Evolution of immune genes is associated with the Black Death.

Infectious diseases are among the strongest selective pressures driving human evolution1,2. This includes the single greatest mortality event in recorded history, the first outbreak of the second pandemic of plague, commonly called the Black Death, which was caused by the bacterium Yersinia pestis3. This pandemic devastated Afro-Eurasia, killing up to 30-50% of the population4. To identify loci that may have been under selection during the Black Death, we characterized genetic variation around immune-related genes from 206 ancient DNA extracts, stemming from two different European populations before, during and after the Black Death. Immune loci are strongly enriched for highly differentiated sites relative to a set of non-immune loci, suggesting positive selection. We identify 245 variants that are highly differentiated within the London dataset, four of which were replicated in an independent cohort from Denmark, and represent the strongest candidates for positive selection. The selected allele for one of these variants, rs2549794, is associated with the production of a full-length (versus truncated) ERAP2 transcript, variation in cytokine response to Y. pestis and increased ability to control intracellular Y. pestis in macrophages. Finally, we show that protective variants overlap with alleles that are today associated with increased susceptibility to autoimmune diseases, providing empirical evidence for the role played by past pandemics in shaping present-day susceptibility to disease.

Cardiomyopathy, an uncommon phenotype of congenital disorders of glycosylation: Recommendations for baseline screening and follow-up evaluation.

INTRODUCTION: Congenital disorders of glycosylation (CDG) are a continuously expanding group of monogenic disorders that disrupt glycoprotein and glycolipid biosynthesis, leading to multi-systemic manifestations. These disorders are categorized into various groups depending on which part of the glycosylation process is impaired. The cardiac manifestations in CDG can significantly differ, not only across different types but also among individuals with the same genetic cause of CDG. Cardiomyopathy is an important phenotype in CDG. The clinical manifestations and progression of cardiomyopathy in CDG patients have not been well characterized. This study aims to delineate common patterns of cardiomyopathy across a range of genetic causes of CDG and to propose baseline screening and follow-up evaluation for this patient population. METHODS: Patients with molecular confirmation of CDG who were enrolled in the prospective or memorial arms of the Frontiers in Congenital Disorders of Glycosylation Consortium (FCDGC) natural history study were ascertained for the presence of cardiomyopathy based on a retrospective review of their medical records. All patients were evaluated by clinical geneticists who are members of FCDGC at their respective academic centers. Patients were screened for cardiomyopathy, and detailed data were retrospectively collected. We analyzed their clinical and molecular history, imaging characteristics of cardiac involvement, type of cardiomyopathy, age at initial presentation of cardiomyopathy, additional cardiac features, the treatments administered, and their clinical outcomes. RESULTS: Of the 305 patients with molecularly confirmed CDG participating in the FCDGC natural history study as of June 2023, 17 individuals, nine females and eight males, were identified with concurrent diagnoses of cardiomyopathy. Most of these patients were diagnosed with PMM2-CDG (n = 10). However, cardiomyopathy was also observed in other diagnoses, including PGM1-CDG (n = 3), ALG3-CDG (n = 1), DPM1-CDG (n = 1), DPAGT1-CDG (n = 1), and SSR4-CDG (n = 1). All PMM2-CDG patients were reported to have hypertrophic cardiomyopathy. Dilated cardiomyopathy was observed in three patients, two with PGM1-CDG and one with ALG3-CDG; left ventricular non-compaction cardiomyopathy was diagnosed in two patients, one with PGM1-CDG and one with DPAGT1-CDG; two patients, one with DPM1-CDG and one with SSR4-CDG, were diagnosed with non-ischemic cardiomyopathy. The estimated median age of diagnosis for cardiomyopathy was 5 months (range: prenatal-27 years). Cardiac improvement was observed in three patients with PMM2-CDG. Five patients showed a progressive course of cardiomyopathy, while the condition remained unchanged in eight individuals. Six patients demonstrated pericardial effusion, with three patients exhibiting cardiac tamponade. One patient with SSR4-CDG has been recently diagnosed with cardiomyopathy; thus, the progression of the disease is yet to be determined. One patient with PGM1-CDG underwent cardiac transplantation. Seven patients were deceased, including five with PMM2-CDG, one with DPAGT1-CDG, and one with ALG3-CDG. Two patients died of cardiac tamponade from pericardial effusion; for the remaining patients, cardiomyopathy was not necessarily the primary cause of death. CONCLUSIONS: In this retrospective study, cardiomyopathy was identified in ∼6% of patients with CDG. Notably, the majority, including all those with PMM2-CDG, exhibited hypertrophic cardiomyopathy. Some cases did not show progression, yet pericardial effusions were commonly observed, especially in PMM2-CDG patients, occasionally escalating to life-threatening cardiac tamponade. It is recommended that clinicians managing CDG patients, particularly those with PMM2-CDG and PGM1-CDG, be vigilant of the cardiomyopathy risk and risk for potentially life-threatening pericardial effusions. Cardiac surveillance, including an echocardiogram and EKG, should be conducted at the time of diagnosis, annually throughout the first 5 years, followed by check-ups every 2-3 years if no concerns arise until adulthood. Subsequently, routine cardiac examinations every five years are advisable. Additionally, patients with diagnosed cardiomyopathy should receive ongoing cardiac care to ensure the effective management and monitoring of their condition. A prospective study will be required to determine the true prevalence of cardiomyopathy in CDG.

Impact of high-risk cytogenetics on outcomes for children and young adults receiving CD19-directed CAR T-cell therapy.

Chimeric antigen receptor (CAR) T-cell therapy can induce durable remissions of relapsed/refractory B-acute lymphoblastic leukemia (ALL). However, case reports suggested differential outcomes mediated by leukemia cytogenetics. We identified children and young adults with relapsed/refractory CD19+ ALL/lymphoblastic lymphoma treated on 5 CD19-directed CAR T-cell (CTL019 or humanized CART19) clinical trials or with commercial tisagenlecleucel from April 2012 to April 2019. Patients were hierarchically categorized according to leukemia cytogenetics: High-risk lesions were defined as KMT2A (MLL) rearrangements, Philadelphia chromosome (Ph+), Ph-like, hypodiploidy, or TCF3/HLF; favorable as hyperdiploidy or ETV6/RUNX1; and intermediate as iAMP21, IKZF1 deletion, or TCF3/PBX1. Of 231 patients aged 1 to 29, 74 (32%) were categorized as high risk, 28 (12%) as intermediate, 43 (19%) as favorable, and 86 (37%) as uninformative. Overall complete remission rate was 94%, with no difference between strata. There was no difference in relapse-free survival (RFS; P = .8112), with 2-year RFS for the high-risk group of 63% (95% confidence interval [CI], 52-77). There was similarly no difference seen in overall survival (OS) (P = .5488), with 2-year OS for the high-risk group of 70% (95% CI, 60-82). For patients with KMT2A-rearranged infant ALL (n = 13), 2-year RFS was 67% (95% CI, 45-99), and OS was 62% (95% CI, 40-95), with multivariable analysis demonstrating no increased risk of relapse (hazard ratio, 0.70; 95% CI, 0.21-2.90; P = .7040) but a higher proportion of relapses associated with myeloid lineage switch and a 3.6-fold increased risk of all-cause death (95% CI, 1.04-12.75; P = .0434). CTL019/huCART19/tisagenlecleucel are effective at achieving durable remissions across cytogenetic categories. Relapsed/refractory patients with high-risk cytogenetics, including KMT2A-rearranged infant ALL, demonstrated high RFS and OS probabilities at 2 years.

Theoretical study of Gibbs free energy and NMR chemical shifts, of the effect of methyl substituents on the isomers of (E)-1-(α,Ꞵ-Dimethylbenzyliden)-2,2-diphenylhydrazine.

A theoretical analysis of free Gibbs Energy and NMR 1H 13C chemical shifts of the effect of introduce methyl groups on diphenyl rings, to produce different isomers of (E)-1-(α,Ꞵ-dimethylbenzylidene)-2,2-diphenylhydrazine, is presented. IR vibrational frequencies, Mulliken charges, molecular electrostatic potential (MEP), Gibbs free energy (G) and 1H- and 13C-NMR chemical shifts were obtained by theoretical calculations. In this analysis it was found that the position of the methyl group affects the values of the 1H- and 13C-NMR chemical shifts and the ∆G and ∆H thermodynamic properties of formation and reaction, these properties vary with the same trend, for the isomers studied. Gibbs free energy calculations show that the theoretical (E)-1-(3,4-Dimethylbenzylidene)-2,2-diphenylhydrazine isomer is the most stable, which explains the success of the experimental synthesis of this compound among the other isomers. For this molecule, the C of the HC=N group is the most nucleophilic and the H is the least acidic. The 1H-NMR chemical shifts of protons show a strong correlation with the C=N distance. It was also observed that methyl affects the ν(C=N) frequencies, the C=N distance increases when the inductive effect of the methyl groups is in the structure.

The End of Compulsory Gender Verification: Is It Progress for Inclusion of Women in Sports?

Recently, the so-called Semenya case has brought the problem of gender in sports competitions back into the spotlight. But the fact is that it is not a unique case; rather, it seems a recurrent and inconclusive problem in the history of sports. In this context, the Spanish athlete Martínez-Patiño is an important figure in the history of sport and gender verification, as well as the Indian sprinter Dutee Chand. Martínez-Patiño's story thus serves as an important case study of the gender-based anxieties that hampered women's advancement in track and field. Martínez-Patiño's experience in Spanish athletics demonstrates the difficulties women faced when attempting to compete in track and field, both in Spain and internationally. Moreover, her experience with gender policies shows the inadequacies of the chromosomal check as a sex marker, as well as the harms caused by the technique. Finally, Martínez-Patiño's protest of the International Association of Athletics Federations' policy started to dismantle compulsory sex verification used as a criterion for gender eligibility. The publicity surrounding her case pushed the track and field federation to abandon mandatory, on-site testing in 1992. Seven years later, the International Olympic Committee also dropped its compulsory control. Martínez-Patiño became the face of the fight against sex/gender verification in sport and helped dismantle the practice. The case of Martinez-Patiño remains in the collective memory of elite sports and serves as an argument for national and international sporting institutions to reconsider discriminating policies in the context of progress being made for women's rights.

Tactical behavior of high-level male marathon runners.

This study analyzes the strategy used by the best male runners who participated in one of the major city marathons (Frankfurt Marathon, 2008-2018), the all-time performances <2:04:00, the male world records achieved during the 21st century and the Nike Breaking2 Project and INEOS 1:59 Challenge (total = 235 races). The races of the best runners in the Frankfurt Marathon (top 10) were analyzed (n = 110 runners, range: 2:03:42-2:14:05 hours); the runners were divided into two groups according to the tactical used. The pace of Group A (stable pace) remained steady throughout the race, while in Group B (decrease in running speed toward the end of the race) a moderate, but significant drop in speed was detected (P ≤ .001), starting from halfway through the race and getting sharper from the 30th kilometer (30-35 km = 1.6%, P ≤ .001 - 35-40 km = 4.3%, P ≤ .001 - 40-42.195 km: 3.9%, P ≤ .001, total = ≈10%). In the races in which the world record is achieved, the running speed tends to be steady and relatively conservative during the first stretch of the race, increasing smoothly in the second half and achieving a significant increase in the last 2195 m of the race (P = .016, ES = 1.14). Among all the possible strategies, running at a steady pace throughout the race seems the most effective option, especially when priority is given to time rather than position (ie, world records and best all-time races).

Pacing strategies during male 1500 m running world record performances.

The aim was to determine the pacing strategies used to achieve male 1500 m running world record performances. Lap times (three first laps and the last 300 m) for the last 37 male 1500 m world record performances achieved since 1917 until 1998 were collected. An analysis of variance with repeated measures and a Bonferroni post hoc test were conducted to determine differences between the percentages of race average speed at each lap. Lap 1 and last 300 m differed from lap 2 and 3, being the latter slower (P < 0.001, 1.44 ≤ ES ≤ 1.95), and displaying a U-shaped pacing profile. Whereas the pacing strategies observed differed from those previously determined for major championship races, a fast endspurt was always present and therefore athletes aiming for a world standard performance should train for developing their anaerobic capacity in addition to a high aerobic power.

4D-CT facilitates focused parathyroidectomy in patients with primary hyperparathyroidism by maintaining a high negative-predictive value for uninvolved quadrants.

INTRODUCTION: Improved preoperative localization facilitates minimally invasive parathyroidectomy for removal of parathyroid lesions therefore preventing an invasive bilateral neck exploration. As 4D-CT has emerged, its high specificity has helped with preoperative parathyroid lesion localization. A high negative predictive value (NPV) would serve to further confirm parathyroid lesion localization and limit unnecessary surgical exploration. This study's objective was to determine the NPV of preoperative 4D-CT and its facilitation of minimally invasive parathyroidectomy. METHODS: A retrospective review was compiled for patients undergoing parathyroidectomy for primary hyperparathyroidism with a preoperative 4D-CT. Included patients were sorted into various groups for comparison: those with 4D-CT localizing to a single lesion, localizing to multiple lesions, and those with nonlocalizing findings; multiple hypercellular parathyroid gland versus single gland findings; extent of surgical exploration; lesion location; and patients with concomitant thyroid nodules. Negative predictive value was calculated and used to quantify the ability for 4D-CT to rule out biochemically significant parathyroid lesions. RESULTS: In our review of 68 patients: sensitivity was 81.3%, specificity was 95.5%, positive predictive value was 87.1%, and negative predictive value was 93.3%. 86% had a single localizing 4D-CT, 7% had a non-localizing 4D-CT, and 7% had a multiple quadrant localizing 4D-CT. NPV for single and multi-localizing 4D-CT were 96.8% and 88.9%, respectively. CONCLUSION: Preoperative 4D-CT has a high negative predictive value (93.3%), suggesting in the majority of cases, a quadrant with no 4D-CT radiographic findings suspicious for parathyroid is unlikely to harbor biochemically significant parathyroid lesions.

Treatment of solitary thyroid nodules according to size, preoperative fine-needle aspiration cytology and frozen section: a retrospective single centre study.

Background: In order to avoid unnecessary thyroidectomies, it is important to predict the nature of thyroid nodules the more accurately possible. The size of the nodule as a predictive factor for malignancy is very controversial. Another point of debate is the accuracy of preoperative fine-needle aspiration cytology (FNAC) and frozen section (FS). The aim of our study is to correlate the nodule size with the final histological diagnosis and to estimate the accuracy of preoperative FNAC and FS. Methods: Retrospective study including 387 operated patients with ultrasound-detected solitary thyroid nodules from 01 January 2001 to 31 December 2013. The following data were collected: patient age and sex, nodule size, FNAC, FS and final histology results. Results: The odds ratio for malignancy within nodules <40 mm was 2.12 (95% CI: 1.104-4.084). The specificity of FNAC was 97.78% and the negative predictive value (NPV) was 97.78% for nodules ≥40 mm and 93.2% and 96.5% for nodules <40 mm, respectively. The observed specificity and NPV of FS ranged from 98% to 100% and from 87.4% to 98%, respectively. When combining FNAC and FS, the specificity and the NPV were 99% and 98%, respectively. Conclusions: The nodule size is not a predictive factor for thyroid cancer and therefore nodules ≥40 mm should not be routinely resected. A lege artis preparation and performance of FNAC along with an expertise on cytological interpretation can considerably diminish false-negative rate. FS can offer additional accuracy on FNAC results and should, therefore, be a part of patient treatment.

Hyperandrogenic athletes: performance differences in elite-standard 200m and 800m finals.

The purpose of this study was to examine whether the difference in elite-standard track and field performance between women athletes with and without hyperandrogenism reaches the 10-12% difference in performance between men and women, using only results from elite-standard track and field final competitions. Officially available data from two hyperandrogenic women (Caster Semenya and Dutee Chand) were compared with the characteristic performance of 200m and 800m elite-standard finals. The finishing times of Caster Semenya, before her ineligibility to compete in 2009 and after the suspension of the 2011 IAAF Hyperandrogenism Regulations were found to be respectively 1.24% and 1.49% faster than the predicted performance in 800m finals. When compared with the result of the second classified, the difference was respectively 0.65% and 2.08%. The analysis of the finishing times of Dutee Chand did not lead to any conclusions due to the lack of available data. The present study indicates that the percentage difference in performance between women with and women without hyperandrogenism does not reach the 3% difference requested by the Court of Arbitration for Sport for the reinstatement of the Hyperandrogenism Regulations, neither does it reach the 10% accepted range of difference in performance between men and women.

Sex-differences in elite-performance track and field competition from 1983 to 2015.

The purpose of this study was to assess the veracity of the Court of Arbitration for Sport's assertion that sex-differences in athletic performance in elite-standard track and field competition is of the order of 10-12%. Exponential curves were fitted to the data of selected track and field events of the finals of all IAAF World Championships and Olympic Games from 1983 to 2016. For each curve, the coefficient of determination R2 was calculated, in combination the corresponding 95% confidence intervals for the curve constants. Sex-differences were evaluated via differences in the fitted curves between men and women. Mean performances of winners, as well as overall performance means of all participants, were also analyzed. The calculated sex-difference was 8.2 ± 1.0% - 11.8 ± 2.1% for sprints, 10.3 ± 3.3% - 12.8 ± 4.0% for middle and long-distance events, 9.7 ± 2.9% - 13.1 ± 2.9% for relays and 14.2 ± 2.2% - 25.0 ± 4.4% for jumps. This study therefore confirms that the percentage difference accepted by the CAS is appropriate for elite-standard track and field events.

The Fluidity of Gender and Implications for the Biology of Inclusion for Transgender and Intersex Athletes.

One of the most contentious issues in modern day sport arises when sports are divided into male and female categories. The International Association of Athletics Federations' (IAAF) previous policy regulating intersex athletes was suspended by the Court of Arbitration for Sport (CAS), resulting in a new policy. The challenge faced by the governing body of athletics is to formulate a policy that upholds both international law and the Olympic charter that stipulates athletes compete without discrimination of any kind. Implementation of the policy has been delayed until after a verdict, expected no later than March 26, 2019, in the Semenya versus IAAF trial in the Court of Arbitration for Sport. If the policy is enacted, it will restrict athletes from competing in the female athletics category with specific differences of sex development (DSD) in races from 400 m up to the mile in international level competitions unless they lower their natural testosterone (T) levels below 5 nmol·L. To thoroughly assess this new IAAF policy, one needs to appreciate its legal, sociological, and scientific underpinnings but also the history of previous policies attempting to define precisely how athletes should be divided into male and female categories. We previously proposed a system to deal with gender variant athletes that relied on a determination of an "athlete/athletic gender." The concept of "athlete gender" was presented to multiple audiences, and the resulting survey is included. A large majority of participants (71% of 153) who answered the survey agreed with the idea of an athlete gender. This position also was accompanied by the request for more studies (20% of those who agreed) and concern over the process of hormone monitoring (32% of those who agreed) to avoid doping misuse. The primary argument of those participating in the survey that disagreed with the position (23% of 153) was that biological differences between males and females remained even after the transition (47% of opposing comments). Mixed gender/sex competitions provide unique opportunities for athletes to compete against one another outside of the traditional male/female divide and pave the way for a more flexible approach for dealing with gender variant athletes.

Total thyroidectomy: a clue to understanding the metabolic changes induced by subclinical hyperthyroidism?

OBJECTIVE: The effects of endogenous subclinical hyperthyroidism (eSCH) on heart and bone have been well documented. There are only limited data available regarding the impact of eSCH on weight regulation and lipid metabolism. Our aim was to evaluate the changes in body weight and metabolic parameters after total thyroidectomy in patients with pre-operative eSCH compared with pre-operative patients with euthyroid (EUT). DESIGN: A retrospective study of 505 patients who underwent total thyroidectomy for benign multinodular goitre in an academic hospital in Brussels (Belgium) was performed. PATIENT'S MEASUREMENTS: Two hundred and 25 patients were included (eSCH group: n = 74; EUT group: n = 151). The mean follow-up time was 26·1 ± 0·8 months and was similar in both groups. RESULTS: Absolute BMI gain was significantly greater in the eSCH group than in the EUT group (1·11 ± 0·17 vs 0·33 ± 0·13 kg/m2 ; P = 0·003). A significant increase in LDL cholesterol was observed in the eSCH group (16·1 ± 3·8 mg/dl; P < 0·001) but not in the EUT group (0·0 ± 3·0 mg/dl; P = 0·88). In a multivariate model, pre-operative TSH levels were the main factor significantly associated with increases in BMI or LDL cholesterol. Post-operative median TSH levels and L-thyroxine substitution were similar in both groups. CONCLUSION: After total thyroidectomy, increases in weight and serum cholesterol were observed in the eSCH group. Given that post-operative TSH levels were similar in the two groups, these observations are probably due to the correction of eSCH, suggesting a direct effect of eSCH on body weight regulation and lipid metabolism.

Molecular and Genomic Alterations in Glioblastoma Multiforme.

In recent years, important advances have been achieved in the understanding of the molecular biology of glioblastoma multiforme (GBM); thus, complex genetic alterations and genomic profiles, which recurrently involve multiple signaling pathways, have been defined, leading to the first molecular/genetic classification of the disease. In this regard, different genetic alterations and genetic pathways appear to distinguish primary (eg, EGFR amplification) versus secondary (eg, IDH1/2 or TP53 mutation) GBM. Such genetic alterations target distinct combinations of the growth factor receptor-ras signaling pathways, as well as the phosphatidylinositol 3-kinase/phosphatase and tensin homolog/AKT, retinoblastoma/cyclin-dependent kinase (CDK) N2A-p16(INK4A), and TP53/mouse double minute (MDM) 2/MDM4/CDKN2A-p14(ARF) pathways, in cells that present features associated with key stages of normal neurogenesis and (normal) central nervous system cell types. This translates into well-defined genomic profiles that have been recently classified by The Cancer Genome Atlas Consortium into four subtypes: classic, mesenchymal, proneural, and neural GBM. Herein, we review the most relevant genetic alterations of primary versus secondary GBM, the specific signaling pathways involved, and the overall genomic profile of this genetically heterogeneous group of malignant tumors.

Thyroid lobectomy is an effective option for unilateral benign nodular disease.

OBJECTIVE: The use of thyroid lobectomy in the treatment of unilateral, benign nodules is limited by the potential of nodular recurrence in the remaining lobe. This study aimed to assess the rate and clinical impact of nodular recurrence in the contralateral lobe after thyroid lobectomy and to identify predictive factors of recurrence. DESIGN: Single-centre retrospective study. PATIENTS: Records of patients that underwent lobectomy for unilateral thyroid nodules between 1991 and 2010 were reviewed and 270 patients were included. Exclusion criteria were: presence of contralateral nodule(s) ≥5 mm on preoperative ultrasound, diagnosis of cancer necessitating completion thyroidectomy or pseudonodules. Recurrence was defined as the occurrence of nodule(s) ≥5 mm in the remaining lobe on at least one postoperative ultrasound. A set of clinical, imaging, histological and biochemical parameters was tested as predictors of recurrence using logistic regression. RESULTS: After a median follow-up of 78 months (range, 12-277 months), the global recurrence rate was 42% and recurrence of nodules of a size ≥1 cm occurred in 19%. Reoperation rate was 1·1%. 90% of patients were treated postoperatively by levothyroxine. Median time to nodular recurrence was 4 years. Preoperative contralateral lobe volume and resected thyroid weight were identified as significant predictors of recurrence (P = 0·045 and P = 0·03 respectively). CONCLUSIONS: Thyroid lobectomy is an effective therapeutic strategy for unilateral, benign nodules, resulting in a low rate of clinically relevant nodular relapse in a mildly iodine-deficient area. Patients with uninodular disease and a contralateral lobe of normal size are particularly good candidates for lobectomy.

The Influence of Assay Design, Blinding, and Gymnema sylvestre on Sucrose Detection by Humans.

The detection and grading of tastes corresponding to different taste modalities can be tested in engaging laboratory sessions using students themselves as test subjects. This article describes a series of experiments in which data pertaining to the detection of salty and sweet tastes are obtained, and the ability of the herb Gymnema sylvestre to disrupt the detection of sucrose is quantified. The effects of blinding and different assay designs on EC50 estimation are also investigated. The data obtained allow for substantial data analysis, including non-linear regression using fixed and free parameters to quantify dose-response relationships, and the use of often under-utilized permutation tests to determine significant differences when the underlying data display heteroscedasticity.

Circulating miR-200c and miR-141 and outcomes in patients with breast cancer.

BACKGROUND: The deregulation of microRNAs in both tumours and blood has led to the search for microRNAs to indicate the presence of cancer and predict prognosis. We hypothesize the deregulation of miR-200c/miR-141 in the whole blood can identify breast cancer (BC), and could be developed into a prognostic signature. METHODS: The expression of miR-200c and miR-141 were examined in bloods (57 stage I-IV BC patients and 20 age-matched controls) by quantitative reverse-transcription PCR. The associations of circulating microRNAs with clinic and pathological characteristics were analysed. Their effects on survival were analysed by the Kaplan-Meier method and Cox regressions. RESULTS: MiR-200c was down regulated (P < 0.0001) in the blood of BC patients, yielded an area under the ROC curve of 0.79 (90% sensitivity, 70.2% specificity) in discriminating BC from controls. Circulating miR-141 was not discriminating. MiR-200c and miR-141 in the blood of BC patients were inversely correlated (P = 0.019). The miR-200c levels were numerically higher in stage IV and tumours with lower MIB-1. MiR-141 was significantly higher in the blood of patients with stage I-III, lymph node metastasis, and HER2 negative tumours. High blood expression of miR-200c and/or low expression of miR-141 was associated with unfavourable overall survival (hazard ratio, 3.89; [95% CI: 1.28-11.85]) and progression-free survival (3.79 [1.41-10.16]) independent of age, stage and hormonal receptors. CONCLUSIONS: Circulating miR-200c and miR-141 were deregulated in BC comparing with controls. Furthermore, miR-200c and miR-141 were independent prognostic factors and associated with distinct outcomes of BC patients.

Hurdling over sex? Sport, science, and equity.

Between 1968 and 1999, the International Olympic Committee (IOC) required all female athletes to undergo genetic testing as part of its sex verification policy, under the assumption that it needed to prevent men from impersonating women and competing in female-only events. After critics convinced officials that genetic testing was scientifically and ethically flawed for this purpose, the IOC replaced the policy in 1999 with a system allowing for medical evaluations of an athlete's sex only in cases of "reasonable suspicion," but this system also created injustice for athletes and stoked international controversies. In 2011, the IOC adopted a new policy on female hyperandrogenism, which established an upper hormonal limit for athletes eligible to compete in women's sporting events. This new policy, however, still leaves important medical and ethical issues unaddressed. We review the history of sex verification policies and make specific recommendations on ways to improve justice for athletes within the bounds of the current hyperandrogenism policy, including suggestions to clarify the purpose of the policy, to ensure privacy and confidentiality, to gain informed consent, to promote psychological health, and to deploy equitable administration and eligibility standards for male and female athletes.

The Risk of Eating Disorders in Adolescent Athletes: How We Might Address This Phenomenon?

Eating disorders are psychiatric and behavioral health pathologies of high complexity and different etiology, which can affect age groups, sexes, and ethnicities indistinctly. This study aimed to evaluate the risk of eating disorders and the possible relation with the sports profile of Colombian adolescent athletes. This was an exploratory cross-sectional quantitative study that used an online form designed with a sociodemographic questionnaire and the EAT-26 scale to determine the eating disorder risk of the object population. A total of 354 adolescent athletes participated. There were 182 men and 172 women and the mean age was 15.59 (range: 10-19 years, SD = 1.938). The participants presented a significantly low risk of eating disorders (21.2%) with no differences in prevalence between both sexes. The risk of eating disorder was related to the result of the last competition (p = 0.01), the type of sport (p = 0.032), the years of sports practice (p = 0.004), and the number of training hours a day (p = 0.011). It is relevant to recognize that adolescents and athletes are vulnerable populations regarding eating disorders. In conclusion, adolescent athletes should be the object of special attention to prevent eating disorders and their consequences on health and sports performance.