Activation of androgen receptor-expressing neurons in the posterior medial amygdala is associated with stress resistance in dominant male hamsters.

Social stress is a negative emotional experience that can increase fear and anxiety. Dominance status can alter the way individuals react to and cope with stressful events. The underlying neurobiology of how social dominance produces stress resistance remains elusive, although experience-dependent changes in androgen receptor (AR) expression is thought to play an essential role. Using a Syrian hamster (Mesocricetus auratus) model, we investigated whether dominant individuals activate more AR-expressing neurons in the posterior dorsal and posterior ventral regions of the medial amygdala (MePD, MePV), and display less social anxiety-like behavior following social defeat stress compared to subordinate counterparts. We allowed male hamsters to form and maintain a dyadic dominance relationship for 12 days, exposed them to social defeat stress, and then tested their approach-avoidance behavior using a social avoidance test. During social defeat stress, dominant subjects showed a longer latency to submit and greater c-Fos expression in AR+ cells in the MePD/MePV compared to subordinates. We found that social defeat exposure reduced the amount of time animals spent interacting with a novel conspecific 24 h later, although there was no effect of dominance status. The amount of social vigilance shown by dominants during social avoidance testing was positively correlated with c-Fos expression in AR+ cells in the MePV. These findings indicate that dominant hamsters show greater neural activity in AR+ cells in the MePV during social defeat compared to their subordinate counterparts, and this pattern of neural activity correlates with their proactive coping response. Consistent with the central role of androgens in experience-dependent changes in aggression, activation of AR+ cells in the MePD/MePV contributes to experience-dependent changes in stress-related behavior.

Cohabitation COVID-19 transmission rates in a United States suburban community: A retrospective study of familial infections.

OBJECTIVES: SARS-CoV-2 is a highly contagious virus that causes coronavirus disease 2019 (COVID-19) and can affect people of any age with potential for serious symptoms. Since the start of the COVID-19 pandemic, global infection rates have been on the rise with world leaders looking to slow and stop viral transmission. This study is looking at suburban cohabitation/familial infection to compare to similar studies from other countries. STUDY DESIGN: A retrospective review of medical records was collected using the Connecticut Electronic Disease Surveillance System. METHODS: A total of 406 cases who tested positive for SARS-COV-2 from February to June 2020 were reviewed from three towns located in Connecticut, USA. Cohabitation infection rates were identified using the home addresses of those with confirmed SARS-CoV-2 test results, with the first documented case being the index case, and additional home members being the secondary cases. RESULTS: Secondary transmission of SARS-CoV-2 developed in 126 of 406 household contacts (31%). Linear regression indicated positive relationship between cohabitation and age. CONCLUSIONS: The cohabitation infection attack rate of SARS-CoV-2 is significantly higher than previously reported. Age of household contacts and spousal relationship to the index case are risk factors for transmission of SARS-CoV-2 within a household.

Imaging perturbed shock propagation in powders.

A novel experimental methodology is presented to study the deviatoric response of powders in shock regimes. The powders are confined to a cylindrical wedge volume, and a projectile-driven shock wave with a sinusoidally varying front propagates through the powder. The perturbed shock wave exhibits a damping behavior due to irreversible processes of viscosity and strength (deviatoric) of the powder with propagation through increasing powder thicknesses. The inclined surface of the wedge is polished and coated to establish a diffuse surface suitable for reflecting incident laser light into a high-speed camera imaging at 5 MHz. Images of the contrast loss upon shock wave arrival at the observation surface are post-processed for qualitative and quantitative information. New data of shock damping behavior with parameters of perturbation wavelength and initial shock strength are presented for powders of copper, tantalum, and tungsten carbide as well as their mixtures. We present the first full-field images showing additional spatial disturbances on the perturbed shock front that appear dependent on particle material and morphology.

Mycobacterium chimaera infection following cardiac surgery in the United Kingdom: clinical features and outcome of the first 30 cases.

OBJECTIVES: Mycobacterium chimaera infection following cardiac surgery, due to contaminated cardiopulmonary bypass heater-cooler units, has been reported worldwide. However, the spectrum of clinical disease remains poorly understood. To address this, we report the clinical and laboratory features, treatment and outcome of the first 30 UK cases. METHODS: Case note review was performed for cases identified retrospectively through outbreak investigations and prospectively through ongoing surveillance. Case definition was Mycobacterium chimaera detected in any clinical specimen, history of cardiothoracic surgery with cardiopulmonary bypass, and compatible clinical presentation. RESULTS: Thirty patients were identified (28 with prosthetic material) exhibiting a spectrum of disease including prosthetic valve endocarditis (14/30), sternal wound infection (2/30), aortic graft infection (4/30) and disseminated (non-cardiac) disease (10/30). Patients presented a median of 14 months post surgery (maximum 5 years) most commonly complaining of fever and weight loss. Investigations frequently revealed lymphopenia, thrombocytopenia, liver cholestasis and non-necrotizing granulomatous inflammation. Diagnostic sensitivity for a single mycobacterial blood culture was 68% but increased if multiple samples were sent. In all, 27 patients started macrolide-based combination treatment and 14 had further surgery. To date, 18 patients have died (60%) a median of 30 months (interquartile range 20-39 months) after initial surgery. Survival analysis identified younger age, mitral valve surgery, mechanical valve replacement, higher serum sodium concentration and lower C-reactive protein as factors associated with better survival. CONCLUSIONS: Mycobacterium chimaera infection following cardiac surgery is associated with a wide spectrum of disease. The diagnosis should be considered in all patients who develop an unexplained illness following cardiac surgery.

Evidence against a role for NLRP3-driven islet inflammation in db/db mice.

OBJECTIVES: Type 2 diabetes (T2D) is associated with chronic, low grade inflammation. Activation of the NLRP3 inflammasome and secretion of its target interleukin-1ß (IL-1ß) have been implicated in pancreatic ß cell failure in T2D. Specific targeting of the NLRP3 inflammasome to prevent pancreatic ß cell death could allow for selective T2D treatment without compromising all IL-1ß-associated immune responses. We hypothesized that treating a mouse model of T2D with MCC950, a compound that specifically inhibits NLRP3, would prevent pancreatic ß cell death, thereby preventing the onset of T2D. METHODS: Diabetic db/db mice were treated with MCC950 via drinking water for 8 weeks from 6 to 14 weeks of age, a period over which they developed pancreatic ß cell failure. We assessed metabolic parameters such as body composition, glucose tolerance, or insulin secretion over the course of the intervention. RESULTS: MCC950 was a potent inhibitor of NLRP3-induced IL-1ß in vitro and was detected at high levels in the plasma of treated db/db mice. Treatment of pre-diabetic db/db mice with MCC950, however, did not prevent pancreatic dysfunction and full onset of the T2D pathology. When examining the NLRP3 pathway in the pancreas of db/db mice, we could not detect an activation of this pathway nor increased levels of its target IL-1ß. CONCLUSIONS: NLRP3 driven-pancreatic IL-1ß inflammation does not play a key role in the pathogenesis of the db/db murine model of T2D.

Endocrine responses and acute mTOR pathway phosphorylation to resistance exercise with leucine and whey.

Leucine ingestion reportedly activates the mTOR pathway in skeletal muscle, contributing to a hypertrophy response. The purpose of the study was to compare the post-resistance exercise effects of leucine and whey protein supplementation on endocrine responses and muscle mTOR pathway phosphorylation. On visit 1, subjects (X±SD; n=20; age=27.8±2.8yrs) provided baseline blood samples for analysis of cortisol, glucose and insulin; a muscle biopsy of the vastus lateralis muscle to assess mTOR signaling pathway phosphorylation; and were tested for maximum strength on the leg press and leg extension exercises. For visits 2 and 3, subjects were randomized in a double-blind crossover design to ingest either leucine and whey protein (10g+10g; supplement) or a non-caloric placebo. During these visits, 5 sets of 10 repetitions were performed on both exercises, immediately followed by ingestion of the supplement or placebo. Blood was sampled 30 min post-, and a muscle biopsy 45 min post-exercise. Western blots quantified total and phosphorylated proteins. Insulin increased (α<.05) with supplementation with no change in glucose compared to placebo. Relative phosphorylation of AKT and rpS6 were greater with leucine and whey supplementation compared to placebo. Supplementation of leucine and whey protein immediately after heavy resistance exercise increases anabolic signaling in human skeletal muscle.

Inhibiting the NLRP3 inflammasome with MCC950 promotes non-phlogistic clearance of amyloid-ß and cognitive function in APP/PS1 mice.

Activation of the inflammasome is implicated in the pathogenesis of an increasing number of inflammatory diseases, including Alzheimer's disease (AD). Research reporting inflammatory changes in post mortem brain tissue of individuals with AD and GWAS data have convincingly demonstrated that neuroinflammation is likely to be a key driver of the disease. This, together with the evidence that genetic variants in the NLRP3 gene impact on the risk of developing late-onset AD, indicates that targetting inflammation offers a therapeutic opportunity. Here, we examined the effect of the small molecule inhibitor of the NLRP3 inflammasome, MCC950, on microglia in vitro and in vivo. The findings indicate that MCC950 inhibited LPS+Aß-induced caspase 1 activation in microglia and this was accompanied by IL-1ß release, without inducing pyroptosis. We demonstrate that MCC950 also inhibited inflammasome activation and microglial activation in the APP/PS1 mouse model of AD. Furthermore, MCC950 stimulated Aß phagocytosis in vitro, and it reduced Aß accumulation in APP/PS1 mice, which was associated with improved cognitive function. These data suggest that activation of the inflammasome contributes to amyloid accumulation and to the deterioration of neuronal function in APP/PS1 mice and demonstrate that blocking assembly of the inflammasome may prove to be a valuable strategy for attenuating changes that negatively impact on neuronal function.

Training non-physicians to do endoscopy: Feasibility, effectiveness and cost-effectiveness.

Colorectal cancer (CRC) is one of the most common cancers in women and men worldwide. Training non-physicians including nurses, nurse practitioners, and physician assistants to perform endoscopy can provide the opportunity to expand access to CRC screening as demand for endoscopic procedures continues to grow. A formal program, incorporating didactic instruction and hands-on practice in addition to oversight, is required to train non-physicians to perform endoscopy as safely and effectively as physicians. Additionally, the context in which the non-physician endoscopy program is organized will dictate key program characteristics including remuneration, participant recruitment and professional and legal considerations. This review explores the evidence in support of non-physician based endoscopy, potential challenges in implementing non-physician endoscopy and requirements for a high-quality program to support training and implementation.

Nitroimidazole carboxamides as antiparasitic agents targeting Giardia lamblia, Entamoeba histolytica and Trichomonas vaginalis.

Diarrhoeal diseases caused by the intestinal parasites Giardia lamblia and Entamoeba histolytica constitute a major global health burden. Nitroimidazoles are first-line drugs for the treatment of giardiasis and amebiasis, with metronidazole 1 being the most commonly used drug worldwide. However, treatment failures in giardiasis occur in up to 20% of cases and development of resistance to metronidazole is of concern. We have re-examined 'old' nitroimidazoles as a foundation for the systematic development of next-generation derivatives. Using this approach, derivatisation of the nitroimidazole carboxamide scaffold provided improved antiparasitic agents. Thirty-three novel nitroimidazole carboxamides were synthesised and evaluated for activity against G. lamblia and E. histolytica. Several of the new compounds exhibited potent activity against G. lamblia strains, including metronidazole-resistant strains of G. lamblia (EC50 = 0.1-2.5 µM cf. metronidazole EC50 = 6.1-18 µM). Other compounds showed improved activity against E. histolytica (EC50 = 1.7-5.1 µM cf. metronidazole EC50 = 5.0 µM), potent activity against Trichomonas vaginalis (EC50 = 0.6-1.4 µM cf. metronidazole EC50 = 0.8 µM) and moderate activity against the intestinal bacterial pathogen Clostridium difficile (0.5-2 µg/mL, cf. metronidazole = 0.5 µg/mL). The new compounds had low toxicity against mammalian kidney and liver cells (CC50 > 100 µM), and selected antiparasitic hits were assessed for human plasma protein binding and metabolic stability in liver microsomes to demonstrate their therapeutic potential.

Inflammasome activity is essential for one kidney/deoxycorticosterone acetate/salt-induced hypertension in mice.

BACKGROUND AND PURPOSE: Inflammasomes are multimeric complexes that facilitate caspase-1-mediated processing of the pro-inflammatory cytokines IL-1ß and IL-18. Clinical hypertension is associated with renal inflammation and elevated circulating levels of IL-1ß and IL-18. Therefore, we investigated whether hypertension in mice is associated with increased expression and/or activation of the inflammasome in the kidney, and if inhibition of inflammasome activity reduces BP, markers of renal inflammation and fibrosis. EXPERIMENTAL APPROACH: Wild-type and inflammasome-deficient ASC(-/-) mice were uninephrectomized and received deoxycorticosterone acetate and saline to drink (1K/DOCA/salt). Control mice were uninephrectomized but received a placebo pellet and water. BP was measured by tail cuff; renal expression of inflammasome subunits and inflammatory markers was measured by real-time PCR and immunoblotting; macrophage and collagen accumulation was assessed by immunohistochemistry. KEY RESULTS: 1K/DOCA/salt-induced hypertension in mice was associated with increased renal mRNA expression of inflammasome subunits NLRP3, ASC and pro-caspase-1, and the cytokine, pro-IL-1ß, as well as protein levels of active caspase-1 and mature IL-1ß. Following treatment with 1K/DOCA/salt, ASC(-/-) mice displayed blunted pressor responses and were also protected from increases in renal expression of IL-6, IL-17A, CCL2, ICAM-1 and VCAM-1, and accumulation of macrophages and collagen. Finally, treatment with a novel inflammasome inhibitor, MCC950, reversed hypertension in 1K/DOCA/salt-treated mice. CONCLUSIONS AND IMPLICATIONS: Renal inflammation, fibrosis and elevated BP induced by 1K/DOCA/salt treatment are dependent on inflammasome activity, highlighting the inflammasome/IL-1ß pathway as a potential therapeutic target in hypertension.

Strain- and host species-specific inflammasome activation, IL-1ß release, and cell death in macrophages infected with uropathogenic Escherichia coli.

Uropathogenic Escherichia coli (UPEC) is the main etiological agent of urinary tract infections (UTIs). Little is known about interactions between UPEC and the inflammasome, a key innate immune pathway. Here we show that UPEC strains CFT073 and UTI89 trigger inflammasome activation and lytic cell death in human macrophages. Several other UPEC strains, including two multidrug-resistant ST131 isolates, did not kill macrophages. In mouse macrophages, UTI89 triggered cell death only at a high multiplicity of infection, and CFT073-mediated inflammasome responses were completely NLRP3-dependent. Surprisingly, CFT073- and UTI89-mediated responses only partially depended on NLRP3 in human macrophages. In these cells, NLRP3 was required for interleukin-1ß (IL-1ß) maturation, but contributed only marginally to cell death. Similarly, caspase-1 inhibition did not block cell death in human macrophages. In keeping with such differences, the pore-forming toxin α-hemolysin mediated a substantial proportion of CFT073-triggered IL-1ß secretion in mouse but not human macrophages. There was also a more substantial α-hemolysin-independent cell death response in human vs. mouse macrophages. Thus, in mouse macrophages, CFT073-triggered inflammasome responses are completely NLRP3-dependent, and largely α-hemolysin-dependent. In contrast, UPEC activates an NLRP3-independent cell death pathway and an α-hemolysin-independent IL-1ß secretion pathway in human macrophages. This has important implications for understanding UTI in humans.

A Follow-Up Study of a Large Group of Children Struck by Lightning

Background. On 11 November 1994; 26 preadolescent girls; 2 adult supervisors and 7 dogs were sleeping in a tent in rural South Africa when the tent was struck by lightning. Four of the girls and 4 of the dogs were killed. The 2 adults were unharmed; but all but 3 of the children suffered significant injuries. An article in 2002 detailed the event and examined the medical and psychological changes in the surviving girls. Objective. To understand the medical and psychological changes secondary to lightning strike years after injury. Methods. An online questionnaire was prepared that included a checklist of physical and psychological symptoms. Participants were asked to report on both initial and current symptoms. Eleven of the 22 survivors were contacted; and 10 completed the survey. Results. Participants reported that initial physical symptoms generally resolved over time; with ~10 - 20% continuing to experience physical symptoms. Vision problems persisted in 50% of respondents. Psychological symptoms; overall; had a later onset and were more likely to be chronic or currently experienced. Depression and anxiety; specifically; were higher among the survivors than the reported incidence in South Africa. Conclusions.Initial and current/chronic physical and psychological symptoms following lightning strike are reported; adding to the body of literature on the long-term after-effects of lightning strike on survivors. A brief discussion on post-traumatic stress disorder symptomatology and post-lightning shock syndrome is provided

Neurobiological mechanisms supporting experience-dependent resistance to social stress.

Humans and other animals show a remarkable capacity for resilience following traumatic, stressful events. Resilience is thought to be an active process related to coping with stress, although the cellular and molecular mechanisms that support active coping and stress resistance remain poorly understood. In this review, we focus on the neurobiological mechanisms by which environmental and social experiences promote stress resistance. In male Syrian hamsters, exposure to a brief social defeat stressor leads to increased avoidance of novel opponents, which we call conditioned defeat. Also, hamsters that have achieved dominant social status show reduced conditioned defeat as well as cellular and molecular changes in the neural circuits controlling the conditioned defeat response. We propose that experience-dependent neural plasticity occurs in the prelimbic (PL) cortex, infralimbic (IL) cortex, and ventral medial amygdala (vMeA) during the maintenance of dominance relationships, and that adaptations in these neural circuits support stress resistance in dominant individuals. Overall, behavioral treatments that promote success in competitive interactions may represent valuable interventions for instilling resilience.

Pathway-selective antagonism of proteinase activated receptor 2.

BACKGROUND AND PURPOSE: Proteinase activated receptor 2 (PAR2) is a GPCR associated with inflammation, metabolism and disease. Clues to understanding how to block PAR2 signalling associated with disease without inhibiting PAR2 activation in normal physiology could be provided by studies of biased signalling. EXPERIMENTAL APPROACH: PAR2 ligand GB88 was profiled for PAR2 agonist and antagonist properties by several functional assays associated with intracellular G-protein-coupled signalling in vitro in three cell types and with PAR2-induced rat paw oedema in vivo. KEY RESULTS: In HT29 cells, GB88 was a PAR2 antagonist in terms of Ca(2+) mobilization and PKC phosphorylation, but a PAR2 agonist in attenuating forskolin-induced cAMP accumulation, increasing ERK1/2 phosphorylation, RhoA activation, myosin phosphatase phosphorylation and actin filament rearrangement. In CHO-hPAR2 cells, GB88 inhibited Ca(2+) release, but activated G(i/o) and increased ERK1/2 phosphorylation. In human kidney tubule cells, GB88 inhibited cytokine secretion (IL6, IL8, GM-CSF, TNF-α) mediated by PAR2. A rat paw oedema induced by PAR2 agonists was also inhibited by orally administered GB88 and compared with effects of locally administered inhibitors of G-protein coupled pathways. CONCLUSIONS AND IMPLICATIONS: GB88 is a biased antagonist of PAR2 that selectively inhibits PAR2/G(q/11)/Ca(2+)/PKC signalling, leading to anti-inflammatory activity in vivo, while being an agonist in activating three other PAR2-activated pathways (cAMP, ERK, Rho) in human cells. These findings highlight opportunities to design drugs to block specific PAR2-linked signalling pathways in disease, without blocking beneficial PAR2 signalling in normal physiology, and to dissect PAR2-associated mechanisms of disease in vivo.

Hypogammaglobulinemia in pediatric systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease typically associated with elevated serum immunoglobulin G (IgG). Hypogammaglobulinemia in SLE patients has been attributed to immunosuppressive treatment or a transient effect associated with nephrotic syndrome. We retrospectively reviewed pediatric SLE patients from a single institution to identify patients with hypogammaglobulinemia and risk factors for hypogammaglobulinemia. METHODS: A total of 116 pediatric SLE cases from 1997 to 2011 were reviewed and patients with hypogammaglobulinemia (IgG < 500 mg/dl) were identified. The two cohorts were evaluated for association with age, sex, presence of lupus nephritis at SLE diagnosis, disease activity at diagnosis, initial IgG level, and drug treatment. RESULTS: Eighty-six patients were included in our study, with a median age of 15 years and a median follow-up of 39.5 months. Seven percent (six of 86) of patients had hypogammaglobulinemia with a median onset of 27 months (0-72 months) after SLE diagnosis. Significant associations were noted for white race (p value 0.029), male sex (p value 0.009), and the presence of lupus nephritis at SLE diagnosis (p value 0.004). Use of immunosuppressive treatment did not show a statistical association with hypogammaglobulinemia, although two of the patients with hypogammaglobulinemia did receive rituximab. Most patients with hypogammaglobulinemia received intravenous immunoglobulin (IVIG) replacement therapy because of infections and/or concern for infection. CONCLUSION: Measurement of immunoglobulin levels during treatment in SLE could help identify patients with hypogammaglobulinemia who might require more aggressive follow-up to monitor for increased risk of infection and need for IVIG treatment. A prospective study is needed to validate associated risk factors identified in this study.

Molecular characterization of the receptor binding structure-activity relationships of influenza B virus hemagglutinin.

Selectivity of α2,6-linked human-like receptors by B hemagglutinin (HA) is yet to be fully understood. This study integrates binding data with structure-recognition models to examine the impact of regional-specific sequence variations within the receptor-binding pocket on selectivity and structure activity relationships (SAR). The receptor-binding selectivity of influenza B HAs corresponding to either B/Victoria/2/1987 or the B/Yamagata/16/88 lineages was examined using surface plasmon resonance, solid-phase ELISA and gel-capture assays. Our SAR data showed that the presence of asialyl sugar units is the main determinant of receptor preference of α2,6 versus α2,3 receptor binding. Changes to the type of sialyl-glycan linkage present on receptors exhibit only a minor effect upon binding affinity. Homology-based structural models revealed that structural properties within the HA pocket, such as a glyco-conjugate at Asn194 on the 190-helix, sterically interfere with binding to avian receptor analogs by blocking the exit path of the asialyl sugars. Similarly, naturally occurring substitutions in the C-terminal region of the 190-helix and near the N-terminal end of the 140-loop narrows the horizontal borders of the binding pocket, which restricts access of the avian receptor analog LSTa. This study helps bridge the gap between ligand structure and receptor recognition for influenza B HA; and provides a consensus SAR model for the binding of human and avian receptor analogs to influenza B HA.

Malignant melanoma in 63 dogs (2001-2011): the effect of carboplatin chemotherapy on survival.

AIMS: The aim of the study was to compare the effect of carboplatin chemotherapy on the survival of canine patients diagnosed with malignant melanoma after loco-regional control or as a sole therapy. METHODS: A retrospective study of 63 dogs with oral, digital or cutaneous malignant melanoma treated with surgery and/or chemotherapy was undertaken. Dogs were grouped based on the anatomical site of melanoma development. For oral melanoma, dogs were subclassified into two groups: loco-regional control and gross disease. All patients in the digital and cutaneous groups had achieved loco-regional control with surgery. Comparisons between survival data for each group at each anatomical site were then made. Within the loco-regional control groups survival time was compared between those treated with and without chemotherapy post surgery. For the oral melanoma patients with gross disease survival was compared between those treated with chemotherapy and palliative therapy. The toxicity of carboplatin chemotherapy was evaluated overall. RESULTS: The overall median survival times for patients with oral, digital and cutaneous melanoma were 389, 1,350 days and not reached (with a median follow-up of 776 days) respectively. Median survival time was defined as "not reached" when less than 50% of the subjects died of the disease at the end of the follow-up period, or at the time they were lost to follow-up. The addition of chemotherapy to surgery did not confer a survival benefit in the loco-regional control setting when assessing survival for each anatomical site. For oral melanoma patients with gross disease there was no difference between survival of patients treated with chemotherapy and palliative intent therapy. There was however an improvement in survival in the three dogs that responded to chemotherapy (978 days; p=0.039) compared to the eight non-responders (147 days). On univariate and multivariate analysis, anatomic location was the only variable that was significantly related to survival (p=0.0002 and p=0.009, respectively). CONCLUSIONS: The addition of chemotherapy to local treatments for canine melanoma at oral, digital and cutaneous sites did not lead to a significant increase in survival times. Carboplatin was well tolerated and appeared to have activity against oral melanoma in a subset of patients with gross disease that responded to treatment. CLINICAL RELEVANCE: Carboplatin with piroxicam could be considered for patients with gross disease when more traditional therapies, such as surgery or radiation therapy, are declined or are not available. In the loco-regional control setting, prospective randomised blinded studies with matched control groups are required to determine if chemotherapy has a role in the treatment of these types of cancer.

Social status alters defeat-induced neural activation in Syrian hamsters.

Although exposure to social stress leads to increased depression-like and anxiety-like behavior, some individuals are more vulnerable than others to these stress-induced changes in behavior. Prior social experience is one factor that can modulate how individuals respond to stressful events. In this study, we investigated whether experience-dependent resistance to the behavioral consequences of social defeat was associated with a specific pattern of neural activation. We paired weight-matched male Syrian hamsters in daily aggressive encounters for 2 weeks, during which they formed a stable dominance relationship. We also included control animals that were exposed to an empty cage each day for 2 weeks. Twenty-four hours after the final pairing or empty cage exposure, half of the subjects were socially defeated in 3, 5-min encounters, whereas the others were not socially defeated. Twenty-four hours after social defeat, animals were tested for conditioned defeat in a 5-min social interaction test with a non-aggressive intruder. We collected brains after social defeat and processed the tissue for c-Fos immunoreactivity. We found that dominants were more likely than subordinates to counter-attack the resident aggressor during social defeat, and they showed less submissive and defensive behavior at conditioned defeat testing compared with subordinates. Also, social status was associated with distinct patterns of defeat-induced neural activation in select brain regions, including the amygdala, prefrontal cortex, hypothalamus, and lateral septum. Our results indicate that social status is an important form of prior experience that predicts both initial coping style and the degree of resistance to social defeat. Further, the differences in defeat-induced neural activation suggest possible brain regions that may control resistance to conditioned defeat in dominant individuals.

Carriage of an ACME II variant may have contributed to methicillin-resistant Staphylococcus aureus sequence type 239-like strain replacement in Liverpool Hospital, Sydney, Australia.

Approximately 39% of methicillin-resistant Staphylococcus aureus (MRSA) sequence type 239 (ST239)-like bloodstream isolates from Liverpool Hospital (obtained between 1997 and 2008) carry an arginine catabolic mobile element (ACME). Whole-genome sequencing revealed that an ACME II variant is located between orfX and SCCmec III, and based on pulsed-field gel electrophoresis patterns and temporal relationships of all ST239-like isolates (n = 360), ACME carriage may have contributed to subpulsotype strain replacement.