Observations on muscle activity in REM sleep behavior disorder assessed with a semi-automated scoring algorithm

Objectives

Rapid eye movement (REM) sleep behavior disorder (RBD) is defined by dream enactment due to a failure of normal muscle atonia. Visual assessment of this muscle activity is time consuming and rater-dependent.

Association between patient and tumor characteristics with clinical outcomes in women with ductal carcinoma in situ

We synthesized the evidence of the association between patient and tumor characteristics with clinical outcomes in women with ductal carcinoma in situ of the breast. We identified five randomized controlled clinical trials and 64 observational studies that were published in English from January 1970 to January 2009. Younger women with clinically presented ductal carcinoma in situ had higher risk of ipsilateral recurrent cancer. African Americans had higher mortality and greater rates of advanced recurrent cancer. Women with larger tumor size, comedo necrosis, worse pathological grading, positive surgical margins, and at a higher risk category, using a composite prognostic index, had worse outcomes. Inconsistent evidence suggested that positive HER2 receptor and negative estrogen receptor status were associated with worse outcomes. Synthesis of evidence was hampered by low statistical power to detect significant differences in predictor categories and inconsistent adjustment practices across the studies. Future research should address composite prediction indices among race groups for all outcomes.     

Intestinal epithelial cell secretion of RELM-β protects against gastrointestinal worm infection

Th2 cells drive protective immunity against most parasitic helminths, but few mechanisms have been demonstrated that facilitate pathogen clearance. We show that IL-4 and IL-13 protect against intestinal lumen-dwelling worms primarily by inducing intestinal epithelial cells (IECs) to differentiate into goblet cells that secrete resistin-like molecule (RELM) β. RELM-β is essential for normal spontaneous expulsion and IL-4–induced expulsion of Nippostrongylus brasiliensis and Heligmosomoides polygyrus, which both live in the intestinal lumen, but it does not contribute to immunity against Trichinella spiralis, which lives within IEC. RELM-β is nontoxic for H. polygyrus in vitro but directly inhibits the ability of worms to feed on host tissues during infection. This decreases H. polygyrus adenosine triphosphate content and fecundity. Importantly, RELM-β–driven immunity does not require T or B cells, alternative macrophage activation, or increased gut permeability. Thus, we demonstrate a novel mechanism for host protection at the mucosal interface that explains how stimulation of epithelial cells by IL-4 and IL-13 contributes to protection against parasitic helminthes that dwell in the intestinal lumen.Gastrointestinal (GI) helminths infect >10⁹ people worldwide (Anthony et al., 2007). Rodent studies demonstrate that IL-4, 5, 9, 13, 25, and 33 promote immunity against worm infections, with IL-4 and IL-13 serving a predominant role in host protection (Fallon et al., 2002, 2006; Humphreys et al., 2008). The IL-4 receptor α chain (IL-4Rα) is essential for both the type I (IL-4Rα/γ_c) and type II (IL-4Rα/IL-13Rα1) IL-4Rs and is responsible for nearly all known biological effects of IL-4 and IL-13 (Junttila et al., 2008). Indeed, IL-4Rα–deficient mice are highly susceptible to most GI nematode species because of impaired effector functions of bone marrow–derived and non–bone marrow–derived cell lineages (Finkelman et al., 1997; Urban et al., 2001).The niche inhabited by a particular worm species dictates the mechanism required for expulsion. IL-4/IL-13 stimulation of macrophage arginase production decreases survival of larvae of the hookworm Heligmosomoides polygyrus as they develop in the intestinal wall, but is not involved in IL-4/IL-13 expulsion of adult worms from the intestinal lumen (Anthony et al., 2006). Expulsion of Nippostrongylus brasiliensis adult worms from the intestinal lumen is mast cell, eosinophil, and antibody independent, but it requires IL-4/13–responsive non–bone marrow–derived cells (Urban et al., 2001), even though infected mice that express IL-4Rα only on bone marrow–derived cells develop strong IL-4/IL-13 responses. In contrast, protection against the human roundworm pathogen Trichinella spiralis, which resides in an intestinal epithelial cell (IEC) syncytium, is mast cell dependent and requires IL-4Rα expression by both bone marrow– and non–bone marrow–derived cells (Urban et al., 2000).The IL-4Rα–expressing cell type required for N. brasiliensis expulsion has been speculated to be smooth muscle (increased contractility) or intestinal epithelium (increased proliferation, permeability, and mucus production), but IL-4/IL-13''s effects on smooth muscle cells contribute only slightly to expulsion (Horsnell et al., 2007), and there has been no direct proof that IL-4/IL-13''s effects on IEC are required for expulsion. This study demonstrates that IL-4/IL-13 contributes importantly to expulsion of N. brasiliensis and H. polygyrus adults from the intestinal lumen by inducing IEC to differentiate into goblet cells that secrete resistin-like molecule (RELM) β, which interferes with worm nutrition.     

Masers to magic bullets: an updated history of lasers in dermatology

Laser therapy is one of the fastest expanding and most exciting fields in dermatology. From its theoretical beginnings in Einstein's imagination, lasers have come to be used in treatments for conditions ranging from skin malignancy and acne to hirsutism and photoaging. We will briefly review the evolution of laser treatment, with a focus on the recent developments surrounding the new millennium.     

Substance P as an immunomodulatory neuropeptide in a mouse model for autoimmune hair loss (alopecia areata)

Alopecia areata (AA) is an autoimmune disorder of the hair follicle characterized by inflammatory cell infiltrates around actively growing (anagen) hair follicles. Substance P (SP) plays a critical role in the cutaneous neuroimmune network and influences immune cell functions through the neurokinin-1 receptor (NK-1R). To better understand the role of SP as an immunomodulatory neuropeptide in AA, we studied its expression and effects on immune cells in a C3H/HeJ mouse model for AA. During early stages of AA development, the number of SP-immunoreactive nerve fibers in skin is increased, compared to non-affected mice. However, during advanced stages of AA, the number of SP-immunoreactive nerves and SP protein levels in skin are decreased, whereas the expression of the SP-degrading enzyme neutral endopeptidase (NEP) is increased, compared to control skin. In AA, NK-1R is expressed on CD8+ lymphocytes and macrophages accumulating around affected hair follicles. Additional SP supply to the skin of AA-affected mice leads to a significant increase of mast cell degranulation and to accelerated hair follicle regression (catagen), accompanied by an increase of CD8+ cells-expressing granzyme B. These data suggest that SP, NEP, and NK-1R serve as important regulators in the molecular signaling network modulating inflammatory response in autoimmune hair loss.     

Subacute thyroiditis after SARS‐CoV‐2 infection

Viral infections are considered as etiologic factors of subacute thyroiditis. The true incidence of subacute thyroiditis, caused by SARS‐CoV‐2 infection, is probably considerable since it is often masked by more dramatic affection of the respiratory system. This report presents two female patients who developed de Quervain''s thyroiditis after COVID‐19 disease.