAs presented in The present study has aimed to evaluate the psychometrics properties of the FertiQoL in a sample of infertile women. FertiQoL is an infertility-specific questionnaire. In contrast to similar generic measures, it limits the factors that affect QoL to only infertility and no other stressful events. To our knowledge, this is the first study that has evaluated the factor structure of FertiQoL after a study by Melo et al. . The fouOur finding confirmed the expected direct relationship between Core FertiQoL and SWLS, which indicated an acceptable convergent validity. As anticipated, the Core FertiQoL and its subscales negatively correlated with anxiety and depression. Infertile women with a high Core FertiQoL score reported lower levels of anxiety or depression and vice versa. These results supported previous studies and confirmed the convergent validity of Core FertiQoL , 26.We also investigated the relationship between demographic characteristics and QoL. Although the difference was not statistically significant, on average, older women reported higher Core FertiQoL, Mind-Body, Emotional and Social subscales. Conversely, older women have reported lower Relational scores than younger women, but this difference was not significant. In general therefore, as women with infertility over 35 are considered old to be pregnant, their sexual relationship seems more pointless. This finding was roughly consistent with Aarts et al. . The resA direct relationship was found with the Core FertiQoL and its subscales in terms of education level; in other words, the higher the education level, the greater the QoL. This result agreed with previous findings from Chachamovich et al.  and Rashin vitro fertilization (IVF) treatment in the study. Those in the pre-treatment, diagnostic phase, or other ART were not investigated. Hence, generalization of the results might be affected by the sample. Second, this was a cross-sectional study and the causal relationship between QoL, SWLS, anxiety, depression, and infertility could not be established. Third, we did not examine test-retest reliability in this study.Limitations of this study should be considered. First, the FertiQoL can separately assess the QoL in both women and men. Due to practical reasons, only the infertile women included in the study and their partners did not participate. We have only included women who were undergoing The Persian version of FertiQoL is a valid, reliable instrument for measuring QoL in infertile women that provide an exhaustive and comprehensive assessment of QoL related to fertility problems across diverse life areas. However, further psychometric studies are needed in diverse populations, especially in infertile men, including test-retest reliability.


Results showed good validity for total energy intake , with no presence of proportional bias . After energy-adjustment and de-attenuation for within-person variation, macronutrient intakes had excellent correlations ranging from 0.55 to 0.70. Validity for micronutrients was mixed. High intraclass correlation coefficients (ICCs) were found for most nutrients between the two seasons, except vitamin A. This dish-based FFQ provided adequate validity to assess and rank long-term dietary intake in rural Bangladesh for most food groups and nutrients, and should be useful for studying dietary-disease relationships.A locally validated tool was needed to evaluate long-term dietary intake in rural Bangladesh. We assessed the validity of a 42-item dish-based semi-quantitative food frequency questionnaire (FFQ) using two 3-day food diaries (FDs). We selected a random subset of 47 families (190 participants) from a longitudinal arsenic biomonitoring study in Bangladesh to administer the FFQ. Two 3-day FDs were completed by the female head of the households and we used an adult male equivalent method to estimate the FD for the other participants. Food and nutrient intakes measured by FFQ and FD were compared using Pearson’s and Spearman’s correlation, paired  Understanding dietary habits is important for studying the development and progression of chronic illnesses. Accurate assessment of dietary habits is crucial in large, prospective epidemiological studies to provide a holistic understanding of health status. Having reliable dietary data allows researchers to examine the relationship of variations in food and nutrient intakes with the susceptibility to adverse effects from environmental factors and diseases. In Bangladesh, limited dietary intake data is available in most epidemiological studies; as a result, most studies had not accounted for individual variations in dietary intakes. Many national surveys employed a labor-intensive 24-h recall method to collect data at the household level ,4,5,6,7,The food frequency questionnaire (FFQ), which is comprised of a predefined list of food and beverages with response categories to indicate consumption frequency, is a low-cost tool and has been the most widely used method for ranking participants’ dietary and nutrient intake in epidemiologic studies . The valt-test, percent difference, cross-classification, weighted Kappa coefficient, and Bland–Altman analysis [In this study, we employed a dish-based semi-quantitative FFQ previously developed for a longitudinal study investigating arsenic exposure and biomarker responses in Bangladesh ,14 and uanalysis .We invited 248 subjects, from 47 households, concurrently enrolled in a longitudinal arsenic biomonitoring study in rural Pabna, Bangladesh, from 2001–2005 ,14 to paA dish-based semi-quantitative FFQ was previously developed to assess subjects’ habitual dietary intake over the past 12 months. Development was based on a prior questionnaire used in a national-level nutritional survey conducted in Bangladesh and followed recommended guidelines on FFQ development ,16. ThroWe instructed the female head of each household to keep a written FD at the time of consumption with quantities and portion sizes of all foods and beverages consumed at the time of consumption for three consecutive days in both winter (February–March 2004) and summer (June–August 2004), with one weekend day included in each period. We instructed the subject to report portion sizes using the same portion size option as specified in the FFQ, including large plate, medium plate, small plate, large bowl, medium bowl, small bow, glass, cup, large spoon, small spoon, and piece. We also asked subjects if the diet recorded each day reflected their usual diet or not. Concurrent with the FD collection, the female heads of the households provided a duplicate food sample (DFS) of each portion consumed and was reimbursed with $9 USD compensation after each sampling period (summer and winter). One field team member visited each participant at midday and in the evening to weigh DFS collected from morning to midday and from midday to evening, respectively. Detailed methods on the process of DFS have been described previously ,14. Measq is the reported quantity, f is the reported frequency per day, p is the pre-specified portion size in grams, for subject i and dish j. Average daily food intake assessed by FD was calculated using the formula:q is the recorded quantity in the FD, mp is the measured food weight in gram for dish j, AME is the adult male equivalent consumption for household members in Bangladesh based on age and sex [n is the number of days the FD was collected, and k is the person who filled out the FD in the household to which i subjects belonged. Food group intake was calculated by directly adding the consumption of each dish by food category, e.g., ‘grain, cereal, and bread-based dish’, ‘vegetable-based dish’, etc. Nutrient intakes and energy intake were calculated by multiplying the nutrient and energy values per 100 g of food adjusted for inedible waste from the Food Composition Table for Bangladesh [Two trained technicians double-entered the primary data from FFQs and FDs to ensure accuracy. Daily nutrient intakes were calculated based on the 2013 Food Composition Table for Bangladesh . The Foo and sex ), n is tngladesh . The con2). For participants under 20 years of age, we calculated age- and sex-specific BMI Z-scores using the WHO Growth Reference Charts [Demographic characteristics of the study population were tabulated. Food and nutrient intakes not normally distributed, as indicated by the Shapiro–Wilk test, were logarithmically transformed using the formula log(x + 1) to achieve a normal distribution. Body mass index (BMI) was calculated for participants aged 20 years of age or older using the formula weight (kg)/height squared  between the winter and summer average dietary intakes derived from the two 3-day FD . The ICChr) between observed and true mean nutrient intakes of the population during the period of observation was calculated using the following formula [wS is the observed within-subject variance, bS is the observed between-subject variance, and D is the number of days of FD collected for each participant.To quantify the accuracy of the two 3-day FD in capturing individual’s intake level, the unobservable  correlation coefficient ( formula :(3)rh=Dt-tests. Differences, ratios, and percent differences between mean values obtained with the FFQ and the FD were calculated to assess the level of agreement and direction of error [xλ represents the ratio of the within- and between-person variances for x, and xn represents the number of replicates for the x variable [n = 3. Within- and between-person variations were calculated by one-way ANOVA for food and nutrient intakes estimated by the two 3-day FD.The validity of the FFQ was assessed by comparing the intake of each nutrient/food group estimated from the FFQ with that estimated from the average of the two 3-day FD. Means and standard deviation (SD) of intakes for each nutrient and food group, as obtained from the FFQ and the FD, were computed separately, and means were compared using paired of error ,29. Pearof error . Brieflyof error . The deavariable . For thiw) with Cicchetti–Allison weights, which measured the inter-rater agreement of categorical items accounting for natural ordering of categories [In addition to using Spearman’s correlation, FFQ’s ability to rank participants correctly was assessed by cross-classification of energy-adjusted nutrient intakes into quintiles. Subjects that were assigned by the FFQ to the opposed extreme quintile of intakes based on their responses in the FD were considered grossly misclassified. The percentage of agreement indicated subjects with intakes ranked in the same quintile, though the agreement may occur by chance . To assetegories ,34,35.y-axis) against the mean of the two measures (x-axis) for each subject were analyzed to assess the presence of proportional bias, as well as the direction of the bias between the FFQ and two 3-day FD for all nutrients and food intakes [Bland–Altman plots with differences between the measurements .t-test of the mean intake was considered good when p > 0.05 and poor if p ≤ 0.05. Percentage difference of the mean intake of 0.0%–10.9% was considered good, 11.0%–20.0% was considered acceptable, and >20.0% was considered poor. Cross-classification with ≤10% in opposite quintile was considered good and >10% was considered poor.Multiple statistical tests were implemented to provide comprehensive evaluations on the various facets of validity. For the ease of visualization, results for the six statistical tests were color-coded based on levels of validity using criteria proposed by reviews of validity on dietary assessment methods . Specifip-value > 0.05 was considered good, whereas p-value ≤ 0.05 was considered poor.Weighted Kappa statistics of ≥0.61 was consider good, 0.15–0.59 was consider acceptable, and <0.15 was considered poor. A Bland–Altman correlation coefficient with a 2. Most of the participants had education levels lower than primary education. Housewives comprised 40.53% of the participants, 16.32% were students, 8.42% were factory labors, and 8.42% were businessmen. There was no missing data for the sex, age, BMI, or education variables. Fourteen percent of the job type category was missing values. Quantity values were missing in 0.06%, frequency values were missing in 0.37%, and portion size values were missing in 0.78% of the FFQ responses, before imputation.All of the 190 subjects had one FFQ and two 3-day FDs. None of the FDs were collected on days of unusual diet . p < 0.001), suggesting similar energy intake between different seasons. Intakes of beverages  and grain, cereal, and bread-based dishes  had the least seasonal variation. Intake of fruits  and legume- and pulse-based dishes  had large seasonal variations. Macronutrient intakes had small seasonal variations. Intake of vitamin A had the highest seasonal variation among all nutrient intakes .hr) between intakes observed from the two 3-day FD and true mean nutrient intakes of the population during the period was 0.928. With hr >0.90, 80% of the individuals can be correctly classified into thirds of the distribution and less than 1% are grossly misclassified with 90% confidence [The unobservable  correlation coefficient (nfidence . The corp < 0.001).p-value > 0.05). Outliers were found for intakes of iron, sodium, zinc, vitamin A, and vitamin B6 (Bland–Altman plots not shown). However, Bland–Altman Spearman’s correlations for these nutrient intakes were not statistically significant both before and after the removal of the outliers, suggesting no significant bias was present. The intake of carbohydrate, calcium, potassium, alpha-carotene, total cryptoxanthin, niacin equivalents, and L-ascorbic acid exhibited linear treads on Bland–Altman plots, among which all had a positive proportional bias except for carbohydrates, which had negative proportional bias, i.e., as the mean of carbohydrate intake measured by the two methods increases, the mean difference decreases.Analysis of Bland–Altman plots revealed that most macronutrient and micronutrient intakes did not show significant proportional bias and most of the points fell within the 95% limits of agreement , and no The sensitivity analysis using only the two 3-day FD from the 47 female heads of the household and found similar results comparing to using the AME method. The overall analysis on the subset of 47 women did show stronger corrections for most intakes but, qualitatively, the results were similar. Data with only the 47 female heads of household are presented in Results of the cross-classification of food and nutrient intakes estimated by the FFQ and the FD are shown in p = 0.04) and that the FFQ agreed well with the FD in classifying total energy intake, although this agreement may be partly due to chance. FFQ had good validity to capture macronutrient intakes  at the group level, except for carbohydrates, which had a large percent difference and presence of bias with a significant negative Bland–Altman Spearman’s correlation, i.e., the difference became more negative as the mean of the consumption increases. The validity for mineral intakes  was good at the group level, except for calcium and potassium, which had the presence of proportional bias in the positive direction, i.e., as average intake increases, so does the difference of intake. The supporting individual level validity was acceptable for mineral intakes. Micronutrient intakes had good group and individual level validity for thiamin, riboflavin, niacin, and folate, with no presence of bias. Intake of L-ascorbic acid measured by FFQ had poor validity at both the group and individual levels. Most nutrient intakes measured by FFQ had poor complete agreement with intake measured by FD, suggesting that the FFQ is not suitable for measuring the absolute intakes.r > 0.7), and the same was true for all macronutrient intakes, dietary fiber, and some micronutrients, including potassium, retinol, vitamin D, niacin, vitamin B6, and folate, after accounting for within-person variations. Caution must be exercised when using the FFQ to assess populations with wide ranges of carbohydrate and potassium intakes since proportional bias existed at the group level. The validity of the FFQ in assessing intake of vitamin A, L-asorbic acid, and total cryptoxanthin was questionable, indicated by weak association, a low level of agreement, and the presences of bias between the FFQ and the two 3-day FD. The FFQ was also not suitable to measure absolute intake.We developed a dish-based semi-quantitative FFQ consisting of 42 food items to assess long-term dietary habits of participants in a longitudinal arsenic biomonitoring study in rural Bangladesh. Performance of the FFQ was evaluated by comparing average food intake and nutrient intakes derived from this instrument with those recorded in two 3-day FD using a combination of six statistical tests. Total energy intake measured by the two 3-day FD had good-to-strong correlations (Compared with previously validated FFQ in Bangladesh that used the USDA nutrient database , our FFQThe seasonal variation in nutrient intake of our study population during the study period was small for total energy, protein, and carbohydrate intakes. Larger seasonal variations were found for vitamin D, beta-carotene, and vitamin A intakes. Small seasonal variation for total energy was expected since energy intake and expenditure is sensitivity-regulated according to body size and metabolism level. Protein and carbohydrates are the main contributors to daily energy intake and are distributed across different types of foods and thus expected to have small seasonal variations. Micronutrients, on the contrary, tend to concentrate in specific foods, so the level of micronutrient intakes is highly dependent on food choices and food availability . PreviouIn settings with wide seasonal variation in diet, the ability to assess the validity of a FFQ in measuring long-term intakes of micronutrients is usually limited and the number of days required for dietary monitoring is greater, in order to allow for true estimation of intakes . A previOur study has several other strengths. All of our FFQs were obtained by trained interviews via in-person, face-to-face interviews. Interviewers can help collect more detailed data; they encourage participation, and can reduce missing data on the dietary assessment. Only 0.4% of all FFQ questions had a missing response. Compared to self-administered FFQ, where food items may be left blank for various reasons, i.e., because the food was not consumed, because of difficulties remembering the frequency or amount of intake, or due to an oversight , having The main limitation of the study was that the FD was only collected from the female head of the household who was in charge of meal preparation, but not for all participants. In Bangladesh, it is common for the female head of the households to be in charge of cooking meals for the entire family at home and for all family members to eat meals cooked at home. Therefore, we found that it was appropriate to estimate the FD for the other members of the household using the AME fraction. Successfully implementation of the AME depends on accurate estimate of energy requirement and ensuring that the consumption of all food is proportional to one’s energy requirement. We used energy requirements derived from a national household survey in Bangladesh, which carefully calculated caloric requirements based on body weight, basal metabolic rate, and physical activity levels for sex and age groups . AlthougAnother limitation was that the number of FD days collected in the study was only six days due to limited resources and manpower. The lack of sufficient days of FD collection might weaken the statistical power to capture the dietary variation of some micronutrients with high variance ratios . NeverthThe dish-based semi-quantitative FFQ developed to assess long-term habitual diet for rural Bangladeshi population provided valid estimates on relative intakes of food dishes and nutrients both at the group and the individual levels for total energy, all macronutrients, and some micronutrients, such as folate, retinol, thiamin, and riboflavin. The instrument had enough statistical power to accurately rank and classify dietary intake into at least three levels. The dish-based FFQ had low participant burden and generated data that was easy to analyze, and is a useful tool to assess dietary intake in large epidemiology studies.


Invasive pulmonary aspergillosis (IPA) is an infection that often occurs in immunocompromised patients and has a high mortality rate. In recent years, the reported incidence of IPA in the context of chronic obstructive pulmonary disease (COPD) has seemingly increased. The combination of factors such as long-term corticosteroid use, increasing rate of bacterial exacerbations over time, lung immune imbalance, and malnutrition are responsible for the emergence of IPA in COPD patients. A diagnosis of IPA in COPD patients is difficult to make, which explains the delay in antifungal therapy and the high mortality rate. The purpose of this study is to increase the recognition and improve the outcomes associated with this situation through the description of our case. In patients in which IPA is suspected, comprehensive analysis of their clinical manifestations, imaging, microbiology and serological examination results are effective means of increasing the rate of reliable diagnosis. If the patient’s condition permits, a pathological specimen should be obtained as soon as possible. Aspergillus fumigatus is a saprophytic fungus that is capable of causing a wide range of conditions, including allergic bronchopulmonary aspergillosis (ABPA), aspergillomas and invasive aspergillosis (IA). Among them, IA is the most common and the most severe. Additionally, this opportunistic disease occurs predominantly in immunocompromised hosts such as those with hematologic malignancy, allogenic bone marrow transplantation, solid organ transplantation and late-stage HIV infection, etc. [on, etc. . Aside fon, etc. . In thisAn 83-year-old woman with a history of exposure to biofuels and stage IV COPD in group D who was under treatment with inhaled corticosteroids (250μg of fluticasone twice daily for more than 6 years) and intravenous systemic methylprednisolone (40-80 mg per day intermittently) was hospitalized due to the exacerbation of dyspnea and fever. She also had a history of hypertension, diabetes mellitus and cardiac insufficiency.At admission, chest X-ray showed opacity in both lower lobes Figure . The blo-1 day-1).Three days later, the patient's condition continued to deteriorate. Therefore, she was intubated and given mechanical ventilation. Chest X-ray showed an enlargement of the opacity in all the lobes Figure . AdditioAspergillus fumigatus was also isolated from both the sputum and the bronchoalveolar lavage fluid (BALF), which showed the typical conidial head of A. fumigatus in lactophenol cotton blue stain  in our patient's bodily fluids due to the lack of the testing reagent. GM is a polysaccharide cell wall component that is released by the BALF ,13. Morethe BALF . Hence, In conclusion, the mortality rate in association with IPA in COPD patients is high because of the difficulty surrounding its diagnosis. Hence, comprehensive analysis of COPD patients’ clinical manifestations, imaging, microbiology and serological examination results are effective means of increasing the rate of reliable diagnosis. If the patient's condition permits, a pathological specimen should be obtained as soon as possible. This is a recommendation for general alertness of the episodes, particularly in patients with COPD who receive prolonged therapy with a steroid, antibiotics, etc.A. fumigatus based on their macroscopic and microscopic characteristics and their ability to grow at 48°C.Two isolates were investigated in this study. One was from the sputum, whereas the other was from the bronchoalveolar lavage fluid (BALF). They were identified as The genomic DNA was isolated from the conidia harvested from cultures grown at 30°C for 3-4 days. DNA extraction was performed, as previously described . The DNABoth the isolates were identified by the sequencing of the β-tubulin region . The ampPart of the CSP gene was amplified using the following primers: 5’-TTGGGTGGCATTGTGCCAA-3’ and 5’-GGAGGAACAGTGCTGTTGGTGA-3’. In addition, the reaction system was the same as above. CSP sequence types were assigned to isolates as defined in the proposed nomenclature .Two isolates were examined regarding their susceptibility to voriconazole, itraconazole, posaconazole and amphotericin B in a broth microdilution susceptibility test .