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Chemical communication is important for many social mammals. Scent-related gene clusters have undergone extraordinary expansion in some species, such as the house mouse (Mus musculus). One such family encodes major urinary proteins (MUPs). MUPs can provide recipients with complex information about the signaller and potentially serve as honest signals of social rank. In this study, we examined the development of overall MUP production in two mouse subspecies in the context of establishing their social hierarchy during the critical period between weaning and 100 days of age. We used fraternal pairs as simple social units, where dominant/subordinate ranks were naturally established between two brothers raised together, to test the hypothesis that dominant males of both taxa excrete higher amounts of MUPs in their urine than subordinates. The results were compared to data on ontogeny of steroid hormone levels gathered in the same individuals during an earlier experiment. Higher MUP levels in dominant males were only corroborated in one subspecies (domesticus), whereas musculus males revealed similar MUP quantities irrespective of rank. These results are consistent with the notion that these closely related taxa adopted different strategies for establishing social hierarchy. [ABSTRACT FROM AUTHOR]

Chemical communication is important for many social mammals. Scent-related gene clusters have undergone extraordinary expansion in some species, such as the house mouse (Mus musculus). One such family encodes major urinary proteins (MUPs). MUPs can provide recipients with complex information about the signaller and potentially serve as honest signals of social rank. In this study, we examined the development of overall MUP production in two mouse subspecies in the context of establishing their social hierarchy during the critical period between weaning and 100 days of age. We used fraternal pairs as simple social units, where dominant/subordinate ranks were naturally established between two brothers raised together, to test the hypothesis that dominant males of both taxa excrete higher amounts of MUPs in their urine than subordinates. The results were compared to data on ontogeny of steroid hormone levels gathered in the same individuals during an earlier experiment. Higher MUP levels in dominant males were only corroborated in one subspecies (domesticus), whereas musculus males revealed similar MUP quantities irrespective of rank. These results are consistent with the notion that these closely related taxa adopted different strategies for establishing social hierarchy. [ABSTRACT FROM AUTHOR]

We tested the hypothesis that hyperandrogenemia in androgen excess polycystic ovary syndrome (AE-PCOS) is a primary driver in blood pressure (BP) dysregulation via altered sympathetic nervous system activity (SNSA), reduced integrated baroreflex gain and increased renin-angiotensin system (RAS) activation. We measured resting SNSA (microneurography), integrated baroreflex gain, and RAS with lower body negative pressure in obese insulin-resistant (IR) women with AEPCOS [n = 8, 23 ± 4 yr; body mass index (BMI) = 36.3 ± 6.4 kg/m2] and obese IR controls (n = 7, control, 29 ± 7 yr; BMI = 34.9 ± 6.8 kg/m²), at baseline (BSL), after 4 days of gonadotropin-releasing hormone antagonist (ANT, 250 µg/day) and 4 days of ANT þ testosterone (ANT þ T, 5 mg/day) administration. Resting BP was similar between groups for systolic blood pressure (SBP; 137 ± 14 vs. 135 ± 14 mmHg, AE-PCOS, control) and diastolic BP (89 ± 21 vs. 76 ± 10 mmHg, AE-PCOS, control). BSL integrated baroreflex gain was similar between groups [1.4 ± 0.9 vs. 1.0 ± 1.3 forearm vascular resistance (FVR) U/mmHg], but AE-PCOS had lower SNSA (10.3 ± 2.0 vs. 14.4 ± 4.4 burst/100 heartbeats, P = 0.04). In AE-PCOS, T suppression increased integrated baroreflex gain, which was restored to BSL with ANT þ T (4.3 ± 6.5 vs. 1.5 ± 0.8 FVR U/mmHg, ANT, and ANT þ T, P = 0.04), with no effect in control. ANT increased SNSA in AE-PCOS (11.2±2.4, P = 0.04). Serum aldosterone was greater in AE-PCOS versus control (136.5 ± 60.2 vs. 75.7 ± 41.4 pg/mL, AE-PCOS, control, P = 0.04) at BSL but was unaffected by intervention. Serum angiotensin-converting enzyme was greater in AE-PCOS versus control (101.9 ± 93.4 vs. 38.2± 14.7 pg/mL, P = 0.04) and reduced by ANT in AE-PCOS (77.7 ± 76.5 vs. 43.4 ± 27.3 lg/L, ANT, and ANT þ T, P = 0.04) with no impact on control. Obese, IR women with AE-PCOS showed decreased integrated baroreflex gain and increased RAS activation compared with control. NEW & NOTEWORTHY Here we present evidence for an important role of testosterone in baroreflex control of blood pressure and renal responses to baroreceptor unloading in women with a common, high-risk androgen excess polycystic ovary syndrome (AE-PCOS) phenotype. These data indicate a direct effect of testosterone on the vascular system of women with AE-PCOS independent of body mass index (BMI) and insulin-resistant (IR). Our study indicates that hyperandrogenemia is a central underlining mechanism of heightened cardiovascular risk in women with PCOS. [ABSTRACT FROM AUTHOR]

It is critical to identify biomarkers for neurological diseases (NLDs) to accelerate drug discovery for effective treatment of patients of diseases that currently lack such treatments. In this work, we retrieved genotyping and clinical data from 1,223 UK Biobank participants to identify genetic and clinical biomarkers for NLDs, including Alzheimer's disease (AD), Parkinson's disease (PD), motor neuron disease (MND), and myasthenia gravis (MG). Using a machine learning modeling approach with Monte Carlo randomization, we identified a panel of informative diagnostic biomarkers for predicting AD, PD, MND, and MG, including classical liver disease markers such as alanine aminotransferase, alkaline phosphatase, and bilirubin. A multinomial model trained on accessible clinical markers could correctly predict an NLD diagnosis with an accuracy of 88.3%. We also explored genetic biomarkers. In a genome-wide association study of AD, PD, MND, and MG patients, we identified single nucleotide polymorphisms (SNPs) implicated in several craniofacial disorders such as apnoea and branchiootic syndrome. We found evidence for shared genetic risk loci among NLDs, including SNPs in cancer-related genes and SNPs known to be associated with non-brain cancers such as Wilms tumor, leukemia, and colon cancer. This indicates overlapping genetic characterizations among NLDs which challenges current clinical definitions of the neurological disorders. Taken together, this work demonstrates the value of data-driven approaches to identify novel biomarkers in the absence of any known or promising biomarkers. [ABSTRACT FROM AUTHOR]

Voltammetric sensors are simple, powerful, and cheap equipment with easy principles, which have been widely used in electrochemical studies to investigate the properties of the electroactive species. Surfactants are frequently used in the construction of voltammetric sensors to enhance the sensitivity and selectivity of the sensor, which significantly impacted the electrode function in terms of dissolving organic compounds, creating a specific orientation of molecules on the surface of the electrodes, and enhancing electron transfer reactions. This review focuses on the recent contributions of surfactants in the development of efficient voltammetric sensors. In addition, other ingredients commonly employed alongside surfactants, such as nanomaterials, conducting polymers, and composite materials, have been discussed. The comprehension of these aspects can guide the expansion and the use of surfactants in the electrochemical sensing scope. [ABSTRACT FROM AUTHOR]

Background and objectives There have been large increases in testosterone prescribing since 2000. The aim of this study was to identify factors associated with testosterone replacement therapy (TRT) initiation Methods Data were from the 45 and Up Study, an ongoing cohort study involving 266,942 participants from New South Wales aged ≥45 years. Baseline data (2006-09) were linked to administrative data on government-subsidised prescriptions and medical services. Results The study included 105,429 men. In two years following baseline, 2.9 per 1000 men (95% confidence interval: 2.6, 3.2) had initiated TRT. Men with self-rated poor health, those treated for osteoporosis; anxiety, depression or high blood cholesterol, and those who lived in major cities or were aged 55-74 years had greater odds of TRT initiation. In the six months before TRT initiation, 41% of men had a hormone test record. Discussion The high rate of TRT initiation and low rate of recommended investigations suggest TRT may have been prescribed outside recommended indications. [ABSTRACT FROM AUTHOR]

Background: Implementing a laboratory-developed test sometimes requires incorporating an unconventional device into the laboratory information system (LIS) and customizing an interface to reduce transcription error and improve turnaround time. Such a custom interface is a necessity for complicated high-volume tests such as 25-OH Vitamin D by liquid chromatography-tandem mass spectrometry (LC-MS/MS) when there is no vendor-or LIS-supplied interface available. Here, we describe our work and experience interfacing a API 5000 LC-MS/MS instrument with our newly implemented LIS, Epic Beaker, using a combination of in-house scripting software and a middleware vendor, Data Innovations. Materials and Methods: For input interfacing, custom scripting software was developed to transcribe batched order lists generated by Epic into files usable by the instrument software, Analyst®. For output interfacing, results from the LC-MS/MS system were fed to a unidirectional instrument driver made by Data Innovations and selected data were transferred to the LIS. Results: Creation and validation of a new driver by Data Innovations took approximately 6 months. The interface was adopted for 25-OH Vitamin D and testosterone testing during periods of increasing test volume (4.5-fold over 8 years and 1.25-fold over 5 years). The amount of time spent reporting 25-OH Vitamin D results decreased 82% per order resulting in a savings of 1370 technician work hours and the amount of time spent reporting testosterone results decreased 75% per order resulting in a savings of 400 technician work hours. Conclusions: A mixed model using custom scripting and curated commercial middleware serve as a durable interface solution for laboratory instrumentation such as an LC-MS/MS and are flexible to future changes in instrument software, networking protocols, and the scope of LISs and work area managers. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the impact of sex and puberty stage on circadian changes in sodium excretion, sodium-regulating hormones, and hemodynamics. Thirty-nine healthy volunteers (9 prepuberty boys, 10 prepuberty girls, 10 puberty boys, and 10 puberty girls) were included. They all underwent a 24-h circadian in-patient study under standardized conditions regarding activity, diet, and fluid intake. Blood samples were drawn every 4 h, and the urine was collected in fractions. Blood pressure and heart rate were noninvasively monitored. Atrial natriuretic peptide (ANP), angiotensin II, aldosterone, and renin were measured in blood. Children in puberty had lower plasma levels of renin (P < 0.05) and angiotensin II (P < 0.05) and a 26% reduction in filtered sodium without changes in sodium excretion compared with prepuberty children. A circadian rhythm in sodium excretion, the renin-angiotensin system, ANP, and blood pressure was found with a midnight ANP peak (P < 0.001), a nighttime decrease in hemodynamic parameters (P < 0.001), an increase in plasma renin (P < 0.001) and angiotensin II (P < 0.001), and a decrease in sodium excretion (P < 0.001) mainly on the basis of increased sodium reabsorption (P < 0.001). The timing of the changes did not depend on sex or puberty group. There is a circadian rhythm of sodium excretion and sodium regulation in 7- to 15-yr-old children. This rhythm is similar in boys and girls. As an important new finding, puberty changes the plasma levels of renin and angiotensin II without changing the amount of sodium excreted or the day to night sodium excretion ratio. [ABSTRACT FROM AUTHOR]

A boy aged 4 with penoscrotal hypospadias and his brother aged 12 with micropenis had typical changes of homozygous 5 alpha-reductase deficiency. After three injections of chorionic gonadotrophin there was a trivial rise in plasma dihydrotestosterone with a normal increase in plasma testosterone. Urine steroid chromatography showed abnormally high 5 beta: 5 alpha ratios and 5 alpha-reductase activity was appreciably reduced in genital skin fibroblasts. The results indicate that 5 alpha-reductase deficiency is not invariably associated with genital ambiguity. [ABSTRACT FROM AUTHOR]

Ionic liquids (ILs) are novel solvents that display a number of unique properties, such as negligible vapor pressure, thermal stability (even at high temperatures), favorable viscosity, and miscibility with water and organic solvents. These properties make them attractive alternatives to environmentally unfriendly solvents that produce volatile organic compounds. In this article, a critical review of state-of-the-art developments in the use of ILs for the separation and preconcentration of bioanalytes in biological samples is presented. Special attention is paid to the determination of various organic and inorganic analytes-including contaminants (e.g., pesticides, nicotine, opioids, gold, arsenic, lead, etc.) and functional biomolecules (e.g., testosterone, vitamin B, hemoglobin)-in urine, blood, saliva, hair, and nail samples. A brief introduction to modern microextraction techniques based on ILs, such as dispersive liquid-liquid microextraction (DLLME) and single-drop microextraction (SDME), is provided. A comparison of IL-based methods in terms of their limits of detection and environmental compatibilities is also made. Finally, critical issues and challenges that have arisen from the use of ILs in separation and preconcentration techniques are also discussed. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Human cytosolic sulfotransferases (SULT) 2A1 is the main enzyme involved in the sulfate conjugation of dehydroepiandrosterone, a weak androgen, and the main androgen pre-cursor, whereas estrogens are mainly conjugated by SULT1A1. Here we have identified a copy number variation (CNV) polymorphism in the SULT2A1 gene in a Swedish population including healthy men (N =30). Moreover, the CNV of SULT1A1 and SULT2A1 was further characterized in relation to urinary levels of androgen sulfate metabolites before and after an intramuscular dose of 500 mg testosterone enanthate. Individuals expressing two or more CNVs excrete 80 and 40% higher levels of DHEAS (p =0.02) and androsteroneS (p =0.01), respectively as compared to individuals with one gene copy. The mean area under the urine concentration time-curve from time 0 (prior to the administration of 500mg testosterone) to 15 days post dose values were 80% higher for DHEAS (p =0.046) and testosteroneS (p =0.019) in individuals with two and three SULT2A1 gene copies as compared to individuals with one gene copy. The SULT1A1 CNV on the other hand did not affect the sulfation activity toward the androgens. In conclusion our results indicate that functional CNV polymorphisms in SULT2A1 and SULT1A1 are common in a Swedish population and that SULT2A1 CNV is associated with the urinary concentrations of androgen sulfate metabolites. [ABSTRACT FROM AUTHOR]

The UDP Glucuronosyl Transferase (UGT) enzymes are important in the pharmacokinetics, and conjugation, of a variety of drugs including non-steroidal anti-inflammatory drugs (NSAIDs) as well as anabolic androgenic steroids (AAS). Testosterone glucuronidation capacity is strongly associated with a deletion polymorphism in the UGT2B17 gene. As the use of high doses of NSAIDs has been observed in athletes there is a risk for a drug-drug interaction that may influence the doping tests for AAS. In vitro studies show inhibitory potential on UGT2B7, 2B15, and 2B17 enzymes by NSAIDs. The aim of this study was to investigate if concomitant use of NSAIDs and a single dose of testosterone enanthate would affect the excretion rate of testosterone and epitestosterone glucuronide (TG and EG) as well as the T/E ratio, thereby affecting the outcome of the testosterone doping test. The study was designed as an open, randomized, cross-over study with subjects being their own control. The 23 male healthy volunteers, with either two, one or no allele (ins/ins, ins/del, or del/del) of the UGT2B17 gene, received the maximum recommended dose of NSAID (Ibuprofen or Diclofenac) for 6 days. On day three, 500mg of testosterone enanthate was administered. Spot urine samples were collected for 17 days. After a wash-out period of 4 months the volunteers received 500mg testosterone enanthate only, with subsequent spot urine collection for 14 days. The glucuronides of testosterone and epitestosterone were quantified. NSAIDs did not affect the excretion of TG or EG before the administration of testosterone. The concomitant use of NSAIDs and testosterone slightly increased the TG excretion while the EG excretion was less suppressed compared to testosterone use only. The effects of the NSAIDs on the TG and EG excretion did not differ between the UGT2B17 genotype groups. In conclusion, the outcome of testosterone doping tests does not seem to be affected by the use of NSAIDs. [ABSTRACT FROM AUTHOR]

Background: Laboratory tests are extensively used for diagnosis and monitoring in UK primary care. Test usage by GPs, and associated costs, have grown substantially in recent years. Aim: This study aimed to quantify temporal growth and geographic variation in utilisation of laboratory tests. Design and setting: Retrospective cohort study using data from general practices in the UK. Method: Data from the General Practice Research Database, including patient demographics, clinical details, and laboratory test results, were used to estimate rates of change in utilisation between 2005 and 2009, and identify tests with greatest inter-regional variation, by fitting random-effects Poisson regression models. The study also investigated indications for test requests, using diagnoses and symptoms recorded in the 2 weeks before each test. Results: Around 660 000 tests were recorded in 230 000 person-years of follow-up. Test use increased by 24.2%, from 23 872 to 29 644 tests per 10 000 person-years, between 2005 and 2009. Tests with the largest increases were faecal occult blood (121%) and C-reactive protein (86%). There was substantial geographic variation in test utilisation; GPs in some regions requested tests such as plasma viscosity and cardiac enzymes at a rate more than three times the national average. Conclusion: Increases in the use of laboratory tests have substantial resource implications. Rapid increases in particular tests may be supported by evidence-based guidelines, but these are often vague about who should be tested, how often, and for how long. Substantial regional variation in test use may reflect uncertainty about diagnostic accuracy and appropriate indications for the laboratory test. There is a need for further research on the diagnostic accuracy, therapeutic impact, and effect on patient health outcomes of the most rapidly increasing and geographically variable tests. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined the bone health of post renal transplantation children and adolescents. All patients underwent clinical evaluation, dual energy x-ray absorptiometry (DXA) for bone mineral density (BMD), and spinal imaging for vertebral fractures. The study concluded that the immediate post-transplantation and pubertal years pose the greatest risk for skeletal health, especially in girls.

Background: Implementing a laboratory-developed test sometimes requires incorporating an unconventional device into the laboratory information system (LIS) and customizing an interface to reduce transcription error and improve turnaround time. Such a custom interface is a necessity for complicated high-volume tests such as 25-OH Vitamin D by liquid chromatography-tandem mass spectrometry (LC-MS/MS) when there is no vendor-or LIS-supplied interface available. Here, we describe our work and experience interfacing a API 5000 LC-MS/MS instrument with our newly implemented LIS, Epic Beaker, using a combination of in-house scripting software and a middleware vendor, Data Innovations. Materials and Methods: For input interfacing, custom scripting software was developed to transcribe batched order lists generated by Epic into files usable by the instrument software, Analyst®. For output interfacing, results from the LC-MS/MS system were fed to a unidirectional instrument driver made by Data Innovations and selected data were transferred to the LIS. Results: Creation and validation of a new driver by Data Innovations took approximately 6 months. The interface was adopted for 25-OH Vitamin D and testosterone testing during periods of increasing test volume (4.5-fold over 8 years and 1.25-fold over 5 years). The amount of time spent reporting 25-OH Vitamin D results decreased 82% per order resulting in a savings of 1370 technician work hours and the amount of time spent reporting testosterone results decreased 75% per order resulting in a savings of 400 technician work hours. Conclusions: A mixed model using custom scripting and curated commercial middleware serve as a durable interface solution for laboratory instrumentation such as an LC-MS/MS and are flexible to future changes in instrument software, networking protocols, and the scope of LISs and work area managers. [ABSTRACT FROM AUTHOR]

Many drugs, including antibiotics, have been implicated in the aetiology of benign intracranial hypertension. We report the development of benign intracranial hypertension after the use of ciprofloxacin in a teenager with cystic fibrosis. [ABSTRACT FROM AUTHOR]

Previous research has established that exposure to novel male mice can disrupt intrauterine implantation of fertilised ova in inseminated females and that much of this effect is mediated by factors in the male urine. The present studies were designed to examine whether the steroid content of male urine is sufficient to account for this effect. Pregnancy was terminated by exogenous 17β-oestradiol administered intranasally on days 2-4 after insemination in doses as low as 0.14 µg/day. Enzyme immunoassay indicated that male mouse urine reliably contains unconjugated 17β-oestradiol and testosterone. A small but significant increase in the amount of urinary oestradiol was observed in males housed nearby previously inseminated females as opposed to those housed in isolation. This influence was absent in the sire and absent in novel males when the sire was also present. The quantity of active steroids in novel male urine approaches the level sufficient to account for the disruption of implantation in nearby inseminated females. [ABSTRACT FROM AUTHOR]