Botulinum Toxin for Scalp Conditions: A Systematic Review.

BACKGROUND: Many reports have described the use of botulinum toxin (BTX) in the treatment of scalp conditions, but no studies have synthesized these collective findings. OBJECTIVE: We conducted a systematic review to summarize the scalp conditions for which treatment with BTX has been described. METHODS: We searched PubMed/MEDLINE and Scopus for articles in English published before November 1, 2022, using the keywords "hair" or "scalp" and BTX-related search terms. Articles that described patients who received injections of BTX for the management of scalp conditions were included. RESULTS: Twenty-four original articles (12 case reports, 9 clinical trials, and 3 case series) were identified that described 309 patients with a scalp condition treated with BTX. Androgenetic alopecia, craniofacial hyperhidrosis, and scalp hyperseborrhea had the most robust data supporting the clinical efficacy of BTX. CONCLUSION: The current quality of evidence is highly variable and, for many conditions, limited to small observational studies. Botulinum toxin may be a promising therapeutic option for patients with various scalp conditions, but future studies are needed to better understand its efficacy and safety.

Guiding, sustaining and growing the public involvement of young people in an adolescent health research community of practice.

BACKGROUND: Public involvement in health research and its translation is well recognized to improve health interventions. However, this approach is insufficiently practised and evidenced in relation to young people. This paper presents an analysis of the process of co-producing a framework, partnership model and a growing network of young people informing and guiding an adolescent health research community of practice. METHODS: A Living Lab is a participatory research approach that brings together a broad range of stakeholders in iterative cycles of research, design, development, pilot-testing, evaluation and delivery to implement effective responses to complex phenomena. The geographical setting for this study was Sydney, NSW, Australia, and involved both youth and adult stakeholders from this region. The study spanned three phases between July 2018 and January 2021, and data collection included a range of workshops, a roundtable discussion and an online survey. RESULTS: The co-production process resulted in three key outputs: first, an engagement framework to guide youth participation in health research; second, a partnership model to sustain youth and adult stakeholder collaboration; third, the growth of the public involvement of young people with a range of projects and partners. CONCLUSIONS: This study investigated the process of co-producing knowledge with young people in an adolescent health community of practice. A reflexive process supported youth and adult stakeholders to collaboratively investigate, design and pilot-test approaches that embed young people's engagement in adolescent health research. Shared values and iterative methods for co-production can assist in advancing mutual learning, commitment and trust in specific adolescent health research contexts. PUBLIC CONTRIBUTION: Young people guiding and informing an adolescent health research community of practice were involved in this study, and one of the participants is a paper co-author.

The psychologic impact of loose anagen syndrome and short anagen syndrome.

Loose anagen syndrome (LAS) and short anagen syndrome (SAS) are congenital hair disorders presenting with reduced hair length with or without hair thinning. We conducted a non-validated online questionnaire of self-identified familial participants in a Facebook support group to assess psychologic symptoms, including anxiety, depression, low self-esteem, sadness, insecurity, worry, frustration, and body dysmorphia, in patients and their caregivers. Of 163 total respondents, negative psychologic symptoms were reported in 44.2% (38/89) of LAS patients, 48.3% (43/89) of LAS caregivers, 56.8% (42/74) of SAS patients, and 47.2% (35/74) of SAS caregivers. Our data indicate that both LAS and SAS have strong psychologic, emotional, and social impacts on affected children and their caregivers.

Assessment of readability and content of patient-initiated google search results for epidermolysis bullosa.

Epidermolysis bullosa describes a group of conditions commonly characterized by fragile skin and blistering of the mucosal membranes. Due to the complex and rare nature of the disease, we sought to evaluate the quality and readability of epidermolysis bullosa information available online. Analysis of the top 50 search results on Google demonstrated that information by non-dermatologists was of a lower reading level and more accessible when compared to information by dermatologists, even though dermatologist written information was more likely to be useful and medically comprehensive. There is an increasing need for dermatologists to provide useful and medically comprehensive EB information that is accessible to patients and patient families.

Huntingtin Haplotypes Provide Prioritized Target Panels for Allele-specific Silencing in Huntington Disease Patients of European Ancestry.

Huntington disease (HD) is a dominant neurodegenerative disorder caused by a CAG repeat expansion in the Huntingtin gene (HTT). Heterozygous polymorphisms in cis with the mutation allow for allele-specific suppression of the pathogenic HTT transcript as a therapeutic strategy. To prioritize target selection, precise heterozygosity estimates are needed across diverse HD patient populations. Here we present the first comprehensive investigation of all common target alleles across the HTT gene, using 738 reference haplotypes from the 1000 Genomes Project and 2364 haplotypes from HD patients and relatives in Canada, Sweden, France, and Italy. The most common HD haplotypes (A1, A2, and A3a) define mutually exclusive sets of polymorphisms for allele-specific therapy in the greatest number of patients. Across all four populations, a maximum of 80% are treatable using these three target haplotypes. We identify a novel deletion found exclusively on the A1 haplotype, enabling potent and selective silencing of mutant HTT in approximately 40% of the patients. Antisense oligonucleotides complementary to the deletion reduce mutant A1 HTT mRNA by 78% in patient cells while sparing wild-type HTT expression. By suppressing specific haplotypes on which expanded CAG occurs, we demonstrate a rational approach to the development of allele-specific therapy for a monogenic disorder.

Eyebrow and Eyelash Alopecia: A Clinical Review.

Madarosis is characterized by either complete or partial loss of eyebrow or eyelash hair. Etiologies for madarosis are varied, and accurate diagnosis is the first step in clinical management. Many studies have described findings related to specific causes of madarosis, but few have summarized the collective literature. The purpose of this review is to provide an updated overview on the symptomatology, diagnosis, trichoscopy findings, and treatment of eyebrow and eyelash alopecia.

Utility of Teledermatology in the Diagnosis of Loose Anagen Syndrome.

Introduction: Teledermatology has been shown to improve efficiency and reduce barriers to care for patients. However, teledermatology is limited by the inability to perform diagnostic tests. With proper planning, teletrichoscopy can be utilized with teledermatology to evaluate patients with hair loss. Case Presentation: Diagnosis of this patient was made using images taken during the televisit, including scalp images taken by the patient using a handheld microscope and images of the hair roots taken by her referring doctor. Conclusion: Hair tests that can be conducted during teledermatology visits include a self-performed pull test, measurement of the thickness of the ponytail, measurement of the distance from the hairline to the glabella, and evaluation of the shedding scale. These tests, in addition to mobile applications for imaging or low-cost handheld microscopes, can be utilized to virtually evaluate patients with hair loss.

Alopecia in patients with COVID-19: A systematic review and meta-analysis.

BACKGROUND: COVID-19 is associated with androgenetic alopecia (AGA), telogen effluvium (TE), and alopecia areata (AA). No studies have analyzed the aggregate data to date. OBJECTIVE: We conducted a systematic review to characterize the types, incidence, timing, and clinical outcomes of COVID-19-associated alopecia. METHODS: We searched PubMed/MEDLINE, Scopus, and Embase for articles published between November 2019 and August 2021 using the key words "alopecia" or "hair" and COVID-19-related search terms, identifying 41 original articles describing patients with alopecia and COVID-19. RESULTS: The current review included 1826 patients with alopecia and COVID-19 (mean age, 54.5 years; 54.3% male). The most common types of alopecia identified were AGA (30.7%, 86.4% male), TE (19.8%, 19.3% male), and AA (7.8%, 40.0% male). AGA preceded COVID-19 symptoms. TE was usually newly triggered by COVID-19 (93.6%). AA usually occurred in patients with preexisting disease (95.1%). LIMITATIONS: Definitions of COVID-19 onset varied. Studies differed in methodology and were susceptible to reporting and sampling bias. Studies with large sample sizes may exert a disproportionate influence on data. CONCLUSION: AGA may be a risk factor for severe COVID-19, whereas TE presents as a sequela of COVID-19. AA generally occurs as a relapse in patients with preexisting alopecia.

Scalp Micropigmentation: A Clinicopathologic Correlation.

Introduction: Scalp micropigmentation is a method of concealing alopecia by depositing permanent pigment in a tattoo-like manner. Pigment is deposited between hair follicles in a stippling pattern that resembles closely cut hair. Case Presentation: On trichoscopy, characteristic findings of scalp micropigmentation include homogenous, grey to black circular dots that are evenly spaced and appear larger than adjacent hair follicles. Findings were correlated with histopathology. Conclusion: Trichoscopy is a useful tool to visualize scalp micropigmentation in place of invasive procedures.

Visualizing the mode of action and supramolecular assembly of teixobactin analogues in Bacillus subtilis.

Teixobactin has been the source of intensive study and interest as a promising antibiotic, because of its excellent activity against drug-resistant Gram-positive pathogens and its novel but not yet fully understood mechanism of action that precludes drug resistance. Recent studies have demonstrated that the mode of action of teixobactin is more complicated than initially thought, with supramolecular assembly of the antibiotic appearing to play a critical role in the binding process. Further studies of the interactions of teixobactin with bacteria and its molecular targets offer the promise of providing deeper insights into its novel mechanism of action and guiding the design of additional drug candidates and analogues. The current study reports the preparation and study of teixobactin analogues bearing a variety of fluorophores. Structured illumination microscopy of the fluorescent teixobactin analogues with B. subtilis enables super-resolution visualization of the interaction of teixobactin with bacterial cell walls and permits the observation of aggregated clusters of the antibiotic on the bacteria. Förster resonance energy transfer (FRET) microscopy further elucidates the supramolecular assembly by showing that fluorescent teixobactin molecules co-localize within a few nanometers on B. subtilis. Fluorescence microscopy over time with a fluorescent teixobactin analogue and propidium iodide in B. subtilis reveals a correlation between cell death and binding of the antibiotic to cellular targets, followed by lysis of cells. Collectively, these studies provide new insights into the binding of teixobactin to Gram-positive bacteria, its supramolecular mechanism of action, and the lysis of bacteria that follows.

Tracking DO2 with Compensatory Reserve During Whole Blood Resuscitation in Baboons.

Hemorrhagic shock can be mitigated by timely and accurate resuscitation designed to restore adequate delivery of oxygen (DO2) by increasing cardiac output (CO). However, standard care of using systolic blood pressure (SBP) as a guide for resuscitation may be ineffective and can potentially be associated with increased morbidity. We have developed a novel vital sign called the compensatory reserve measurement (CRM) generated from analysis of arterial pulse waveform feature changes that has been validated in experimental and clinical models of hemorrhage. We tested the hypothesis that thresholds of DO2 could be accurately defined by CRM, a noninvasive clinical tool, while avoiding over-resuscitation during whole blood resuscitation following a 25% hemorrhage in nonhuman primates. To accomplish this, adult male baboons (n = 12) were exposed to a progressive controlled hemorrhage while sedated that resulted in an average (±â€ŠSEM) maximal reduction of 508 ±â€Š18 mL of their estimated circulating blood volume of 2,130 ±â€Š60 mL based on body weight. CRM increased from 6 ±â€Š0.01% at the end of hemorrhage to 70 ±â€Š0.02% at the end of resuscitation. By linear regression, CRM values of 6% (end of hemorrhage), 30%, 60%, and 70% (end of resuscitation) corresponded to calculated DO2 values of 5.9 ±â€Š0.34, 7.5 ±â€Š0.87, 9.3 ±â€Š0.76, and 11.6 ±â€Š1.3 mL O2·kg·min during resuscitation. As such, return of CRM to ∼65% during resuscitation required only ∼400 mL to restore SBP to 128 ±â€Š6 mmHg, whereas total blood volume replacement resulted in over-resuscitation as indicated by a SBP of 140 ±â€Š7 mmHg compared with an average baseline value of 125 ±â€Š5 mmHg. Consistent with our hypothesis, thresholds of calculated DO2 were associated with specific CRM values. A target resuscitation CRM value of ∼65% minimized the requirement for whole blood while avoiding over-resuscitation. Furthermore, 0% CRM provided a noninvasive metric for determining critical DO2 at approximately 5.3 mL O2·kg·min.

A Fluorescent Teixobactin Analogue.

This report describes the first synthesis and application of a fluorescent teixobactin analogue that exhibits antibiotic activity and binds to the cell walls of Gram-positive bacteria. The teixobactin analogue, Lys(Rhod)9,Arg10-teixobactin, has a fluorescent tag at position 9 and an arginine in place of the natural allo-enduracididine residue at position 10. The fluorescent teixobactin analogue retains partial antibiotic activity, with minimum inhibitory concentrations of 4-8 µg/mL across a panel of Gram-positive bacteria, as compared to 1-4 µg/mL for the unlabeled Arg10-teixobactin analogue. Lys(Rhod)9,Arg10-teixobactin is prepared by a regioselective labeling strategy that labels Lys9 with an amine-reactive rhodamine fluorophore during solid-phase peptide synthesis, with the resulting conjugate tolerating subsequent solid-phase peptide synthesis reactions. Treatment of Gram-positive bacteria with Lys(Rhod)9,Arg10-teixobactin results in septal and lateral staining, which is consistent with an antibiotic targeting cell wall precursors. Concurrent treatment of Lys(Rhod)9,Arg10-teixobactin and BODIPY FL vancomycin results in septal colocalization, providing further evidence that Lys(Rhod)9,Arg10-teixobactin binds to cell wall precursors. Controls with either Gram-negative bacteria, or an inactive fluorescent homologue with Gram-positive bacteria, showed little or no staining in fluorescence micrographic studies. Lys(Rhod)9,Arg10-teixobactin can thus serve as a functional probe to study Gram-positive bacteria and their interactions with teixobactin.

DAPK1 Promotes Extrasynaptic GluN2B Phosphorylation and Striatal Spine Instability in the YAC128 Mouse Model of Huntington Disease.

Huntington disease (HD) is a devastating neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. Disrupted cortico-striatal transmission is an early event that contributes to neuronal spine and synapse dysfunction primarily in striatal medium spiny neurons, the most vulnerable cell type in the disease, but also in neurons of other brain regions including the cortex. Although striatal and cortical neurons eventually degenerate, these synaptic and circuit changes may underlie some of the earliest motor, cognitive, and psychiatric symptoms. Moreover, synaptic dysfunction and spine loss are hypothesized to be therapeutically reversible before neuronal death occurs, and restoration of normal synaptic function may delay neurodegeneration. One of the earliest synaptic alterations to occur in HD mouse models is enhanced striatal extrasynaptic NMDA receptor expression and activity. This activity is mediated primarily through GluN2B subunit-containing receptors and is associated with increased activation of cell death pathways, inhibition of survival signaling, and greater susceptibility to excitotoxicity. Death-associated protein kinase 1 (DAPK1) is a pro-apoptotic kinase highly expressed in neurons during development. In the adult brain, DAPK1 becomes re-activated and recruited to extrasynaptic NMDAR complexes during neuronal death, where it phosphorylates GluN2B at S1303, amplifying toxic receptor function. Approaches to reduce DAPK1 activity have demonstrated benefit in animal models of stroke, Alzheimer's disease, Parkinson's disease, and chronic stress, indicating that DAPK1 may be a novel target for neuroprotection. Here, we demonstrate that dysregulation of DAPK1 occurs early in the YAC128 HD mouse model, and contributes to elevated extrasynaptic GluN2B S1303 phosphorylation. Inhibition of DAPK1 normalizes extrasynaptic GluN2B phosphorylation and surface expression, and completely prevents YAC128 striatal spine loss in cortico-striatal co-culture, thus validating DAPK1 as a potential target for synaptic protection in HD and warranting further development of DAPK1-targeted therapies for neurodegeneration.