Chilblain-Like Eruption Unveiling Cutaneous Aleukemic Relapse of Acute Myeloid Leukemia.

ABSTRACT: Leukemia cutis corresponds to skin infiltration by malignant hematopoietic cells. It is most commonly reported in acute myeloid leukemia, particularly in subtypes with a monocytic component. Its clinical manifestations are extremely variable, and histopathologic diagnosis of cutaneous leukemic infiltrates may be challenging. We report the first case of cutaneous, that is, extramedullary, aleukemic relapse of acute myeloid leukemia within an unusual chilblain-like eruption that imposed a challenging clinical and histopathologic diagnosis. Primary chilblains are uncommon in the elderly, and a systemic underlying cause should be thoroughly investigated. In patients presenting with atypical chilblains (ie, persistent chilblains developing even without exposure to cold temperatures and/or refractory to therapy) and with a history of hematologic disorders such as leukemias, histopathologic examination is crucial to identify leukemic or aleukemic phases of relapse of underlying leukemia and initiate timely treatment.

Myopericytoma presenting as a painful dark subungual discoloration.

Myopericytoma is an uncommon benign neoplasm that arises from the perivascular myoid cells. It typically presents as a painless well-circumscribed cutaneous or soft-tissue nodule, most commonly on the extremities of adults. Histologically, it is characterized by spindle-shaped myoid-appearing cells with a concentric arrangement in vessel walls, that are immunoreactive to alpha-smooth muscle actin and often for h-caldesmon, but negative for other smooth muscle markers. Herein, we present an unusual case of a painful subungual myopericytoma presenting as a dark subungual discoloration.

Leukemia cutis and eccrine squamous syringometaplasia.

Eccrine squamous syringometaplasia (ESS) is a histological term describing a mature squamous metaplasia of the eccrine ducts. Eccrine squamous syringometaplasia is not an infrequent histological finding and may be associated with chemotherapy or with a variety of non-specific conditions including infections, neoplastic conditions, and inflammatory skin diseases. We report a 75-year-old man who developed ESS within lesions of leukemia cutis (LC). The patient had an inaugural diagnosis of acute myeloid leukemia (AML) and he was not on chemotherapy when the biopsy was performed.

One person, two bilateral symmetrical giant Becker nevi.

Becker nevus, first described by Samuel William Becker in 1949, is a focal epidermal hypermelanotic disorder. It commonly presents as a unilateral hyperpigmented patch that is predominantly distributed on the upper trunk and proximal extremities and frequently associated with hypertrichosis. There have been few reports in the literature of Becker nevus with bilateral involvement; multiple Becker nevi is also unusual. Herein, we report a young man with two bilateral symmetrical giant Becker nevi, one on the trunk with extension to both arms and the second on the abdomen.

Intercellular Variability in Protein Levels from Stochastic Expression and Noisy Cell Cycle Processes.

Inside individual cells, expression of genes is inherently stochastic and manifests as cell-to-cell variability or noise in protein copy numbers. Since proteins half-lives can be comparable to the cell-cycle length, randomness in cell-division times generates additional intercellular variability in protein levels. Moreover, as many mRNA/protein species are expressed at low-copy numbers, errors incurred in partitioning of molecules between two daughter cells are significant. We derive analytical formulas for the total noise in protein levels when the cell-cycle duration follows a general class of probability distributions. Using a novel hybrid approach the total noise is decomposed into components arising from i) stochastic expression; ii) partitioning errors at the time of cell division and iii) random cell-division events. These formulas reveal that random cell-division times not only generate additional extrinsic noise, but also critically affect the mean protein copy numbers and intrinsic noise components. Counter intuitively, in some parameter regimes, noise in protein levels can decrease as cell-division times become more stochastic. Computations are extended to consider genome duplication, where transcription rate is increased at a random point in the cell cycle. We systematically investigate how the timing of genome duplication influences different protein noise components. Intriguingly, results show that noise contribution from stochastic expression is minimized at an optimal genome-duplication time. Our theoretical results motivate new experimental methods for decomposing protein noise levels from synchronized and asynchronized single-cell expression data. Characterizing the contributions of individual noise mechanisms will lead to precise estimates of gene expression parameters and techniques for altering stochasticity to change phenotype of individual cells.

Quantifying gene expression variability arising from randomness in cell division times.

The level of a given mRNA or protein exhibits significant variations from cell-to-cell across a homogeneous population of living cells. Much work has focused on understanding the different sources of noise in the gene-expression process that drive this stochastic variability in gene-expression. Recent experiments tracking growth and division of individual cells reveal that cell division times have considerable inter-cellular heterogeneity. Here we investigate how randomness in the cell division times can create variability in population counts. We consider a model by which mRNA/protein levels in a given cell evolve according to a linear differential equation and cell divisions occur at times spaced by independent and identically distributed random intervals. Whenever the cell divides the levels of mRNA and protein are halved. For this model, we provide a method for computing any statistical moment (mean, variance, skewness, etcetera) of the mRNA and protein levels. The key to our approach is to establish that the time evolution of the mRNA and protein statistical moments is described by an upper triangular system of Volterra equations. Computation of the statistical moments for physiologically relevant parameter values shows that randomness in the cell division process can be a major factor in driving difference in protein levels across a population of cells.

Solar fuels design: Porous cathodes modeling for electrochemical carbon dioxide reduction in aqueous electrolytes.

The reduction of carbon dioxide emissions is crucial to reduce the atmospheric greenhouse effect, fighting climate change and global warming. Electrochemical CO2 reduction is one of the most promising carbon capture and utilization technologies, that can be powered by solar energy and used to make added-value chemicals and green fuels, providing grid-stability, energy security, and environmental benefits. A two-dimensional finite-elements model for porous electrodes was developed and validated against experimental data, allowing the design and performance improvement of a porous zinc cathode morphology and its operational conditions for an electrolyzer producing syngas via the co-electrolysis of CO2 and water. Porosity, pore length, fiber geometric shape, inlet pressure, system temperature, and catholyte flow rate were explored, and these parameters were thoroughly tuned by using the smart-search Nelder-Mead's multi-parameter optimization algorithm to achieve pronouncedly higher, industrial-relevant current density values than those previously reported, up to 263.6 mA/cm2 at an applied potential of -1.1 V vs. RHE.

Onychomatricoma on the fourth toenail: A rare tumor in a rare localization.

Onychomatricoma is a rare benign tumor of the nail matrix, characterized by finger-like projections that invade the nail plate. The fingernails of Caucasian women are most commonly affected. Because this tumor can easily mimic other more prevalent ungual diseases, it is crucial to be acquainted with its characteristic clinical and histopathologic features. The authors present a case of a 40-year-old man with an onychomatrichoma in the fourth left toenail, which was initially misdiagnosed and treated as onychomycosis.

A randomised controlled feasibility study of food-related computerised attention training versus mindfulness training and waiting-list control for adults with overweight or obesity: the FOCUS study.

BACKGROUND: In a feasibility randomised controlled trial in people with overweight/obesity with and without binge eating disorder (BED) symptoms, we assessed eight weekly sessions of attention bias modification training (ABMT) and mindfulness training (MT) versus waiting list (WL) and explored potential mechanisms. METHODS: 45 participants were randomly allocated to one of three trial arms. Primary outcomes were recruitment, retention and treatment adherence rates. Secondary outcomes included measures of eating behaviour, mood, attention and treatment acceptability. Assessments were conducted at baseline, post-intervention (week 8), and follow-up (week 12). RESULTS: Participant retention at follow-up was 84.5% across groups. Session completion rates in the laboratory were 87% for ABMT and 94% for MT, but home practice was much poorer for ABMT. Changes in BMI and body composition were small between groups and there was a medium size BMI reduction in the MT group at follow-up. Effect sizes of eating disorder symptom changes were not greater for either intervention group compared to WL, but favoured ABMT compared to MT. Hedonic hunger and mindful eating scores favoured MT compared to ABMT and WL. ABMT reduced attention biases towards high-calorie food cues, which correlated with lower objective binge eating days at post-intervention. No significant changes were observed in the MT, or WL conditions. CONCLUSIONS: Both ABMT and MT have potential value as adjuncts in the treatment of obesity and BED, and a larger clinical trial appears feasible and indicated. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN15745838. Registered on 22 May 2018.

In this small research study, people who were classified as overweight or living with obesity (with or without symptoms of binge eating disorder) received either a mindfulness intervention, a "subconscious" attention-based intervention called attention bias modification training (ABMT) or were put on a waiting list for 8 weeks. People in the mindfulness group experienced improvements in emotional eating, mindful eating, and "impulsive" eating. Those who received the attention-based training paid less attention to highly caloric food after the intervention which correlated with fewer binge eating episodes. Results from this study suggest that both types of interventions have potential as add-on treatments for obesity and binge eating disorder, but larger studies are necessary to assess their clinical impact.

Myositis Multidisciplinary Clinic in a Tertiary Referral Center.

Background: Idiopathic inflammatory myopathies (IIM) are a rare heterogeneous group of diseases characterised by chronic skeletal muscle inflammation, but other organs are also frequently involved. IMM represent a diagnostic challenge and a multidisciplinary approach is important to ensure successful diagnosis and adequate follow-up of these patients. Objective: To describe the general functioning of our multidisciplinary myositis clinic, highlighting the benefits of multidisciplinary team management in patients with confirmed or suspected IIM and to characterise our clinical experience. Methods: Description of the organization of a dedicated multidisciplinary myositis outpatient clinic, supported by IMM specific electronic assessment tools and protocols based on our Portuguese Register - Reuma.pt. In addition, an overview of our activity between 2017 and 2022 is provided. Results: An IIM multidisciplinary care clinic, based on a close collaboration between Rheumatologists, Dermatologists and Physiatrist is detailed in this paper. One hundred and eighty-five patients were assessed in our myositis clinic; 138 (75%) of those were female, with a median age of 58 [45-70] years. At the last appointment, 130 patients had a confirmed IIM diagnosis, and the mean disease duration was 4 [2-6] years. The most frequent diagnosis was dermatomyositis (n = 34, 26.2%), followed by antisynthetase syndrome (n = 27, 20.8%) and clinically amyopathic/paucimyopathic dermatomyositis (n = 18, 13.8%). Twenty-four patients (18.5%) were on monotherapy and 94 (72.3%) were on combination therapy. Conclusion: A multidisciplinary approach is important to ensure the correct diagnosis and follow-up of these patients. A myositis clinic, with a standardised practice at a tertiary hospital level, contributes to a standardization of care and opens research opportunities.