TYK2 inhibition with deucravacitinib ameliorates erosive oral lichen planus.

Erosive oral lichen planus (OLP) is a challenging disease. This T cell driven disorder frequently shows a treatment unresponsive course and strongly limits patients' quality of life. The disease lacks FDA or EMA approved drugs for its treatment and the efficacy of the commonly administered treatments (i.e. topical and systemic steroids, steroid sparing agents) is often only partial. Although the etiopathogenesis of the disease still needs to be fully elucidated, recent advances helped to identify interferon-É£ (IFN-É£) as a pivotal cytokine in OLP pathogenesis, thus making the interference with its signalling a therapeutic target. Janus kinase (JAK) inhibitors therefore gained relevance for their inhibitory effect on IFN-É£ signalling. While some drugs such as abrocitinib, upadacitinib, tofacitinib directly interfere with IFN-É£ signalling through blockade of JAK1 and/or JAK2, deucravacitinib, a selective TYK-2 inhibitor indirectly interferes on IFN-É£ activation through interference with interleukin (IL)-12, a potent promotor for Th1/IFN-É£ responses. This mechanism of action makes deucravacitinib a candidate drug for the treatment of OLP. Here we provide initial evidence that deucravacitinib 6 mg daily has a beneficial effect in three patients with oral OLP.

Upregulation of psoriasin/S100A7 correlates with clinical severity in patients with oral lichen planus.

OBJECTIVES: The aim of this study was to: (1) investigate the expression patterns of antimicrobial peptides (AMPs), specifically psoriasin (S100A7) and calgranulin A and B (S100A8/A9), in patients with oral lichen planus (OLP) compared to healthy individuals; (2) evaluate the oral health-related quality of life (OHrQoL) in OLP patients versus healthy controls; (3) investigate the impact of clinical severity of OLP on OHrQoL; and (4) assess the influence of AMP expression on clinical severity and OHrQoL in OLP patients. MATERIALS AND METHODS: Oral mucosal biopsies (n = 38) were collected from healthy individuals (n = 17) and patients with OLP (n = 21). Levels of AMPs (S100A7, S100A8, S100A9) and pro-inflammatory cytokines interleukin-8 (IL-8) and tumor necrosis factor alpha (TNFα) were assessed by RT-qPCR. AMP protein localization was identified by indirect immunofluorescence analysis. OHrQoL was assessed using the OHIP-G14 questionnaire, and clinical severity was evaluated with the Oral Disease Severity Score (ODSS). Correlations between OLP manifestation, OHrQoL, and AMP expression were evaluated. RESULTS: (1) S100A7 (p < 0.001), IL-8 (p < 0.001), and TNFα (p < 0.001) mRNA levels were significantly upregulated in OLP tissue compared to healthy tissue, while S100A8 (p < 0.001) and S100A9 (p < 0.001) mRNA levels were downregulated. Immunofluorescence staining revealed an enhanced expression of S100A7 and decreased protein expression of S100A9 in OLP tissue. (2) OLP patients (9.58 ± 8.32) reported significantly higher OHIP-G14 scores compared to healthy individuals (0.67 ± 0.87; p < 0.001), particularly in the categories "physical pain" (p < 0.001) and "psychological discomfort" (p = 0.025). (3,4) Clinical severity (25.21 ± 9.77) of OLP correlated positively with OHrQoL (ρ = 0.497) and psoriasin expression (ρ = 0.402). CONCLUSIONS: This study demonstrated differential expression patterns of AMPs in OLP and highlighted the correlation between the clinical manifestation of OLP and OHrQoL. Further research approaches should address the role of psoriasin in the risk of malignant transformation of OLP. CLINICAL RELEVANCE: Psoriasin is a putative biomarker to monitor disease severity including malignant transformation of OLP lesions. OHIP-G14 scores can be useful to monitor OHrQoL in OLP patients.

Diverging roles for Lrp4 and Wnt signaling in neuromuscular synapse development during evolution.

Motor axons approach muscles that are prepatterned in the prospective synaptic region. In mice, prepatterning of acetylcholine receptors requires Lrp4, a LDLR family member, and MuSK, a receptor tyrosine kinase. Lrp4 can bind and stimulate MuSK, strongly suggesting that association between Lrp4 and MuSK, independent of additional ligands, initiates prepatterning in mice. In zebrafish, Wnts, which bind the Frizzled (Fz)-like domain in MuSK, are required for prepatterning, suggesting that Wnts may contribute to prepatterning and neuromuscular development in mammals. We show that prepatterning in mice requires Lrp4 but not the MuSK Fz-like domain. In contrast, prepatterning in zebrafish requires the MuSK Fz-like domain but not Lrp4. Despite these differences, neuromuscular synapse formation in zebrafish and mice share similar mechanisms, requiring Lrp4, MuSK, and neuronal Agrin but not the MuSK Fz-like domain or Wnt production from muscle. Our findings demonstrate that evolutionary divergent mechanisms establish muscle prepatterning in zebrafish and mice.

Lrp4 is a receptor for Agrin and forms a complex with MuSK.

Neuromuscular synapse formation requires a complex exchange of signals between motor neurons and skeletal muscle fibers, leading to the accumulation of postsynaptic proteins, including acetylcholine receptors in the muscle membrane and specialized release sites, or active zones in the presynaptic nerve terminal. MuSK, a receptor tyrosine kinase that is expressed in skeletal muscle, and Agrin, a motor neuron-derived ligand that stimulates MuSK phosphorylation, play critical roles in synaptic differentiation, as synapses do not form in their absence, and mutations in MuSK or downstream effectors are a major cause of a group of neuromuscular disorders, termed congenital myasthenic syndromes (CMS). How Agrin activates MuSK and stimulates synaptic differentiation is not known and remains a fundamental gap in our understanding of signaling at neuromuscular synapses. Here, we report that Lrp4, a member of the LDLR family, is a receptor for Agrin, forms a complex with MuSK, and mediates MuSK activation by Agrin.

Understanding the "Sometimes Masker": Political Orientation and Trust in the Media During the COVID-19 Pandemic.

OBJECTIVES: The COVID-19 pandemic in the United States has brought to light the problematic way partisan politics interferes with public health prevention and control measures. This study aims to investigate how Americans responded to the novel coronavirus with respect to their sociopolitical identity and masking habits. STUDY DESIGN: This mixed-methods study incorporated three ethnographic projects and surveys together, from two rural areas (in Iowa and California) and one suburban community in California. METHODS: We interviewed 156 Americans about how masking habits related to six themes: participants' perceived risk level, concern for themselves and others, support for President Trump, trust in scientific organizations, and confidence in major news outlets. We conducted content analysis of qualitative interviews and evaluated survey questions to understand how and why people masked or engaged in public health prevention practices. RESULTS: Greater perceived risk, concern for others, and trust in health and media institutions was correlated with increased masking, while support for Trump was predictive of anti-masking sentiments. Participants who diverged from these trends, specifically those who sometimes wore masks, but not always were called "sometimes maskers". These sometimes maskers often identified as politically moderate and were more likely to mask due to concern for a vulnerable person or group in their lives. CONCLUSIONS: Since one in three Americans are political moderates, understanding what promotes their adherence to public health guidelines is essential for policy makers interested in pandemic containment. Relatedly, the conservative tendency to distrust mainstream media is what separated those who reported sometimes masking from those who reported always masking.

The evaluation of Cannabidiol's effect on the immunotherapy of Burkitt lymphoma.

AIM: AF1q has a precise oncogenic function. The purpose of this study is to investigate whether CBD has an effect on the AF1q/ICAM-1 regulatory axis in Burkitt's lymphoma (BL), and thus has potential to enhance immunotherapy and reduce side effects. METHODS: We established BL cell lines with altered AF1q expression using lentivirus. After confirmation of gene expression by RT-PCR, cells were treated with CBD followed by co-culture of killing assay. RESULTS: AF1q increased oncogenic growth and colony formation, and induced resistance against cell-mediated cytotoxic chemotherapy through attenuation of ICAM-1 expression in BL. CBD was able to reverse the acquired resistance mediated by AF1q/ICAM-1 regulatory axis. CONCLUSION: CBD holds potential to enhance the efficacy of immunotherapy for BL with hyperactive AF1q/ICAM-1 regulatory axis, and warrants further study.

IL-1ß promotes transendothelial migration of PBMCs by upregulation of the FN/α5ß1 signalling pathway in immortalised human brain microvascular endothelial cells.

Neuroinflammation is often associated with pathological changes in the function of the blood-brain barrier (BBB) caused by disassembly of tight and adherens junctions that under physiological conditions are important for the maintenance of the BBB integrity. Consequently, in inflammation the BBB becomes dysfunctional, facilitating leukocyte traversal of the barrier and accumulation of immune cells within the brain. The extracellular matrix (ECM) also contributes to BBB integrity but the significance of the main ECM receptors, the ß1 integrins also expressed on endothelial cells, is less well understood. To evaluate whether ß1 integrin function is affected during inflammation and impacts barrier function, we used a transformed human brain microvascular endothelial cell (THBMEC)-based Interleukin 1ß (IL-1ß)-induced inflammatory in vitro BBB model. We demonstrate that IL-1ß increases cell-matrix adhesion and induces a redistribution of active ß1 integrins to the basal surface. In particular, binding of α5ß1 integrin to its ligand fibronectin is enhanced and α5ß1 integrin-dependent signalling is upregulated. Additionally, localisation of the tight junction protein claudin-5 is altered. Blockade of the α5ß1 integrin reduces the IL-1ß-induced transendothelial migration of peripheral blood mononuclear cells (PBMCs). These data imply that IL-1ß-induced inflammation not only destabilizes tight junctions but also increases α5ß1 integrin-dependent cell-matrix adhesion to fibronectin.

Quantitative evaluation of skin shrinkage associated with non-invasive skin tightening: a simple method for reproducible linear measurement using microtattoos.

Non-invasive skin-tightening devices can induce thermal denaturation and skin shrinkage via externally applied radiofrequency emissions or high-frequency ultrasound. Therefore, the purpose of this study is to develop and test a method for measurement of skin reduction associated with application of such energy devices. Twenty-five healthy participants with mild to moderate skin laxity of the arms were enrolled. Pinpoint microtattoos were placed at each of the treatment sites to delineate two 6 × 12 cm rectangles per subject. A non-stretchable filament, tape and marking pen apparatus was used to measure the size of each rectangle before treatment and at follow-up visit by two blinded investigators. After randomization, one side received a single pass with a radiofrequency device (6.78 MHz), while the contralateral side received multiple passes. Participants underwent two treatment sessions to each side 2 weeks apart, and returned for follow-up 4 weeks after the second treatment. Length and area measurement were analyzed to assess precision and accuracy of measurements and to compare efficacy of treatment between pre- and post-treatment. Concordance correlation coefficients (CCC) demonstrated substantial inter-investigator reliability and precision in length measurements (CCC, 0.94 to 0.98 in pre-treatment; 0.95 to 0.98 in post-treatment). Measurements at the 6-week post-treatment follow-up demonstrated a statistically significant skin reduction in all six of the measured parameters. A simple skin measurement method requiring minimal instrumentation can quantitatively evaluate skin shrinkage associated with non-invasive skin-tightening devices.

Lrp4 is a retrograde signal for presynaptic differentiation at neuromuscular synapses.

Motor axons receive retrograde signals from skeletal muscle that are essential for the differentiation and stabilization of motor nerve terminals. Identification of these retrograde signals has proved elusive, but their production by muscle depends on the receptor tyrosine kinase, MuSK (muscle, skeletal receptor tyrosine-protein kinase), and Lrp4 (low-density lipoprotein receptor (LDLR)-related protein 4), an LDLR family member that forms a complex with MuSK, binds neural agrin and stimulates MuSK kinase activity. Here we show that Lrp4 also functions as a direct muscle-derived retrograde signal for early steps in presynaptic differentiation. We demonstrate that Lrp4 is necessary, independent of MuSK activation, for presynaptic differentiation in vivo, and we show that Lrp4 binds to motor axons and induces clustering of synaptic-vesicle and active-zone proteins. Thus, Lrp4 acts bidirectionally and coordinates synapse formation by binding agrin, activating MuSK and stimulating postsynaptic differentiation, and functioning in turn as a muscle-derived retrograde signal that is necessary and sufficient for presynaptic differentiation.

Circulating Extracellular DNA: Cause or Consequence of Thrombosis?

Thrombosis leads to ischemic organ damage in cardiovascular and thromboembolic diseases. Neutrophils promote thrombosis in vitro and in vivo by releasing neutrophil extracellular traps (NETs). NETs are composed of DNA filaments coated with histones and neutrophil enzymes such as myeloperoxidase (MPO). Circulating extracellular DNA (ceDNA) is widely used as a surrogate marker to monitor NET formation in thrombosis. This narrative review summarizes the association of ceDNA with human thrombosis. Levels of ceDNA indicate the extent and outcome of several cardiovascular and thromboembolic diseases, including myocardial infarction, stroke, and venous thromboembolism. ceDNA correlates with markers of coagulation and platelet consumption, thus supporting the hypothesis that ceDNA may be a surrogate marker of thrombus formation. In addition, ceDNA levels correlate with markers of cell injury and size of ischemic lesions, suggesting that ceDNA does not derive from NETs but is probably released from damaged organs. Few studies identified NET-specific biomarkers such as DNA-MPO complexes in the blood of patients with thrombosis. In conclusion, it remains to be established whether ceDNA in patients derives from NETs and is a cause or consequence of thrombosis.

Utility of recorded guided imagery and relaxing music in reducing patient pain and anxiety, and surgeon anxiety, during cutaneous surgical procedures: A single-blinded randomized controlled trial.

BACKGROUND: Guided imagery and music can reportedly reduce pain and anxiety during surgery, but no comparative study has been performed for cutaneous surgery to our knowledge. OBJECTIVES: We sought to determine whether short-contact recorded guided imagery or relaxing music could reduce patient pain and anxiety, and surgeon anxiety, during cutaneous surgical procedures. METHODS: Subjects were adults undergoing excisional surgery for basal and squamous cell carcinoma. Randomization was to guided imagery (n = 50), relaxing music (n = 54), or control group (n = 51). Primary outcomes were pain and anxiety measured using visual analog scale and 6-item short-form of the State-Trait Anxiety Inventory, respectively. Secondary outcomes were anxiety of surgeons measured by the 6-item short-form of the State-Trait Anxiety Inventory and physical stress of patients conveyed by vital signs, respectively. RESULTS: There were no significant differences in subjects' pain, anxiety, blood pressure, and pulse rate across groups. In the recorded guided imagery and the relaxing music group, surgeon anxiety was significantly lower than in the control group. LIMITATIONS: Patients could not be blinded. CONCLUSION: Short-contact recorded guided imagery and relaxing music appear not to reduce patient pain and anxiety during excisional procedures under local anesthetic. However, surgeon anxiety may be reduced when patients are listening to such recordings.

The critical role of agrin in the hematopoietic stem cell niche.

Hematopoiesis is the process leading to the sustained production of blood cells by hematopoietic stem cells (HSCs). Growth, survival, and differentiation of HSCs occur in specialized microenvironments called "hematopoietic niches," through molecular cues that are only partially understood. Here we show that agrin, a proteoglycan involved in the neuromuscular junction, is a critical niche-derived signal that controls survival and proliferation of HSCs. Agrin is expressed by multipotent nonhematopoietic mesenchymal stem cells (MSCs) and by differentiated osteoblasts lining the endosteal bone surface, whereas Lin(-)Sca1(+)c-Kit(+) (LSK) cells express the α-dystroglycan receptor for agrin. In vitro, agrin-deficient MSCs were less efficient in supporting proliferation of mouse Lin(-)c-Kit(+) cells, suggesting that agrin plays a role in the hematopoietic cell development. These results were indeed confirmed in vivo through the analysis of agrin knockout mice (Musk-L;Agrn(-/-)). Agrin-deficient mice displayed in vivo apoptosis of CD34(+)CD135(-) LSK cells and impaired hematopoiesis, both of which were reverted by an agrin-sufficient stroma. These data unveil a crucial role of agrin in the hematopoietic niches and in the cross-talk between stromal and hematopoietic stem cells.

Species diversity and molecular characterization of Alternaria section Alternaria isolates collected mainly from cereal crops in Canada.

Alternaria is often one on the most abundant fungal genera recovered from a wide array of plant hosts and environmental substrates. Many species within the sub-generic Alternaria section Alternaria are common plant pathogens that cause pre-harvest losses due to reduced productivity and post-harvest losses due to spoilage and contamination with mycotoxins. As certain species of Alternaria may have distinct mycotoxin profiles, and very broad host ranges, understanding the distribution of species by geography and host is critical for disease prediction, toxicological risk assessment, and guiding regulatory decisions. In two previous reports, we performed phylogenomic analyses to identify highly informative molecular markers for Alternaria section Alternaria, and validated their diagnostic ability. Here, we perform molecular characterization of 558 section Alternaria strains, collected from 64 host genera in 12 countries, using two of these section-specific loci (ASA-10 and ASA-19) along with the RNA polymerase II second largest subunit (rpb2) gene. The majority of strains (57.4%) originated from various cereal crops in Canada, which formed the main focus of our study. Phylogenetic analyses were used to classify strains into section Alternaria species/lineages, demonstrating that the most common species on Canadian cereal crops are Alternaria alternata and A. arborescens. Further population genetic analyses were consistent with A. alternata being a widely distributed species with relatively low levels of geographic isolation (i.e., Canadian isolates did not form distinct clades when compared to other regions). Our expanded sampling of A. arborescens has greatly increased the known diversity of this group, with A. arborescens isolates forming at least three distinct phylogenetic lineages. Proportionally, A. arborescens is more prevalent in Eastern Canada than in Western Canada. Sequence analyses, putative hybrids, and mating-type distributions provided some evidence for recombination events, both within and between species. There was little evidence for associations between hosts and genetic haplotypes of A. alternata or A. arborescens.

State medical board regulation of minimally invasive cosmetic procedures.

BACKGROUND: There is little information regarding commonalities, differences, and trends in the regulation of minimally invasive cosmetic procedures (MICP) across different state medical boards in the United States. OBJECTIVE: We sought to assess current state medical board regulations regarding MICP, so as to better understand current and emerging trends in rules regarding delegation, and management of patient complaints. METHODS: We conducted structured interviews with officials at US allopathic medical boards, supplemented with information from board World Wide Web sites. RESULTS: A total of 31 (62%) boards participated. Most (20 boards; 63% of total respondents) reported that all MICP can be delegated at the physician's discretion and responsibility to at least one category of nonphysician; 7 states were expecting changes in delegation rules; and 4 states had very specific delegation requirements. Approximately equal numbers of boards required some general supervision of nonphysicians (14, 45%), or required some type of on-site supervision (13, 42%); a small number explicitly permitted off-site supervision (4, 13%). There was variation in the number of physician assistants one physician could supervise. Most boards (15 states) required some type of mandatory reporting, but not necessarily of incidents involving MICP. Very few (4) required reporting of both office- and nonoffice-based MICP incidents. Western states had liberal delegation and supervision requirements; these requirements were more stringent in Southern states. LIMITATIONS: Not all boards participated in this study. CONCLUSION: There is substantial variation in board regulation of MICP. Many boards are promulgating new rules. Medical boards also have limited ability to regulate nonphysicians.

Rescuing Z+ agrin splicing in Nova null mice restores synapse formation and unmasks a physiologic defect in motor neuron firing.

Synapse formation at the neuromuscular junction (NMJ) requires an alternatively spliced variant of agrin (Z(+) agrin) that is produced only by neurons. Here, we show that Nova1 and Nova2, neuron-specific splicing factors identified as targets in autoimmune motor disease, are essential regulators of Z(+) agrin. Nova1/Nova2 double knockout mice are paralyzed and fail to cluster AChRs at the NMJ, and breeding them with transgenic mice constitutively expressing Z(+) agrin in motor neurons rescued AChR clustering. Surprisingly, however, these rescued mice remained paralyzed, while electrophysiologic studies demonstrated that the motor axon and synapse were functional-spontaneous and evoked recordings revealed synaptic transmission and muscle contraction. These results point to a proximal defect in motor neuron firing in the absence of Nova and reveal a previously unsuspected role for RNA regulation in the physiologic activation of motor neurons.

Interest of pregnant women in the use of SMS (short message service) text messages for the improvement of perinatal and postnatal care.

BACKGROUND: Mobile health (mHealth) is emerging as a useful tool to improve healthcare access especially in the developing world, where limited access to health services is linked to poor antenatal care, and maternal and perinatal mortality.The objective of this study is to 1) understand pregnant women's access and usage of cell phones and 2) survey the health information needs and interests in a population attending public hospitals and health centers of two cities in Argentina. This information is not available and it is the basis to develop a strategy for improving maternal care via cell phones. METHODS: Questionnaires were verbally administered to pregnant women who were attending an antenatal care visit in community health centers and public hospitals in Rosario, Santa Fe and Mercedes, Corrientes. Participants were 18 years of age or older and had previously given birth. The data obtained was qualitative and analyzed using SPSS version 18. RESULTS: A total of 147 pregnant women meeting inclusion criteria (Rosario: 63; Mercedes: 84) were approached and verbally consented to participate. The average age was 29.5 years, most lived in urban areas (89%) with a mean travel time of 43.4 minutes required to get to the health center and 57.3 minutes to get the hospital.Ninety-six percent of women (n = 140) responded that they would like to receive text messages and cell phone calls with information regarding prenatal care, although the topics and period of time to receive information varied greatly. CONCLUSIONS: Considering the vast majority of the interviewed women had access to and were interested in receiving text messages and calls with educational information regarding pregnancy and infant health, pregnant women in Argentina could benefit from such an mHealth program. The low access to Internet suggests it is not an option for this population; however, this cannot be assumed as representative of the country's situation.To retain active participation, other forms of health communication, such as a 2-way text message systems or toll-free numbers, could be considered in the future. Cost of use and implementing these options should be studied.

MuSK controls where motor axons grow and form synapses.

Motor axons approach muscles that are regionally prespecialized, as acetylcholine receptors are clustered in the central region of muscle before and independently of innervation. This muscle prepattern requires MuSK, a receptor tyrosine kinase that is essential for synapse formation. It is not known how muscle prepatterning is established, and whether motor axons recognize this prepattern. Here we show that expression of Musk is prepatterned in muscle and that early Musk expression in developing myotubes is sufficient to establish muscle prepatterning. We further show that ectopic Musk expression promotes ectopic synapse formation, indicating that muscle prepatterning normally has an instructive role in directing where synapses will form. In addition, ectopic Musk expression stimulates synapse formation in the absence of Agrin and rescues the lethality of Agrn mutant mice, demonstrating that the postsynaptic cell, and MuSK in particular, has a potent role in regulating the formation of synapses.

Discordance Between Subjective and Objective Measures of Smell and Taste in US Adults.

OBJECTIVE: Examine the rates and factors associated with under- and overreporting of subjective changes in smell or taste as compared with objective measures. STUDY DESIGN: Cross-sectional analysis. SETTING: National Health and Nutrition Examination Survey (2013-2014). METHODS: We examined participants ≥40 years old who completed subjective questionnaires (smell, n = 3510; taste, n = 3089), validated objective 8-odor pocket smell tests, and NaCl/quinine taste tests. Over- and underreporting was determined by the difference in subjective and objective results. Univariate and multivariate logistic regression analyses incorporated sampling weights. RESULTS: A majority of participants correctly classified impairment: smell (73.7%; 95% CI, 71.2%-76.1%) and taste (78.3%; 95% CI, 75.6%-80.7%). Age ≥65 years (odds ratio, 2.23; P = .001) was associated with underreporting impairment, and persistent cold symptoms (odds ratio, 2.15; P = .001) were associated with overreporting smell impairment. Smoke, onion, and natural gas scents were incorrectly identified more frequently by individuals aged ≥65 years after Bonferroni correction. No factors were associated with under- and overreporting taste impairment. CONCLUSION: Although the concordance rate between subjective and objective assessment of smell and taste impairment remains high, we found that older age was associated with incorrect report of impairment. This suggests that the subjective perception of smell varies across demographical and clinical factors, and it is important to not overlook such factors in clinical practice. Potentially using a simplified odor assessment regularly in the clinical setting may aid in early detection and intervention.

Untargeted metabolomics screening reveals unique secondary metabolite production from Alternaria section Alternaria.

Alternaria section Alternaria is comprised of many species that infect a broad diversity of important crop plants and cause post-harvest spoilage. Alternaria section Alternaria species, such as A. alternata and A. arborescens, are prolific producers of secondary metabolites that act as virulence factors of disease and are mycotoxins that accumulate in infected tissues-metabolites that can vary in their spectrum of production between individuals from the same fungal species. Untargeted metabolomics profiling of secondary metabolite production using mass spectrometry is an effective means to detect phenotypic anomalies in secondary metabolism within a species. Secondary metabolite phenotypes from 36 Alternaria section Alternaria isolates were constructed to observe frequency of production patterns. A clear and unique mass feature pattern was observed for three of the strains that were linked with the production of the dehydrocurvularin family of toxins and associated detoxification products. Examination of corresponding genomes revealed the presence of the dehydrocurvularin biosynthesis gene cluster associated with a sub-telomeric accessory region. A comparison of sequence similarity and occurrences of the dehydrocurvularin biosynthetic gene cluster within Pleosporalean fungi is presented and discussed.

The use of brachytherapy in the treatment of nonmelanoma skin cancer: a review.

Nonmelanoma skin cancers can be treated by various modalities, including electrodessication and curettage, excisional techniques, and radiation. In selected cases, radiation may be preferable to surgery. When radiation is an option, brachytherapy, a form of radiation therapy that places the radiation source close to the area to be treated, may have advantages relative to conventional external beam radiation in particular patients. After brachytherapy, recurrence rates for nonmelanoma skin cancers are low, especially for small, superficial lesions, with good to excellent functional and cosmetic results. This article reviews the indications, efficacy, and adverse effects of brachytherapy in the treatment of nonmelanoma skin cancers.