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It remains unclear whether airway smooth muscle (ASM) mechanics is altered in asthma. While efforts have originally focussed on contractile force, some evidence points to an increased velocity of shortening. A greater rate of airway renarrowing after a deep inspiration has been reported in asthmatics compared to controls, which could result from a shortening velocity increase. In addition, we have recently shown in rats that increased shortening velocity correlates with increased muscle shortening, without increasing muscle force. Nonetheless, establishing whether or not asthmatic ASM shortens faster than that of normal subjects remains problematic. Endobronchial biopsies provide excellent tissue samples because the patients are well characterized, but the size of the samples allows only cell level experiments. Whole human lungs from transplant programs suffer primarily from poor patient characterization, leading to high variability. ASM from several animal models of asthma has shown increased shortening velocity, but it is unclear whether this is representative of human asthma. Several candidates have been suggested as responsible for increased shortening velocity in asthma, such as alterations in contractile protein expression or changes in the contractile apparatus structure. There is no doubt that more remains to be learned about the role of shortening velocity in asthma.

Reginald M Gorczynski,1 Fang Zhu2 1Department of Surgical Research, University Health Network, 2Department of Surgical Research, Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada Abstract: In the ontogeny of a normal immune response, a series of checkpoints must be overcome to ensure that unwanted and/or harmful self-directed activation responses are avoided. Many of the molecules now known to be active in this overseeing of the evolving immune activation cascade, contributing inhibitory signals to dampen an overexuberant response, belong to the immunoglobulin supergene family. These include members of the CD28/CTLA-4:B7.1/B7.2 receptor/ligand family, PD-1 and PDL-1, CD200 and CD200R, and the more recently described V-domain immunoglobulin suppressor of T-cell activation and its ligand (VSIG-3/IGSF11). Unfortunately, from the point of view of improving immunotargeting of cancer cells, triggering these checkpoint inhibitory signaling pathways, so necessary to maintain self-tolerance, simultaneously acts to prevent effective tumor immunity. The recent development of reagents, predominantly antibodies, to act as checkpoint blockade agents, has had a dramatic effect on human cancer treatment, with a marked reported success for anti-CTLA-4 and PD-1 in particular in clinical trials. This review provides a general overview of the data now available showing the promise of such treatments to our cancer armamentarium and elaborates in depth on the potential promise of what can be regarded as an underappreciated target molecule for checkpoint blockade in chronic lymphocytic leukemia and solid tumors, CD200. Keywords: checkpoint blockade, immunotherapy, oncology, inhibitory pathways, stimulatory pathways, activated T cells

Background: Several practice guidelines recommend screening for depression in cancer care, but no systematic reviews have examined whether there is evidence that depression screening benefits cancer patients. The objective was to evaluate the potential benefits of depression screening in cancer patients by assessing the (1) accuracy of depression screening tools; (2) effectiveness of depression treatment; and (3) effect of depression screening, either alone or in the context of comprehensive depression care, on depression outcomes.Methods: Data sources were CINAHL, Cochrane, EMBASE, ISI, MEDLINE, PsycINFO and SCOPUS databases through January 24, 2011; manual journal searches; reference lists; citation tracking; trial registry reviews. Articles on cancer patients were included if they (1) compared a depression screening instrument to a valid criterion for major depressive disorder (MDD); (2) compared depression treatment with placebo or usual care in a randomized controlled trial (RCT); (3) assessed the effect of screening on depression outcomes in a RCT.Results: There were 19 studies of screening accuracy, 1 MDD treatment RCT, but no RCTs that investigated effects of screening on depression outcomes. Screening accuracy studies generally had small sample sizes (median = 17 depression cases) and used exploratory methods to set sample-specific cutoff scores that varied substantially across studies. A nurse-delivered intervention for MDD reduced depressive symptoms moderately (effect size = 0.37).Conclusions: The one treatment study reviewed reported modest improvement in depressive symptoms, but no evidence was found on whether or not depression screening in cancer patients, either alone or in the context of optimal depression care, improves depression outcomes compared to usual care. Depression screening in cancer should be evaluated in a RCT in which all patients identified as depressed, either through screening or via physician recognition and referral in a control group, have access to comprehensive depression care.

Genomic imprinting is a form of epigenetic inheritance whereby the regulation of a gene or chromosomal region is dependent on the sex of the transmitting parent. During gametogenesis, imprinted regions of DNA are differentially marked in accordance to the sex of the parent, resulting in parent-specific expression. While mice are the primary research model used to study genomic imprinting, imprinted regions have been described in a broad variety of organisms, including other mammals, plants, and insects. Each of these organisms employs multiple, interrelated, epigenetic mechanisms to maintain parent-specific expression. While imprinted genes and imprint control regions are often species and locus-specific, the same suites of epigenetic mechanisms are often used to achieve imprinted expression. This review examines some examples of the epigenetic mechanisms responsible for genomic imprinting in mammals, plants, and insects.

Ramanathan K Kasimanickam,1 Ashish Ranjan,2 GV Asokan,3 Vanmathy R Kasimanickam,1 John P Kastelic41Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA; 2Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, USA; 3College of Health Sciences, University of Bahrain, Salmaniya Medical Complex, Manama, Bahrain; 4Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, CanadaAll authors contributed equally to this workAbstract: Bacteria growing as adherent biofilms are difficult to treat and frequently develop resistance to antimicrobial agents. To counter biofilms, various approaches, including prevention of bacterial surface adherence, application of device applicators, and assimilation of antimicrobials in targeted drug delivery machinery, have been utilized. These methods are also combined to achieve synergistic bacterial killing. This review discusses various multimodal technologies, presents general concepts, and describes therapies relying on the principles of electrical energy, ultrasound, photodynamics, and targeted drug delivery for prevention and treatment of biofilms.Keywords: biofilm, antimicrobial, drug carrier, hybrid technology, nanotechnology

This paper is a report of an integrative review conducted to assess the methodological and ethical strategies used to protect participants and researchers in conducting violence against women (VAW) studies in Pakistan. The measurement of the prevalence of violence against women in Pakistan is challenging for researchers given the cultural norms and the traditional role of women. Lack of methodological rigor in addressing the concerns can result in underreporting of violence, create physical and emotional risk for the participants, interviewers, and researchers, and impose threats to internal and external validity of VAW studies. Using Whittemore and Knafl’s process for conducting an integrative review, 11 studies published between 1999 and 2012, reporting on prevalence, experiences, and factors associated with violence in a marital relationship were analyzed. Overall, studies reveal an underreporting of exposure to violence and threats to women and interviewers’ safety in the conduct of such studies, both of which present threats to study rigor. The utilization of WHO ethical and safety recommendations to guide VAW studies in this context should be considered.