Scalp Samples Research Articles

Comparative proteomic analysis of male and female androgenetic alopecia: elucidating gender-specific molecular patterns.

This study presents a comprehensive comparative proteomic analysis aimed at elucidating the molecular mechanisms underlying male androgenetic alopecia (AGA) and female AGA. Scalp samples from both male AGA and female AGA patients, along with their respective normal controls, were subjected to proteomic analysis, followed by bioinformatics investigations. Our findings revealed distinct proteomic profiles between male AGA and female AGA, with a total of 68 differentially expressed proteins identified in male AGA and 84 in female AGA. Among these, specific proteins were altered in male AGA and female AGA, highlighting the sex-specific molecular pathways involved in the pathogenesis of pattern hair loss. Protein-protein interaction network analyses further delineated the most impacted biological processes, including cytoskeleton organization, stress response, and metabolic pathways, with particular emphasis on the differing altered stress responses and metabolic states associated with hair loss between sexes. Our study not only uncovered the complex molecular landscape of male AGA and female AGA but also identified potential biomarkers and therapeutic targets, offering new insights into the sex-specific pathogenesis of pattern hair loss.

Monocentric evaluation of the Novaplex dermatophyte multiplex qPCR assay in the diagnosis of dermatophytoses.

Superficial fungal infections caused by dermatophytes are a prevalent global health concern. Rapid and accurate diagnosis of these pathogens through molecular tools would offer a substantial advantage for early detection and effective treatment. The conventional fungal culture presents inherent limitations, including extended result delivery delay and variable sensitivity. This study aimed to evaluate the performance of the multiplex real-time PCR Novaplex dermatophyte assay (Seegene) in comparison to traditional mycological methods including direct examination and culture. A total of 312 nail, skin, and scalp samples collected from patients with suspected superficial fungal infections for mycological diagnosis were retrospectively subjected to the Novaplex dermatophyte assay. Overall, 170 (54.6%) and 186 (59.6%) samples tested positive for dermatophyte culture and dermatophyte PCR, respectively. The concordance between PCR and culture for dermatophyte detection was 87.2%. There were 158 culture-positive/PCR-positive samples, 12 culture-positive/PCR-negative samples, and 28 culture-negative/PCR-positive samples. The sensitivity of PCR against culture varied according to the dermatophyte target, ranging from 90.5% (Trichophyton mentagrophytes/interdigitale/benhamiae), 91.2% (Trichophyton rubrum), to 100% (Microsporum spp. and Trichophyton tonsurans). When considering the final diagnosis using composite criteria, the sensitivity and specificity for the diagnosis of dermatophytosis were 92.9% and 96.6% for PCR, 86.7% and 100% for culture, and 95.4% and 92.2% for direct examination and culture combined, respectively. The Seegene Novaplex dermatophyte assay is an easy-to-use automated one-step extraction-PCR system that offers satisfactory performance for routine diagnosis of dermatophytoses in clinical laboratories, particularly in non-specialized centers. However, it cannot fully replace conventional mycology due to its inability to detect mold infections and to identify dermatophytes at the species level.

Surveillance fœtale : limites actuelles et nouvelles pistes basées sur l’analyse du système nerveux autonome fœtal

ObjectiveCurrently, fetal monitoring during labor is based on visual analysis of the fetal heart rate (FHR). This test is imperfect, with high intra- and inter-observer variability and a moderate to poor prediction of the occurrence of neonatal acidosis or anoxic-ischaemic encephalopathy. In situations where there is an intermediate risk of acidosis, it is possible to use second-line tests such as blood scalp sampling (with pH or lactate measurement) or ST segment analysis of the fetal ECG. However, these invasive tests have many limitations and their place is debated. Some authors suggest a more physiological approach to FHR assessment. The main actor in maintaining fetal homeostasis is the autonomic nervous system (ANS). Its activity can be assessed by analysing heart rate variability (HRV). The aim is to assess whether HRV can be used to identify situations at risk of acidosis. Materials and methodsOur team has developed an index, the Fetal Stress Index, to measure HRV. To test it in a situation of acidosis, we used a pregnant ewe model. We also developed in parallel a human fetal ECG recording system. ResultsIn our experimental model, we have shown that this index reflects variations in the parasympathetic system and correlates with the onset of acidosis. As its use in clinical practice requires the acquisition of a beat-to-beat FHR signal, we have also developed an abdominal patch that allows highly accurate analysis of the fetal ECG. ConclusionThe future is therefore to validate the FSI as a marker of acidosis in a prospective cohort using the signal obtained from our patch. This could be a new tool for fetal monitoring during labor.

Comparative Whole Metagenome Analysis in Lesional and Nonlesional Scalp Areas of Patients with Psoriasis Capitis and Healthy Individuals

Psoriasis is an immune-mediated inflammatory disorder, where the majority of the patients suffer from psoriasis capitis or scalp psoriasis. Current therapeutics remain ineffective to treat scalp lesions. Here, we present a whole-metagenome characterisation of the scalp microbiome in psoriasis capitis. We investigated how changes in the homeostatic cutaneous microbiome correlate with the condition and identified metagenomic biomarkers (taxonomic, functional, virulence factors, antimicrobial resistance genes) that could partly explain its emergence. Within this study, 83 top and back scalp samples from healthy individuals and 64 lesional and non-lesional scalp samples from untreated psoriasis capitis subjects were analysed. Using qPCR targeting the 16S and 18S rRNA genes, we found a significant decrease in microbial load within scalp regions affected by psoriasis compared to their non-lesional counterparts. Metagenomic analysis revealed that psoriatic lesions displayed significant lower Cutibacterium species (incl. C. modestum, C. namnetense, C. granulosum, C. porci), along with an elevation in Staphylococcus aureus. A heightened relative presence of efflux pump protein-encoding genes was detected, suggesting potential antimicrobial resistance mechanisms. These mechanisms are known to specifically target human antimicrobial peptides (incl. cathelicidin LL-37) which are frequently encountered within psoriasis lesions. These shifts in microbial community dynamics may contribute to psoriasis disease pathogenesis.

Presence of Demodex spp. on the face and scalp in patients affected by papulopustular rosacea of face.

The increased proliferation of Demodex mites in the pilosebaceous unit can be the cause of rosacea flare-ups on the face. Signs and symptoms of the scalp (e.g., itching, dandruff) have sometimes been reported in patients with papulopustular rosacea of face; they may be due to a proliferation of Demodex mites on the scalp. To study the Demodex mites count, a standardized skin surface biopsy was performed on the cheek and on the scalp. Microscopic examination and molecular identification of Demodex were performed. Pearson's χ2 Test or Fisher's Exact Test were used to test for any association between categorical variables and outcome. Patients affected by papulopustular rosacea had a greater frequency of Demodex-positive standardized skin surface biopsy than controls at the scalp (35.0% vs. 0%, P=0.033), at the face and/or at the scalp (50% vs. 10%, P=0.032). Demodex positive patients with a Demodex-positive face sample were more frequently found to have a Demodex-positive scalp sample (P=0.035). The predominant species was found to be Demodex folliculorum (92.6% of samples); the species Demodex brevis was identified only in 7.4% of samples. Demodex folliculorum is more frequently found on the scalp and face of patients with rosacea than controls, even though it is not statistically associated with scalp symptoms. The scalp may be a reservoir area for Demodex mites which could migrate on the face again after an acaricidal treatment.

Impact of Some Hair Cream Compositions on the Flora Density of Human Scalp

The study assessed the effect of some brands of hair creams coded MBB and SDR on the flora density of the human scalp in parts of Port Harcourt. Twenty volunteered persons subjected their scalp aseptically; for swap collection before and after application of the coded hair creams. Standard microbiological procedure was adopted to culture the scalp samples on prepared sterile nutrient agar, mannitol salt agar, MacConkey agar and Sabouraud destrose agar media. All the inoculated culture media plates were incubated in their respective temperature requirements and after which colonies that developed were counted. The result showed heterotrophic bacteria counts of 9.8 x 103 and 9.3 x 103CFU/ml for before and after application of SDR hair cream, while counts of 1.05 x 104 and 1.07 x 104CFU/ml were obtained from MBB hair volunteers before and after application respectively. Similarly, a Staphylococcal count of 4.5 x 103 and 3.7 x 103CFU/ml were obtained before and after application of SDR hair cream, while counts of 6.2 x 103 and 5 x 102 CFU/ml were obtained from MBB hair before and after application respectively. A total of 53 isolates were recovered from which two bacteria genera namely: Staphylococcus epidermidis, Staphylococcus aureus and a fungi genera named Candida krusei were identified. Staphylococcus aureus and Staphylococcus epidermidis were noted with a 12% and 56% occurrence respectively, in sample SDR volunteers. MBB cream volunteers, recovered 14.8 and 7.4 % frequency occurrence for Staphylococcus epidermidis and Staphylococcus aureus respectively. Thus, a negative effect of hair cream SDR on the human scalp was observed. The SDR hair cream significantly, reduced the Staphylococcal normal flora of the scalp, which can lead to the development of opportunistic infection. The study recommends that users of SDR cream to be mindful in application due to creams composition.

Low-cost low-fidelity task trainer for fetal scalp blood sampling

Fetal blood scalp sampling (FBS) is a critical obstetrical procedure used to assess intrapartum fetal well-being. Unfortunately, standardized task trainers for training Obstetrics and Gynecology (OB-GYN) residents in this technique are currently lacking. In response to this gap, we present a cost-effective task trainer designed to assist trainees in mastering the art of performing FBS. We provide a step-by-step guideline for the development of a cost-effective task trainer tailored for simulating FBS. Six OB-GYN residents underwent a structured theoretical session followed by practical training with the task trainer. Pre- and post-training questionnaires were administered to evaluate the simulator’s efficacy as an educational tool. All participants acknowledged the task trainer’s efficacy in enhancing their understanding of the procedure, resulting in elevated knowledge and confidence across all assessed aspects. Furthermore, every participant endorsed the training for fellow trainees and “agreed or strongly agreed” that the simulator faithfully replicated the procedural experience. This low-cost simulation model for FBS is a valuable training tool with high acceptance and satisfaction rates among participants. Its use has the potential to improve patient safety and increases participants confidence in performing the procedure.

Molecular identification of keratinophilic fungi associated with hair scalp and antifungal activity of green-synthesis zinc oxide nanoparticles.

A diverse population of fungi colonizes human hair and skin due to millions of years of functional integration and mutual adaptation. The human body, with its fungal communities, forms a complex entity. Microbial imbalance is promoted by instabilities in the host-mycobiota interaction system, which can be related to the development of various diseases. By morphological and molecular identification, 15 genera comprising 24 species were isolated from 18 scalp samples collected from girls. Yeast-like structures were the most common species in this study; they were recovered from six samples (33.3%). They were represented by five species: Arachniotus ruber; Cosmospora aurantiicola; Cutaneotrichosporon oleaginosum; Geotrichum candidum and Suhomyces tanzawaensis. For the synthesis of zinc oxide nanoparticles (ZnO NPs), an aqueous extract of Zingiber officinale was utilized as a reducing and capping agent. The prepared NPs tested by X-ray diffraction, they had a hexagonal wurtzite structure. Most of the ZnO NPs were spherical, and their diameter was about 38.9 nm using a transmission electron microscope. ZnO NPs of the Fourier-transform infrared spectroscopy spectra were recorded in the range of 400-4000 cm-1. UV-visible diffuse reflectance spectroscopy showed the 200-800 nm wavelength range. ZnO NPs showed the highest activity against Ambrosiella hartigii Ambh2; Cladosporium cladosporioides Cladcl12; C. cf. cucumerinum Cladcu13; S. tanzawaensis Suht34, with minimal inhibitory concentrations 1.25 × 103 µg/mL on the four isolates.

Inhibition of Cholesterol Biosynthesis Modulates Epithelial-Mesenchymal Transition in Primary Cicatricial Alopecia Through TGFβ and Angiotensin Receptors

Introduction: Primary Cicatricial Alopecia (PCA) is an autoimmune condition that affects the skin and causes hair loss in patients. In PCA the hair follicles of the patients are irreversibly damaged and replaced with fibrous tissue. This diseased condition lends relevance to our work since the fibrosis raises the potential that PCA may be affected in some way by the Epithelial Mesenchymal Transition (EMT). We used small interfering RNAs (siRNA) of TGFβ, AGTR and their regulators to identify the EMT modulation. Because these molecules mediate the induction of EMT. This study explores the idea of lowering PCA fibrosis by modifying EMT markers. Methods: We chose 7 DHC and BM15766 to investigate the function of cholesterol biosynthesis inhibition. We employed the HFORS in vitro and the mouse in vivo model system to examine EMT regulation PCA. Quantitative real-time PCR was utilised to examine the expression of genes in PCA scalp samples, compound-treated HFORS, and mouse tissues; immunohistochemistry was used to confirm the protein estimate in the scalp samples; and small interfering RNA (siRNA) transfection was used to identify the functional analysis of TGFβ and AGTR. Results: Reduced cholesterol production in PCA patients leads to permanent hair follicle damage. The in vitro and in vivo study using 7DHC and BM15766 revealed cells were positive for the EMT markers. PPARγ, AhR, and AGTR together can act as vital EMT regulators. As a result, the PPARγ agonist, AhR, and AGTR antagonist significantly downregulate the expression of CDH1, SNAIL1, and SMA. The markers of EMT are likewise deregulated by the transfection of siRNA for TGFβ and AGTR. Conclusion: We clarify how EMT is regulated in hair loss circumstances by suppressing cholesterol biosynthesis. We further confirm that EMT modulators (PPARγ, AhR, AGTR, and TGFβ) and siRNA can be employed as potentially effective strategies to slow the advancement of EMT. As a result, we propose these cholesterol and EMT modulators as potential inhibitors in PCA etiology.

Superficial fungal infections in the south of France - is fusariosis the next emergent onychopathy?

In France, onychomycoses represent about 30% of superficial mycoses seen by the dermatologists. In recent years, it is observed an increased number of mycoses due to non-dermatophytic molds. The purpose of this study was to evaluate the epidemiological profile of identified superficial fungal infections in the Laboratory of Parasitology-Mycology of the University Hospital of Nice over a two-year period. A retrospective study was performed from the nail, skin and scalp samples of patients analyzed from January 2018 to December 2019. In this study, 3074 samples (54.2% nails, 39.7% skin and 6.1% scalp) were analyzed representing 1922 patients. Among them, 809 (42.1%) patients were sampled by dermatologists and 1113 (57.9%) were sampled by our experts in the clinical unit of the University Hospital of Nice. In total, 1159 (37.7%) samples had a positive culture (1195 strains identified) including 712 (59.6%) dermatophytes, 345 (28.9%) yeasts and 138 (11.5%) other filamentous molds. Trichophyton rubrum was the main dermatophyte (563; 47.1%) followed by T. interdigitale (84; 7.0%) and T. soudanense (25; 2.1%). Yeasts were mostly represented by Candida albicans (155; 13.0%). Among the other molds, Fusarium sp. was the most isolated (61; 5.1%). Dermatophytes stay predominant in superficial fungal infections where the anthropophilic species T. rubrum was found in almost half of the positive cultures. Interestingly, molds represented an important part of infections in our population. This study highlights the increasing share of Fusarium sp. superficial fungal infection in our patients' populations, perhaps requiring a major therapeutic adaptation in the years to come.

Evaluation of a new-formula shampoo containing 6% glycyrrhetinic acid complex for scalp seborrheic dermatitis: A pilot study.

BackgroundScalp seborrheic dermatitis (SD) is a chronic inflammatory dermatosis associated with sebum imbalance and proliferation of Malassezia species. Various antifungal shampoos are commonly used for scalp SD.AimsGlycyrrhetinic acid is known to have antioxidative, anti‐inflammatory, and anti‐allergic effects. This study was designed to evaluate the effectiveness of a new‐formula shampoo that contains glycyrrhetinic acid for the treatment of scalp SD.Patients/MethodsThirty‐four patients were enrolled and treated with the 6% glycyrrhetinic acid complex shampoo. Efficacy was assessed clinically with Dermatology Life Quality Index (DLQI) and Adherent Scalp Flaking Score (ASFS) by the same dermatologist at baseline, week 2, and week 5. Among the 24 subjects with the most significant clinical improvement, four common microorganisms from scalp samples were analyzed by quantitative polymerase chain reaction (qPCR) at baseline, and week 5.ResultsThe DLQI and ASFS at week 2 and week 5 improved significantly relative to baseline. The bacteria profiles showed a significant increase of Cutibacterium acnes and a decrease of Staphylococcus epidermidis at week 5. The fungi profiles showed significant decreases of both Malassezia restricta and Malassezia globosa. The ratio of C. acne to S. epidermidis increased significantly from 0.93 at baseline to 1.55 at week 5. The ratio of M. restricta to M. globosa decreased from 5.02 at baseline to 1.00 at week 5.ConclusionsThe effectiveness of this new regimen was objectively demonstrated at the clinical and microbiological levels. This new formula may alleviate the bacterial and fungal dysbiosis in scalp SD.

Mid forceps did not cause “compromised babies” – “compromise” caused forceps: an approach toward safely lowering the cesarean delivery rate*

Objective Over 5 decades, Cesarean Delivery rates (CDR) have risen 6-fold while vaginal operative deliveries [VODs] decreased from >20% to ∼3%. Poor outcomes (HIE and cerebral palsy) haven’t improved. Potentiating the virtual abandonment of forceps (F), particularly midforceps (Mid), were allegations about various poor neonatal outcomes. Here, we evaluate VOD and CDR outcomes controlling for prior fetal risk metrics (PR) ascertained an hour before birth. Methods Our 45-year-old database from a labor research unit of moderate/high risk laboring patients (288 NSVDs, 120 Lows, 30 Mids, and 32 CDs) had multiple fetal scalp samples for base excess (BE), pH, cord blood gases (CB), and umbilical artery bloods. ANOVA established relationships between birth methods and outcomes (Cord blood BE and pH and 1 and 5 min Apgar scores); correlations, and two-step multiple regression assessed PR for delivery method and neonatal outcomes. The main outcome measures were correlations of outcome measures with fetal scalp sample BE and pH up to an hour before delivery and fetal reserve index scores scored concurrently. Results NSVDs had the best immediate neonatal outcomes with significantly higher CB pH and BE as compared to forceps and CDs. However, controlling for PR revealed: (1) PR at 1 h before delivery correlated with delivery mode, i.e. the decrements in outcomes were already present before the delivery was performed; and (2) The presumed deleterious effects of interventional deliveries, per se, were significantly reduced, and (3) Fetal Reserve Index predicted neonatal outcomes better than fetal scalp sample BE, pH, or delivery mode. Conclusion The historical belief that MF deliveries caused poorer outcomes than NSVDs seems mostly backwards. Appreciating PR’s impact on delivery routes, and when appropriate, properly performing VODs could safely reduce CDR. If our approach lowered CDR by only ∼2%, in the United States about 80,000 CDs might be avoided, saving ∼$750 Million yearly. In the post pandemic world, safely apportioning medical expenses will be even more critical than previously.

Load-deformation characteristics of acellular human scalp: assessing tissue grafts from a material testing perspective

Acellular matrices seem promising scaffold materials for soft tissue regeneration. Biomechanical properties of such scaffolds were shown to be closely linked to tissue regeneration and cellular ingrowth. This given study investigated uniaxial load-deformation properties of 34 human acellular scalp samples and compared these to age-matched native tissues as well as acellular dura mater and acellular temporal muscle fascia. As previously observed for human acellular dura mater and temporal muscle fascia, elastic modulus (p = 0.13) and ultimate tensile strength (p = 0.80) of human scalp samples were unaffected by the cell removal. Acellular scalp samples showed a higher strain at maximum force compared to native counterparts (p = 0.02). The direct comparison of acellular scalp to acellular dura mater and temporal muscle fascia revealed a higher elasticity (p < 0.01) and strain at maximum force (p = 0.02), but similar ultimate tensile strength (p = 0.47). Elastic modulus and ultimate tensile strength of acellular scalp decreased with increasing post-mortem interval. The elongation behavior formed the main biomechanical difference between native and acellular human scalp samples with elastic modulus and ultimate tensile strength being similar when comparing the two.

Scalp hair as a screening tool for detecting trace elements concentration

Health issues associated with critical trace elements that arise from insufficient (i.e. poor intake) and over-exposure. Measuring sensitivity is also a major problem for geneticists. Among noninvasive assays designed to quantify long-standing exposure to critical trace elements, scalp hair could be the most theoretically biological network. This analysis collects recent information relating to the safety of the scalp as a critical predictor of sensitivity to trace minerals such as cobalt, copper, boron, manganese, iron, selenium, molybdenum, silicon, zinc and vanadium. Particular consideration has been given to the exposure period through which the hair of the scalp is represented, and to the human variation of exposure rates over time in this matrix and the association between scalp hair and other essential markers, human characteristics and environmental influences. Where conventional and contemporary methods of washing and digesting scalp samples have been tested to train models for the measuring of trace metals in the scalp hair. The emergence of different approaches and new analytical procedures has made the usage of other less intrusive or noninvasive matrixes, for example hair. The existence of a chemical in these matrices indicates toxicity; however, associations between blood and the levels of non-invasive media must be established in order to insure that these quantities are associated to the total body load. The development of unique biomarkers which can be tested in this matrix would enhance non-invasive bio monitoring. Common spectral techniques such as inductively coupled plasma mass spectrometry "ICP-MS", plasma spectroscopy laser ablation "LA-ICP-MS", atomic absorption spectroscopy, etc. They have very good analytical performance, but the samples in them are subject to significant damage or are destroyed in addition to being environmentally hazardous because they require the use of hazardous chemicals and take a relatively long time. Compared to the laser induced breakdown spectroscopy "LIBS" process we find that this process has several advantages, such as the flexibility and smallness of the device and the convenience of sample preparation, as well as the ability to analyze samples from a distance, particularly in hazardous and inaccessible places.

Earlier and improved screening for impending fetal compromise

Objective The use of pH and base excess (FSSPHBE) from fetal scalp sampling (FSS) was abandoned when cardiotocography (CTG) was believed to be sufficiently accurate to direct patient management. We sought to understand the fetus’ tolerance to stress in the 1st stage of labor and to develop a better and earlier screening test for its risk for developing acidosis. To do so, we investigated sequential changes in fetal pH and BE obtained from FSS in the 1st stage of labor as part of a research protocol from the 1970s. We then examined the utility of multiple of the median (MoM’s) conversion of BE and pH values, and the capacity of Fetal Reserve Index (FRI) scores to be a proxy for such changes. We then sought to examine the predictive capacity of 1st stage FRI and its change over the course of the first stage of labor for the subsequent development of acidosis risk in the 2nd stage of labor. Methods Using a retrospective research database evaluation, we evaluated FSSPHBE data from 475 high-risk parturients monitored in labor and their neonates for 1 h postpartum. We categorized specimens according to cervical dilatation (CxD) at the time of FSSPHBE and developed non-parametric, multiples of the median (MOMs) assessments. FRI scores and their change over time were used as predictors of FSSPHBE. Our main outcome measures were the changes in BE and pH at different cervical dilatations (CxD) and acidosis risk in the early 2nd stage of labor. Results FSSPHBE worsens over the course of the 1st stage. The implications of any given BE are very different depending upon CxD. At 9 cm, −8 Mmol/L is 1.1 MOM; at 3 cm, it would be 2.0 MOM. The FRI level and its trajectory provide a 1st stage screening tool for acidosis risk in the second stage. Conclusions Fetal acid-base balance (“reserve”) deteriorates beginning early in the 1st stage of labor, irrespective of whether the fetus reaches a critical threshold of concern for actual acidosis. The use of MoM’s logic improves appreciation of such information. The FRI and its trajectory reasonably approximate the trajectory of the FSSPHBE and appears to be a suitable screening test for early deterioration and for earlier interventions to keep the fetus out of trouble rather than wait until high risk status develops.

712 Using scanning electron microscopy to elucidate the role of hair shaft malformation in the pathogenesis of Central Centrifugal Cicatricial Alopecia

Central Centrifugal Cicatricial Alopecia (CCCA) is a scarring alopecia most common in black women. Its presentation follows a seemingly genetic pattern affecting clusters of women within a family. A study that aimed to elucidate the genetic basis for CCCA found an increased incidence of mutations and decreased expression of PID3, a gene that encodes for peptidyl arginine deiminase type 3, essential for the formation of a normal hair shaft, in scalp samples of patients with CCCA (1). Of note, PID3 is one of three genes implicated in uncombable hair syndrome, a disorder where the hair shaft appears triangular or heart shaped in cross section when viewed under scanning electron microscopy (SEM) (2).

Mutations in SREBF1, Encoding Sterol Regulatory Element Binding Transcription Factor 1, Cause Autosomal-Dominant IFAP Syndrome

IFAP syndrome is a rare genetic disorder characterized by ichthyosis follicularis, atrichia, and photophobia. Previous research found that mutations in MBTPS2, encoding site-2-protease (S2P), underlie X-linked IFAP syndrome. The present report describes the identification via whole-exome sequencing of three heterozygous mutations in SREBF1 in 11 unrelated, ethnically diverse individuals with autosomal-dominant IFAP syndrome. SREBF1 encodes sterol regulatory element-binding protein 1 (SREBP1), which promotes the transcription of lipogenes involved in the biosynthesis of fatty acids and cholesterols. This process requires cleavage of SREBP1 by site-1-protease (S1P) and S2P and subsequent translocation into the nucleus where it binds to sterol regulatory elements (SRE). The three detected SREBF1 mutations caused substitution or deletion of residues 527, 528, and 530, which are crucial for S1P cleavage. Invitro investigation of SREBP1 variants demonstrated impaired S1P cleavage, which prohibited nuclear translocation of the transcriptionally active form of SREBP1. As a result, SREBP1 variants exhibited significantly lower transcriptional activity compared to the wild-type, as demonstrated via luciferase reporter assay. RNA sequencing of the scalp skin from IFAP-affected individuals revealed a dramatic reduction in transcript levels of low-density lipoprotein receptor (LDLR) and of keratin genes known to be expressed in the outer root sheath of hair follicles. An increased rate of in situ keratinocyte apoptosis, which might contribute to skin hyperkeratosis and hypotrichosis, was also detected in scalp samples from affected individuals. Together with previous research, the present findings suggest that SREBP signaling plays an essential role in epidermal differentiation, skin barrier formation, hair growth, and eye function.

Passive load-deformation properties of human temporal muscle

The passive load-deformation properties of the human temporal muscle applicable to computer simulations of the human head or the comparison of the temporal muscle to other graft materials are unexplored to date and it is unclear, if these properties depend on age, sex, post-mortem interval or body side. Eighty-eight fresh temporal muscle samples from 69 human cadavers (age range 4 months – 94 years) were investigated in a quasi-static tensile setup. For comparative reasons, 20 age-matched human temporal muscle fascia and scalp samples were tested in the same manner as the temporal muscle. Human temporal muscle showed an elastic modulus of 1.58 ± 0.64 MPa, an ultimate tensile strength of 0.26 ± 0.11 MPa and a strain at maximum force of 26.21 ± 12.48%. These parameters were independent of sex (p > 0.88), side (p > 0.92) and post-mortem interval (p > 0.09). All passive load-deformation parameters of the human temporal muscle differed from temporal muscle fascia and scalp except for the strain at maximum force of the temporal muscle and scalp. Significantly different load-deformation properties of the human temporal muscle from temporal muscle fascia and scalp indicate the need for a separate simulation of these soft tissue layers in computational head models to reflect lifelike conditions. Contrary to other tissues such as scalp or temporal muscle fascia the biomechanical temporal muscle properties in head models may not require adjustments for sex, side and age based on the here-presented findings.

A study of a group of genes involved in the hair growth cycle

Individual hairs grow from follicles which go through a cycle of different stages. During ‘anagen’ the hair is actively growing, in ‘catagen’ the follicle shrinks, while ‘telogen’ is the resting phase when the hair sheds before the next anagen. Abnormal hair growth usually reflects an abnormal hair cycle. For example, failure to re‐enter anagen from telogen, or short duration of anagen, cause poor hair growth, while excessive switching from telogen back to anagen causes excessive hair. If we could understand what controls these stages, it might be possible to develop effective treatments. Previously, scientists have managed to grow individual human anagen hair follicles in the laboratory but could only study the switch from anagen to catagen. The authors of this latest study, from the UK, Spain, Germany and the USA, managed for the first time to isolate human telogen and early anagen hairs. They used scalp samples from five men undergoing hair transplantation and dissected out the relevant hairs under the microscope. Using specific antibodies (a type of protein in the body) to examine telogen follicles they discovered that a group of genes called the WNT pathway induce anagen by prompting certain cells in the hair germ (part of the follicle) to multiply. By studying a whole range of proteins that switch WNT processes on or off they were able to build up a picture of events occurring at the start of anagen which will help future scientists to develop targeted treatments for hair disorders. This is a summary of the study: Deciphering the molecular morphology of the human hair cycle: Wnt signalling during the telogen–anagen transformation.

Safety and efficacy of sildenafil citrate to reduce operative birth for intrapartum fetal compromise at term: a phase 2 randomized controlled trial

Sildenafil citrate is a vasodilator used in erectile dysfunction and pulmonary hypertension. We tested whether it reduces emergency operative births for fetal compromise and improves fetal or uteroplacental perfusion in labor in a phase 2 double-blind randomized controlled trial. Women at term in early labor or undergoing scheduled induction of labor at Mater Mother's Hospital, Brisbane, Australia, were randomly allocated 50 mg of sildenafil citrate orally 8hourly up to 150 mg or placebo. Intrapartum fetal monitoring followedRoyal Australian and New Zealand College of Obstetricians andGynaecologists guidelines. Primary outcomes were (1) emergency operative birth (by cesarean delivery or instrumental vaginal birth)forintrapartum fetal compromise and (2) mean indices of fetalanduteroplacental perfusion using Doppler ultrasound. Analysiswas by intention-to-treat. ANZCTRN12615000319572 RESULTS: Between September 2015 and January 2019, 300 women were randomized equally to sildenafil citrate or placebo. Sildenafil citrate reduced the risk of emergency operative birth by 51% (18% vs 36.7%; relative risk, 0.49, 95% confidence interval, 0.33-0.73, P=.0004, number needed to treat= 5 [3-11]). There was no difference in indices of fetal and uteroplacental perfusion, but these were ascertained in only 71 women. Sildenafil citrate reduced the risk of meconium-stained liquor or pathologic fetal heart rate patterns by 43% (25.3% vs 44.7%; relative risk, 0.57, 95% confidence interval, 0.41-0.79, P=.0005), but its effects on fetal scalp sampling rates (2.0% vs 6.7%; relative risk, 0.30, 95% confidence interval, 0.08-1.07, P=.06) and adverse neonatal outcome (20.7% vs 21.3%; relative risk, 0.97, 95% confidence interval, 0.62-1.50, P=.89) were inconclusive. Only 3.6% of maternal levels of sildenafil citrate or its metabolite were detected in cord blood. No differences in maternal adverse events were seen. Sildenafil citrate reduced operative birth for intrapartum fetal compromise, but much larger phase 3 trials of its effects on mother and child are needed before it can be routinely recommended.