Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy

Post-transplant lymphomas or other lymphoproliferative lesions, which were usually associated with Epstein-Barr virus infections, developed in 8, 4, 3, and 2 recipients, respectively, of cadaveric kidney, liver, heart, and heart-lung homografts. Reduction or discontinuance of immunosuppression caused regression of the lesions, often without subsequent rejection of the grafts. Chemotherapy and irradiation were not valuable. The findings may influence policies about treating other kinds of post-transplantation neoplasms

In silico and in vitro drug screening identifies new therapeutic approaches for Ewing sarcoma.

The long-term overall survival of Ewing sarcoma (EWS) patients remains poor; less than 30% of patients with metastatic or recurrent disease survive despite aggressive combinations of chemotherapy, radiation and surgery. To identify new therapeutic options, we employed a multi-pronged approach using in silico predictions of drug activity via an integrated bioinformatics approach in parallel with an in vitro screen of FDA-approved drugs. Twenty-seven drugs and forty-six drugs were identified, respectively, to have anti-proliferative effects for EWS, including several classes of drugs in both screening approaches. Among these drugs, 30 were extensively validated as mono-therapeutic agents and 9 in 14 various combinations in vitro. Two drugs, auranofin, a thioredoxin reductase inhibitor, and ganetespib, an HSP90 inhibitor, were predicted to have anti-cancer activities in silico and were confirmed active across a panel of genetically diverse EWS cells. When given in combination, the survival rate in vivo was superior compared to auranofin or ganetespib alone. Importantly, extensive formulations, dose tolerance, and pharmacokinetics studies demonstrated that auranofin requires alternative delivery routes to achieve therapeutically effective levels of the gold compound. These combined screening approaches provide a rapid means to identify new treatment options for patients with a rare and often-fatal disease

Single-cell transcriptional profiling reveals cellular diversity and intercommunication in the mouse heart

Characterization of the cardiac cellulome, the network of cells that form the heart, is essential for understanding cardiac development and normal organ function and for formulating precise therapeutic strategies to combat heart disease. Recent studies have reshaped our understanding of cardiac cellular composition and highlighted important functional roles for non-myocyte cell types. In this study, we characterized single-cell transcriptional profiles of the murine non-myocyte cardiac cellular landscape using single-cell RNA sequencing (scRNA-seq). Detailed molecular analyses revealed the diversity of the cardiac cellulome and facilitated the development of techniques to isolate understudied cardiac cell populations, such as mural cells and glia. Our analyses also revealed extensive networks of intercellular communication and suggested prevalent sexual dimorphism in gene expression in the heart. This study offers insights into the structure and function of the mammalian cardiac cellulome and provides an important resource that will stimulate studies in cardiac cell biology

Evaluation of renal perfusion in hyperthyroid cats before and after radioiodine treatment

Background: Hyperthyroidism and chronic kidney disease (CKD) are common in elderly cats. Consequently, both diseases often occur concurrently. Furthermore, renal function is affected by thyroid status. Because changes in renal perfusion play an important role in functional renal changes in hyperthyroid cats, investigation of renal perfusion may provide novel insights. Objectives: To evaluate renal perfusion in hyperthyroid cats with contrast-enhanced ultrasound (CEUS). Animals: A total of 42 hyperthyroid cats was included and evaluated before and 1 month after radioiodine treatment. Methods: Prospective intrasubject clinical trial of contrast-enhanced ultrasound using a commercial contrast agent (SonoVue) to evaluate renal perfusion. Time-intensity curves were created, and perfusion parameters were calculated by off-line software. A linear mixed model was used to examine differences between pre-and post-treatment perfusion parameters. Results: An increase in several time-related perfusion parameters was observed after radioiodine treatment, indicating a decreased blood velocity upon resolution of the hyperthyroid state. Furthermore, a small post-treatment decrease in peak enhancement was present in the renal medulla, suggesting a lower medullary blood volume. Conclusions and Clinical Importance: Contrast-enhanced ultrasound indicated a higher cortical and medullary blood velocity and higher medullary blood volume in hyperthyroid cats before radioactive treatment in comparison with 1-month post-treatment control

Parenting behavior and the risk of becoming a victim and a bully/victim : a meta-analysis study

Objective: Being bullied has adverse effects on children's health. Children's family experiences and parenting behavior before entering school help shape their capacity to adapt and cope at school and have an impact on children's peer relationship, hence it is important to identify how parenting styles and parent–child relationship are related to victimization in order to develop intervention programs to prevent or mitigate victimization in childhood and adolescence. Methods: We conducted a systematic review of the published literature on parenting behavior and peer victimization using MEDLINE, PsychINFO, Eric and EMBASE from 1970 through the end of December 2012. We included prospective cohort studies and cross-sectional studies that investigated the association between parenting behavior and peer victimization. Results: Both victims and those who both bully and are victims (bully/victims) were more likely to be exposed to negative parenting behavior including abuse and neglect and maladaptive parenting. The effects were generally small to moderate for victims (Hedge's g range: 0.10–0.31) but moderate for bully/victims (0.13–0.68). Positive parenting behavior including good communication of parents with the child, warm and affectionate relationship, parental involvement and support, and parental supervision were protective against peer victimization. The protective effects were generally small to moderate for both victims (Hedge's g: range: −0.12 to −0.22) and bully/victims (−0.17 to −0.42). Conclusions: Negative parenting behavior is related to a moderate increase of risk for becoming a bully/victim and small to moderate effects on victim status at school. Intervention programs against bullying should extend their focus beyond schools to include families and start before children enter school

Swordtail Fry Attend to Chemical and Visual Cues in Detecting Predators and Conspecifics

Predation pressure and energy requirements present particularly salient opposing selective pressures on young fish. Thus, fry are expected to possess sophisticated means of detecting predators and resources. Here we tested the hypotheses that fry of the swordtail fish Xiphophorus birchmanni use chemical and visual cues in detection of predators and conspecifics. To test these hypotheses we presented young (<7 day-old) fry with combinations of visual and chemical stimuli from adult conspecifics and predators. We found that exposure to predator odors resulted in shoal tightening similar to that observed when fry were presented with visual cues alone. In trials with conspecific stimuli, fry were particularly attracted to adult conspecifics when presented simultaneous visual and chemical stimuli compared to the visual stimulus alone. These results show that fry attend to the odors of adult conspecifics, whose presence in a particular area may signal the location of resources as well as an absence of predators. This is one of the first studies to show that such young fish use chemical and visual cues in predator detection and in interactions with conspecifics. Previous research in X. birchmanni has shown that anthropogenic alteration of the chemical environment disrupts intraspecific chemical communication among adults; we suggest that because fry use the same chemosensory pathways to detect predators and conspecifics, alteration of the chemical environment may critically disrupt predator and resource detection

SCLC extensive disease – treatment guidance by extent or/and biology of response?

In extensive disease of small cell lung cancer a doubling of the one-year-survival rate was reported in August 2007 by prophylactic cranial irradiation applied to patients who experienced any response to initial chemotherapy. We discuss the treatment concept of extensive disease in the face of the latest results and older studies with additional thoracic irradiation in this subgroup. A randomized trial with prophylactic cranial irradiation published in 1999 demonstrated an improvement of 5-year-overall-survival for complete responders (at least at distant levels) receiving additional thoracic radiochemotherapy compared to chemotherapy alone (9.1% vs. 3.7%). But, these results were almost neglected and thoracic radiotherapy was not further investigated for good responders of extensive disease. However, in the light of current advances by prophylactic cranial irradiation these findings are noteworthy on all accounts. Considering both, a possible interpretation of these data could be a survival benefit of local control by simultaneous thoracic radiochemotherapy in the case of improved distant control due to chemotherapy and prophylactic cranial irradiation. Furthermore the question arises whether the tumor biology indicated by the response to chemotherapy should be integrated in the present classification

Core components for effective infection prevention and control programmes: new WHO evidence-based recommendations

Abstract Health care-associated infections (HAI) are a major public health problem with a significant impact on morbidity, mortality and quality of life. They represent also an important economic burden to health systems worldwide. However, a large proportion of HAI are preventable through effective infection prevention and control (IPC) measures. Improvements in IPC at the national and facility level are critical for the successful containment of antimicrobial resistance and the prevention of HAI, including outbreaks of highly transmissible diseases through high quality care within the context of universal health coverage. Given the limited availability of IPC evidence-based guidance and standards, the World Health Organization (WHO) decided to prioritize the development of global recommendations on the core components of effective IPC programmes both at the national and acute health care facility level, based on systematic literature reviews and expert consensus. The aim of the guideline development process was to identify the evidence and evaluate its quality, consider patient values and preferences, resource implications, and the feasibility and acceptability of the recommendations. As a result, 11 recommendations and three good practice statements are presented here, including a summary of the supporting evidence, and form the substance of a new WHO IPC guideline