Rosacea – global diversity and optimized outcome: proposed international consensus from the Rosacea International Expert Group

Background The absence of specific histological or serological markers, the gaps in understanding the aetiology and pathophysiology of rosacea, and the broad diversity in its clinical manifestations has made it difficult to reach international consensus on therapy guidelines. Objectives The main objective was to highlight the global diversity in current thinking about rosacea pathophysiology, classification and medical features, under particular consideration of the relevance of the findings to optimization of therapy. Methods The article presents findings, proposals and conclusions reached by the ROSacea International Expert group (ROSIE), comprising European and US rosacea experts. Results New findings on pathogenesis provide a rationale for the development of novel therapies. Thus, recent findings suggest a central role of the antimicrobial peptide cathelicidin and its activator kallikrein‐5 by eliciting an exacerbated response of the innate immune system. Cathelicidin/kallikrein‐5 also provide a rationale for the effect of tetracyclines and azelaic acid against rosacea. Clinically, the ROSIE group emphasized the need for a comprehensive therapy strategy – the triad of rosacea care – that integrates patient education including psychological and social aspects, skin care with dermo‐cosmetics as well as drug‐ and physical therapies. Classification of rosacea into stages or subgroups, with or without progression, remained controversial. However, the ROSIE group proposed that therapy decision making should be in accordance with a treatment algorithm based on the signs and symptoms of rosacea rather than on a prior classification. Conclusion The ROSIE group reviewed rosacea pathophysiology and medical features and the impact on patients and treatment options. The group suggested a rational, evidence‐based approach to treatment for the various symptoms of the condition. In daily practice this approach might be more easily handled than prior subtype classification, in particular since patients often may show clinical features of more than one subtype at the same time.     

Continuing Risk Behaviors Among HIV-Seropositive Chronic Drug Users in Miami, Florida

This study investigates continuing risk behaviors among HIV-seropositive chronic drug users in Miami, Florida. Data were collected on 490 injecting and noninjecting seropositive drug users. Results indicate that from baseline to follow-up, HIV-seropositive injectors and non-injectors reported significant decreases of approximately 50% in risky sexual and injecting practices (IDUs only) associated with transmission of HIV. However, our findings also indicate that approximately one third of HIV-positive injectors and one half of HIV-positive noninjectors continue to have unprotected sex and one third of HIV-positive injectors are continuing to engage in risky injecting practices. Change in one risk behavior was predictive of change in other risk behaviors. Women were more likely to change injection behaviors than sexual practices. Injecting drug users showed greater overall behavioral change than noninjectors. These findings underscore the need to develop, disseminate, and implement effective intervention models specifically targeting HIV-positive drug users.     

Once-daily feeding is associated with better health in companion dogs: results from the Dog Aging Project

GeroScience - A variety of diets have been studied for possible anti-aging effects. In particular, studies of intermittent fasting and time-restricted feeding in laboratory rodents have found...     

Prognostic impact of cytogenetic and interphase fluorescence in situ hybridization-defined chromosome 13 deletion in multiple myeloma: early results of total therapy II

Cytogenetic abnormalities of chromosome 13 (CA 13) and those detected by fluorescence in situ hybridization (FISH 13) have both been associated with poor prognosis in multiple myeloma (MM) patients. The prognostic implications of CA, FISH 13 and other standard laboratory parameters were examined in the first 231 patients enrolled in Total Therapy II, an intensive cytotoxic chemotherapy programme with tandem autotransplants. Three-year projections of event-free survival (EFS) and overall survival (OS) were 71% and 77% respectively. CA 13 was detected in 14% and significantly correlated with FISH 13 (present in 51%), tumour burden, proliferative activity and lactic dehydrogenase (LDH). Both EFS and OS were significantly shorter in patients with CA 13, FISH 13, LDH >or= 190 U/l, beta2 microglobulin >or= 4 mg/l and C reactive protein >or= 4.0 mg/l; other CA was an additional risk factor for OS. Two-thirds of CA 13 patients were identified by FISH 13 and plasma-cell-labelling index (PCLI) >or= 0.4%; however, PCLI failed to identify additional risk groups in FISH subsets. Although present in considerably fewer patients, CA 13 imparted more rapid relapse (61% at 3 years) and death (43% at 3 years) than FISH 13 (38% and 35%; P = 0.02 and 0.1 respectively) and should be part of the initial work-up of patients with MM.     

Diagnostic accuracy of oropharyngeal cultures in infants and young children with cystic fibrosis.

The objective of this study was to assess the diagnostic accuracy of oropharyngeal (OP) cultures relative to simultaneous bronchoalveolar lavage (BAL) cultures in very young children with CF, and to examine the effects of bacterial density, age, and study cohort on diagnostic accuracy. Respiratory culture data were analyzed from three independent, prospective studies involving simultaneous collection of 286 OP and BAL cultures from 141 children with CF <5 years of age. For predicting any growth of Pseudomonas aeruginosa (Pa) from the lower airway in subjects /=10(3) or >/=10(5) cfu/mL. Specificity for Pa declined significantly with increasing age. In children with CF <5 years of age, the specificity and negative predictive value of OP cultures for Pa are high, while the sensitivity and positive predictive value are poor. Thus, in this age range, a negative throat culture is helpful in "ruling out" lower airway infection with Pa. However, a positive culture does not reliably "rule in" the presence of Pa in the lower respiratory tract. These findings may have implications for study design and interpretation as well as clinical management of young children with CF.     

Cell-mediated immunity in human acute leukemia.

The general cell-mediated immunological reactivity of patients with acute leukemia has been found to be intact, although it may be depressed by extensive disease or by chemotherapy. Patients with acute leukemia also have cellular immune reactivity against tumor associated antigens, as measured by skin tests for delayed hypersensitivity, lymphocyte stimulation, and 51Cr release cytotoxicity. Skin reactions to autologous and allogeneic crude membrane extracts of blast cells correlated with disease state, positive in many patients in remission and negative in most patients in relapse. Extracts of human lymphoid tissue culture cell lines derived from lymphomas or leukemia also gave positive reactions in patients with acute leukemia, and also in patients with lymphoma and nasopharyngeal carcinoma. The antigens detected in the skin tests with the lymphoid cell lines appear to be different from those associated with Epstein-Barr virus (EBV) and from those detected in the 51Cr release assay. Evidence is presented which suggests a complex variety of antigens on blast cells and on the cell lines. Although leukemia associated antigens were also detected by lymphocyte stimulation and by cytotoxicity assays, the results did not correlate with the skin tests nor with each other. The possible use of these assays for monitoring the chemotherapy and immunotherapy of acute leukemia patients is discussed.     

Cellular and peptide requirements for in vitro clonal deletion of immature thymocytes.

Thymocytes from DO10 T-cell-receptor transgenic mice undergo apoptosis, or programmed cell death, when chicken ovalbumin-(323-339) peptide is administered in vivo. Using DO10 mice thymocytes, we have now developed a simple in vitro model system that recapitulates the in vivo clonal-deletion process. When transgenic thymocytes were cocultured with fibroblasts, B cells, or thymic nurse cell lines (all bearing I-Ad) in the presence of chicken ovalbumin-(323-339), deletion of the transgenic TCR+CD4+CD8+ thymocytes was seen within 8-20 hr. Thymocytes designed to bear I-Ad on their surface could mediate the deletion themselves. Thus, thymocyte clonal deletion entirely depends on the stage at which the thymocytes are vulnerable to the onset of apoptosis, rather than on the nature of the peptide antigen-presenting cells. Furthermore, thymic nurse cell line TNC-R3.1 could cause deletion, strongly suggesting that some thymic epithelial/stromal components are potentially capable of participating in negative selection. In all cases examined, little deletion could be induced at a peptide concentration less than 10 nM, thus defining the minimum amount of peptide antigen required for negative selection. The peptide-dependent in vitro negative-selection system will allow further dissection of the molecular and cellular processes involved in clonal deletion due to apoptosis in the thymus.     

IL-33 signaling contributes to the pathogenesis of myeloproliferative neoplasms

Myeloproliferative neoplasms (MPNs) are characterized by the clonal expansion of one or more myeloid cell lineage. In most cases, proliferation of the malignant clone is ascribed to defined genetic alterations. MPNs are also associated with aberrant expression and activity of multiple cytokines; however, the mechanisms by which these cytokines contribute to disease pathogenesis are poorly understood. Here, we reveal a non-redundant role for steady-state IL-33 in supporting dysregulated myelopoiesis in a murine model of MPN. Genetic ablation of the IL-33 signaling pathway was sufficient and necessary to restore normal hematopoiesis and abrogate MPN-like disease in animals lacking the inositol phosphatase SHIP. Stromal cell–derived IL-33 stimulated the secretion of cytokines and growth factors by myeloid and non-hematopoietic cells of the BM, resulting in myeloproliferation in SHIP-deficient animals. Additionally, in the transgenic JAK2^V617F model, the onset of MPN was delayed in animals lacking IL-33 in radio-resistant cells. In human BM, we detected increased numbers of IL-33–expressing cells, specifically in biopsies from MPN patients. Exogenous IL-33 promoted cytokine production and colony formation by primary CD34⁺ MPN stem/progenitor cells from patients. Moreover, IL-33 improved the survival of JAK2^V617F-positive cell lines. Together, these data indicate a central role for IL-33 signaling in the pathogenesis of MPNs.     

Speaking under pressure: Low linguistic complexity is linked to high physiological and emotional stress reactivity

What can a speech reveal about someone's state? We tested the idea that greater stress reactivity would relate to lower linguistic cognitive complexity while speaking. In Study 1, we tested whether heart rate and emotional stress reactivity to a stressful discussion would relate to lower linguistic complexity. In Studies 2 and 3, we tested whether a greater cortisol response to a standardized stressful task including a speech (Trier Social Stress Test) would be linked to speaking with less linguistic complexity during the task. We found evidence that measures of stress responsivity (emotional and physiological) and chronic stress are tied to variability in the cognitive complexity of speech. Taken together, these results provide evidence that our individual experiences of stress or “stress signatures”—how our body and mind react to stress both in the moment and over the longer term—are linked to how complex our speech under stress.