Luminescence Immunoassay Research Articles

Functional Status of Hypothalamic-Pituitary-Thyroid and Hypothalamic-Pituitary-Adrenal Axes in Hospitalized Schizophrenics in Shanghai.

ObjectiveNeuroendocrine dysfunction is related to the pathogenesis of mental disorders, but conclusions from clinical research lack consistency. We aimed to investigate the neuroendocrinal pathophysiology and its correlation with clinical symptoms in patients with schizophrenia.MethodsThe present cross-sectional study included 486 inpatients with schizophrenia admitted at a psychiatric hospital in Shanghai within one year, and 154 healthy controls (HC) matched on age and gender. The serum hemoconcentrations of thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), free thyroxine (FT4), adrenocorticotrophic hormone (ACTH), and cortisol (COR) were measured via electrochemical luminescence immunoassay. Pathophysiological conversions of neuroendocrine were then associated with gender, age, age at onset, antipsychotic treatment using hierarchical multiple linear regression.ResultsWhen compared to HC, the schizophrenia group showed elevated ACTH and COR levels and decreased TT3 and TT4 levels (p‘s < 0.05). First-episode patients showed lower TSH and higher FT3 and FT4 (p’s < 0.05) compared to recurrent patients. Female patients showed higher TSH and lower TT3, FT3, and ACTH levels (p’s < 0.05) compared to males. We observed the area under the curve (AUC) of the predictive model to distinguish between schizophrenia and HC to be 0.737 among total samples and between first-episode and recurrent schizophrenia to be 0.890 among subgroups.ConclusionsDecreased TT3 and TT4 and elevated ACTH and COR levels appear to be associated with schizophrenia symptoms. The chronic recurrent trait of schizophrenia may cause long-term effects on FT3 and FT4 while changes in thyroid, and adrenal function as a result of mental disorder varied with gender. The pathophysiological parameters provide fair to good accuracy of these models.

Vitamin B12 deficiency without anemia in the middle- and old-aged population in Sulaymaniyah City

Background: In our laboratory, we received many cases of Vitamin B12 deficiency without anemia, and we observed that the deficiency is more prominent in females than males. It is well known that Vitamin B12 deficiency is usually associated with macrocytic anemia. However, the clinical importance of Vitamin B12 insufficiency without any hematological abnormality is underestimated in the Sulaymaniyah city population. Thus, the aim of this study is to assess the frequency of Vitamin B12 deficiency with normal complete blood counts (CBCs), especially in the middle- and old-aged population. Materials and Methods: Within the period from April 2018 to April 2019, the patients came to the Dr. Hisham Alrawi Private Laboratory for Vitamin B12 level estimation; the CBCs for all patients with Vitamin B12 deficiency have been collected. We selected patients with low-level Vitamin B12, which were 149 patients, aged 30 years and above. Normal serum Vitamin B12 value in our laboratory is 191–633 pg/ml according to the e411 Roche competitive-binding luminescence immunoassay system. CBC has been collected were done for all patients with Vitamin B12 deficiency by Orphee Mythic 18 Hematology Analyzer. Results: The mean of their age is 64 years, and the mean of hemoglobin (Hb) level is 12.1 g/dL, whereas the mean of Vitamin B12 level is 131.3 pg/ml. About 74 (49.6%) of them have anemia, and 75 (51.4%) are with the normal CBC parameters. The mean of the Hb in females is with the normal range (12.1 g/dL), whereas the mean of the Hb in the males is lower than the normal range (12 g/dL). Conclusions: Vitamin B12 deficiency is common in middle and old age in Sulaymaniyah city, especially in females. Thus, screening programs for B12 levels estimation for this age group are recommended to avoid expected complications.

Amphiphilic ligand modified gold nanocarriers to amplify lanthanide loading for ultrasensitive DELFIA detection of Cronobacter.

Conventional dissociation-enhanced lanthanide (Ln3+) fluoroimmunoassays (DELFIAs) using Ln3+ chelate-labeled antibodies as molecular probes exhibit limited sensitivity because of their relatively low Ln3+ labeling ratio per biomolecule. Herein, we applied gold nanoflowers (AuNFs) as amplified nanocarriers to increase the Ln3+ labeling ratio in a single molecular binding event for improving the sensitivity of traditional DELFIA. Two thiolated amphiphilic ligands (thiolated ethylenediaminetetraacetic acid (EDTA) and thiolated acylhydrazine-terminated ligands), consisting of a hydrophobic alkane chain, oligo(ethylene glycol) unit, and functional terminal of the EDTA or acylhydrazine group, were designed for the surface modification of AuNFs. The resultant ligand-coated AuNFs exhibited dual functions of Ln3+ chelation via the EDTA group and oriented attachment of antibodies via the acylhydrazine group. By utilizing 80 nm AuNFs as amplified carriers, we demonstrated that the maximum Eu3+ loading amount reached 1.07 × 104 Eu3+ ions per AuNF, which is approximately two to three orders of magnitude higher than that of traditional molecular probes, thereby amplifying the luminescence signal and enhancing the sensitivity of DELFIA. By combining a magnetic-mediated sandwich-type DELFIA method, the designed amplified AuNF nanoprobes achieved an ultrasensitive luminescence detection of Cronobacter muytjensii with a limit of detection (LOD) of 1.2 × 102 cfu mL-1 in a powdered infant formula. This LOD value was ca. 230-fold lower than that of the traditional colorimetric immunoassay. The designed signal amplification strategy using bifunctional ligand-modified AuNFs as enhanced Ln3+ nanocarriers provided a huge potential for building various ultrasensitive luminescence immunoassays for in vitro biodetection.

Association between Abdominal Fat Distribution and Free Triiodothyronine in a Euthyroid Population

Background: Obesity is closely related to thyroid hormones; however, the relationship between abdominal fat distribution and thyroid hormones has rarely been explored. Objectives: This study aimed to explore the relationship between abdominal fat distribution and free triiodothyronine (FT3) and FT3 to free thyroxine (FT4) ratio (FT3/FT4) in a euthyroid population. Methods: The present study enrolled 1,036 participants (age range 27–81 years; 445 men and 591 women). The visceral fat area (VFA) and the subcutaneous fat area (SFA) were determined by magnetic resonance imaging. FT3, FT4, and thyroid-stimulating hormone were measured by an electrochemical luminescence immunoassay. Results: In both men and women, SFA increased according to the increase of FT3 and FT3/FT4 tertiles (p for trend <0.05), while VFA did not significantly change. In the multivariate stepwise regression analysis, SFA was independently and positively related to FT3 in both men and women, the standardized β (95% CI) were 0.183 (0.094, 0.272) (p < 0.001) and 0.089 (0.007, 0.171) (p = 0.033), respectively. Moreover, SFA was independently and positively related to FT3/FT4 in men, the standardized β (95% CI) was 0.196 (0.101, 0.290) (p < 0.001). However, VFA was not related to either FT3 or FT3/FT4 in both genders. Conclusions: Abdominal subcutaneous fat was independently related to increased FT3 in a euthyroid population.

P5450Evening levels and circadian changes of salivary cortisol predict adverse events in heart failure patients with comorbid depression - a MOOD-HF substudy

Abstract Background Depression is frequent in heart failure (HF) and associated with adverse clinical outcomes. The randomized MOOD-HF trial showed that in depressed patients with systolic heart failure (HF) the selective serotonin reuptake inhibitor escitalopram (E) improved neither survival nor depression compared to placebo (P). The hypothalamic-pituitary-adrenocortical axis is known to be altered in depression or HF. This MOOD-HF substudy aimed to clarify whether circadian salivary cortisol levels (SCL) were predictive of adverse events in depressed MOOD-HF participants and whether outcomes differed according to treatment with E. Methods MOOD-HF participants (all suffering from symptomatic systolic HF with left ventricular ejection fraction (LVEF) &lt;45% and current major depression) were eligible for the present analysis if providing samples for SCL determination (luminescence immunoassay) at baseline visit (BL) and if not on oral glucocorticosteroid therapy. Depression severity was determined with the Montgomery–Åsberg Depression Rating Scale (MADRS) and LVEF measured by echocardiography. Results In the total study cohort (146 patients on E, 147 on P) median morning SCL at BL was 0.210 μg/dL (IQR 0.141–0.338 μg/dL) and median evening (pm) SCL 0.067 μg/dL (0.036–0.128 μg/dL, p&lt;0.001). Median circadian change was 0.124 μg/dL (0.044–0.239 μg/dL). In patients with BL pm-SCL above the median MADRS-score was 21.7±9.1 and LVEF 33.7±8.4% respectively, in patients with pm-SCL below the median these values were 19.6±9.1 and 36.5±7.8% (p=0.048; p=0.004). During 12 months follow-up the composite endpoint (all-cause death or rehospitalization) occurred least in E-treated patients with low pm-SCL and most often in E-treated patients with high pm-SCL (HR 2.02, 95% CI 1.12–3.65, p=0.010); patients on P had comparable event rates irrespective of BL pm-SCL (Figure A). Thus, numerically patients on E with low BL pm-SCL had lower event rates compared with corresponding P-treated patients (HR 0.76 (0.41–1.40, p=0.796)), while patients with high BL pm-SCL had higher event rates (HR 1.29 (0.74–2.24, p=0.799)) than corresponding P-treated patients. Patients with circadian SCL changes above the median receiving P experienced the composite primary endpoint least, while both subgroups with circadian SCL changes below the median and also patients with circadian SCL changes above the median on E had higher event rates (HR 0.66 (0.45–0.97, p=0.039), Figure B). Conclusion In depressed patients with systolic HF high pm-SCL are associated with more severe disease (depression and cardiac dysfunction). Extending primary MOOD-HF results indicating unfavourable outcomes related to E, the current findings suggest a SCL x treatment interaction with higher event rates in (sicker) patients with high pm-SCL and lower event rates in (less sick) patients with low pm-SCL when treated with the antidepressant. Low circadian changes of SCL were always associated with higher event rates. Acknowledgement/Funding BMBF (Grant 01 KG0702) and Lundbeck A/S Denmark

Trunk fat and leg fat in relation to free triiodothyronine in euthyroid postmenopausal women.

BackgroundA high level of free triiodothyronine (FT3) within the reference range may be a potential metabolic risk marker. However, the relationship between different fat depots and FT3 has remained unclear.ObjectiveWe aimed to explore the relationships between segmental fat distribution and FT3 in euthyroid middle-aged and elderly men and postmenopausal women.MethodsA total of 891 subjects (394 men and 497 women) were enrolled. A bioelectrical impedance analyzer was used to measure total, trunk, arm and leg fat mass (FM) and fat percentage (fat%). The leg fat mass to trunk fat mass ratio (LTR) was calculated to evaluate the relative distribution of leg fat compared with that of trunk fat. Thyroid hormones were measured by electrochemical luminescence immunoassay.ResultsFT3 in men did not change significantly with increases in LTR quartiles, while FT3 in women decreased significantly (P for trend = 0.004). In multivariate linear regression analysis, multiple metabolic and cardiovascular risk factors were adjusted. The LTR was negatively related to FT3 in women (P < 0.05). After further mutual adjustment for trunk fat and leg fat parameters, trunk FM and fat% were positively related to FT3, while leg FM and fat% were negatively related to FT3 in women (all P < 0.05).ConclusionsIn euthyroid postmenopausal women, trunk fat was positively correlated with FT3, whereas leg fat was negatively correlated with FT3. Our findings supported that a high level of FT3 within the reference range was related to adverse fat distribution.

Low hair cortisol concentration predicts the development of attention deficit hyperactivity disorder

ObjectiveLow activity of the hypothalamic-pituitary-adrenal axis (HPAA) resulting from genetic and early environmental factors has been thought to indicate risk for the development of attention deficit hyperactivity disorder (ADHD) and externalizing disorders. However, longitudinal research on this issue is scarce. We analyzed whether hair cortisol concentration (HCC), i.e. accumulated long-term HPAA activity, predicts the development of ADHD between preschool and school age. MethodsA community-based sample of 126 children was assessed at the ages of 4, 5 and 8 years. ADHD and symptoms of oppositional defiant and conduct disorder (ODD/CD), callous unemotional (CU) traits, and internalizing symptoms were measured by clinical parent interviews and parent and teacher questionnaires. HCC was analyzed in the most proximal 3-cm scalp hair segment using luminescence immunoassay. ResultsLow HCC at preschool age predicted an increase in ADHD symptoms between preschool and school age while adjusting for gender of child, maternal education level, and internalizing symptoms (F(1,119) = 6.5; p = .012). The prediction held after additionally adjusting for ODD/CD symptoms and CU traits (F(1,116) = 4.1; p = .045). The same was true for the prediction of the ADHD diagnosis at the age of 8 years (Chi2(1) = 7.3; p = .007). The prediction of ADHD was mainly based on the presentation of inattention symptoms (F(1,119) = 7.4, p = .008). ConclusionLow HCC in preschool children indicates an increased risk of developing ADHD at school age. In future research, it would be of theoretical and clinical importance to further circumscribe this HCC-related developmental pathway and track its further course of development.

Depression and one carbon metabolic pathway: A study among a mendelian population from North India

Depression is multi-factorial in origin and results from intricate mechanisms with no single identifiable risk factor. The present study is a cross-sectional study, conducted among 808 participants aged 30–70 years from a single mendelian, largely vegetarian population from North India. Socio- demographic and depression status were assessed through standard interview schedule among recruited individuals. Chemi- luminescence Immunoassay technique by Immulite®1000 is used to analyse homocysteine, folate and vitamin B12 levels. Of the total studied subjects, 31.1% were found to be having depression with higher rate among females (35.7%) compared to males (24.6%) (p = 0.002). Hyperhomocysteinemia and folate deficiency were found to pose an increased risk for moderate/ severe depression, though not significant. Folate repletion was playing a compensatory role for vitamin B12 deficiency among depressed individuals. MTHFR C677T gene polymorphism was not associated with depression in the present study.

Hair cortisol concentration in mothers and their children: roles of maternal sensitivity and child symptoms of attention-deficit/hyperactivity disorder.

Associations between mothers' and children's cortisol secretion parameters are well established. According to the bio-behavioral synchrony model, these associations reflect influences of the mother-child relationship, the child's social adjustment, and might also reflect shared genetic dispositions. From the bio-behavioral synchrony model, we predicted a stronger mother-child hair cortisol concentration (HCC) link in mothers showing highly adequate (compared to those showing less adequate) parenting behaviors and in children showing low (compared to those showing high) ADHD symptoms. From a genetic perspective, no such moderator effects, or a stronger mother-child HCC link in children with high ADHD symptoms, can be expected. The study sample consisted of 111 4-5-year-old children (64 of whom screened positive for increased ADHD symptoms) and their mothers. ADHD symptoms were assessed by a clinical interview and parent and teacher questionnaires. Maternal sensitive/responsive parenting behavior was assessed by an at-home behavior observation procedure. In mothers and children, HCC in the most proximal 3-cm scalp hair segment was analyzed using luminescence immunoassay. Overall HCCs of mothers and their children correlated significantly. Maternal sensitivity/responsiveness and child ADHD symptoms proved to be significant moderator variables of this association: High maternal sensitivity/responsiveness and low ADHD symptoms of the child were associated with a stronger mother-child link in HCC. The findings are in line with the bio-behavioral synchrony model in the mother-child relationship, and are less compatible with a genetic perspective. The results might hint at environmental events influencing the development of stress axis functioning in subgroups of preschoolers with high ADHD symptoms.

Do Psychosocial Factors Moderate the Relation between Testosterone and Female Sexual Desire? The Role of Interoception, Alexithymia, Defense Mechanisms, and Relationship Status

Low sexual desire is a common complaint among women in the reproductive years. There is controversy regarding the relationship between testosterone (T) and female desire, but there is also lack of research on moderators. Lack of awareness of effects of T on emotions and bodily sensations might interfere with the subjective experience of desire. Moreover, T appears to be more important for searching and competing for partners than for long-term pair bonding. Therefore, we examined if interoception, alexithymia, maladaptive psychological defenses, and relationship status, moderated the relationship between salivary T and female desire. One hundred sixty eight Portuguese women of reproductive age completed the desire dimension of the Female Sexual Function Index, the Toronto Alexithymia Scale (TAS-20), and the Defense Style Questionnaire (DSQ-40). Interoception was determined by a heartbeat detection task. Participants reported if they had a regular sexual partner. Luminescence immunoassays were used to determine salivary T. Three multiple regressions models revealed that, among unpartnered women, higher desire was predicted by the combinations of 1) higher T and lesser alexithymia, 2) higher T and less use of maladaptive defenses, 3) higher T and greater interoception. For partnered women, neither T nor the interactions of T with indices of emotional and bodily awareness predicted desire. These findings provide preliminary evidence that T is more important for the desire of unpartnered women, and that lack of conscious awareness of emotions and bodily sensations interferes with the effects of T on the subjective experience of desire.

Highly luminescent green-emitting Au nanocluster-based multiplex lateral flow immunoassay for ultrasensitive detection of clenbuterol and ractopamine

A multiplex lateral flow immunoassay sensor based on highly luminescent green-emitting Au nanoclusters (AuNCs-MLFIA sensor) was successfully established for the simultaneous and quantitative determination of clenbuterol (Clen) and ractopamine (RAC) in swine urine. The antigens of Clen and RAC were dispersed on a nitrocellulose membrane as two test lines, and the Au nanoclusters were synthesized from 6-aza-2-thiothymine and l-arginine to obtain highly green luminescence and ultra-small nanoparticles (Arg/ATT/AuNCs). Free carboxyl groups on Arg/ATT/AuNCs enabled conjugation with biomolecules to afford an indicator for the biosensor. The AuNCs-MLFIA sensor is based on the indirect competition assay and could successfully detect samples within 18 min without sample pretreatment, qualitative results can be obtained by visual inspection under a UV lamp. The limits of detection of Clen and RAC by the naked eye were both 0.25 μg L−1. In addition, the AuNCs-MLFIA sensor allowed quantitative detection combined with a portable fluorescence reader. The half-maximal inhibitory concentrations of Clen and RAC were 0.06 and 0.32 μg L−1, respectively, with detection limits of 0.003 and 0.023 μg L−1. Thirty blind-spiked swine urine samples were analyzed by the AuNCs-MLFIA sensor and liquid chromatography–tandem mass spectrometry, and the results of the two methods showed a significant correlation. The newly developed AuNCs-MLFIA sensor overcomes several limitations of conventional LFIA sensors, including their low sensitivity, limitation to quantify analytes, and single-analyte detection.

Serum GFAP level: A novel adjunctive diagnostic test in differentiate epileptic seizures from psychogenic attacks

PurposeThere has been increasing interest in the use of different biomarkers to help distinguish psychogenic from epileptic seizures, in patients presenting acutely with seizure-like events. In the present study, we measured serum glial fibrillary astrocytic protein (GFAP) levels in patients presenting with such events who were subsequently diagnosed as epileptic seizures (ESs) or psychogenic non-epileptic seizures (PNESs) and compared GFAP levels obtained with those found in healthy subjects. MethodsSixty-three patients with seizures (43 with ES and 20 with PNES), and 19 healthy subjects participated in the study. Venous blood samples were obtained within the first 6 h after seizures and serum GFAP levels were measured by protein quantification (ELIZA kit) with an electrochemical luminescence immunoassay. ResultsSerum GFAP levels were significantly higher in patients with ES compared to PNES or healthy controls. A cut-off point of 2.71 ng/ml was found optimally to differentiate ES from PNES (sensitivity 72%, specificity 59%). ConclusionOur study suggests that post-seizure serum GFAP levels could be used in future studies better to understand the underlying mechanism of seizures and may offer as an adjunctive diagnostic test in differentiating ES from PNES.

Lower birthweight and left-/mixed-handedness are associated with intensified age-related sex steroid decline in men. Findings from the Men's Health 40+ Study.

SummaryIn males, age‐related decline in free testosterone (T) and dehydroepiandrosterone (DHEA) by 2–3% per year has been reported. Estradiol (E2) and progesterone (P) seem to decrease as well, but to a lesser extent. Lower sex steroid levels in men have been related to physical and mental symptoms. Low birthweight and left‐/mixed‐handedness (L/MH) are indicators of an adverse fetal environment during pregnancy, and both have been linked to morbidity in later life. The aim of this study is to examine the relationship between lower birthweight as well as L/MH and age‐related sex steroid decline. In a cross‐sectional study design, saliva samples were collected under standardized conditions from healthy men for subsequent steroid hormone analysis using standard luminescence immunoassays. T (M = 67.57 pg/mL), DHEA (M = 247.91 pg/mL), E2 (M = 1.29 pg/mL), and P (M = 28.20 pg/mL) have been quantified leading to a final sample of 256 men providing complete data on sex hormones (M Age=57.8; SDAge = 10.8). Information on participants’ birthweight was obtained from birth reports (N = 134), and participants were asked about their handedness (right‐handed, left‐handed, mixed‐handed) (N = 256). Multivariate‐adjusted linear regression models relating each sex hormone individually and the principal component of declining steroid hormones (DSH)—an integrated hormonal parameter—with handedness and birthweight did not identify significant associations except for handedness and E2. Moderation analysis using robust regression accounting for bias due to influential data points detected a significant association between age and DSH for handedness (β = −0.0314, p = 0.040) but only a trend for birthweight (β = 0.0309, p = 0.073). For lower birthweight, a trend toward intensified age‐related sex steroid decline in men was observed, while for L/MH, a significant association with intensified age‐related sex steroid decline was identified. These results indicate that L/MH and potentially also lower birthweight might be considered as early risk factors for endocrine health in later life.

The Role of Uron and Chlorobenzene Derivatives, as Potential Endocrine Disrupting Compounds, in the Secretion of ACTH and PRL.

Uron herbicides polluting the environment represent a serious concern for environmental health and may be regarded as endocrine-disrupting compounds (EDCs), which influence the regulation of human homeostasis. We aimed to investigate the effect of EDC urons (phenuron: PU, monuron: MU, and diuron: DU) and chlorobenzenes on the basal release of the adrenocorticotropic hormone (ACTH), which is a part of the adenohypophysis-adrenocortical axis. Hormone secretion in the presence of EDC was studied in two cell types: normal adenohypophysis cells (AdH) and cells of prolactinomas (PRLOMA). PRLOMA was induced in female Wistar rats by subcutaneously injecting them with estrone acetate for 6 months. AdH and PRLOMA were separated from treated and untreated experimental animals, dissociated enzymatically and mechanically in order to create monolayer cell cultures, which served as an experimental in vitro model. We investigated the effects of ED agents separately and in combination on ACTH and prolactin (PRL) release through the hypophyseal-adrenal axis. Hormone determination was carried out by the luminescent immunoassay and the radioimmunoassay methods. Our results showed that (1) uron agents separately did not change ACTH and PRL release in AdH culture; (2) ACTH secretion in arginine vasopressin- (AVP-) activated AdH cells was significantly increased by EDC treatment; (3) ED agents increased the basal hormone release (ACTH, PRL) in PRLOMA cells; and (4) EDC exposure increased ACTH release in AVP-activated PRLOMA cells. We conclude that the herbicides PU, MU, and DU carry EDC effects and show human toxicity potential.

Autofluorescence-Free Immunoassay Using X-ray Scintillating Nanotags.

Autofluorescence background in complex biological samples is a major challenge in achieving high sensitivity of fluorescence immunoassays (FIA). Here we report an X-ray luminescence-based immunoassay for high-sensitivity detection of biomarkers using X-ray scintillating nanotags. Due to the weak scattering and absorption of most biological chromophores by X-ray excitation, a low-dose X-ray source can be used to produce intense scintillating luminescence from the nanotags for autofluorescence-free biosensing. To demonstrate this concept, we designed and synthesized NaGdF4:Tb@NaYF4 core/shell nanoparticles as kind of high-efficiency X-ray scintillating nanotags, which are able to convert high-energy X-ray photons to visible light without autofluorescence in biological samples. Notably, strong X-ray absorption and minimized surface quenching arising from the heavy Gd3+/Tb3+ atoms and core/shell architecture of the nanoparticles were found to be critically important for high-efficiency X-ray excited luminescence for high-sensitivity biosensing. Our method allows for sensing alpha-fetoprotein (AFP) biomarkers with a detection limit down to 0.25 ng/mL. Moreover, the as-described X-ray luminescence immunoassay exhibited an excellent biological specificity, high stability, and sample recovery, implying an opportunity for applications in complex biological samples. Consequently, our method can be readily extended for multiplexing sensing and medical diagnosis.

Sex hormones play roles in determining musk composition during the early stages of musk secretion by musk deer (Moschus berezovskii).

Musk is a secreted external hormone or information compound that is stored in musk scent glands of the males of species within the family Moschidae, such as Moschus berezovskii. The secretion of musk changes periodically during the courtship and reproduction periods, with the early stage of secretion occurring from May to July, and the maturation stage occurring from August to April of the following year. In this study, we analyzed the dynamic changes in musk components from June to April of the following year. The result showed that musk morphological character, water content, total ion chromatographic pattern, and composition undergo seasonal change. Luminescence immunoassay and radioimmunoassay analyses were performed to determine corresponding fecal hormone levels. The results showed that testosterone, estrogen, and cortisol levels in feces change on a seasonal basis, and are significantly higher in June than in other months (p < 0.01). Correlation analysis showed that the contents of four examined musk components (muscone, cyclopentadecanone, cholesterol, and cholestenol) from June to August were significantly highly negatively correlated with fecal testosterone and estradiol levels (p < 0.01). In contrast, the correlation coefficients were low or not significant from August to April of the following year. These results indicate that testosterone and estradiol may play a major role in determining musk composition during the early stage of musk secretion but not during the course of musk maturation, which suggests that musk secretion may be promoted by increases in sex hormones in June.

Effects of Stress and Stress Hormones on Heart Rate Variability Parameters in 1st Year Medical Students

Stress in present world is inevitable where each individual in pursuit of achieving the maximum undergoes through this event. stress in medical education has resulted in decreasing the confidence of students and cause of various abnormal psychological conditions. Anxiety induced stress is common and this exaggerates during the time of examinations. This altered state of mind results in variation of heart rate variability indices and biochemical parameters which needs to be examined. The present study attempts to correlate stress with biochemical and HRV parameters. The present study inducted first year medical graduate course students after obtaining informed consent. 30 students participated in the study among them 18 were male and 12 female students with mean age of 17.9±0.55 years The students were subjected for 5minute recording of ECG under standard conditions for heart rate variability parameters. The recording of these parameters was done once when the students joined the course and the second recording was obtained after 6 months when the 2ndInternal examination Viva-voce were conducted similarly for evaluation of the biochemical physiological stressors was evaluated by collecting 5ml of venous blood and subjected to serum cortisol and uric acid levels analysis immediately using Fully automated Bidirectionally Interfaced Chemi Luminescent Immuno Assay for cortisol and Photometry for uric acid levels twice when the recording of heart rate variability (HRV) was done. Results were subjected to statistical analysis using statistical software sPss 20.0. students ”t” test and Pearson's tests were done. A p value of <0.05 was considered to be statistically significant. Our results showed correlation of uric acid levels with time domain parameters of heart rate variability and LF/HF ratio of frequency domain. The cortisol levels could not directly link with heart rate variability parameters. Serum cortisol and uric acid levels are good indicators for determination of stress as demonstrated in our study of academic environment. Though we could establish uric acid levels correlating with decrease in short term recording of heart rate variability parameters. We would suggest further studies with larger sample size and recordings during university examinations which would predict its usefulness. We suggest academic stress can lead to chronic illness and thus detoriate the quality of life lead by health professionals. Hence we suggest early intervention and change curriculum as well as evaluation process which can reduce the stress perceived by students.

Functional diagnostics for thyrotropin hormone receptor autoantibodies: bioassays prevail over binding assays.

Autoantibodies to the thyrotropin hormone receptor (TSH-R) are directly responsible for the hyperthyroidism in Graves' disease and mediate orbital manifestations in Graves' orbitopathy (otherwise known as thyroid eye disease). These autoantibodies are heterogeneous in their function and collectively referred to as TRAbs. Measurement of TRAbs is clinically important for diagnosis of a variety of conditions and different commercial assays with high sensitivity and specificity are available for diagnostic purposes. This review provides overwhelming evidence that the TRAbs detected in binding assays by mainly the automated electrochemical luminescence immunoassays (ECLIA) do not distinguish TRAbs that stimulate the TSH-R (called TSIs or TSAbs) and TRAbs that just inhibit the binding of TSH without stimulating the TSH-R (called TBAbs). However, TSAbs and TBAbs have divergent pathogenic roles, and depending which fraction predominates cause different clinical symptoms and engender different therapeutic regimen. Therefore, diagnostic distinction of TSAbs and TBAbs is of paramount clinical importance. To date, only bioassays such as the Mc4 TSH-R bioassay (ThyretainTM, Quidel) and the Bridge assay (Immulite 2000, Siemens) can measure TSAbs, with only the former being able to distinguish between TSAbs and TBAbs. On this note, it is strongly recommended to only use the term TSI or TSAb when reporting the results of bioassays, whereas the results of automated TRAb binding assays should be reported as TRAbs (of undetermined functional significance). This review aims to present a technical and analytical account of leading commercial diagnostic methods of anti-TSH-R antibodies, a metaanalysis of their clinical performance and a perspective for the use of cell based TSH-R bioassays in the clinical diagnostics of Graves' disease.

Human milk cortisol concentration predicts experimentally induced infant fear reactivity: moderation by infant sex.

Little consideration has been given to the possibility of human infant development being shaped via lactocrine programming, and by breast milk cortisol levels specifically. Despite animal models indicating that glucocorticoid (GC) exposure via lactation might modify brain development and behavior, only one study has reported that milk cortisol levels were positively associated with infant negative affectivity, especially fearfulness and sadness-early emerging risk factors for internalizing difficulties such as anxiety. The aim of the current study was to investigate whether human milk cortisol is associated with mother-reported fearfulness and experimentally induced infant fear reactivity. Mother-infant dyads (n = 65) enrolled in the FinnBrain Cohort Study participated. Breast milk samples were obtained 2.5 months postpartum, and milk cortisol concentrations were ascertained using validated luminescence immunoassay methodology. Infant fear reactivity was assessed using maternal reports 6 months postpartum and in a laboratory 8 months postpartum. There was a significant interaction between infant sex and milk cortisol such that higher milk cortisol was related to higher infant fear reactivity in a laboratory setting in girls (β = 0.36, p = .04) but not in boys (β = -0.15, p = .40). Milk cortisol was not associated with mother-reported infant fearfulness. Results suggest that higher human milk cortisol concentrations are associated with elevated experimentally induced fear in infancy. Findings support lactocrine programming, and suggest that mothers may "communicate" vital information about stressful environments via cortisol contained in breast milk, shaping girls' early emotional reactivity.

Hair cortisol concentration in preschoolers with attention-deficit/hyperactivity symptoms—Roles of gender and family adversity

ObjectivePrevious studies on the association between hypothalamic-pituitary-adrenal axis (HPAA) activity and ADHD yielded inconsistent findings, particularly in younger children. This might be due to the heterogeneity of the disorder, making moderator effects of variables probable, which circumscribe more homogenous subgroups. There have been indications of moderator effects on this association by gender of child and exposure to family adversity. Moreover, difficulties in capturing long-term basal HPAA activity in younger children might have contributed to the inconsistencies. We therefore analyzed moderator effects of gender and family adversity while using the hair cortisol concentration (HCC) to assess integrated long-term HPAA. MethodsThe community-based sample consisted of 122 4–5-year-old preschoolers (71 screened positive for elevated ADHD symptoms). ADHD symptoms were measured by a clinical parent interview and parent and teacher questionnaires. HCC in the most proximal 3-cm scalp hair segment was analyzed using luminescence immunoassay. An extended family adversity index was used. ResultsHierarchical linear regression analyses yielded an interaction effect (p<.05) between ADHD symptom groups and gender on HCC, indicating a low HCC in boys with elevated ADHD symptoms. Further exploratory analyses revealed that this interaction effect was most pronounced under the condition of family adversity. The results held after controlling for oppositional, anxiety, and depressive symptoms. ConclusionLow HCC might indicate a specific pathogenic mechanism in boys with elevated ADHD symptoms. This mechanism might further involve an exposure to family adversity. However, the results need to be cross-validated before definitive conclusions can be drawn.