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Hair follicles provide an easily accessible tissue for interrogating gene expression for multiple purposes in mammals. RNAlater® is a liquid storage solution that stabilises and preserves cellular RNA, eliminating the need to immediately process or freeze tissue specimens. The manufacturer advises storage of samples at 2-8°C overnight before transfer to –20°C. This study aimed to evaluate RNA integrity in hair follicle samples collected from horses, stabilized in RNAlater®, and stored under three short-term storage conditions. Mane hair samples complete with follicles were collected from four horses at a single time point. Approximately 15 hairs were placed in each of three 2 mL tubes containing 0.75ml RNAlater® solution. Test group A was stored at 4°C for 24-h, then decanted and stored at -20°C. Test groups B and C were stored at 4°C and 19°C (room temperature) respectively for 7 days, then decanted and stored at -20°C. RNA was isolated from all samples and RNA quantity and quality were measured. One-way ANOVA revealed no difference in RNA concentration (A:516 +/-125 ng/ml, B:273+/-93 ng/ml, C:476+/-176 ng/ml;P = 0.2) or quality (A:9.5 +/-0.19, B:9.8+/-0.09, C:9.2+/-0.35 RIN; P = 0.46) between the test groups. There were no group differences in mean Cycle Threshold values from qPCR validation assays confirming high-quality template cDNA. The results suggest that storage of hair follicles for one week in RNAlater® at cool or room temperature conditions will not compromise RNA integrity and will permit extended transport times from remote sampling locations without the need for freezing. [ABSTRACT FROM AUTHOR]

Introduction: Functional near-infrared spectroscopy (fNIRS) is a promising tool for studying brain activity, offering advantages such as portability and affordability. However, challenges in data collection persist due to factors like participant physiology, environmental light, and gross-motor movements, with limited literature on their impact on fNIRS signal quality. This study addresses four potentially influential factors–hair color, hair cleanliness, environmental light, and gross-motor movements–on fNIRS signal quality. Our aim is to raise awareness and offer insights for future fNIRS research. Methods: Six participants (4 Females, 2 Males) took part in four different experiments investigating the effects of hair color, hair cleanliness, environmental light, and gross-motor movements on fNIRS signal quality. Participants in Experiment 1, categorized by hair color, completed a finger-tapping task in a between-subjects block design. Signal quality was compared between each hair color. Participants in Experiments 2 and 3 completed a finger-tapping task in a within-subjects block design, with signal quality being compared across hair cleanliness (i.e., five consecutive days without washing the hair) and environmental light (i.e., sunlight, artificial light, no light, etc.), respectively. Experiment 4 assessed three gross-motor movements (i.e., walking, turning and nodding the head) in a within-subjects block design. Motor movements were then compared to resting blocks. Signal quality was evaluated using Scalp Coupling Index (SCI) measurements. Results: Lighter hair produced better signals than dark hair, while the impact of environmental light remains uncertain. Hair cleanliness showed no significant effects, but gross motor movements notably reduced signal quality. Conclusion: Our results suggest that hair color, environmental light, and gross-motor movements affect fNIRS signal quality while hair cleanliness does not. Nevertheless, future studies with larger sample sizes are warranted to fully understand these effects. To advance future research, comprehensive documentation of participant demographics and lab conditions, along with signal quality analyses, is essential. [ABSTRACT FROM AUTHOR]

Globally, the rapid aging of the population is predicted to become even more severe in the second half of the 21st century. Thus, it is expected to establish a growing expectation for innovative, non-invasive health indicators and diagnostic methods to support disease prevention, care, and health promotion efforts. In this study, we aimed to establish a new health index and disease diagnosis method by analyzing the minerals and free amino acid components contained in hair shaft. We first evaluated the range of these components in healthy humans and then conducted a comparative analysis of these components in subjects with diabetes, hypertension, androgenetic alopecia, major depressive disorder, Alzheimer's disease, and stroke. In the statistical analysis, we first used a student's t test to compare the hair components of healthy people and those of patients with various diseases. However, many minerals and free amino acids showed significant differences in all diseases, because the sample size of the healthy group was very large compared to the sample size of the disease group. Therefore, we attempted a comparative analysis based on effect size, which is not affected by differences in sample size. As a result, we were able to narrow down the minerals and free amino acids for all diseases compared to t test analysis. For diabetes, the t test narrowed down the minerals to 15, whereas the effect size measurement narrowed it down to 3 (Cr, Mn, and Hg). For free amino acids, the t test narrowed it down to 15 minerals. By measuring the effect size, we were able to narrow it down to 7 (Gly, His, Lys, Pro, Ser, Thr, and Val). It is also possible to narrow down the minerals and free amino acids in other diseases, and to identify potential health indicators and disease-related components by using effect size. [ABSTRACT FROM AUTHOR]

Parabens are compounds widely utilized in the industry as preservative additives to personal care products, cosmetics and food. They pollute the environment and penetrate to the living organisms through the digestive tract, respiratory system and skin. Till now the knowledge about exposure of terrestrial wild mammals to parabens is extremely scarce. Therefore, this study for the first time assessed the concentration levels of five parabens commonly used in industry (methylparaben—MeP, ethylparaben—EtP propylparaben–PrP, benzylparaben -BeP and butylparaben–BuP). Substances have been analyzed in hair samples collected from wild boars using liquid chromatography-mass spectrometry (LC-MS) method. The hair is a matrix, which allows to study long-term exposure of organisms to parabens. During this study MeP was noted in 96.3% of samples with mean 88.3±72.9 pg/mg, PrP in 87.0% of samples with mean 8.5±3.3 pg/mg, BeP in 44.4% of samples with mean 17.2±12.3 pg/mg and EtP in 11.1% of samples with mean 17.2±4.8 pg/mg. In turn BuP was noted only in 3.7% of samples with concentration levels below limit of quantification (2.6 pg/mg). Statistically significant intragender differences in parabens levels have not been noted. Only BeP concentration levels depended on industrialization and density of human population of area, where the animals lived. This study indicates that wild boars are exposed to parabens, especially to MeP and PrP, and analysis of the hair seems to be a useful tool of biomonitoring of parabens in wild mammals. [ABSTRACT FROM AUTHOR]

Purpose: Testosterone analysis in hair allows for retrospective evaluation of endogenous testosterone concentrations, but studies devoted to investigating confounders in hair testosterone analysis have hitherto been scarce. The current study examined the stability of testosterone concentrations between two hair samples collected three months apart and investigated two potential confounding factors: natural hair colour and cosmetic hair treatments. Methods: Testosterone was analysed with an in-house radioimmunoassay with a limit of detection adequate for the purpose. Results: The testosterone concentrations from the two samplings, at baseline and three months later, had an intra-individual correlation of moderate strength (rho = 0.378, p<0.001, n = 146). Hair treatment, such as colouring or bleaching, seemed to increase testosterone concentrations (p = 0.051, n = 191, and in a paired analysis in a subset of the cohort p = 0.005, n = 24), while no effect of natural colour in untreated hair (p = 0.133) could be detected. Conclusion: The current results suggest that cosmetic hair treatments need to be considered in hair testosterone analyses and demonstrate the utility of a radioimmunoassay to reliably measure testosterone concentrations in small hair samples in women. [ABSTRACT FROM AUTHOR]

Chronic exposure to toxic metals is a serious global health concern. However, population-wide biomonitoring is costly and carries several sampling constraints. Though hair sampling can be a useful way to assess environmental exposure, external contamination is a long-standing concern, and a pre-cleaning step prior to metal quantification has long been recommended despite a lack of evidence for its efficacy. In this study, we quantified the spatial distribution of 16 elements in unwashed human hair samples using Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS), then tested how two common pre-cleaning treatments (Triton-ethanol, Triton-nitric acid) affected metal content in external and interior layers of hair using LA-ICP-MS. We show that elements differ in their spatial distribution across hair and that pre-cleaning is not consistent in its effect on element concentrations and decreases interior concentrations of some elements. We demonstrate that differences among individuals can be quantified reliably with LA-ICP-MS analysis of interior concentrations of unwashed hair. Our study tests the widespread notion that pre-cleaning is essential in analyses of hair for environmental exposure to metals, and examines the benefits of a unified approach to analysis of metals in hair using LA-ICP-MS. [ABSTRACT FROM AUTHOR]

Objective measures of adherence for antiretrovirals used as pre-exposure prophylaxis (PrEP) are critical for improving preventative efficacy in both clinical trials and real-world application. Current objective adherence measures either reflect only recent behavior (eg days for plasma or urine) or cumulative behavior (eg months for dried blood spots). Here, we measured the accumulation of the antiretroviral drug maraviroc (MVC) in hair strands by infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry imaging (MSI) to evaluate adherence behavior longitudinally at high temporal resolution. An MSI threshold for classifying daily adherence was established using clinical samples from healthy volunteers following directly observed dosing of 1 to 7 doses MVC/week. We then used the benchmarked MSI assay to classify adherence to MVC-based PrEP regimens in hair samples collected throughout the 48-week HPTN069/ACTGA5305 study. We found that only ~32% of investigated hair samples collected during the study's active dosing period showed consistent daily PrEP adherence throughout a retrospective period of 30 days, and also found that profiles of daily individual adherence from MSI hair analysis could identify when patients were and were not taking study drug. The assessment of adherence from MSI hair strand analysis was 62% lower than adherence classified using paired plasma samples, the latter of which may be influenced by white-coat adherence. These findings demonstrate the ability of MSI hair analysis to examine daily variability of adherence behavior over a longer-term measurement and offer the potential for longitudinal comparison with risk behavior to target patient-specific adherence interventions and improve outcomes. [ABSTRACT FROM AUTHOR]

Background: Lasers of different wavelengths have been developed for use in permanent hair reduction. An increase in the manufacturing of home-use laser hair removal devices allows for these treatments to be performed in the comfort of your own home at an affordable cost. Objective: To evaluate the effectiveness of permanent hair reduction using a Diode laser in comparison to the Silk'n™ Flash and Go Lux (475–1200 nm) home-use laser. Methods: Fifteen females received six axillae laser hair removal treatments at two to four-week intervals using either a professional laser or home-use laser device. Photographs and hair counts were taken before each treatment and at a three week follow up. A T–test was used to evaluate statistical significance, and regression analysis to determine a difference in the effects. Pain scores and side effects were recorded by a visual analogue scale in a satisfaction questionnaire. Results: The professional laser showed an overall hair reduction of 85% on the right axilla and 88% on the left axilla. The home-use laser showed an overall reduction of 52% on the right axilla and 46,3% on the left axilla. Mild side effects were experienced for both laser devices. There were no serious adverse effects reported, safety features are effective to a certain extent. Conclusion: The Flash & Go Lux home-use laser can effectively reduce hair at a slower rate than the Diode laser. The home-use laser device offers protection against accidental exposure to light and use on darker skin types. Risks of retinal damage due to long-term exposure to home-use laser light are still cause for concern. [ABSTRACT FROM AUTHOR]

Animal models have shown that chronic stress increases cortisol, which contributes to overeating of highly palatable food, increased abdominal fat and lower cortisol reactivity. Few studies in humans have simultaneously examined these trajectories. We examined premenopausal women, either mothers of children with a diagnosis of an autism spectrum disorder (n = 92) or mothers of neurotypical children (n = 91). At baseline and 2-years, we assessed hair cortisol, metabolic health, and reward-based eating. We compared groups cross-sectionally and prospectively, accounting for BMI change. Caregivers, relative to controls, had lower cumulative hair cortisol at each time point, with no decreases over time. Caregivers also had stable levels of poor metabolic functioning and greater reward-based eating across both time points, and evidenced increased abdominal fat prospectively (all ps ≤.05), independent of change in BMI. This pattern of findings suggest that individuals under chronic stress, such as caregivers, would benefit from tailored interventions focusing on better regulation of stress and eating in tandem to prevent early onset of metabolic disease, regardless of weight status.

Purpose: Caizhixuan hair tonic (CZX) is a topical traditional Chinese medicine (TCM) preparation for the treatment of androgenetic alopecia (AGA). However, its active compounds and underlying mechanism for treating AGA are still unclear. The purpose of this study was to observe the effects of CZX on hair growth promotion in AGA mice and to explore the active components and mechanism. Methods: Testosterone propionate was administered subcutaneously to mice to establish an AGA mouse model. The therapeutic effects of CZX on AGA were evaluated by observing skin colour changes, hair growth time, and average hair length; calculating the hair growth score; and performing skin histopathological analysis. Following that, CZX chemical components were analysed by ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC–Q–TOF/MS). Network pharmacology was used to predict the major effects and possible mechanisms of CZX for the treatment of AGA. Furthermore, RT-qPCR and Western blotting were performed to assess the expression of key genes and proteins involved in PI3K/Akt and apoptosis pathways in order to validate CZX's predicted mechanism in AGA. Results: CZX promoted hair growth and improved the pathological morphology of hair follicles in the skin. In UPLC–Q–TOF/MS analysis, 69 components from CZX were isolated. Based on network pharmacology, CZX alleviated AGA by regulating PI3K/Akt and apoptosis pathways. According to RT-qPCR and Western blotting, CZX upregulated the expressions of PI3K, Akt, and Bcl-2, while downregulating that of Bax and caspase-3. Conclusions: CZX promotes hair growth to treat AGA by regulating the PI3K/Akt and apoptosis pathways. [ABSTRACT FROM AUTHOR]

The effective segmentation of lesion(s) from dermoscopic skin images assists the Computer-Aided Diagnosis (CAD) systems in improving the diagnosing rate of skin cancer. The results of the existing skin lesion segmentation techniques are not up to the mark for dermoscopic images with artifacts like varying size corner borders with color similar to lesion(s) and/or hairs having low contrast with surrounding background. To improve the results of the existing skin lesion segmentation techniques for such kinds of dermoscopic images, an effective skin lesion segmentation method is proposed in this research work. The proposed method searches for the presence of corner borders in the given dermoscopc image and removes them if found otherwise it starts searching for the presence of hairs on it and eliminate them if present. Next, it enhances the resultant image using state-of-the-art image enhancement method and segments lesion from it using machine learning technique namely, GrabCut method. The proposed method was tested on PH2 and ISIC 2018 datasets containing 200 images each and its accuracy was measured with two evaluation metrics, i.e., Jaccard index, and Dice index. The evaluation results show that our proposed skin lesion segmentation method obtained Jaccard Index of 0.77, 0.80 and Dice index of 0.87, 0.82 values on PH2, and ISIC2018 datasets, respectively, which are better than state-of-the-art skin lesion segmentation techniques. [ABSTRACT FROM AUTHOR]

Unidentified human remains have historically been investigated nationally by law enforcement authorities. However, this approach is outdated in a globalized world with rapid transportation means, where humans easily move long distances across borders. Cross-border cooperation in solving cold-cases is rare due to political, administrative or technical challenges. It is fundamental to develop new tools to provide rapid and cost-effective leads for international cooperation. In this work, we demonstrate that isotopic measurements are effective screening tools to help identify cold-cases with potential international ramifications. We first complete existing databases of hydrogen and sulfur isotopes in human hair from residents across North America by compiling or analyzing hair from Canada, the United States (US) and Mexico. Using these databases, we develop maps predicting isotope variations in human hair across North America. We demonstrate that both δ2H and δ34S values of human hair are highly predictable and display strong spatial patterns. Multi-isotope analysis combined with dual δ2H and δ34S geographic probability maps provide evidence for international travel in two case studies. In the first, we demonstrate that multi-isotope analysis in bulk hair of deceased border crossers found in the US, close to the Mexico-US border, help trace their last place of residence or travel back to specific regions of Mexico. These findings were validated by the subsequent identification of these individuals through the Pima County Office of the Medical Examiner in Tucson, Arizona. In the second case study, we demonstrate that sequential multi-isotope analysis along the hair strands of an unidentified individual found in Canada provides detailed insights into the international mobility of this individual during the last year of life. In both cases, isotope data provide strong leads towards international travel. [ABSTRACT FROM AUTHOR]

Background: Dupilumab is a human antibody that blocks the signaling of both interleukin-4 and interleukin-13 receptors. It has been approved for the treatment of moderate-to-severe atopic dermatitis. However, several case reports have reported conflicting effects of dupilumab on alopecia. Objectives: This study aimed to examine dupilumab-related hair disorders using the large real-world database, VigiBase. Methods: All individual case safety reports associated with dupilumab in the Uppsala Monitoring Center VigiBase until December 29, 2019, were analyzed. Hair disorder-related terms were defined in High Level Terms with "alopecias," "pilar disorders NEC (not elsewhere classified)," and "hypertrichoses," using the Medical Dictionary for Regulatory Activities Hierarchy. Hair disorder reports associated with dupilumab and other biologics that inhibit the Th2 axis (omalizumab, mepolizumab, reslizumab, and benralizumab) were analyzed to determine their association with hair disorders. Disproportionality analysis was performed based on the proportional reporting ratio, reporting odds ratio, and information components. Results: Among the 20,548 total dupilumab adverse event (AE) reports, hair disorders were reported in 462 dupilumab cases (2.2%), most of which reported hair loss, and only eight cases reported an increase in hair growth. The paradoxical trend in hair loss and growth after dupilumab use was confirmed using a disproportionality analysis. Among the other investigated biologics on Th2 immunity, only omalizumab was associated with hair loss. Additionally, hair disorders after dupilumab treatment were more frequently reported in women than in men. The proportion of hair disorder cases was high in Europe, accounting for 20.8% of hair disorder reports, whereas only 9.7% of all dupilumab-related AEs were reported in Europe. In conclusion, our analysis using a large real-world database confirmed that dupilumab is associated with hair disorders. [ABSTRACT FROM AUTHOR]

Scat is frequently used to study animal diets because it is easy to find and collect, but one concern is that gross fecal analysis (GFA) techniques exaggerate the importance of small-bodied prey to mammalian mesopredator diets. To capitalize on the benefits of scat, we suggest the analysis of scat carbon and nitrogen isotope values (δ13C and δ15N). This technique offers researchers a non-invasive method to gather short-term dietary information. We conducted three interrelated studies to validate the use of isotopic values from coyote scat: 1) we determined tissue-to-tissue apparent C and N isotope enrichment factors (ε13* and ε15*) for coyotes from road kill animals (n = 4); 2) we derived diet-to-scat isotope discrimination factors for coyotes; and 3) we used field collected coyote scats (n = 12) to compare estimates of coyote dietary proportions from stable isotope mixing models with estimates from two GFA techniques. Scat consistently had the lowest δ13C and δ15N values among the tissues sampled. We derived a diet-to-scat Δ13C value of -1.5‰ ± 1.6‰ and Δ15N value of 2.3‰ ± 1.3‰ for coyotes. Coyote scat δ13C and δ15N values adjusted for discrimination consistently plot within the isotopic mixing space created by known dietary items. In comparison with GFA results, we found that mixing model estimates of coyote dietary proportions de-emphasize the importance of small-bodied prey. Coyote scat δ13C and δ15N values therefore offer a relatively quick and non-invasive way to gain accurate dietary information.

The chance discovery of a 1.5-3.5 years old mummified girl presents a unique opportunity to further our understanding of health and disease among children in 19th Century San Francisco. This study focuses on carbon and nitrogen stable isotope signatures in serial samples of hair that cover the last 14 months of her life. Results suggest an initial omnivorous diet with little input from marine resources or C4 plants. Around six months before death δ15N starts a steady increase, with a noticeable acceleration just two months before she died. The magnitude of δ15N change, +1.5‰ in total, is consistent with severe undernourishment or starvation. Cemetery records from this time period in San Francisco indicate high rates of infant and child mortality, mainly due to bacterial-borne infectious diseases, about two orders of magnitude higher than today. Taken together, we hypothesize that the girl died after a prolonged battle with such an illness. Results highlight the tremendous impacts that modern sanitation and medicine have had since the 1800s on human health and lifespan in the United States.

Experimental and comparative evidence suggests that the striped coats of zebras deter biting fly attack, but the mechanisms by which flies fail to target black-and-white mammals are still opaque. Two hypotheses have been proposed: stripes might serve either to defeat polarotaxis or to obscure the form of the animal. To test these hypotheses, we systematically photographed free-living plains zebras in Africa. We found that black and white stripes both have moderate polarization signatures with a similar angle, though the degree (magnitude) of polarization in white stripes is lower. When we modeled the visibility of these signals from different distances, we found that polarization differences between stripes are invisible to flies more than 10 m away because they are averaged out by the flies' low visual resolution. At any distance, however, a positively polarotactic insect would have a distinct signal to guide its visual approach to a zebra because we found that polarization of light reflecting from zebras is higher than from surrounding dry grasses. We also found that the stripes themselves are visible to flies at somewhat greater distances (up to 20 m) than the polarization contrast between stripes. Together, these observations support hypotheses in which zebra stripes defeat visually guided orienting behavior in flies by a mechanism independent of polarotaxis.

Human identification from biological material is largely dependent on the ability to characterize genetic polymorphisms in DNA. Unfortunately, DNA can degrade in the environment, sometimes below the level at which it can be amplified by PCR. Protein however is chemically more robust than DNA and can persist for longer periods. Protein also contains genetic variation in the form of single amino acid polymorphisms. These can be used to infer the status of non-synonymous single nucleotide polymorphism alleles. To demonstrate this, we used mass spectrometry-based shotgun proteomics to characterize hair shaft proteins in 66 European-American subjects. A total of 596 single nucleotide polymorphism alleles were correctly imputed in 32 loci from 22 genes of subjects' DNA and directly validated using Sanger sequencing. Estimates of the probability of resulting individual non-synonymous single nucleotide polymorphism allelic profiles in the European population, using the product rule, resulted in a maximum power of discrimination of 1 in 12,500. Imputed non-synonymous single nucleotide polymorphism profiles from European-American subjects were considerably less frequent in the African population (maximum likelihood ratio = 11,000). The converse was true for hair shafts collected from an additional 10 subjects with African ancestry, where some profiles were more frequent in the African population. Genetically variant peptides were also identified in hair shaft datasets from six archaeological skeletal remains (up to 260 years old). This study demonstrates that quantifiable measures of identity discrimination and biogeographic background can be obtained from detecting genetically variant peptides in hair shaft protein, including hair from bioarchaeological contexts.

BackgroundTuberculosis (TB) is the leading cause of death from an infectious pathogen worldwide and the most prevalent opportunistic infection in people living with HIV. Isoniazid preventive therapy (IPT) reduces the incidence of active TB and reduces morbidity and mortality in HIV-infected patients independently of antiretroviral therapy. However, treatment of latent or active TB is lengthy and inter-patient variability in pharmacokinetics and adherence common. Current methods of assessing adherence to TB treatment using drug levels in plasma or urine assess short-term exposure and pose logistical challenges. Drug concentrations in hair assess long-term exposure and have demonstrated pharmacodynamic relevance in HIV.MethodsA large hair sample from a patient with active TB was obtained for assay development. Methods to pulverize hair and extract isoniazid were optimized and then the drug detected by liquid chromatography/ tandem mass spectrometry (LC/MS-MS). The method was validated for specificity, accuracy, precision, recovery, linearity and stability to establish the assay's suitability for therapeutic drug monitoring (TDM). Hair samples from patients on directly-observe isoniazid-based latent or active TB therapy from the San Francisco Department of Public Health TB clinic were then tested.ResultsOur LC/MS-MS-based assay detected isoniazid in quantities as low as 0.02ng/mg using 10-25 strands hair. Concentrations in spiked samples demonstrated linearity from 0.05-50ng/mg. Assay precision and accuracy for spiked quality-control samples were high, with an overall recovery rate of 79.5%. In 18 patients with latent or active TB on treatment, isoniazid was detected across a wide linear dynamic range.ConclusionsAn LC-MS/MS-based assay to quantify isoniazid levels in hair with performance characteristics suitable for TDM was developed and validated. Hair concentrations of isoniazid assess long-term exposure and may be useful for monitoring adherence to latent or active TB treatment in the setting of HIV.

Human hair absorbs numerous biomolecules from the body during its growth. This can act as a fingerprint to determine substance intake of an individual, which can be useful in forensic studies. The cocaine concentration profile along the growth axis of hair indicates the time evolution of the metabolic incorporation of cocaine usage. It could be either assessed by chemical extraction and further analysis of hair bundels, or by direct single hair fibre analysis with mass spectroscopy imaging (MSI). Within this work, we analyzed the cocaine distribution in individual hair samples using MeV-SIMS. Unlike conventional surface analysis methods, we demonstrate high yields of nonfragmented molecular ions from the surface of biological materials, resulting in high chemical sensitivity and non-destructive characterisation. Hair samples were prepared by longitudinally cutting along the axis of growth, leaving half-cylindrical shape to access the interior structure of the hair by the probing ion beam, and attached to the silicon wafer. A focused 5.8 MeV 35Cl6+ beam was scanned across the intact, chemically pristine hair structure. A non-fragmented protonated [M+ H]+ cocaine molecular peak at m/z = 304 was detected and localized along the cross-section of the hair. Its intensity exhibits strong fluctuations along the direction of the hair's growth, with pronounced peaks as narrow as 50 micrometres, corresponding to a metabolic incorporation time of approx. three hours. [ABSTRACT FROM AUTHOR]

Tasmanian devil (tde) mice are deaf and exhibit circling behaviour. Sensory hair cells of mutants show disorganised hair bundles with abnormally thin stereocilia. The origin of this mutation is the insertion of a transgene which disrupts expression of the Grxcr1 (glutaredoxin cysteine rich 1) gene. We report here that Grxcr1 exons and transcript sequences are not affected by the transgene insertion in tde homozygous (tde/tde) mice. Furthermore, 5'RACE PCR experiments showed the presence of two different transcripts of the Grxcr1 gene, expressed in both tde/tde and in wild-type controls. However, quantitative analysis of Grxcr1 transcripts revealed a significantly decreased mRNA level in tde/tde mice. The key stereociliary proteins ESPN, MYO7A, EPS8 and PTPRQ were distributed in hair bundles of homozygous tde mutants in a similar pattern compared with control mice. We found that the abnormal morphology of the stereociliary bundle was associated with a reduction in the size and Ca2+-sensitivity of the mechanoelectrical transducer (MET) current. We propose that GRXCR1 is key for the normal growth of the stereociliary bundle prior to the onset of hearing, and in its absence hair cells are unable to mature into fully functional sensory receptors. [ABSTRACT FROM AUTHOR]

Introduction: Prevention of mother to child transmission of HIV (PMTCT) is frequently challenged by irregular access to more effective anti-retroviral therapy. Nevirapine single dose (sdNVP), sdNVP+AZT+3TC for MTCT prophylaxis and NVP+ AZT+3TC for treatment and PMTCT were withdrawn due to low genetic resistance barrier and low efficacy. However current PMTCT lines in Mozambique include DTG+3TC+TDF, TDF+3TC+EFV, DTG +ABC+3TC, and AZT + NVP syrup prophylaxis for exposed babies. We assessed NVP hair and plasma concentrations and association with HIV-1RNA suppression among HIV+ ante-partum and post-partum women under PMTCT in Maputo, Mozambique. Methods: From December 2013 to November 2014, prospectively were enrolled 200 HIV+ ante-partum women on 200mg nevirapine and zidovudine 300 plus lamivudine 150mg twice daily at least with 3 months treatment and seen again at 24 weeks post-partum. Self-reported pill-taking adherence, NVP concentrations in hair, plasma, hemoglobin, CD4 cell count, HIV-1 RNA load was evaluated. NVP concentration in hair and plasma was analyzed as categorical quartile variable based on better data fit. NVP concentration was set between ≤3.77 ng/ml in plasma and ≤17,20 ng/mg in hair in quartile one to ≥5.36 ng/ml in plasma and ≥53.21 ng/mg in hair in quartile four. Logistic regression models for repeated measures were calculated. Following the World Health Organization (WHO) guidelines we set viral suppression at HIV-1RNA < 1000 c/mL. Outcome was HIV-1 RNA<1000 copies/ml. Predictor was NVP concentration in hair categorized in quartiles. Results: In total 369 person-visits (median of 1.85) were recorded. Self-reported adherence was 98% (IQR 97–100%) at ante-partum. In 25% person visits, NVP concentrations were within therapeutic levels (3.77 ng/ml to 5.35 ng/ml) in plasma and (17.20 ng/mg to 53.20 ng/mg) in hair. In 50% person visits NVP concentrations were above 5.36 ng/ml in plasm and 53.21 ng/mg in hair. HIV-1 RNA suppression was found in 34.7% of women with two viral loads, one at enrollment and another in post-partum. Odds of HIV-1 RNA suppression in quartile 4, was about 6 times higher than in quartile 1 (p-value = 0.006) for NVP hair concentration and 7 times for NVP plasma concentration (p-value = 0.012). Conclusions: The study results alert for potential low efficacy of current PMTCT drug regimens in use in Mozambique. Affordable means for individual monitoring adherence, ART plasma and hair levels, drug resistant and HIV-1 RNA levels monitoring are recommended for prompt identification of inadequate drug regimens exposure patterns and adjust accordingly. [ABSTRACT FROM AUTHOR]

Dietary homogenization has progressed worldwide due to westernization and the globalization of food production systems. We investigated dietary heterogeneity in South Korea by examining the spatial distribution of carbon (C), nitrogen (N), and sulfur (S) isotope ratios using 264 human hair samples. Overall, variation in isotope values was small, indicating low dietary heterogeneity. We detected differences in δ13C, δ15N, and δ34S values between administrative provinces and metropolitan cities; inter-regional differences were typically < 1 ‰. Values of δ34S were significantly lower in hair samples from inland regions relative to those from coastal locations, and a similar pattern was observed in δ15N values. Understanding geographic variation in δ34S and δ15N values in human hair is useful for provenancing humans in South Korea. [ABSTRACT FROM AUTHOR]

BackgroundPre-exposure prophylaxis (PrEP) trials using tenofovir-based regimens have demonstrated that high levels of adherence are required to evaluate efficacy; the incorporation of objective biomarkers of adherence in trial design has been essential to interpretation, given the inaccuracy of self-report. Antiretroviral measurements in scalp hair have been useful as a marker of long-term exposure in the HIV treatment setting, and hair samples are relatively easy and inexpensive to collect, transport, and store for analysis. To evaluate the relationship between dose and tenofovir concentrations in hair, we examined the dose proportionality of tenofovir in hair in healthy, HIV-uninfected adults.MethodsA phase I, crossover pharmacokinetic study was performed in 24 HIV-negative adults receiving directly-observed oral tenofovir tablets administered 2, 4, and 7 doses/week for 6 weeks, with a ≥3-week break between periods. Small samples of hair were collected after each six-week period and analyzed for tenofovir concentrations. Geometric-mean-ratios compared levels between each pair of dosing conditions. Intensive plasma pharmacokinetic studies were performed during the daily-dosing period to calculate areas-under-the-time-concentration curves (AUCs).ResultsOver 90% of doses were observed per protocol. Median tenofovir concentrations in hair increased monotonically with dose. A log-linear relationship was seen between dose and hair levels, with an estimated 76% (95% CI 60-93%) increase in hair level per 2-fold dose increase. Tenofovir plasma AUCs modestly predicted drug concentrations in hair.ConclusionsThis study found a strong linear relationship between frequency of dosing and tenofovir levels in scalp hair. The analysis of quantitative drug levels in hair has the potential to improve adherence measurement in the PrEP field and may be helpful in determining exposure thresholds for protection and explaining failures in PrEP trials. Hair measures for adherence monitoring may also facilitate adherence measurement in real-world settings and merit further investigation in upcoming PrEP implementation studies and programs.Trial registrationClinicalTrials.gov NCT00903084.

Understanding the farming system impact on animals is crucial for evaluating welfare. Rabbits exhibit distinct behaviours influenced by their surroundings. The conditions in which they are raised directly influence behaviour and stress responses, emphasizing the importance of providing an optimal environment for their overall well-being and growth. In this study, we assessed the behaviour and welfare of two Italian local rabbit populations, namely the grey rabbit of Carmagnola and the grey rabbit of Monferrato. These rabbits are not yet officially recognized as breeds, but they are commonly used in Italy for meat production and represent a distinctive phenotype and local heritage among farmers and consumers. We analysed the behavioural patterns, physiological responses, and blood parameters of the animals to assess the influence of both age and three distinct housing systems (traditional single cages, group farming, and a mixed system) on rabbits' welfare. In this study, 294 weaned males with 35 days old were divided into three housing systems with seven replicates each until reaching slaughtering age (100 days of age). A traditional single cage system, a group farming with 10 animals each replicate and a Mixed pilot system with 10 rabbits initially grouped, then transferred to single cages. The findings from the behavioural analysis and the evaluation of salivary and hair corticosterone levels demonstrate that both the housing system and the age of the rabbits exerted significant effects on their welfare. Rabbits in group housing displayed a wider range of behavioural patterns, including increased kinetic activities such as running, walking, and exploration. However, this housing system was associated with higher levels of both salivary and hair corticosterone, indicating a high acute and chronic stress condition. The single cage system was associated with higher levels of acute stress and a low frequency of kinetic activities and social interactions, with a predominant behaviour of turning on themselves. The age factor significantly influenced the occurrence of behaviours, with younger rabbits exhibiting higher levels of kinetic activities, while social behaviours such as attacks and dominance were more prevalent as the rabbits reached sexual maturity (around 80-85 days of age). Moreover, the attainment of sexual maturity coincided with an increase in salivary corticosterone levels. We found a significant association between attack behaviours, escape attempts, and elevated corticosterone levels, by demonstrating that these behaviours can be used as indicators of decreased animals' well-being. Our findings underscore the importance of considering both the housing environment and the temporal dimension in the study of behaviour and welfare. This enables a comprehensive assessment of appropriate rearing management techniques. By understanding the social dynamics and stress sources within housing systems, farmers can implement measures to enhance animal welfare and create a conducive environment for the health and behaviour of rabbits., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ozella et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The cat (Felis silvestris catus) shows significant variation in pelage, morphological, and behavioral phenotypes amongst its over 40 domesticated breeds. The majority of the breed specific phenotypic presentations originated through artificial selection, especially on desired novel phenotypic characteristics that arose only a few hundred years ago. Variations in coat texture and color of hair often delineate breeds amongst domestic animals. Although the genetic basis of several feline coat colors and hair lengths are characterized, less is known about the genes influencing variation in coat growth and texture, especially rexoid - curly coated types. Cornish Rex is a cat breed defined by a fixed recessive curly coat trait. Genome-wide analyses for selection (di, Tajima's D and nucleotide diversity) were performed in the Cornish Rex breed and in 11 phenotypically diverse breeds and two random bred populations. Approximately 63K SNPs were used in the analysis that aimed to localize the locus controlling the rexoid hair texture. A region with a strong signature of recent selective sweep was identified in the Cornish Rex breed on chromosome A1, as well as a consensus block of homozygosity that spans approximately 3 Mb. Inspection of the region for candidate genes led to the identification of the lysophosphatidic acid receptor 6 (LPAR6). A 4 bp deletion in exon 5, c.250_253_delTTTG, which induces a premature stop codon in the receptor, was identified via Sanger sequencing. The mutation is fixed in Cornish Rex, absent in all straight haired cats analyzed, and is also segregating in the German Rex breed. LPAR6 encodes a G protein-coupled receptor essential for maintaining the structural integrity of the hair shaft; and has mutations resulting in a wooly hair phenotype in humans.

Mutant laboratory mice with distinctive hair phenotypes are useful for identifying genes responsible for hair diseases. The work presented here demonstrates that shotgun proteomic profiling can distinguish hair shafts from different inbred mouse strains. For this purpose, analyzing the total hair shaft provided better discrimination than analyzing the isolated solubilized and particulate (cross-linked) fractions. Over 100 proteins exhibited significant differences among the 11 strains and 5 mutant stocks across the wide spectrum of strains surveyed. Effects on the profile of single gene mutations causing hair shaft defects were profound. Since the hair shaft provides a discrete sampling of the species proteome, with constituents serving important functions in epidermal appendages and throughout the body, this work provides a foundation for non-invasive diagnosis of genetic diseases of hair and perhaps other tissues.

Corticotropin-releasing factor (CRF) signaling pathways are involved in the stress response, and there is growing evidence supporting hair growth inhibition of murine hair follicle in vivo upon stress exposure. We investigated whether the blockade of CRF receptors influences the development of hair loss in CRF over-expressing (OE)-mice that display phenotypes of Cushing's syndrome and chronic stress, including alopecia. The non-selective CRF receptors antagonist, astressin-B (5 µg/mouse) injected peripherally once a day for 5 days in 4-9 months old CRF-OE alopecic mice induced pigmentation and hair re-growth that was largely retained for over 4 months. In young CRF-OE mice, astressin-B prevented the development of alopecia that occurred in saline-treated mice. Histological examination indicated that alopecic CRF-OE mice had hair follicle atrophy and that astressin-B revived the hair follicle from the telogen to anagen phase. However, astressin-B did not show any effect on the elevated plasma corticosterone levels and the increased weights of adrenal glands and visceral fat in CRF-OE mice. The selective CRF₂ receptor antagonist, astressin₂-B had moderate effect on pigmentation, but not on hair re-growth. The commercial drug for alopecia, minoxidil only showed partial effect on hair re-growth. These data support the existence of a key molecular switching mechanism triggered by blocking peripheral CRF receptors with an antagonist to reset hair growth in a mouse model of alopecia associated with chronic stress.

Background: The association between personal hair dye use and breast cancer risk is currently debated. The aim of this work is to investigate the association between the use of hair care products and breast cancer risk in women. Methods: Based on the PRISMA-IPD statement, the PubMed, Embase, Cochrane Library, Web of Science, OVID and Scopus databases were used to identify eligible studies published from inception to 22 April 2020. A pooled odds ratio (OR) with a 95% confidential interval (CI) was calculated to assess this correlation via fixed- or random-effect Mantel-Haenszel models using a heterogeneity Chi2 test with a significance level of p<0.1. All statistical tests were performed using StataSE software (version 12.0). Results: The analyzed data comprised 14 eligible studies with 210319 unique subjects. The pooled results suggested that there was a significant association between the use of hair dyes and breast cancer occurrence (pooled OR = 1.07; 95% CI, 1.01–1.13). Regarding the individual analysis regarding the different types of hair chemicals, permanent hair dye users (pooled OR = 1.08; 95% CI, 1.03–1.14) and rinse users (pooled OR = 1.17; 95% CI, 1.02–1.35) were both found to have a significantly elevated breast cancer risk compared to natural hair subjects, whereas there was an insignificant relationship between the use of semipermanent hair dyes (pooled OR = 1.09; 95% CI, 0.92–1.28) and straighteners (pooled OR = 1.04; 95% CI, 0.96–1.14) and breast cancer risk. No impact on the overall correlation between hair dyes and breast cancer risk due to race (White vs non-White) (pooled OR = 1.05; 95% CI, 0.86–1.29), timing of use (<10 years vs ≥10 years) (pooled OR = 0.96; 95% CI, 0.85–1.08) or dye color (Darker than natural hair vs Lighter than natural hair) (pooled OR = 0.91; 95% CI, 0.62–1.32) was found. Conclusions: Chemicals in hair dyes may play a role in breast carcinogenesis and increase breast cancer risk. [ABSTRACT FROM AUTHOR]

Background: There is a need for empirical studies assessing the psychometric properties of self-reported alcohol use as measures of excessive chronic drinking (ECD) compared to those of objective measures, such as ethyl glucuronide (EtG). Objectives: To test the quality of self-reported measures of alcohol use and of risky single-occasion drinking (RSOD) to detect ECD assessed by EtG. Methods: A total of 227 samples of hair from young Swiss men were used for the determination of EtG. Self-reported measures of alcohol use (previous twelve-month and previous-week alcohol use) and RSOD were assessed. Using EtG (<30 pg/mg) as the gold standard of ECD assessment, the sensitivity and specificity were computed, and the AUROC were compared for alcohol use measures and RSOD. Logistic regressions were used to test the contribution of RSOD to the understanding of ECD after controlling for alcohol use. Results: A total of 23.3% of participants presented with ECD. Previous twelve-month alcohol use with a cut-off of >15 drinks per week (sensitivity = 75.5%, specificity = 78.7%) and weekly RSOD (sensitivity = 75.5%, specificity = 70.1%) yielded acceptable psychometric properties. No cut-off for previous-week alcohol use gave acceptable results. In the multivariate logistic regression, after controlling for the previous twelve months of alcohol use, RSOD was still significantly associated with EtG (p =.016). Conclusion: Self-reported measures of the previous twelve months of alcohol use and RSOD were acceptable measures of ECD for population-based screening. Self-reported RSOD appeared to be an interesting screening measure, in addition to the previous twelve months of alcohol use, to understand ECD among young people. [ABSTRACT FROM AUTHOR]

Studying the isotope variability in fast-growing human tissues (e.g., hair, nails) is a powerful tool to investigate human nutrition. However, interpreting the controls of this isotopic variability at the population scale is often challenging as multiple factors can superimpose on the isotopic signals of a current population. Here, we analyse carbon, nitrogen, and sulphur isotopes in hair from 590 Canadian resident volunteers along with demographics, dietary and geographic information about each participant. We use a series of machine-learning regressions to demonstrate that the isotopic values in Canadian residents' hair are not only influenced by dietary choices but by geographic controls. First, we show that isotopic values in Canadian residents' hair have a limited range of variability consistent with the homogenization of Canadian dietary habits (as in other industrialized countries). As expected, some of the isotopic variability within the population correlates with recorded individual dietary choices. More interestingly, some regional spatial patterns emerge from carbon and sulphur isotope variations. The high carbon isotope composition of the hair of eastern Canadians relative to that of western Canadians correlates with the dominance of corn in the eastern Canadian food-industry. The gradient of sulphur isotope composition in Canadian hair from coast to inland regions correlates with the increasing soil pH and decreasing deposition of marine-derived sulphate aerosols in local food systems. We conclude that part of the isotopic variability found in the hair of Canadian residents reflects the isotopic signature associated with specific environmental conditions and agricultural practices of regional food systems transmitted to humans through the high consumption rate of intra-provincial food in Canada. Our study also underscores the strong potential of sulphur isotopes as tracers of human and food provenance. [ABSTRACT FROM AUTHOR]

The greying of human head hair is arguably the most salient marker of human aging. In wild mammal populations, greying can change with life history or environmental factors (e.g., sexual maturity in silverback gorillas). Yet, whether humans are unique in our pattern of age-related hair depigmentation is unclear. We examined the relationship between pigmentation loss in facial hair (greying) to age, population, and sex in wild and captive chimpanzees (Pan troglodytes). Digital facial photographs representing three chimpanzee populations (N = 145; ages 1–60 years) were scored for hair greying on a scale of one [~100% pigmented] to six [~0% pigmented]. Our data suggest that chimpanzee head and facial hair generally greys with age prior to mid-life (~30 years old), but afterwards, greying ceases to increase incrementally. Our results highlight that chimpanzee pigmentation likely exhibits substantial variation between populations, and that both 'grey' and pigmented phenotypes exist across various age classes. Thus, chimpanzee facial hair greying is unlikely a progressive indicator of age beyond mid-life, and thus facial greying in chimpanzees seems different from the pattern observed in humans. Whether this reflects neutral differences in senescence, or potential differences in selection pressures (e.g. related to conspecific communication), is unclear and worthy of more detailed examination across populations and taxa. [ABSTRACT FROM AUTHOR]

Trace elements in hair originate from intake (e.g., diet, inhalation, skin absorption), are transported in the bloodstream, and then incorporated during hair formation. However, the trace element abundance and isotopic compositions may be altered by post-eruption environmental processes. Such alterations must be addressed to obtain a meaningful interpretation of hair analysis for biomonitoring. In this study, we used strontium (Sr) isotopic analysis together with sorption kinetics of ionic Sr to quantify the rate and extent of replacement of endogenous Sr in hair by exogenous Sr from ambient water. We found that with only 10 minutes of exposure at room temperature (22°C), more than 30% of original endogenous Sr in hair was replaced with exogenous Sr from the solution. After 16 days of exposure to the solution, more than 90% of endogenous Sr was replaced, with a warmer temperature (60°C) accelerating the exchange substantially. We also found that acid leaching of exposed hair did not remove or isolate the exogenous Sr; therefore, neither the original endogenous nor the exogenous 87Sr/86Sr signal could be separated. Nonetheless, these findings illustrated that the quantitative correlation between the fraction of exogenous Sr and the soaking time, if established, could be used to estimate the length of water contact time for hair in forensic studies. Even if such time since initial contact cannot be established, the combination of acid leaching and 87Sr/86Sr analysis of hair samples may still be valuable in provenance studies to identify recent changes in the exogenous Sr pool, including movements or changes in water source. [ABSTRACT FROM AUTHOR]

Background: Hair cortisol concentration (HCC) is an increasingly used measure of systemic cortisol concentration. However, determinants of HCC in children and adolescents are unclear because few prospective studies have been conducted to date. Study design: We followed 725 children in Project Viva, a pre-birth cohort study of mothers and children, who provided hair samples at mid-childhood (median age: 7.7 years) or early adolescence (median age: 12.9 years). We examined associations of various factors measured from pregnancy to mid-childhood with HCC in mid-childhood and early adolescence, as well as change in HCC between these time points (ΔHCC). Results: There were 426 children with HCC measurements in both mid-childhood and early adolescence, 173 children with measures only in mid-childhood, and 126 with measures only in early adolescence. HCC was lower in mid-childhood (median 1.0pg/mg [interquartile range, IQR: 0.5, 2.4]) than early adolescence (2.2pg/mg [1.1, 4.4]). In multivariable-adjusted regression models, female sex (β = -0.41, 95% CI: -0.67, -0.15) and birth weight-for-gestational age z-score (β = -0.19, 95% CI: -0.33, -0.04) were associated with lower mid-childhood HCC, while prenatal smoking was associated with higher mid-childhood HCC (β = 0.53, 95% CI: 0.04, 1.01). In early adolescence, child age (β = 0.34 per year, 95% CI: 0.21, 0.46) female sex (β = 0.33, 95% CI: 0.10, 0.57), and maternal pre-pregnancy body mass index (β = 0.15 per 5-kg/m2, 95% CI: 0.01, 0.29) were positively associated with HCC. Child anthropometric measures and biomarker concentrations were not associated with HCC. Conclusion: Maternal pre-pregnancy BMI, maternal prenatal smoking, and low birth weight were associated with higher mid-childhood and adolescent HCC. However, few postnatal characteristics were associated with HCC. [ABSTRACT FROM AUTHOR]

Introduction: Across the African Diaspora, hair is synonymous with identity. As such, Black women use a variety of hair products, which often contain more endocrine-disrupting chemicals than products used by women of other races. An emerging body of research is linking chemicals in hair products to breast cancer, but there is no validated instrument that measures constructs related to hair, identity, and breast health. The objective of this study was to develop and validate the Black Identity, Hair Product Use, and Breast Cancer Scale (BHBS) in a diverse sample of Black women to measure the social and cultural constructs associated with Black women's hair product use and perceived breast cancer risk. Methods: Participants completed a 27-item scale that queried perceptions of identity, hair products, and breast cancer risk. Principal Component Analyses (PCA) were conducted to establish the underlying component structures, and confirmatory factor analysis (CFA) was used to determine model fit. Results: Participants (n = 185) were African American (73%), African, and Caribbean Black women (27%) aged 29 to 64. PCA yielded two components that accounted for 61% of total variance. Five items measuring sociocultural perspectives about hair and identity loaded on subscale 1 and accounted for 32% of total variance (α = 0.82; 95% CI = 0.77–0.86). Six items assessing perceived breast cancer risk related to hair product use loaded on subscale 2 and accounted for 29% of total variance (α = 0.82 (95% CI = 0.74–0.86). CFA confirmed the two-component structure (Root Mean Square Error of Approximation = 0.03; Comparative Fit Index = 0.91; Tucker Lewis Index = 0.88). Conclusions: The BHBS is a valid measure of social and cultural constructs associated with Black women's hair product use and perceived breast cancer risk. This scale is useful for studies that assess cultural norms in the context of breast cancer risk for Black women. [ABSTRACT FROM AUTHOR]

Hypotrichosis simplex (HS) with and without woolly hair (WH) comprises a group of rare, monogenic disorders of hair loss. Patients present with a diffuse loss of scalp and/or body hair, which usually begins in early childhood and progresses into adulthood. Some of the patients also show hair that is tightly curled. Approximately 10 genes for autosomal recessive and autosomal dominant forms of HS have been identified in the last decade, among them five genes for the dominant form. We collected blood and buccal samples from 17 individuals of a large British family with HS and WH. After having sequenced all known dominant genes for HS in this family without the identification of any disease causing mutation, we performed a genome-wide scan, using the HumanLinkage-24 BeadChip, followed by a classical linkage analysis; and whole exome-sequencing (WES). Evidence for linkage was found for a region on chromosome 4q35.1-q35.2 with a maximum LOD score of 3.61. WES led to the identification of a mutation in the gene SORBS2, encoding sorbin and SH3 domain containing 2. Unfortunately, we could not find an additional mutation in any other patient/family with HS; and in cell culture, we could not observe any difference between cloned wildtype and mutant SORBS2 using western blotting and immunofluorescence analyses. Therefore, at present, SORBS2 cannot be considered a definite disease gene for this phenotype. However, the locus on chromosome 4q is a robust and novel finding for hypotrichosis with woolly hair. Further fine mapping and sequencing efforts are therefore warranted in order to confirm SORBS2 as a plausible HS disease gene. [ABSTRACT FROM AUTHOR]

The present study investigates the wound healing potential of three chitosan-based topical preparations loaded with either tea tree essential oil, rosemary essential oil or a mixture of both oils in vivo. Essential oils of M. alternifolia and R. officinalis were analyzed using GC/MS. Essential oil-loaded chitosan topical preparations were formulated. Wound healing potential was evaluated in vivo using an excision wound model in rats. GC/MS analysis of M. alternifolia and R. officinalis essential oils revealed richness in oxygenated monoterpenes, representing 51.06% and 69.61% of the total oil composition, respectively. Topical application of chitosan-based formulation loaded with a mixture of tea tree and rosemary oils resulted in a significant increase in wound contraction percentage compared to either group treated with individual essential oils and the untreated group. Histopathological examination revealed that topical application of tea tree and rosemary oil combination demonstrated complete re-epithelialization associated with activated hair follicles. The high percentage of oxygenated monoterpenes in both essential oils play an important role in the antioxidant and wound healing potential observed herein. Incorporation of tea tree and rosemary essential oils in chitosan-based preparations in appropriate combination could efficiently promote different stages of wound healing. [ABSTRACT FROM AUTHOR]

Dutasteride, a dual inhibitor of both type I and II 5α-reductases, is used to treat male pattern hair loss (MPHL). However, patient response to dutasteride varies in each individual, the cause of which is yet to be identified. To identify genetic variants associated with response to dutasteride treatment for MPHL, a total of 42 men with moderate MPHL who had been treated with dutasteride for 6 months were genotyped and analysed by quantitative linear regression, case-control association tests, and Fisher’s exact test. The synonymous single nucleotide polymorphism (SNP) rs72623193 in DHRS9 was most significantly associated with response to dutasteride, followed by the non-synonymous SNP rs2241057 in CYP26B1. Additionally, variants in ESR1, SRD5A1, CYP19A1, and RXRG are suggested to be associated with response to dutasteride. Cumulative effect and interaction among these SNPs were presented in both additive and non-additive models. [ABSTRACT FROM AUTHOR]

Ten Hyptis suaveolens hairy root lines were established by infecting nodal explants with K599+pGus-GFP+ and ATCC15834+pTDT strains from Agrobacterium rhizogenes. Genetic transformation was confirmed by epifluorescence and plagiotropic hairy root growth in absence of growth regulators. Cytotoxicity was determined using the sulforhodamine B method, and the production of podophyllotoxin (PTOX) was measured by high performance thin layer chromatography scanning. Through these methodologies, HsTD10 was identified as the hairy root line with the highest cytotoxicity and PTOX production, which was corroborated by liquid chromatography-mass spectrometry and micrOTOF-Q II. A suspension culture of HsTD10 was established in which PTOX and carbohydrate consumption during growth kinetics were quantified by high-performance liquid chromatography. Procedures to increase the production and retrieval of PTOX in the HsTD10 line included selection of culture medium, addition of thiamine, and modification of the PTOX extraction method. The best combination of these variables was MS medium at 75% of its components with the addition of 2 mg L-1 of thiamine, extraction with methanol-dichloromethane, and sonication at 40 ± 5°C. During kinetics, growth-associated PTOX accumulation was observed. The specific growth rate (μ) was 0.11 d-1. The highest concentration of PTOX obtained with HsTD10 (5.6 mg g-1 DW) was 100 times higher than that reported for roots of wild plants and 56 times higher than that for in vitro nontransformed roots of H. suaveolens. [ABSTRACT FROM AUTHOR]

The human hair follicle is a neuroendocrine mini-organ that can be used to study aging processes in vitro. Neurotrophins maintain homeostasis in hair biology via the Trk-family of receptors. TrkA, the high affinity receptor for nerve growth factor (NGF), is expressed in hair follicle melanocytes and keratinocytes, where it regulates proliferation, differentiation and apoptosis and may thereby play a role in hair pigmentation and growth. We investigated TrkA expression during the human hair cycle and the effects of a selective high affinity TrkA agonist, Gambogic Amide, on hair pigmentation and hair growth in human hair follicles in vitro. In human scalp skin, TrkA expression was strongest in proliferating melanocytes re-establishing the pigmentary unit in the hair bulb during the early hair growth phase, anagen. During high anagen and in the de-composing pigmentary-unit of the regression phase, catagen, bulb-melanocytes lost TrkA expression and only undifferentiated outer root sheath melanocytes maintained it. In cultured human anagen hair follicles, Gambogic Amide was able to prevent gradual pigment loss, while it stimulated hair shaft elongation. This was achieved by increased melanocyte activation, migration and dendricity, highlighted by distinct c-KIT-expression in melanocyte sub-populations. Our results suggest that Gambogic Amide can maintain hair follicle pigmentation by acting on undifferentiated melanocytes residing in the outer root sheath and making them migrate to establish the pigmentary-unit. This suggests that the selective TrkA agonist Gambogic Amide acts as an anti-hair greying and hair growth promoting molecule in vitro. [ABSTRACT FROM AUTHOR]

The measurement of hair cortisol is increasingly used to understand the effect of natural and anthropogenic stressors on wild animals, but it is potentially confounded by individual, seasonal and sex-dependant variations in baseline cortisol secretion. This study validated an enzyme-linked immunoassay for hair cortisol measurement and characterized its baseline variation in a wild population of Egyptian mongoose. The analysis encompassed individuals of both sexes and all ages, across a range of geographic, environmental and seasonal conditions that the species experiences in Portugal allowing us to account for spatial, temporal and biological factors that contribute to hair cortisol variation. Our results showed that age, sex and storage time had an effect on hair cortisol, but season did not. Hair cortisol was higher in early stage juveniles compared to other age cohorts, in males when compared to females, and decreased with longer storage time. By identifying the factors that influence baseline hair cortisol in this wild population, we establish the basis for its application as an indicator of the effect of natural and anthropogenic stressors. [ABSTRACT FROM AUTHOR]

The lymphatic vascular system plays important roles in the control of tissue fluid homeostasis and immune responses. While VEGF-A-induced angiogenesis promotes hair follicle (HF) growth, the potential role of lymphatic vessels (LVs) in HF cycling has remained unknown. In this study, we found that LVs are localized in close proximity to the HF bulge area throughout the postnatal and depilation-induced hair cycle in mice and that a network of LVs directly connects the individual HFs. Increased LV density in the skin of K14-VEGF-C transgenic mice was associated with prolongation of anagen HF growth. Conversely, HF entry into the catagen phase was accelerated in K14-sVEGFR3 transgenic mice that lack cutaneous LVs. Importantly, repeated intradermal injections of VEGF-C promoted hair growth in mice. Conditioned media from lymphatic endothelial cells promoted human dermal papilla cell (DPC) growth and expression of IGF-1 and alkaline phosphatase, both activators of DPCs. Our results reveal an unexpected role of LVs in coordinating and promoting HF growth and identify potential new therapeutic strategies for hair loss-associated conditions. [ABSTRACT FROM AUTHOR]

Podoplanin (PDPN) is a glycoprotein that is expressed by various cell types, including keratinocytes, fibroblasts, and lymphatic endothelial cells. We found that PDPN is expressed in the hair follicle (HF) keratinocyte region and HF stem cell area during the late anagen phase but not during the telogen phase in mice. Importantly, keratinocyte-specific PDPN deletion in mice (K5-Cre;PDPNflox/flox) promoted anagen HF growth after depilation-induced HF regeneration as compared to control mice. RNA sequencing, followed by gene ontology analysis, showed down-regulation of focal adhesion and extracellular matrix interaction pathways in HF stem cells isolated from K5-Cre;PDPNflox/flox mice as compared to control mice. Furthermore, HF keratinocytes isolated from K5-Cre;PDPNflox/flox mice exhibited a decreased ability to interact with collagen type I in cell adhesion assays. Taken together, these results show that PDPN deletion promotes HF cycling, possibly via reduced focal adhesion and concomitantly enhanced migration of HF stem cells towards the bulb region. They also indicate potential new therapeutic strategies for the treatment of conditions associated with hair loss. [ABSTRACT FROM AUTHOR]

Alopecia areata (AA) is a hair loss disorder resulting from an autoimmune reaction against hair follicles. T-helper 1 cells are a major contributor to this disorder, but little is known about the role of T-regulatory cells (Tregs) in AA. Here, we analysed the distribution of circulating Treg subsets in twenty AA patients with active hair loss and fifteen healthy subjects by flow cytometry. The Treg suppressor HLA-DR+ subpopulation was significantly reduced in the patients (P<0.001) and there were significantly fewer cells expressing CD39 among the CD4+CD25+Foxp3+ Treg subpopulation in patients (P = 0.001). FOXP3 CD39 Treg cells were also reduced in hair follicles; by 75% in non-lesional skin and 90% in lesional skin, when compared to control healthy skin. To further characterise Treg cells in AA; Tregs (CD4+CD25+FOXP3+) were investigated for their TCRβ sequence. PCR products analysed by Next Generation Sequencing techniques, showed that all frequent public clonotypes in AA Tregs were also present in controls at relatively similar frequencies, excepting two public clonotypes: (V15 D1 J1-4) and (V2 D1 J1-2), which were exclusively present in controls. This suggests that these Treg clonotypes may have a protective effect and that they may be an exciting subject for future therapeutic applications. [ABSTRACT FROM AUTHOR]

Uranium (U) measurements in water, soil, and food related to gold mining activities in populated areas in Gauteng Province, South Africa, suggest the possibility of exposure levels that may lead to adverse health consequences, including cancer. Theoretical considerations on pathways of human uptake of significant exposures are plausible, but few data on directly measured human exposure are available. A cross-sectional study was conducted using human measurements to compare U levels with other settings around the globe (based on literature review), to explore potential exposure variability within the province, and to test the feasibility of recruiting subjects partially coming from vulnerable and difficult-to-reach populations. Wards of potentially high (HE) and low exposure (LE) were identified. Composite hair samples representing the respective local populations were collected from regular customers of selected barber shops over a period of 1–2 months. A total of 70 U concentrations were determined in 27 composite samples from 1332 individuals. U concentrations ranged from 31 μg/kg to 2524 μg/kg, with an arithmetic mean of 192 μg/kg (standard deviation, 310 μg/kg) and a median of 122 μg/kg. Although HE wards collectively showed higher U levels than LE wards (184 vs 134 μg/kg), differences were smaller than expected. In conclusion, detected U levels were higher than those from most other surveys of the general public. The barber-based approach was an efficient hair collection approach. Composite hair samples are not recommended, due to technical challenges in measuring U, and individual hair samples are needed in follow-up studies to determine predictors of exposure. [ABSTRACT FROM AUTHOR]

Background: Patients with sarcoidosis often experience fatigue and psychological distress, but little is known about the etiology of these conditions. While serum and saliva steroid hormones are used to monitor acute steroid levels, scalp hair analysis is a relatively new method enabling measurement of long-term steroid levels, including hair cortisol reflecting chronic stress. We investigated whether scalp hair cortisol and testosterone levels differ between sarcoidosis patients both with and without fatigue and general population controls. Additionally, we studied if these hormones could serve as objective biomarkers for psychological distress in patients with sarcoidosis. Methods: We measured hair steroid levels using liquid chromatography–tandem mass spectrometry in glucocorticoid naïve sarcoidosis patients. Patients completed the Perceived Stress Scale, Fatigue Assessment Scale, Hospital Anxiety and Depression Scale and Short Form 36 (SF-36). Hair steroid levels from 293 participants of the population-based Lifelines cohort study served as controls. Results: Thirty-two patients (14 males) were included. Hair cortisol, but not testosterone, concentrations were significantly higher in patients with sarcoidosis than in general population controls (mean 6.6 versus 2.7 pg/mg, p<0.001). No differences were found in hair cortisol and testosterone levels between fatigued and non-fatigued patients with sarcoidosis. Hair cortisol of sarcoidosis patients correlated significantly with anxiety (r = 0.47, p = 0.01), depression (r = 0.46, p = 0.01), and SF-36 mental domain (r = -0.38, p = 0.03), but not with fatigue. Conclusions: Patients with sarcoidosis have chronically higher levels of the stress hormone cortisol than the normal population, while testosterone levels in hair did not differ. Hair cortisol levels were positively related to subjective measures of psychological distress, but not to fatigue. Our study shows that hair cortisol is a promising non-invasive biomarker for psychological distress in patients with sarcoidosis. Trial registration: ClinicalTrials.gov: . Registered 31 March 2017, retrospectively registered. [ABSTRACT FROM AUTHOR]

Hair is an emerging biological matrix in which to measure chronic HPA axis activity, offering a longer term view into an animal’s life. We explored effects of exogenous (e.g. lifestyle, medications, social environment) and endogenous (e.g. disease, behaviour) stressors on hair cortisol concentration (HCC) in a population of Border Collies (BCs). Owners of BCs were recruited and reported their dog’s lifestyle, clinical history, anxiety-related behaviour, and collected a white hair sample from their dog’s dorsal neck region. HCC was determined using established methods with a commercial cortisol assay kit. Samples from 135 BCs were analysed, with 91 healthy controls and 44 diagnosed with epilepsy as a model disease. Factors associated with higher HCC included psychosocial stressors (living with three or more other dogs) and lifestyle (engaging in competitive flyball); while factors associated with lower HCC included anxiety (stranger-directed and non-social), health (epilepsy diagnosis, with number of seizures to date negatively correlated with HCC) and medication (certain anti-epileptic drugs were associated with elevated or reduced HCC). These novel results highlight the potential of chronic stress with frequent or persisting HPA-axis hyperactivity leading to a state of hypocortisolism, and the need to consider stressor recency and recurrence when interpreting HCC data. [ABSTRACT FROM AUTHOR]

In addition to large plexiform neurofibromas (pNF), NF1 patients are frequently disfigured by cutaneous neurofibromas (cNF) and are often afflicted with chronic pain and itch even from seemingly normal skin areas. Both pNFs and cNF consist primarily of benign hyperproliferating nonmyelinating Schwann cells (nSC). While pNF clearly arise within deep nerves and plexuses, the role of cutaneous innervation in the origin of cNF and in chronic itch and pain is unknown. First, we conducted a comprehensive, multi-molecular, immunofluorescence (IF) analyses on 3mm punch biopsies from three separate locations in normal appearing, cNF-free skin in 19 NF1 patients and skin of 16 normal subjects. At least one biopsy in 17 NF1 patients had previously undescribed micro-lesions consisting of a small, dense cluster of nonpeptidergic C-fiber endings and the affiliated nSC consistently adjoining adnexal structures—dermal papillae, hair follicles, sweat glands, sweat ducts, and arterioles—where C-fiber endings normally terminate. Similar micro-lesions were detected in hind paw skin of mice with conditionally-induced SC Nf1-/- mutations. Hypothesizing that these microlesions were pre-cNF origins of cNF, we subsequently analyzed numerous overt, small cNF (s-cNF, 3–6 mm) and discovered that each had an adnexal structure at the epicenter of vastly increased nonpeptidergic C-fiber terminals, accompanied by excessive nSC. The IF and functional genomics assays indicated that neurturin (NTRN) and artemin (ARTN) signaling through cRET kinase and GFRα2 and GFRα3 co-receptors on the aberrant C-fiber endings and nSC may mutually promote the onset of pre-cNF and their evolution to s-cNF. Moreover, TrpA1 and TrpV1 receptors may, respectively, mediate symptoms of chronic itch and pain. These newly discovered molecular characteristics might be targeted to suppress the development of cNF and to treat chronic itch and pain symptoms in NF1 patients. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin disease resulting in non-healing wounds affecting body areas of high hair follicle and sweat gland density. The pathogenesis of HS is not well understood but appears to involve dysbiosis-driven aberrant activation of the innate immune system leading to excessive inflammation. Marked dysregulation of antimicrobial peptides and proteins (AMPs) in HS is observed, which may contribute to this sustained inflammation. Here, we analyzed HS skin transcriptomes from previously published studies and integrated these findings through a comparative analysis with a published wound healing data set and with immunofluorescence and qPCR analysis from new HS patient samples. Among the top differently expressed genes between lesional and non-lesional HS skin were members of the S100 family as well as dermcidin, the latter known as a sweat gland-associated AMP and one of the most downregulated genes in HS lesions. Interestingly, many genes associated with sweat gland function, such as secretoglobins and aquaporin 5, were decreased in HS lesional skin and we discovered that these genes demonstrated opposite expression profiles in healing skin. Conversely, HS lesional and wounded skin shared a common gene signature including genes encoding for S100 proteins, defensins, and genes encoding antiviral proteins. Overall, our results suggest that the pathogenesis of HS may be driven by changes in AMP expression and altered sweat gland function, and may share a similar pathology with chronic wounds. [ABSTRACT FROM AUTHOR]

Androgenetic alopecia is the most common form of hair loss in males. It is a multifactorial condition involving genetic predisposition and hormonal changes. The role of microflora during hair loss remains to be understood. We therefore analyzed the microbiome of hair follicles from hair loss patients and the healthy. Hair follicles were extracted from occipital and vertex region of hair loss patients and healthy volunteers and further dissected into middle and lower compartments. The microbiome was then characterized by 16S rRNA sequencing. Distinct microbial population were found in the middle and lower compartment of hair follicles. Middle hair compartment was predominated by Burkholderia spp. and less diverse; while higher bacterial diversity was observed in the lower hair portion. Occipital and vertex hair follicles did not show significant differences. In hair loss patients, miniaturized vertex hair houses elevated Propionibacterium acnes in the middle and lower compartments while non-miniaturized hair of other regions were comparable to the healthy. Increased abundance of P. acnes in miniaturized hair follicles could be associated to elevated immune response gene expression in the hair follicle. [ABSTRACT FROM AUTHOR]