Phytoestrogens are found in many plants used in traditional medicines. Increasingly, plant extracts (botanicals) are also being added to foods or marketed as dietary supplements. Especially such ...powder formulations are susceptible to adulteration and falsification, given the global processing chain. To detect estrogen-like compounds in such multicomponent mixtures, non-target screening for hormonally active or endocrine disrupting compounds in plant products is becoming more important. Unfortunately, the current planar yeast estrogen screen (pYES) is prone to zone diffusion on the normal-phase high-performance thin-layer chromatography (NP-HPTLC) plate due to long incubation times in the aqueous bioassay.
The present study aimed to reduce zone diffusion on NP plates, which provides the basis for extending pYES to a multiplex bioassay, offering 4 different biological activity principles, followed by targeted identification of active zones.
The reduction of substance diffusion via a polyisobutyl methacrylate polymer coating was studied. After successful zone fixation (fix), a multiplex bioassay was developed, in which a 17β-estradiol-strip was applied along each sample track to detect synergists and antagonists (A), and for verification (V), a 4-methyl umbelliferone-strip to exclude false-positives. After multiplex bioassay screening of 68 botanicals, the zones with hormonal activities were heart-cut eluted to reversed-phase high-performance liquid chromatography−diode array detection−high-resolution tandem mass spectrometry (RP-HPLC–DAD–HESI-HRMS/MS).
The separated substances were successfully fixed by the chromatogram coating. The zone sharpness (achieved after the bioassay) made it possible to add two strips, the 17β-estradiol-strip for antagonistic and synergistic, and the 4-methyl umbelliferone-strip for false-positive effect detection, resulting in a multiplex bioassay. Using the 12D hyphenation NP-HPTLCfix–UV/Vis/FLD–pYAVES–FLD heart-cut RP-HPLC–DAD–HESI-HRMS/MS, it was possible to obtain information on estrogens, antiestrogens, false-positives, and synergists, and (tentatively) assign 17 hormonally active compounds, of which only 7 have been known to affect the human estrogen receptor, while another 4 had structural similarity to common phytoestrogens and antiestrogens.
The streamlined 12D hyphenation including a multiplex bioassay has been shown to differentiate hormonal effects, leading to new insights and better understanding. It can generally be used to identify unknown hormonally active compounds in complex samples.
Cross-sex hormonal therapy (CHT) in trans persons affects their total body fat and total lean body mass. However, it is unknown how separate body regions are affected and whether these changes alter ...body shape. Therefore, the aim of this study was to determine the effects on body fat and lean body mass in separate body regions and on body shape after one year of CHT.
In a multicenter prospective study at university hospitals, 179 male-to-female gender dysphoric persons, referred to as transwomen, and 162 female-to-male gender dysphoric persons, referred to as transmen, were included. All underwent whole-body dual-energy X-ray absorptiometry and anthropometric measurements before and after one year of CHT.
In transwomen, increases in body fat ranged from +18% (95% CI: 13%;23%) in the android region to +42% (95% CI: 37%;46%) in the leg region and +34% (95% CI: 29%;38%) in the gynoid region. In transmen, changes in body fat ranged from -16% (95% CI: -19;-14%) in the leg region and -14% in the gynoid region (95% CI: -16%;-12) to no change in the android region (+1%, 95% CI: -3%;5%). Waist-to-hip ratio (WHR) decreased in transwomen (-0.03, 95% CI: -0.04;-0.02) mainly due to an increase in hip circumference (+3.2 cm, 95% CI: 2.3;4.0). Transmen have a decrease in hip circumference (-1.9 cm, 95% CI: -3.1;-0.7) resulting in an increase in WHR (+0.01, 95% CI: 0.00;0.02).
CHT causes a more feminine body fat distribution and a lower WHR in transwomen and a more masculine body fat distribution with a lower hip circumference in transmen.
To assess the evolution of body composition and bone metabolism in trans men during the first year of cross-sex hormonal therapy.
In a prospective controlled study, we included 23 trans men ...(female-to-male trans persons) and 23 age-matched control women. In both groups, we examined grip strength (hand dynamometer), biochemical markers of bone turnover (C-terminal telopeptides of type 1 collagen (CTX) and procollagen 1 aminoterminal propeptide (P1NP)), total body fat and lean mass, and areal bone mineral density (aBMD) by dual-X-ray absorptiometry (DXA) and fat and muscle area at the forearm and calf, bone geometry, and volumetric bone mineral density (vBMD) by peripheral quantitative computed tomography (pQCT), before treatment and after 1 year of treatment with undecanoate (1000 mg i.m./12 weeks).
Before hormonal treatment, trans men had similar bone and body composition compared with control women. Testosterone treatment induced in trans men a gain in muscle mass (+10.4%) and strength and loss of fat mass (-9.7%) (all P<0.001) and increased the levels of P1NP and CTX (both P<0.01). Areal and volumetric bone parameters remained largely unchanged apart from a small increase in trabecular vBMD at the distal radius and in BMD at the total hip in trans men (P=0.036 and P=0.001 respectively). None of these changes were observed in the control group.
Short-term testosterone treatment in trans men increased muscle mass and bone turnover. The latter may rather reflect an anabolic effect of testosterone treatment rather than bone loss.
Enterovirus D68 was responsible for widespread outbreaks of respiratory illness throughout the United States in August and September 2014. During this time, several patients presented to our ...institution with acute flaccid paralysis and cranial nerve dysfunction. The purpose of this report is to describe the unique imaging findings of this neurologic syndrome occurring during an enterovirus D68 outbreak.
Patients meeting a specific case definition of acute flaccid paralysis and/or cranial nerve dysfunction and presenting to our institution during the study period were included. All patients underwent routine MR imaging of the brain and/or spinal cord, including multiplanar T1, T2, and contrast-enhanced T1-weighted imaging.
Eleven patients met the inclusion criteria and underwent MR imaging of the brain and/or spinal cord. Nine patients presented with brain stem lesions, most commonly involving the pontine tegmentum, with bilateral facial nerve enhancement in 1 patient. Ten patients had longitudinally extensive spinal cord lesions; those imaged acutely demonstrated involvement of the entire central gray matter, and those imaged subacutely showed lesions restricted to the anterior horn cells. Ventral cauda equina nerve roots enhanced in 4 patients, and ventral cervical nerve roots enhanced in 3, both only in the subacute setting.
Patients presenting with acute flaccid paralysis and/or cranial nerve dysfunction during the recent enterovirus D68 outbreak demonstrate unique imaging findings characterized by brain stem and gray matter spinal cord lesions, similar to the neuroimaging findings described in previous outbreaks of viral myelitis such as enterovirus 71 and poliomyelitis.
Summary
Although trans women before the start of hormonal therapy have a less bone and muscle mass compared with control men, their bone mass and geometry are preserved during the first 2 years of ...hormonal therapy, despite of substantial muscle loss, illustrating the major role of estrogen in the male skeleton.
Purpose
The aim of this study is to examine the evolution of areal and volumetric bone density, geometry, and turnover in trans women undergoing sex steroid changes, during the first 2 years of hormonal therapy.
Methods
In a prospective observational study, we examined 49 trans women (male-to-female) before and after 1 and 2 years of cross-sex hormonal therapy (CSH) in comparison with 49 age-matched control men measuring grip strength (hand dynamometer), areal bone mineral density (aBMD), and total body fat and lean mass using dual X-ray absorptiometry (DXA), bone geometry and volumetric bone mineral density, regional fat, and muscle area at the forearm and calf using peripheral quantitative computed tomography. Standardized treatment regimens were used with oral estradiol valerate, 4 mg daily (or transdermal 17-β estradiol 100 μg/24 h for patients >45 years old), both combined with oral cyproterone acetate 50 mg daily.
Results
Prior to CSH, trans women had lower aBMD at all measured sites (all
p
< 0.001), smaller cortical bone size (all
p
< 0.05), and lower muscle mass and strength and lean body mass (all
p
< 0.05) compared with control men. During CSH, muscle mass and strength decreased and all measures of fat mass increased (all
p
< 0.001). The aBMD increased at the femoral neck, radius, lumbar spine, and total body; cortical and trabecular bone remained stable and bone turnover markers decreased (all
p
< 0.05).
Conclusions
Although trans women, before CSH, have a lower aBMD and cortical bone size compared with control men, their skeletal status is well preserved during CSH treatment, despite of substantial muscle loss.
Cross-sex hormone therapy is an essential part of gender affirming treatment of transgender individuals. Studies systematically describing the physical and psychological effects of hormonal treatment ...of transgender persons are scarce.
The aim of the current protocol is to evaluate clinical and side-effects of cross-sex hormonal treatment in trans persons.
The European Network for the Investigation of Gender Incongruence (ENIGI) is a multicenter prospective study. Because of the relatively low prevalence of the condition and small number of specialized centers, international collaboration is warranted. Four European treatment centers, Ghent, Oslo, Florence, and Amsterdam, developed a common study and treatment protocol.
Outcome measures include hormonal and metabolic parameters, bone density, secondary sex and anthropometric characteristics, and physical and psychological well-being.
Thus far, 333 trans women and 343 trans men have been included in the ENIGI Endocrine protocol. The study is still ongoing.
In recent years, the number of trans persons seeking gender affirming treatment has increased. However, well-designed prospective studies evaluating safety and effectiveness of current hormonal treatment protocols are lacking. Therefore we started the ENIGI collaboration. In this article we give a detailed description of the study protocol, objectives, and design of the ENIGI Endocrine protocol.
Abstract Objective Cross-sex hormonal therapy and sex reassignment surgery (including gonadectomy) in transsexual persons has an impact on body composition and bone mass and size. However, it is not ...clear whether baseline differences in bone and body composition between transsexual persons and controls before cross-sex hormonal therapy play a role. Design A cross-sectional study with 25 male-to-female transsexual persons (transsexual women) before cross-gender sex steroid exposure (median age 30 years) in comparison with 25 age-matched control men and a male reference population of 941 men. Main outcome measures Areal and volumetric bone parameters using respectively dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT), body composition (DXA), grip strength (hand dynamometer), Baecke physical activity questionnaire, serum testosterone and 25-OH vitamin D. Results Transsexual women before cross-sex hormonal therapy presented with less muscle mass ( p ≤ 0.001) and strength ( p ≤ 0.05) and a higher prevalence of osteoporosis (16%) with a lower aBMD at the hip, femoral neck, total body (all p < 0.001) and lumbar spine ( p = 0.064) compared with control men. A thinner radial cortex ( p ≤ 0.01) and lower cortical area at the radius and tibia (both p < 0.05) was found in transsexual women vs. control men. Serum testosterone was comparable in all 3 groups, but 25-OH vitamin D was lower in transsexual women ( p ≤ 0.001). Conclusions Transsexual women before the start of hormonal therapy appear to have lower muscle mass and strength and lower bone mass compared with control men. These baseline differences in bone mass might be related to a less active lifestyle.
Background
It is assumed that the beneficial effect of sleep on memory relies on spontaneous reactivation of memories during sleep. We recently showed that reactivation by re-exposure to previously ...learned foreign vocabulary cues during sleep benefits vocabulary learning. Cueing foreign vocabulary during active or passive wakefulness at night did not improve memory, suggesting that memory benefits of cueing are specific to sleep. However, the ineffectiveness of cueing during wakefulness might also be explained by increased tiredness of the participants in this former study.
Objectives
To exclude tiredness as a confounding factor, we tested the effect of vocabulary cueing during active and passive daytime wakefulness. It was hypothesized that cueing during waking does not improve memory consolidation, even when participants are well rested.
Methods
A total of 32 subjects learned 120 Dutch–German word pairs. During a 3 h retention interval, parts of the previously learned Dutch words were replayed. Subjects of the active waking group (
N
= 16) were distracted from hearing the Dutch words by an n-back task, while subjects of the passive waking group (
N
= 16) were not distracted. After the retention interval, memory for word pairs was tested by a cued recall.
Results
Replay of Dutch words during daytime wake did not improve later memory for the German translation in either of the waking groups. We observed no difference in recall performance between cued and uncued words, neither in the active waking nor in the passive waking group.
Conclusion
Cueing Dutch words during wakefulness does not exert beneficial effects on memory, even when subjects are well rested and under full control of their cognitive capacities. This result gives further evidence that the beneficial effects of cueing are solely specific to sleep.
To examine the prevalence of thyroid disease and dysfunction including thyroid autoimmunity in Norway.
All inhabitants 20 years and older (94009) in Nord-Trondelag were invited to participate in a ...health survey with a questionnaire and blood samples.
The prevalence of former diagnosed hyperthyroidism was 2.5% in females and 0.6% in males, hypothyroidism 4.8% and 0.9%, and goitre 2.9% and 0.4% respectively. In both sexes the prevalence increased with age. In individuals without a history of thyroid disease the median, 2.5 and 97.5 percentiles for TSH (mU/l) were 1.80 and 0.49-5.70 for females and 1. 50 and 0.56-4.60 for males. The TSH values increased with age. When excluding individuals with positive thyroid peroxidase antibodies (TPOAb) (>200U/ml), the 97.5 percentiles dropped to 3.60 mU/l and 3. 40 mU/l respectively. The prevalence of pathological TSH values in females and males were TSH >/=10mU/l 0.90% and 0.37%; TSH 4.1-9. 9mU/l 5.1% and 3.7%; and TSH</=0.05mU/l 0.45% and 0.20% respectively. The prevalence of positive TPOAb (>200U/ml) was 13.9% in females and 2.8% in males. In females the lowest percentage (7.9%) of positive TPOAb was seen with TSH 0.2-1.9mU/l and increased both with lower and higher levels of TSH. The percentage of males with positive TPOAb was lower than in females in all TSH groups except for those with TSH>10mU/l (85% TPOAb positive).
In spite of a high prevalence of recognised thyroid disease in the population a considerable number of inhabitants have undiagnosed thyroid dysfunction and also positive TPOAb.
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