Cognitive–Behavioral Treatment of Posttraumatic Stress in Patients With Implantable Cardioverter Defibrillators: Results From a Randomized Controlled Trial

Approximately 20% of patients with implantable cardioverter defibrillators (ICDs) suffer from posttraumatic stress disorder (PTSD) due to a history of cardiac arrest, device implantation, and ICD shock. There has been very little examination of treatment of PTSD symptoms in these patients. This study evaluated the effect of a specific cognitive–behavioral therapy (CBT) intervention for ICD patients with high levels of PTSD symptoms: a manualized program consisting of 8 telephone sessions with a trained counselor, a patient education book, and a stress management procedure on compact disc. Participants were 193 ICD patients, who were randomized to CBT or usual cardiac care (UCC) who completed self‐report surveys at the time of recruitment and 6 and 12 months after initial measurement. Previous publication on the primary research evaluation questions reported that the CBT condition resulted in greater improvement on PTSD and depression symptoms than the UCC for the general population of ICD patients, but did not evaluate the effect on those with elevated symptoms of PTSD. The authors conducted secondary analyses of the effect of treatment on high and low PTSD symptom groups based on a cutoff for the Impact of Event Scale‐Revised (Weiss & Marmar, 1997). Participants in the CBT group who had high symptoms experienced significantly greater symptom reduction from baseline to 12 months (d = 2.44, p = .021) than the UCC group (d = 1.12). Participants with low symptoms had small reductions regardless of group assignment (d = 0.16, p = .031). ICD‐focused CBT was sufficient to produce a large, statistically significant reduction in PTSD symptoms in ICD patients with indications for treatment.     

Comparison of Dexmedetomidine–Ketamine with Isoflurane for Anesthesia of Chinchillas (Chinchilla lanigera)

The objective of this study was to compare isoflurane with a combination of dexmedetomidine and ketamine, administered intramuscularly, for anesthesia in chinchillas (Chinchilla lanigera). In a prospective, complete crossover study, adult chinchillas (n = 8; age, 2 to 5 y) were anesthetized with a combination of dexmedetomidine (0.015 mg/kg IM) and ketamine (4 mg/kg IM). Atipamezole (0.15 mg/kg) was injected subcutaneously 45 min after dexmedetomidine–ketamine administration. For comparison, anesthesia also was induced and maintained with isoflurane in 100% oxygen, delivered by facemask. Anesthetic and physiologic parameters were recorded during each anesthesia, including various reflexes, heart rate, respiratory rate, body temperature, and SpO₂. Food intake, fecal output, and body weight were recorded daily for 6 d after each anesthetic trial. Induction time, heart rate, respiratory rate, and body temperature did not differ significantly between the 2 anesthetic protocols. Recovery times were shorter and SpO₂ was higher in animals that received isoflurane delivered in 100% oxygen. Food intake and fecal output were reduced in the dexmedetomidine–ketamine group for as long as 3 d after anesthesia, whereas isoflurane had no signifcant effect on food intake or fecal output. Both anesthetic protocols provided effective anesthesia in chinchillas. However, when anesthetized with dexmedetomidine–ketamine, chinchillas received room air and became hypoxemic. Future studies are needed to evaluate the effect of oxygen supplementation on anesthetic recovery and on the recovery of food intake and fecal output in chinchillas.Abbreviation: DK, dexmedetomidine–ketamineChinchillas are used extensively in research to study otitis media, hearing loss, and ototoxicity.^1,11,19,25 In addition, chinchillas are becoming increasingly popular as companion animals and, therefore, are more frequently presented for veterinary care. Common diseases of chinchillas include dental disease, gastrointestinal disorders, and ocular disorders.^13,14 Chemical immobilization is often required to perform diagnostic (for example, radiography, CT), therapeutic, or experimental procedures.^3,5,7,21 Research regarding the efficacy and safety of anesthetic protocols in chinchillas is limited and currently recommended protocols rely largely on extrapolation from other species or anecdotal reports.^13,21,27Isoflurane is used routinely in chinchillas for the induction and maintenance of anesthesia. A study investigating the echocardiographic effects of isoflurane in chinchillas found significant effects on several echocardiographic parameters, but no complications or other side effects were reported.¹² Isoflurane typically is delivered by facemask to chinchillas, given that endotracheal intubation is technically challenging and therefore not performed routinely.^10,21 However, using a facemask increases the risk of exposure of the veterinary staff to waste gases, which is a significant occupational health concern.^20,23 Therefore, alternative anesthetic protocols that reduce waste-gas exposure are desired, such as exclusively using injectable anesthetic drugs for induction and maintenance of anesthesia. Intravascular access is challenging to obtain in conscious chinchillas, and thus parenteral, nonvascular protocols provide the most accommodating route for anesthesia induction and maintenance.¹⁴ Only one study in chinchillas has investigated the effects of various injectable anesthetics: a combination of medetomidine (0.06 mg/kg) and ketamine (5 mg/kg) was compared with other parenteral protocols.¹⁴ Although anesthesia was successful with this protocol, the authors reported respiratory and cardiac depression in the animals. Furthermore, although atipamezole is commonly administered in clinical and research settings to promote rapid recovery and prevent complications, such as hypothermia, it was not used in the cited study.¹⁴To our knowledge, no studies have been published that assess the effects of anesthetic protocols on recovery of food intake and fecal output in chinchillas. The objective of this study was to compare the anesthesia induced in chinchillas by using either dexmedetomidine and ketamine or isoflurane and to evaluate the effects of both anesthetic protocols on subsequent food intake, fecal output, and body weight.     

The pain of fibromyalgia syndrome is due to muscle hypoperfusion induced by regional vasomotor dysregulation

Fibromyalgia syndrome (FMS) is a condition of chronic muscle pain and fatigue of unknown etiology and pathogenesis. There is limited support for the various hypotheses espoused to account for the manifestations of FMS, including immunogenic, endocrine, and neurological mechanisms. Treatment, partially effective at best, is directed toward symptomatic relief without the benefit of targeting known, underlying pathology. A noteworthy commonality among partially effective therapies is a vasodilatory effect. This is true both of conventional treatments, unconventional treatments such as intravenous micronutrient therapy, and lifestyle treatments, specifically graduated exercise. The pain of fibromyalgia is described in terms suggestive of the pain in muscles following extreme exertion and anaerobic metabolism. Taken together, these characteristics suggest that the pain could be induced by vasomotor dysregulation, and vasoconstriction in muscle, leading to low-level ischemia and its metabolic sequelae. Vasodilatory influences, including physical activity, relieve the pain of FMS by increasing muscle perfusion. There are some preliminary data consistent with this hypothesis, and nothing known about FMS that refutes it. The hypothesis that the downstream cause of FMS symptoms is muscle hypoperfusion due to regional vasomotor dysregulation has clear implications for treatment; is testable with current technology; and should be investigated.     

Btk regulates multiple stages in the development and survival of B-1 cells

B-1 cells are important players in the first line of defense against pathogens. According to current models for the origin of B-1 cells, they either represent a separate lineage from conventional B-2 cells or differentiate from conventional B-2 cells via an intermediate, B-1(int), in response to positive selection by antigen. Here we show that Btk, a Tec family kinase that mediates B cell antigen receptor (BCR) signaling, is required at multiple stages of B-1 cell development. VH12 anti-phosphatidylcholine (PtC) IgH transgenic mice provide a model for the induced differentiation of B-1 cells. This transgene selects for PtC-reactive cells and induces them to adopt a B-1 phenotype. Both processes have been shown to depend on Btk. To determine whether this is secondary to a requirement for Btk in the development of mature B-2 cells, we crossed VH12 transgenic mice to mice expressing low levels of Btk. B-2 cell development occurs normally in Btk(lo) mice despite reduced responsiveness to BCR crosslinking. Analysis of VH12.Btk(lo) mice reveals that Btk regulates the B-1(int) to B-1 transition and/or the survival of splenic B-1 cells, in part via a mechanism independent of its role in BCR signaling. We also show that Btk mediates the survival of, and expression of IL-10 by, those B-1 cells that do develop and migrate to the peritoneum. Multiple roles for Btk in B-1 cell development and maintenance may explain the particular sensitivity of this population to mutations in components of Btk signaling pathways.     

HIV-1 prophylactic vaccine comprised of topical DermaVir prime and protein boost elicits cellular immune responses and controls pathogenic R5 SHIV162P3

Topical DNA vaccination (DermaVir) facilitates antigen presentation to naive T cells. DermaVir immunization in mice, using HIV-1 Env and Gag, elicited cellular immune responses. Boosting with HIV-1 gp120 Env and p41 Gag augmented Th1 cytokine levels. Intramuscular DNA administration was less efficient in priming antigen-specific cytokine production and memory T cells. In rhesus macaques, DermaVir immunization induced Gag- and Env-specific Th1 and Th2 cytokines and generation of memory T cells. Boosting of DermaVir-primed serum antibody levels was noted following gp140(SHIV89.6P)/p27(SIV) immunization. Rectal challenge with pathogenic R5-tropic SHIV162P3 resulted in control of plasma viremia (4/5 animals) that was reflected in jejunum, colon and mesenteric lymph nodes. An inverse correlation was found between Gag- and Env-specific central memory T cell responses on the day of challenge and plasma viremia at set point. Overall, the topical DermaVir/protein vaccination yields central memory T cell responses and facilitates control of pathogenic SHIV infection.     

Overexpression of carcinoma and embryonic cytotrophoblast cell-specific Mig-7 induces invasion and vessel-like structure formation

Molecular requirements for carcinoma cell interactions with the microenvironment are critical for disease progression but are poorly understood. Integrin alpha v beta 5, which senses the extracellular matrix, is important for carcinoma cell dissemination in vivo. alpha v beta 5 signaling induces Mig-7, a novel human gene product that is apparently carcinoma-specific. We hypothesized that Mig-7 expression facilitates tumor cell dissemination by increasing invasion and vasculogenic mimicry. Results show that embryonic cytotrophoblasts up-regulated Mig-7 expression before they acquired an invasive phenotype capable of pseudovasculogenesis. Mig-7 protein primarily co-localized with vasculogenic mimicry markers factor VIII-associated antigen, vascular endothelial-cadherin, and laminin 5 gamma 2 chain domain III fragment in lymph node metastases. Overexpression of Mig-7 increased gamma 2 chain domain III fragments known to contain epidermal growth factor (EGF)-like repeats that can activate EGF receptor. Interestingly, EGF also induced Mig-7 expression. Carcinoma cell adhesion to laminins was significantly reduced by Mig-7 expression. Remarkably, in two-dimensional and three-dimensional Matrigel cultures, Mig-7 expression caused invasion and vessel-like structures. Melanoma cells, which were previously characterized to invade aggressively and to undergo vasculogenic mimicry, expressed Mig-7. Taken together, these data suggest that Mig-7 expression allows cells to sense their environment, to invade, and to form vessel-like structures through a novel relationship with laminin 5 gamma 2 chain domain III fragments.     

A histological survey of green fluorescent protein expression in 'green' mice: implications for stem cell research

AIMS: The transgenic enhanced green fluorescent protein (EGFP) expressing 'green' mouse (C57BL/6-TgN(ACTbEGFP)1Osb) is a widely used tool in stem cell research, where the ubiquitous nature of EGFP expression is critical to track the fate of single or small groups of transplanted haematopoietic stem cells (HSC). Our aim was to investigate this assumed ubiquitous expression by performing a detailed histological survey of EGFP expression in these mice. METHODS: Fluorescent microscopy of frozen tissue sections was used to perform a detailed histological survey of the pattern of EGFP expression in these mice. Flow cytometry was also used to determine the expression pattern in blood and bone marrow. RESULTS: Three patterns of EGFP expression were noted. In most tissues there was an apparently stochastic variegation of the transgene, with individual cell types demonstrating highly variable rates of EGFP expression. Certain specific cell types such as pancreatic ductal epithelium, cerebral cortical neurones and glial cells and glomerular mesangial cells consistently lacked EGFP expression, while others, including pancreatic islet cells, expressed EGFP only at extremely low levels, barely distinguishable from background. Lastly, in the colon and stomach the pattern of EGFP expression was suggestive of clonal inactivation. Only cardiac and skeletal muscle showed near ubiquitous expression. CONCLUSIONS: These findings raise questions regarding the 'ubiquitous' expression of EGFP in these transgenic mice and suggest caution in relying overly on EGFP alone as an infallible marker of donor cell origin.     

Arguments Used in Public Comments to Support or Oppose the US Department of Agriculture’s Minimum Stocking Requirements: A Content Analysis

Background

In 2016, the US Department of Agriculture (USDA)’s Supplemental Nutrition Assistance Program (SNAP) Retailer Rule proposed several changes for SNAP-authorized retailers, including: requiring retailers to have at least 85% of their food sales come from items that are not cooked or heated on site before or after purchase; requiring stores to stock seven varieties of qualifying foods from four staple food groups; requiring stores to carry perishable foods in three of the four staple groups; requiring stores to carry six units of qualifying foods at all times (depth of stock); disqualifying multiple ingredient foods and accessory foods from counting toward depth of stock requirements.