Mitogen-Activated Protein Kinase Inhibitor-Induced Inflammatory Alopecia in Woman With Ovarian Cancer.

Inflammatory alopecia is an increasingly reported side effect of targeted cancer therapies. Here we report one case of inflammatory alopecia secondary to mitogen-activated protein kinase kinase (MEK) inhibitor agent Trametinib in a woman with ovarian cancer. Biopsies of the scalp were consistent with early scarring alopecia compatible with drug-induced alopecia. Significant improvement in hair loss occurred after treatment with intralesional Kenalog (ILK) injections and oral isotretinoin. Though acute alopecia has been described in patients using MEK inhibitors, this is the first reported case of inflammatory alopecia.  J Drugs Dermatol. 2024;23(4):7802.     doi:10.36849/JDD.7802e  .

Retrospective cohort study of CDK4/6-inhibitor-induced alopecia in breast cancer patients.

PURPOSE: Dermatologic adverse events commonly result in the interruption of oncologic treatment, and targeted therapies are the most frequently interrupted class of anticancer agents. Alopecia is a common cutaneous adverse event reported with CK4/6i therapy. Though the clinical characteristics and therapeutic response of EIA have been well documented, few studies have characterized alopecia in patients treated with CDK4/6i. METHODS: This study analyzed a retrospective cohort of 28 breast cancer patients diagnosed with endocrine-induced alopecia (EIA) or CDKiA. Comparative analysis of the clinical characteristics of alopecia and therapeutic response to minoxidil was conducted. Therapeutic response to minoxidil (LDOM or topical [5%] solution or foam) was assessed by both Dean Scale and qualitative clinical improvement by comparison of pretreatment and posttreatment clinical images by single-blinded, board-certified academic dermatologists (ST and BD). RESULTS: CDKiA was clinically similar to androgenetic alopecia and specific vertex involvement was more common in patients treated with CDK4/6i + ET than endocrine monotherapy (n = 7 [70.0%] vs n = 4 [36.4%]; p = 0.04), respectively. After 4-6 months of minoxidil, there was a moderate to significant qualitative alopecia improvement in 80% of CDKiA patients versus 94.4% of EIA patients. Additionally, superior improvement of mean Dean Score grade was observed in EIA (with change from pre- to posttreatment - 0.44; p = 0.0002). CONCLUSION: Compared to endocrine monotherapy, patients on combination CDK4/6i + ET had greater extent of vertex involvement and were more recalcitrant to minoxidil. The preferential vertex involvement observed in CDKiA suggests that combination therapy with minoxidil and topical antiandrogens with poor systemic absorption should be studied in this setting.

Loss of TSC1 in secondary angiosarcoma of the breast.

Key Clinical Message: Post-radiation angiosarcoma of the breast is a rare complication associated with a poor prognosis. This case reports the first loss of function mutation in TSC1 in breast radiation-induced angiosarcoma and illustrates the utility of evaluating these markers to identify potential therapeutic targets. Abstract: Post-radiation angiosarcoma of the breast is rare and associated with a poor prognosis. This case presents the first loss of function mutation in TSC1 in breast radiation-induced angiosarcoma. Evaluation of these markers can aid in identifying potential therapeutic targets.

Hair loss during and after breast cancer therapy.

For patients diagnosed with breast cancer, alopecia can be a distressing side effect of treatment. Major surgeries, cytotoxic chemotherapy, and endocrine therapy may result in several different types of alopecia. This article reviews the underlying mechanisms, etiology, prevention strategies, and treatment options for chemotherapy-induced alopecia, telogen effluvium, and endocrine-induced alopecia. Here, we aim to provide breast oncologists with a review of the types of hair loss related to cancer therapy and current preventative and treatment options to facilitate informative patient counseling.

Retrospective cohort study of scalp cooling in breast cancer patients.

For patients with cancer, alopecia is a common side effect that negatively impacts personal identity, body image, self-esteem, quality of life, and medical decision-making. Scalp cooling is a technique used to prevent alopecia in patients undergoing chemotherapy in which patients wear a cooled cap during chemotherapy infusions, causing localized vasoconstriction of blood vessels on the scalp. Because of the recent emergence of scalp cooling, there is a need to explore further the reasons why patients pursue this treatment. A retrospective chart review of women with breast cancer treated at The Ohio State University was conducted to investigate how factors such as patient age, race, ethnicity, insurance status, stage of cancer, and chemotherapy regimen influenced patients' decisions to incorporate scalp cooling into their treatment plan as compared to those who did not. Findings revealed that patient age, race, insurance status, and chemotherapy regimen were predictors of a patient's likelihood to undergo scalp cooling. Patients diagnosed at younger age and those with private insurance were more likely to utilize scalp cooling. In comparison to White patients, non-White patients were less likely to choose scalp cooling. Furthermore, patients placed on the chemotherapy regimen of AC or AC-T were less likely to pursue scalp cooling than patients on PTCH or TC regimens. These findings provide background for the development of educational resources for both patients interested in this therapy and healthcare providers discussing this treatment option in dermatology and oncology settings.

Unprocessed Atmospheric Nitrate in Waters of the Northern Forest Region in the U.S. and Canada.

Little is known about the regional extent and variability of nitrate from atmospheric deposition that is transported to streams without biological processing in forests. We measured water chemistry and isotopic tracers (δ18O and δ15N) of nitrate sources across the Northern Forest Region of the U.S. and Canada and reanalyzed data from other studies to determine when, where, and how unprocessed atmospheric nitrate was transported in catchments. These inputs were more widespread and numerous than commonly recognized, but with high spatial and temporal variability. Only 6 of 32 streams had high fractions (>20%) of unprocessed atmospheric nitrate during baseflow. Seventeen had high fractions during stormflow or snowmelt, which corresponded to large fractions in near-surface soil waters or groundwaters, but not deep groundwater. The remaining 10 streams occasionally had some (<20%) unprocessed atmospheric nitrate during stormflow or baseflow. Large, sporadic events may continue to be cryptic due to atmospheric deposition variation among storms and a near complete lack of monitoring for these events. A general lack of observance may bias perceptions of occurrence; sustained monitoring of chronic nitrogen pollution effects on forests with nitrate source apportionments may offer insights needed to advance the science as well as assess regulatory and management schemes.

Temporally restricted death and the role of p75NTR as a survival receptor in the developing sensory nervous system.

The peripheral somatosensory system overproduces neurons early in development followed by a period of cell death during final target innervation. The decision to survive or die in somatosensory neurons of the dorsal root ganglion (DRG) is mediated by target-derived neurotrophic factors and their cognate receptors. Subsets of peripheral somatosensory neurons can be crudely defined by the neurotrophic receptors that they express: peptidergic nociceptors (TrkA+), nonpeptidergic nociceptors (Ret+), mechanoreceptors (Ret+ or TrkB+), and proprioceptors (TrkC+). A direct comparison of early developmental timing between these subsets has not been performed. Here we characterized the accumulation and death of TrkA, B, C, and Ret+ neurons in the DRG as a function of developmental time. We find that TrkB, TrkC, and Ret-expressing neurons in the DRG complete developmental cell death prior to TrkA-expressing neurons. Given the broadly defined roles of the neurotrophin receptor p75NTR in augmenting neurotrophic signaling in sensory neurons, we investigated its role in supporting the survival of these distinct subpopulations. We find that TrkA+, TrkB+, and TrkC+ sensory neuron subpopulations require p75NTR for survival, but proliferating progenitors do not. These data demonstrate how diverging sensory neurons undergo successive waves of cell death and how p75NTR represses the magnitude, but not developmental window of this culling. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 701-717, 2018.

Classification of intra-specific variation in plant functional strategies reveals adaptation to climate.

Background and Aims: In plants, extensive intra-specific variation exists in the allocation of resources between vegetative growth and reproduction, reflecting different functional strategies. A simple method for the classification of intra-specific variation in these strategies would enable characterization of evolutionary and ecological processes. Methods: C-S-R theory can be applied to classify functional strategies (competitive C; stress tolerant, S; ruderal, R) in different plant species. Using a diverse set of arabidopsis ( Arabidopsis thaliana ) accessions grown under common conditions, it was tested whether a simple approach designed for allocating C-S-R strategies at the species level can also be used to analyse intra-specific variation. Key Results: Substantial intra-specific variation between arabidopsis accessions was found along the S-R axis. There was a positive correlation of temperature at the geographical origin with the dimension of S and a negative correlation with the dimension of R. Flowering time in a natural annual cycle and leaf dry matter content were identified as the main determinants of this adaptation, with plants originating from warmer climates having a higher leaf dry matter content and flowering earlier in a common garden. Conclusions: It was shown that functional strategies reflect adaptation to climate, with consequences for important traits such as fecundity and total plant dry weight. The approach could be used in genome-wide association studies to determine the genetic basis of functional strategies in wild species or crops.

The Influence of Marcellus Shale Extraction Emissions on Regionally Monitored Dry Reactive Nitrogen Deposition.

Emissions of nitrogen oxides (NOx) in the United States (U.S.) from large stationary sources, such as electric generating units, have decreased since 1995, driving decreases in nitrogen deposition. However, increasing NOx emissions from emerging industries, such as unconventional natural gas (UNG) extraction, could offset stationary source emission reductions in shale gas producing regions of the U.S. The Marcellus Shale in the northeastern U.S. has seen dramatic increases in the number of wells and associated natural gas production during the past 10 years. In this study, we examine the potential impacts of shale gas development on regional NOx emission inventories and dry deposition fluxes to Clean Air Status and Trends (CASTNET) sites in Pennsylvania and New York. Our results demonstrate that the current distribution of CASTNET sites is ineffective for monitoring the influence of Marcellus well NOx emissions on regional nitrogen deposition. Despite the fact that existing CASTNET sites are not influenced by UNG extraction activity, NOx emissions densities from shale gas extraction are substantial and are estimated to reach up to 21 kg NOx ha-1 year-1 in some regions. If these emissions deposit locally, UNG extraction activity could contribute to critical nitrogen load exceedances in areas of high well density.

New Introductions, Spread of Existing Matrilines, and High Rates of Pyrethroid Resistance Result in Chronic Infestations of Bed Bugs (Cimex lectularius L.) in Lower-Income Housing.

Infestations of the common bed bug (Cimex lectularius L.) have increased substantially in the United States in the past 10-15 years. The housing authority in Harrisonburg, Virginia, conducts heat-treatments after bed bugs are detected in a lower-income housing complex, by treating each infested unit at 60°C for 4-6 hours. However, a high frequency of recurrent infestations called into question the efficacy of this strategy. Genetic analysis using Bayesian clustering of polymorphic microsatellite loci from 123 bed bugs collected from 23 units from May 2012 to April 2013 in one building indicated that (a) 16/21 (73%) infestations were genetically similar, suggesting ineffective heat-treatments or reintroductions from within the building or from a common external source, followed by local spread of existing populations; and (b) up to 5 of the infestations represented new genotypes, indicating that 5 new populations were introduced into this building in one year, assuming they were not missed in earlier screens. There was little to no gene flow among the 8 genetic clusters identified in the building. Bed bugs in the U.S. often possess one or both point mutations in the voltage-gated sodium channel, termed knockdown resistance (kdr), from valine to leucine (V419L) and leucine to isoleucine (L925I) that confer target-site resistance against pyrethroid insecticides. We found that 48/121 (40%) bed bugs were homozygous for both kdr mutations (L419/I925), and a further 59% possessed at least one of the kdr mutations. We conclude that ineffective heat treatments, new introductions, reintroductions and local spread, and an exceptionally high frequency of pyrethroid resistance are responsible for chronic infestations in lower-income housing. Because heat treatments fail to protect from reintroductions, and pesticide use has not decreased the frequency of infestations, preventing new introductions and early detection are the most effective strategies to avoid bed bug infestations in multistory apartment buildings.

Cost-effective conservation of an endangered frog under uncertainty.

How should managers choose among conservation options when resources are scarce and there is uncertainty regarding the effectiveness of actions? Well-developed tools exist for prioritizing areas for one-time and binary actions (e.g., protect vs. not protect), but methods for prioritizing incremental or ongoing actions (such as habitat creation and maintenance) remain uncommon. We devised an approach that combines metapopulation viability and cost-effectiveness analyses to select among alternative conservation actions while accounting for uncertainty. In our study, cost-effectiveness is the ratio between the benefit of an action and its economic cost, where benefit is the change in metapopulation viability. We applied the approach to the case of the endangered growling grass frog (Litoria raniformis), which is threatened by urban development. We extended a Bayesian model to predict metapopulation viability under 9 urbanization and management scenarios and incorporated the full probability distribution of possible outcomes for each scenario into the cost-effectiveness analysis. This allowed us to discern between cost-effective alternatives that were robust to uncertainty and those with a relatively high risk of failure. We found a relatively high risk of extinction following urbanization if the only action was reservation of core habitat; habitat creation actions performed better than enhancement actions; and cost-effectiveness ranking changed depending on the consideration of uncertainty. Our results suggest that creation and maintenance of wetlands dedicated to L. raniformis is the only cost-effective action likely to result in a sufficiently low risk of extinction. To our knowledge we are the first study to use Bayesian metapopulation viability analysis to explicitly incorporate parametric and demographic uncertainty into a cost-effective evaluation of conservation actions. The approach offers guidance to decision makers aiming to achieve cost-effective conservation under uncertainty.