The Medical Research Council Myeloma IX trial: the impact on treatment paradigms*

Osteolytic bone disease is a hallmark of symptomatic multiple myeloma. Bisphosphonates have been the mainstay of treatment to preserve skeletal integrity and prevent skeletal-related events in patients with myeloma-related bone disease. Recently, the MRC Myeloma IX trial demonstrated for the first time improved survival and delayed disease progression with the use of an intravenous amino-bisphosphonate, zoledronic acid, vs. an oral agent, clodronate, with intensive and non-intensive anti-myeloma treatment regimens in patients with newly diagnosed multiple myeloma. These results validate a large body of preclinical, translational and other clinical data suggesting anti-myeloma effects of amino-bisphosphonates. In addition, this trial also provided the first head-to-head evidence for superiority of one bisphosphonate over another (zoledronic acid vs. clodronate) for reducing skeletal morbidity in patients with multiple myeloma, as well as a prospective comparison of toxicities. Despite the use of non-bortezomib containing anti-myeloma treatment regimens in the MRC Myeloma IX trial, these results are encouraging and provide an impetus to continue to evaluate current treatment guidelines for myeloma-associated bone disease

Cultural Influences in the Processing of Emotion Schemas Related to Death and Violence: A Pilot Study

Culture is a key element in determining emotions that people experience when facing death. Recent studies revealed a specific emotion schema for the affective response to death (in comparison with unpleasant/violence-related stimulus), influenced by differences in the personalities and learning processes of the individuals, on the one hand, and differences in the cultural and social contexts of the two groups, on the other. The objective of the research was to compare the English participants’ affective response to pictures of death to those of the Spanish participants, who viewed other types of affective pictures (pleasant, unpleasant/violence-related and neutral). A total of 38 young adults took part in an emotional assessment using a set of pictures from the International Affective Picture System (IAPS) database. They indicated the values of valence, arousal and dominance for each affective image. The results show that the images related to death were less unpleasant and caused a lower activation in the English population, while there were no differences in the two group’s responses to unpleasant/violent images

Risk of high-grade serous ovarian cancer associated with pelvic inflammatory disease, parity and breast cancer

Background: Ovarian carcinoma is not a single disease, but rather a collection of subtypes with differing molecular properties and risk profiles. The most common of these, and the subject of this work, is high-grade serous ovarian carcinoma (HGSC). Methods: In this population-based study we identified a cohort of 441,382 women resident in Western Australia who had ever been admitted to hospital in the State. Of these, 454 were diagnosed with HGSC. We used Cox regression to derive hazard ratios (HRs) comparing the risk of disease in women who had each of a range of medical diagnoses and surgical procedures with women who did not. Results: We found an increased risk of HGSC associated with a diagnosis of pelvic inflammatory disease (PID) (HR 1.47, 95% CI 1.04–2.07) but not with a diagnosis of infertility or endometriosis with HRs of 1.12 (95% CI 0.73–1.71) and 0.82 (95% CI 0.55–1.22) respectively. A personal history of breast cancer was associated with a three-fold increase in the rate of HGSC. Increased parity was associated with a reduced risk of HGSC in women without a personal history of breast cancer (HR 0.57; 95% CI 0.44-0.73), but not in women with a personal history of breast cancer (HR 1.48; 95% CI 0.74–2.95). Conclusions: Our finding of an increased risk of HGSC associated with PID lends support to the hypothesis that inflammatory processes may be involved in the etiology of HGSC

Fission Yeast Cells Undergo Nuclear Division in the Absence of Spindle Microtubules

Through a previously undescribed mechanism, fission yeast cells can undergo nuclear division and enter the next cell cycle, even in the absence of spindle microtubules

A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2013 Recommendations by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM)a

The critical role of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician and the microbiologists who provide enormous value to the health care team. This document, developed by both laboratory and clinical experts, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. Sections are divided into anatomic systems, including Bloodstream Infections and Infections of the Cardiovascular System, Central Nervous System Infections, Ocular Infections, Soft Tissue Infections of the Head and Neck, Upper Respiratory Infections, Lower Respiratory Tract infections, Infections of the Gastrointestinal Tract, Intraabdominal Infections, Bone and Joint Infections, Urinary Tract Infections, Genital Infections, and Skin and Soft Tissue Infections; or into etiologic agent groups, including Tickborne Infections, Viral Syndromes, and Blood and Tissue Parasite Infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. There is redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a reference to guide physicians in choosing tests that will aid them to diagnose infectious diseases in their patients

Local flexibility in feeding behaviour and contrasting microhabitat use of an omnivore across latitudes

As the environment is getting warmer and species are redistributed, consumers can be forced to adjust their interactions with available prey, and this could have cascading effects within food webs. To better understand the capacity for foraging flexibility, our study aimed to determine the diet variability of an ectotherm omnivore inhabiting kelp forests, the sea urchin Echinus esculentus, along its entire latitudinal distribution in the northeast Atlantic. Using a combination of gut content and stable isotope analyses, we determined the diet and trophic position of sea urchins at sites in Portugal (42° N), France (49° N), southern Norway (63° N), and northern Norway (70° N), and related these results to the local abundance and distribution of putative food items. With mean estimated trophic levels ranging from 2.4 to 4.6, omnivory and diet varied substantially within and between sites but not across latitudes. Diet composition generally reflected prey availability within epiphyte or understorey assemblages, with local affinities demonstrating that the sea urchin adjusts its foraging to match the small-scale distribution of food items. A net “preference” for epiphytic food sources was found in northern Norway, where understorey food was limited compared to other regions. We conclude that diet change may occur in response to food source redistribution at multiple spatial scales (microhabitats, sites, regions). Across these scales, the way that key consumers alter their foraging in response to food availability can have important implication for food web dynamics and ecosystem functions along current and future environmental gradients

Mechanisms and mechanics of cell competition in epithelia

When fast-growing cells are confronted with slow-growing cells in a mosaic tissue, the slow-growing cells are often progressively eliminated by apoptosis through a process known as cell competition. The underlying signalling pathways remain unknown, but recent findings have shown that cell crowding within an epithelium leads to the eviction of cells from the epithelial sheet. This suggests that mechanical forces could contribute to cell elimination during cell competition

Finding the Cell Center by a Balance of Dynein and Myosin Pulling and Microtubule Pushing: A Computational Study

By comparing computer modeling predictions with observations, we conclude that strong dynein and weaker myosin-generated forces pull the microtubules inward competing with microtubule plus-ends pushing the microtubule aster outward and that the balance of these forces positions the centrosome at the cell center

Guidelines for diagnosis and management of the cobalamin-related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency

BACKGROUND: Remethylation defects are rare inherited disorders in which impaired remethylation of homocysteine to methionine leads to accumulation of homocysteine and perturbation of numerous methylation reactions. OBJECTIVE: To summarise clinical and biochemical characteristics of these severe disorders and to provide guidelines on diagnosis and management. DATA SOURCES: Review, evaluation and discussion of the medical literature (Medline, Cochrane databases) by a panel of experts on these rare diseases following the GRADE approach. KEY RECOMMENDATIONS: We strongly recommend measuring plasma total homocysteine in any patient presenting with the combination of neurological and/or visual and/or haematological symptoms, subacute spinal cord degeneration, atypical haemolytic uraemic syndrome or unexplained vascular thrombosis. We strongly recommend to initiate treatment with parenteral hydroxocobalamin without delay in any suspected remethylation disorder; it significantly improves survival and incidence of severe complications. We strongly recommend betaine treatment in individuals with MTHFR deficiency; it improves the outcome and prevents disease when given early