Meshed dermal regeneration template for traumatic periocular tissue loss in the young population.

The IntegraⓇ Dermal Regeneration Template (DRT) is a bioengineered dermal substitute that is becoming increasingly popular in the field of reconstruction. Its unique properties allow for immediate wound closure while providing a scaffold for tissue regeneration. Currently, it is commonly used to treat burns, ulcers, and complex wounds. In the setting of traumatic periocular tissue loss, only two prior reports have been published on its use for primary reconstruction. We present our institution's experience with a series of four young patients who received primary reconstruction with IntegraⓇ DRT as a full-thickness skin substitute for their large traumatic periorbital skin defects.

Apremilast and narrowband ultraviolet B combination therapy suppresses Th17 axis and promotes melanogenesis in vitiligo skin: a randomized, split-body, pilot study in skin types IV-VI.

Improved repigmentation of generalized vitiligo in skin types IV-VI has been reported in clinical response to combined therapy with apremilast and narrowband (NB)-UVB; however, tissue responses to combined therapy versus NB-UVB monotherapy have not been elucidated. We compared the change from baseline in cellular and molecular markers in vitiligo skin after combined therapy versus NB-UVB monotherapy. We assessed lesional and nonlesional skin samples from enrolled subjects and evaluated for immune infiltrates, inflammatory, and melanogenesis-related markers which were compared across different treatment groups. Combined therapy resulted in significant reduction of CD8+T cells and CD11c+ dendritic cells, downregulation of PDE4B and Th17-related markers, and upregulation of melanogenesis markers. This study was limited to small sample size, skin types IV-VI, and high dropout rate. Our molecular findings support the clinical analysis that apremilast may potentiate NB-UVB in repigmentation of generalized vitiligo in skin types IV-VI.

Diversity and distribution of the tick-borne relapsing fever spirochete Borrelia turicatae.

Borrelia turicatae is a causative agent of tick-borne relapsing fever (TBRF) in the subtropics and tropics of the United States and Latin America. Historically, B. turicatae was thought to be maintained in enzootic cycles in rural areas. However, there is growing evidence that suggests the pathogen has established endemic foci in densely populated regions of Texas. With the growth of homelessness in the state and human activity in city parks, it was important to implement field collection efforts to identify areas where B. turicatae and its vector circulate. Between 2017 and 2020 we collected Ornithodoros turicata ticks in suburban and urban areas including public and private parks and recreational spaces. Ticks were fed on naïve mice and spirochetes were isolated from the blood. Multilocus sequence typing (MLST) was performed on eight newly obtained isolates and included previously reported sequences. The four chromosomal loci targeted for MLST were 16S ribosomal RNA (rrs), flagellin B (flaB), DNA gyrase B (gyrB), and the intergenic spacer (IGS). Given the complexity of Borrelia genomes, plasmid diversity was also evaluated. These studies indicate that the IGS locus segregates B. turicatae into four genomic types and plasmid diversity is extensive between isolates. Furthermore, B. turicatae and its vector have established endemic foci in parks and recreational areas in densely populated settings of Texas.

Five-year changes in ovarian function restoration in premenopausal patients with breast cancer taking tamoxifen after chemotherapy: An ASTRRA study report.

BACKGROUND: Adding ovarian function suppression (OFS) after chemotherapy improves survival in young women with moderate- and high-risk breast cancer. Assessment of ovarian function restoration after chemotherapy becomes critical for subsequent endocrine treatment and addressing fertility issues. PATIENTS AND METHODS: In the adding OFS after chemotherapy trial, patients who resumed ovarian function up to 2 years after chemotherapy were randomised to receive either 5 years of tamoxifen or adding 2 years of OFS with tamoxifen. Ovarian function was evaluated from enrolment to randomisation, and patients who did not randomise because of amenorrhoea for 2 years received tamoxifen and were followed up for 5 years. Prospectively collected consecutive hormone levels (proportion of patients with premenopausal follicle-stimulating hormone [FSH] levels <30 mIU/mL and oestradiol [E2] levels ≥40 pg/mL) and history of menstruation were available for 1067 patients with breast cancer. RESULTS: Over 5 years of tamoxifen treatment, 69% of patients resumed menstruation and 98% and 74% of patients satisfied predefined ovarian function restoration as per serum FSH and E2 levels, respectively. Menstruation was restored in 91% of patients younger than 35 years at baseline, but in only 33% of 45-year-old patients over 5 years. Among these patients, 41% experienced menstruation restoration within 2 years after chemotherapy and 28% slowly restored menstruation after 2-5 years. Younger age (<35 years) at baseline, anthracycline without taxanes and ≤90 days of chemotherapy were predictors of menstruation restoration. CONCLUSIONS: During 5 years of tamoxifen treatment after chemotherapy, two-thirds of the patients experienced menstruation restoration, especially patients younger than 35 years. Young age, Adriamycin without taxanes and short duration of chemotherapy appeared to have a positive effect on ovarian reserves in the long term. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00912548.

Identification of Host Bloodmeal Source in Ornithodoros turicata Dugès (Ixodida: Argasidae) Using DNA-Based and Stable Isotope-Based Techniques.

The ecology and host feeding patterns of many soft ticks (Ixodida: Argasidae) remain poorly understood. To address soft tick-host feeding associations, we fed Ornithodoros turicata Dugès on multiple host species and evaluated quantitative PCR (qPCR) and stable isotope analyses to identify the vertebrate species used for the bloodmeal. The results showed that a qPCR with host-specific probes for the cytochrome b gene successfully identified bloodmeals from chicken (Gallus gallus L.), goat (Capra aegagrus hircus L), and swine (Sus scrofa domesticus) beyond 330 days post-feeding and through multiple molting. Also, qPCR-based bloodmeal analyses could detect multiple host species within individual ticks that fed upon more than one species. The stable isotope bloodmeal analyses were based on variation in the natural abundance of carbon (13C/12C) and nitrogen (15N/14N) isotopes in ticks fed on different hosts. When compared to reference isotope signatures, this method discerned unique δ13C and δ15N signatures in the ticks fed on each host taxa yet could not discern multiple host species from O. turicata that fed on more than one host species. Given the significance of soft tick-borne zoonoses and animal diseases, elucidating host feeding patterns from field-collected ticks using these methods may provide insight for an ecological basis to disease management.

Humoral immune response of pigs, Sus scrofa domesticus, upon repeated exposure to blood-feeding by Ornithodoros turicata Duges (Ixodida: Argasidae).

BACKGROUND: Ornithodoros turicata is an important vector of both human and veterinary pathogens. One primary concern is the global spread of African swine fever virus and the risk of its re-emergence in the Americas through potential transmission by O. turicata to domestic pigs and feral swine. Moreover, in Texas, African warthogs were introduced into the state for hunting purposes and evidence exists that they are reproducing and have spread to three counties in the state. Consequently, it is imperative to develop strategies to evaluate exposure of feral pigs and African warthogs to O. turicata. RESULTS: We report the development of an animal model to evaluate serological responses of pigs to O. turicata salivary proteins after three exposures to tick feeding. Serological responses were assessed for ~ 120 days by enzyme-linked immunosorbent assay and immunoblotting using salivary gland extracts from O. turicata. CONCLUSIONS: Our findings indicate that domestic pigs seroconverted to O. turicata salivary antigens that is foundational toward the development of a diagnostic assay to improve soft tick surveillance efforts.

Crisaborole 2% ointment for the treatment of intertriginous, anogenital, and facial psoriasis: A double-blind, randomized, vehicle-controlled trial.

BACKGROUND: Psoriasis of the intertriginous, anogenital, and facial regions remains a therapeutic challenge, with current algorithms lacking a topical agent that exhibits both high efficacy and minimal side effects. OBJECTIVE: To assess the safety and efficacy of crisaborole 2% ointment-a nonsteroidal phosphodiesterase 4 inhibitor-in the treatment of intertriginous, anogenital, and facial psoriasis. METHODS: A double-blind, randomized, vehicle-controlled trial was conducted in 21 participants. Participants were randomized 2:1 to receive 4 weeks of twice-daily treatment with either crisaborole 2% ointment (n = 14) or vehicle ointment (n = 7), followed by 4 weeks of open-label treatment with crisaborole 2% ointment. Disease severity was measured by using the Target Lesion Severity Scale (TLSS). RESULTS: After 4 weeks, participants in the crisaborole group demonstrated 66% improvement compared with 9% in the vehicle group (P = .0011). Participants in the crisaborole group continued to experience improvement through the open-label phase, demonstrating 81% lesional improvement by week 8, with 71% of these participants achieving clinical clearance. There were no adverse events. LIMITATIONS: The study was limited to a single tertiary care center and small sample size. CONCLUSION: Treatment with crisaborole 2% ointment was well-tolerated and led to clinical improvement in participants with intertriginous, anogenital, or facial psoriasis.

Blood endotyping distinguishes the profile of vitiligo from that of other inflammatory and autoimmune skin diseases.

BACKGROUND: Peripheral blood skin-homing/cutaneous lymphocyte antigen (CLA)+ T cells emerge as biomarkers of cutaneous immune activation in patients with inflammatory skin diseases (atopic dermatitis [AD] and alopecia areata [AA]). However, blood phenotyping across these subsets is not yet available in patients with vitiligo. OBJECTIVE: We sought to measure cytokine production by circulating skin-homing (CLA+) versus systemic (CLA-) "polar" CD4+/CD8+ ratio and activated T-cell subsets in patients with vitiligo compared with patients with AA, AD, or psoriasis and control subjects. METHODS: Flow cytometry was used to measure levels of the cytokines IFN-γ, IL-13, IL-9, IL-17, and IL-22 in CD4+/CD8+ T cells in the blood of 19 patients with moderate-to-severe nonsegmental/generalized vitiligo, moderate-to-severe AA (n = 32), psoriasis (n = 24), or AD (n = 43) and control subjects (n = 30). Unsupervised clustering differentiated subjects into groups based on cellular frequencies. RESULTS: Patients with Vitiligo showed the highest CLA+/CLA- TH1/type 1 cytotoxic T-cell polarization, with parallel TH2/TH9/TH17/TH22 level increases to levels often greater than those seen in patients with AA, AD, or psoriasis (P < .05). Total regulatory T-cell counts were lower in patients with vitiligo than in control subjects and patients with AD or psoriasis (P < .001). Vitiligo severity correlated with levels of multiple cytokines (P < .1), whereas duration was linked with IFN-γ and IL-17 levels (P < .04). Patients and control subjects grouped into separate clusters based on blood biomarkers. CONCLUSIONS: Vitiligo is characterized by a multicytokine polarization among circulating skin-homing and systemic subsets, which differentiates it from other inflammatory/autoimmune skin diseases. Future targeted therapies should delineate the relative contribution of each cytokine axis to disease perpetuation.

Biologics and Psoriasis: The Beat Goes On.

Psoriasis is a chronic, immune-mediated, inflammatory skin disease that requires long-term therapy for disease control. This article reviews data presented in clinical trials to evaluate and compare various characteristics of biologics that are currently approved for the treatment of psoriasis. Attributes of biological agents that are examined in this article include efficacy, long-term maintenance, overall safety, median time to onset of efficacy, adjustment for body weight, frequency of injections, indication for psoriatic arthritis, and safety in pregnancy. Here, we evaluate what the ideal choice of biological therapy may be for psoriasis patients with specific needs.

Long-Term Isolation Elicits Depression and Anxiety-Related Behaviors by Reducing Oxytocin-Induced GABAergic Transmission in Central Amygdala.

Isolation stress is a major risk factor for neuropsychiatric disorders such as depressive and anxiety disorders. However, the molecular mechanisms underlying isolation-induced neuropsychiatric disorders remain elusive. In the present study, we investigated the subcellular mechanisms by which long-term isolation elicits depression and anxiety-related behaviors in mice. First, we found that long-term isolation induced depression-related behaviors in the forced swimming test (FST) and the sucrose preference test, as well as anxiety-related behaviors in the elevated zero maze test (EZMT) and the open field test. Next, we showed that intracentral amygdala (CeA) injection of oxytocin (OXT), but not intracerebroventricular injection, attenuated isolation-induced depression and anxiety-related behaviors via oxytocin receptor (OXTR), not vasopressin-1a receptor (V1aR), in the FST and EZMT, respectively. Quantitative real-time polymerase chain reaction analysis revealed that after 5 weeks of isolation, mRNA transcription of OXTR in the CeA, but not that of V1aR, significantly decreased, whereas OXT and vasopressin mRNA transcription in the paraventricular nucleus of hypothalamus did not change significantly. Whole-cell patch clamping of acute brain slices demonstrated that the frequency of miniature inhibitory postsynaptic currents (mIPSCs) in CeA neurons, but not their amplitude, was lower in isolated mice than in group-housed mice. Notably, OXT treatment increased the mIPSC frequency in the CeA neurons, but to a lesser extent in the case of isolated mice than in that of group-housed mice via OXTR. Taken together, our findings suggest that long-term isolation down-regulates OXTR mRNA transcription and diminishes OXT-induced inhibitory synaptic transmission in the CeA and may contribute to the development of depression and anxiety-related behaviors in isolated mice through the enhancement of CeA activity.

An unexplained three-dimensional percept emerging from a bundle of lines.

Perceptual grouping has been extensively studied, but some areas are still unexplored-in particular, the figural organizations that emerge when bundles of intersecting lines are drawn. Here, we will describe some figural organizations that emerge after the superimposition of bundles of lines forming the profile of regular triangular waves. By manipulating the lines' jaggedness and junction geometry (regular or irregular X junction) we could generate the following organizations: (a) a grid, or a figural configuration in which both the lines and closed contours are perceived, (b) a figure-ground organization composed of figures separated by portions of the background, and (c) a corrugated surface appearing as a multifaceted polyhedral shell crossed by ridges and valleys. An experiment was conducted with the aim at testing the role of the good-continuation and closure Gestalt factors. Good continuation prevails when the lines are straight or close to straightness, but its role is questionable in the appearance of a corrugated surface. This perceptual organization occurs despite the violation of the good-continuation rule and consists of a structure of such complexity so as to challenge algorithms of computer vision and stimulate a deeper understanding of the perceptual interpretation of groups of lines.

Hallmarks of Treatment Aspects: Parkinson's Disease Throughout Centuries Including l-Dopa.

Deficit of striatal dopamine was first discovered in postmortem brain of patients with Parkinson's disease in 1960. This observation was the starting point for dopamine replacement therapy, and successful introduction of high dose l-dopa therapy in the 1969 revolutionized the treatment of Parkinson's disease. Since then, constant attempts have been made to enhance the efficacy of l-dopa and reduce motor complications by providing more continuous dopamine stimulation. This chapter traces the hallmarks of medical treatments for Parkinson's disease throughout centuries including the first description of antiparkinsonian effects of anticholinergics, the birth of apomorphine in the 1900s, then discovery of l-dopa in the 1960s, and development of dopamine agonists since the 1970s.

Assessment of the Geographic Distribution of Ornithodoros turicata (Argasidae): Climate Variation and Host Diversity.

BACKGROUND: Ornithodoros turicata is a veterinary and medically important argasid tick that is recognized as a vector of the relapsing fever spirochete Borrelia turicatae and African swine fever virus. Historic collections of O. turicata have been recorded from Latin America to the southern United States. However, the geographic distribution of this vector is poorly understood in relation to environmental variables, their hosts, and consequently the pathogens they transmit. METHODOLOGY: Localities of O. turicata were generated by performing literature searches, evaluating records from the United States National Tick Collection and the Symbiota Collections of Arthropods Network, and by conducting field studies. Maximum entropy species distribution modeling (Maxent) was used to predict the current distribution of O. turicata. Vertebrate host diversity and GIS analyses of their distributions were used to ascertain the area of shared occupancy of both the hosts and vector. CONCLUSIONS AND SIGNIFICANCE: Our results predicted previously unrecognized regions of the United States with habitat that may maintain O. turicata and could guide future surveillance efforts for a tick capable of transmitting high-consequence pathogens to human and animal populations.

Blood viscosity in subcortical vascular mild cognitive impairment with versus without cerebral amyloid burden.

BACKGROUND: Subcortical vascular dementia (SVaD) is a common form of dementia, attributed to ischemic small-vessel disease. Blood viscosity (BV) may contribute to the pathophysiology of SVaD. However, SVaD patients with coexisting amyloid deposition may not show differences in BV because their small-vessel disease may result from amyloid angiopathy independently of BV. We, therefore, hypothesized that BV might show different changes compared with control subjects in subcortical vascular mild cognitive impairment (svMCI) that refers to the prodromal stage of SVaD according to cerebral amyloid burden detected by the [(11)C] Pittsburgh compound B (PiB) PET (positron emission tomography), and apolipoprotein 4 (ApoE4) genotype (a known risk factor for vascular and parenchymal amyloid). METHODS: Our subjects consisted of 33 healthy normal controls (NC), 28 patients with PiB(-) svMCI, and 12 with PiB(+) svMCI. They underwent scanning capillary tube viscometer measuring BV during systolic and diastolic phases. RESULTS: Compared with the NC group, the PiB(-) svMCI group showed increased diastolic blood viscosity (DBV) but no difference in systolic blood viscosity (SBV). By contrast, there was no significant difference in SBV and DBV between the NC and PiB(+) svMCI groups. Within the PiB(+) svMCI group, ApoE4(-) subgroup showed increased DBV compared with the ApoE4(+) subgroup. CONCLUSIONS: Increased DBV is an important contributor to the development of "pure" svMCI (ie, without cerebral amyloid deposition). The relationship between BV and PiB(+) svMCI differed according to ApoE genotype, suggesting that the pathogenesis of PiB(+) svMCI might also be heterogeneous.

Alveolar soft-part sarcoma of the orbit: report of 2 cases with review of the literature.

Alveolar soft-part sarcoma (ASPS) is a translocation-associated sarcoma that occurs most commonly in the lower extremities and rarely in orbit. Only 34 orbital cases have been reported in the literature, and it is often misdiagnosed due to its rare occurrence and nonspecific clinical findings. The optimal treatment remains controversial, although in general, aggressive surgical resection is advocated. Here, the authors present 2 cases of orbital ASPS and a review of the literature.

Not physically present contours can yield illusory motion.

We demonstrate a perceptual effect whereby contours not physically present in a visual scene can yield striking illusory motion. The not physically present contours are paths of invariant contrast polarity (CP). For example, when a square checkerboard composed of dark and light square checks with small black and white discs covering the vertices is put in lateral motion, there is the striking perception of vertical expansion/contraction. Such a checkerboard has (not physically present) diagonal paths of CP presentation with vertical components. However, when a square checkerboard made up of square black and very light checks with gray discs of luminance intermediate to the checks is put in lateral motion, no expansion/contraction is seen. For this checkerboard the vertical components of paths of CP preservation cancel each other out, predicting the lack of perception of vertical expansion/contraction. We also discuss how not physically present contours can explain previously described effects and suggest new effects to be explored.