Perceived social support-giving moderates the association between social relationships and interleukin-6 levels in blood.

Although positive social relationships are assumed to relate to lower levels of chronic systemic inflammation, the empirical evidence on this association is mixed. This study examines whether perceived social support-giving (i.e., the belief that one can be available to give social support to others, henceforward referred to as perceived support-giving) moderates associations between social relationships and inflammation using data from the longitudinal follow-up of the National Survey of Midlife Development in the U.S. (MIDUS II). Middle-aged adults (N = 1054) completed self-report questionnaires on social integration, perceived support-availability from others, positive relations with others, perceived support-giving, socio-demographic information, and health-related information and provided blood samples for measurement of interleukin-6 (IL-6) as a marker of systemic inflammation. The results showed that perceived support-giving moderated the associations between IL-6 and indicators of positive social relationships, including social integration, perceived support-availability, and positive relations with others. Indicators of positive social relationships were associated with lower IL-6 among individuals higher, but not lower, in perceived support-giving. The moderating effects of perceived support-giving held after adjusting for socio-demographic and health-related covariates. Therefore, positive social relationships are associated with lower IL-6 only for individuals who believe they can give more support in those relationships. In addition, preliminary evidence indicated that the moderating effects of perceived support-giving might be further qualified by gender, being significant only in women.

Racial and Economic Adversity Differences in Stress Markers and Immune Function Among Urban Adolescents.

BACKGROUND: Exposure to racism and associated adversities, such as poverty, is hypothesized to contribute to racial inequities in health via stress and immune pathways. Furthermore, the effects of adversity may be more salient during sensitive developmental periods. Our study examined racial differences in stress and immune biomarkers during adolescence and the effects of exposure to economic adversity at distinct developmental time periods and cumulatively in accounting for potential racial differences. METHODS: Secondary analysis of the Adolescent Health and Development in Context study was conducted. Data were derived from self-administered surveys; interviews; smartphone-based, geographic-explicit ecological momentary assessment; stress biomarkers (evening salivary cortisol over six nights and hair cortisol); and immune biomarkers (salivary shedding of Epstein-Barr virus [EBV] DNA among EBV-positive adolescents). Current socioeconomic status measures included annual household income and caregiver education. Caregivers also reported experiences of bankruptcy, difficulty paying bills, receipt of food stamps/Supplemental Nutrition Assistance Program/electronic benefit transfer, and job loss when the child was of ages birth-5 years, 6-10 years, and 11 years or older. An affirmative response to any item was defined as exposure to economic adversity for that developmental time period (yes/no). A cumulative economic adversity measure was calculated as the sum of exposures across developmental periods (0 = never exposed to 3 = exposed across all time periods). Descriptive and multivariable regression analyses were conducted, accounting for covariates. RESULTS: Black/African American adolescents had higher salivary cortisol concentration, higher hair cortisol concentration, and an increased odd of salivary shedding of EBV DNA compared to White adolescents. Racial differences were not attenuated by the current socioeconomic status or economic adversity (developmental period or cumulatively). DISCUSSION: Our study provides evidence that stress and immune biomarkers differ by race as early as adolescence and may be one pathway through which racism and associated adversities contribute to racial health inequities. Further research on the contribution of multiple adversities beyond poverty to racial inequities in physiological stress and health is critical for informing effective prevention and intervention efforts.

The use of a patch to augment rotator cuff surgery - A survey of UK shoulder and elbow surgeons.

BACKGROUND: Rotator cuff tears are a common cause of shoulder pain and can result in prolonged periods of pain, disability and absence from work. Rotator cuff repair surgery is increasingly used in an attempt to resolve symptoms but has failure rates of around 40%. There is a pressing need to improve the outcome of rotator cuff repairs. Patch augmentation increasingly being used within the NHS in an attempt to reduce repair failures. The aim of this survey was to determine current UK practice and opinion relating to the factors that influence choice of patch, current patient selection and willingness to assist with generation of improved evidence. METHODS: An online survey was sent to the surgeon members of the British Elbow and Shoulder Society (BESS). Questions covered respondent demographics, experience with patches, indications for patch augmentation and willingness to be involved in a randomised trial of patch augmented rotator cuff surgery. RESULTS: The response rate was 105/550 (19%). 58% of respondents had used a patch to augment rotator cuff surgery. 70% of patch users had undertaken an augmented repair within the last 6 months. A wide surgical experience in augmentation was reported (ranging 1 to 200 implants used). However, most surgeons reported low volume usage, with a median of 5 rotator cuff augmentation procedures performed. At least 10 different products had been used. Most of the patches used were constructed from human decellularised dermis tissue, although porcine derived and synthetic based patches had also been used. Only 3-5% stated they would undertake an augmented repair for small tears across ages, whereas 28-40% and 19-59% would do so for large or massive tears respectively. When assessing patient suitability, patient age seemed relevant only for those with large and massive tears. Half of the surgeons reported an interest in taking part in a randomised controlled trial (RCT) evaluating the role of patch augmentation for rotator cuff surgery, with a further 22% of respondent's undecided. CONCLUSIONS: A variety of patches have been used by surgeons to augment rotator cuff repair with a wide range of operator experience. There was substantial uncertainty about which patch to use and differing views on which patients were most suitable. There is a clear need for robust clinical evaluation and further research in this area.

Synchronous cerebral arteriovenous malformation and lung adenocarcinoma carcinoma brain metastases: A case study and literature review.

INTRODUCTION: While there are numerous published cases of arteriovenous malformations (AVMs) developing in the setting of malignancy, it is extremely rare to find them concurrently associated in the brain. CLINICAL CASE: This is the case of a 55-year-old male who presented to the emergency department complaining of headaches, memory and visual changes. Neuro-imaging revealed a right temporal parietal AVM and an adjoining hyperenhancing occipitotemporal lobe lesion with concern for a possible evolving stroke. The patient was treated with radiosurgery for the AVM. His symptoms progressed one month later, and repeat imaging suggested interval enlargement of the previously presumed stroke that was intricately associated with the AVM, in addition to two new small enhancing lesions of the left temporal lobe. Microsurgical resection of the temporal lobe mass revealed adenocarcinoma of the lung. CONCLUSION: This case represents a previously undocumented confluence of cranial AVM that initially masked a non-small cell lung cancer brain metastasis.

Discordant Observation of Brain Injury by MRI and Malignant Electroencephalography Patterns in Comatose Survivors of Cardiac Arrest following Therapeutic Hypothermia.

BACKGROUND AND PURPOSE: Malignant electroencephalography patterns are considered predictive of poor outcome in comatose survivors of cardiac arrest. We hypothesized that malignant patterns on electroencephalography are associated with evidence of more severe brain injury on MR imaging. MATERIALS AND METHODS: Retrospective review of clinical, imaging, and electroencephalography data of 33 adult comatose survivors of cardiac arrest following therapeutic hypothermia was performed. Outcomes measured included discharge destination and survival. Imaging studies were visually scored for severity of brain injury. Mean whole-brain apparent diffusion coefficient and percentage of severely injured brain (ADC < 700 × 10-6 mm2/s) were calculated. Continuous electroencephalographic interpretation was characterized as malignant or nonmalignant. Nonparametric tests were performed to assess the relationship of patient outcome, MR imaging, and electroencephalography patterns. RESULTS: Subjects with anatomic evidence of diffuse brain injury were less likely to have malignant electroencephalography patterns. Subjects with malignant electroencephalography patterns, invariably associated with bad outcomes, were observed to have whole-brain apparent diffusion coefficient measures similar to those in subjects with nonmalignant electroencephalography patterns and good outcome and different from those in subjects with nonmalignant electroencephalography patterns and bad outcomes. Regional hippocampal or basal ganglia injury was associated with a bad outcome regardless of electroencephalography findings. CONCLUSIONS: We found discordant evidence of brain injury by MR imaging and electroencephalography, refuting our initial hypothesis. Malignant electroencephalography patterns were generally more frequent in subjects with less severe brain injury by MR imaging. These findings suggest a complementary role of MR imaging and electroencephalography and support the aggressive treatment of malignant electroencephalography patterns in this population.

Effects of oxytocin administration on spirituality and emotional responses to meditation.

The oxytocin (OT) system, critically involved in social bonding, may also impinge on spirituality, which is the belief in a meaningful life imbued with a sense of connection to a Higher Power and/or the world. Midlife male participants (N = 83) were randomly assigned to receive intranasal OT or placebo. In exploratory analyses, participants were also genotyped for polymorphisms in two genes critical for OT signaling, the oxytocin receptor gene (OXTR rs53576) and CD38 (rs6449182 and rs3796863). Results showed that intranasal OT increased self-reported spirituality on two separate measures and this effect remained significant a week later. It also boosted participants' experience of specific positive emotions during meditation, at both explicit and implicit levels. Furthermore, the effect of OT on spirituality was moderated by OT-related genotypes. These results provide the first experimental evidence that spirituality, endorsed by millions worldwide, appears to be supported by OT.

Alterations in Resting-State Functional Connectivity Link Mindfulness Meditation With Reduced Interleukin-6: A Randomized Controlled Trial.

BACKGROUND: Mindfulness meditation training interventions have been shown to improve markers of health, but the underlying neurobiological mechanisms are not known. Building on initial cross-sectional research showing that mindfulness meditation may increase default mode network (DMN) resting-state functional connectivity (rsFC) with regions important in top-down executive control (dorsolateral prefrontal cortex [dlPFC]), here we test whether mindfulness meditation training increases DMN-dlPFC rsFC and whether these rsFC alterations prospectively explain improvements in interleukin (IL)-6 in a randomized controlled trial. METHODS: Stressed job-seeking unemployed community adults (n = 35) were randomized to either a 3-day intensive residential mindfulness meditation or relaxation training program. Participants completed a 5-minute resting-state scan before and after the intervention program. Participants also provided blood samples at preintervention and at 4-month follow-up, which were assayed for circulating IL-6, a biomarker of systemic inflammation. RESULTS: We tested for alterations in DMN rsFC using a posterior cingulate cortex seed-based analysis and found that mindfulness meditation training, and not relaxation training, increased posterior cingulate cortex rsFC with left dlPFC (p < .05, corrected). These pretraining to posttraining alterations in posterior cingulate cortex-dlPFC rsFC statistically mediated mindfulness meditation training improvements in IL-6 at 4-month follow-up. Specifically, these alterations in rsFC statistically explained 30% of the overall mindfulness meditation training effects on IL-6 at follow-up. CONCLUSIONS: These findings provide the first evidence that mindfulness meditation training functionally couples the DMN with a region known to be important in top-down executive control at rest (left dlPFC), which, in turn, is associated with improvements in a marker of inflammatory disease risk.

Improving the quality of operative notes for laparoscopic cholecystectomy: Assessing the impact of a standardized operation note proforma.

INTRODUCTION: Operative notes are the recognized standard for documenting the details of an operation yet key procedural details are frequently missing. With the aim of improving standards, based on the Royal College of Surgeons (RCS) and Dutch Society of Surgery (DSS) Guidelines, we introduced an operation note proforma for use following laparoscopic cholecystectomy in a tertiary centre in the UK. METHODS: This study audited 130 consecutive laparoscopic cholecystectomy operation notes against accepted guidelines across three hospital sites within the same NHS Trust. Following analysis of these operation notes a standardized operation note proforma was designed and introduced across the Trust, which included all items from the DSS and RCS guidelines in the form of keyword prompts or simple yes/no responses. A further 128 operation notes were analysed. Guideline compliance was compared pre- and post-introduction of the proforma. Non-parametric data were analysed using Fisher's exact and Mann-Whitney U tests. Statistical significance was set at p < 0.05. RESULTS: On a global assessment of operation note completeness against all guideline items, introduction of an operation note proforma significantly improved documentation rates for both DSS guidelines (p < 0.001) and RCS guidelines (p < 0.001). DISCUSSION: We have demonstrated that the introduction of a procedure-specific proforma to assist with writing the post-operative note following laparoscopic cholecystectomy can result in significant improvements in documentation of generic and procedure-specific items that should be recorded for every operation. Procedure-specific proformas, based on established guidelines can help to produce more complete and medico-legally robust operation notes.

Evidence for a role of the oxytocin system, indexed by genetic variation in CD38, in the social bonding effects of expressed gratitude.

Oxytocin is thought to play a central role in promoting close social bonds via influence on social interactions. The current investigation targeted interactions involving expressed gratitude between members of romantic relationships because recent evidence suggests gratitude and its expression provides behavioral and psychological 'glue' to bind individuals closer together. Specifically, we took a genetic approach to test the hypothesis that social interactions involving expressed gratitude would be associated with variation in a gene, CD38, which has been shown to affect oxytocin secretion. A polymorphism (rs6449182) that affects CD38 expression was significantly associated with global relationship satisfaction, perceived partner responsiveness and positive emotions (particularly love) after lab-based interactions, observed behavioral expression of gratitude toward a romantic partner in the lab, and frequency of expressed gratitude in daily life. A separate polymorphism in CD38 (rs3796863) previously associated with plasma oxytocin levels and social engagement was also associated with perceived responsiveness in the benefactor after an expression of gratitude. The combined influence of the two polymorphisms was associated with a broad range of gratitude-related behaviors and feelings. The consistent pattern of findings suggests that the oxytocin system is associated with solidifying the glue that binds adults into meaningful and important relationships.

Hypoalbuminemia and early mortality after lung transplantation: a cohort study.

Hypoalbuminemia predicts disability and mortality in patients with various illnesses and in the elderly. The association between serum albumin concentration at the time of listing for lung transplantation and the rate of death after lung transplantation is unknown. We examined 6808 adults who underwent lung transplantation in the United States between 2000 and 2008. We used Cox proportional hazard models and generalized additive models to examine multivariable-adjusted associations between serum albumin and the rate of death after transplantation. The median follow-up time was 2.7 years. Those with severe (0.5-2.9 g/dL) and mild hypoalbuminemia (3.0-3.6 g/dL) had posttransplant adjusted mortality rate ratios of 1.35 (95% CI: 1.12-1.62) and 1.15 (95% CI: 1.04-1.27), respectively. For each 0.5 g/dL decrease in serum albumin concentration the 1-year and overall mortality rate ratios were 1.48 (95% CI: 1.21-1.81) and 1.26 (95% CI: 1.11-1.43), respectively. The association between hypoalbuminemia and posttransplant mortality was strongest in recipients with cystic fibrosis and interstitial lung disease. Hypoalbuminemia is an independent risk factor for death after lung transplantation.

Neural sensitivity to social rejection is associated with inflammatory responses to social stress.

Although stress-induced increases in inflammation have been implicated in several major disorders, including cardiovascular disease and depression, the neurocognitive pathways that underlie inflammatory responses to stress remain largely unknown. To examine these processes, we recruited 124 healthy young adult participants to complete a laboratory-based social stressor while markers of inflammatory activity were obtained from oral fluids. A subset of participants (n = 31) later completed an fMRI session in which their neural responses to social rejection were assessed. As predicted, exposure to the laboratory-based social stressor was associated with significant increases in two markers of inflammatory activity, namely a soluble receptor for tumor necrosis factor-alpha (sTNFalphaRII) and interleukin-6 (IL-6). In the neuroimaging subsample, greater increases in sTNFalphaRII (but not IL-6) were associated with greater activity in the dorsal anterior cingulate cortex and anterior insula, brain regions that have previously been associated with processing rejection-related distress and negative affect. These data thus elucidate a neurocognitive pathway that may be involved in potentiated inflammatory responses to acute social stress. As such, they have implications for understanding how social stressors may promote susceptibility to diseases with an inflammatory component.

Increased perfusion and angiogenesis in a hindlimb ischemia model with plasmid FGF-2 delivered by noninvasive electroporation.

Gene therapy approaches delivering fibroblast growth factor-2 (FGF-2) have shown promise as a potential treatment for increasing blood flow to ischemic limbs. Currently, effective noninvasive techniques to deliver plasmids encoding genes of therapeutic interest, such as FGF-2, are limited. We sought to determine if intradermal injection of plasmid DNA encoding FGF-2 (pFGF) followed by noninvasive cutaneous electroporation (pFGFE+) could increase blood flow and angiogenesis in a rat model of hindlimb ischemia. pFGFE+ or control treatments were administered on postoperative day 0. Compared to injection of pFGF alone (pFGFE-), delivery of pFGFE+ significantly increased FGF-2 expression for 10 days. Further, the increase in FGF-2 expression with pFGFE+ was sufficient to significantly increase ischemic limb blood flow, measured by laser Doppler perfusion imaging, beginning on postoperative day 3. Ischemic limb blood flow in the pFGFE+ treatment group remained significantly higher than all control groups through the end point of the study, postoperative day 14. Immunohistochemical staining of gastrocnemius cross sections determined there was a twofold increase in capillary density in the pFGFE+ treatment group. Our results suggest that pFGFE+ is a potential noninvasive, nonviral therapeutic approach to increase perfusion and angiogenesis for the treatment of limb ischemia.

Electroporation-mediated delivery of a naked DNA plasmid expressing VEGF to the porcine heart enhances protein expression.

Gene therapy is an attractive method for the treatment of cardiovascular disease. However, using current strategies, induction of gene expression at therapeutic levels is often inefficient. In this study, we show a novel electroporation (EP) method to enhance the delivery of a plasmid expressing an angiogenic growth factor (vascular endothelial growth factor, VEGF), which is a molecule previously documented to stimulate revascularization in coronary artery disease. DNA expression plasmids were delivered in vivo to the porcine heart with or without coadministered EP to determine the potential effect of electrically mediated delivery. The results showed that plasmid delivery through EP significantly increased cardiac expression of VEGF compared with injection of plasmid alone. This is the first report showing successful intracardiac delivery, through in vivo EP, of a protein expressing plasmid in a large animal.

Methamphetamine increases basal ganglia iron to levels observed in aging.

Increases in basal ganglia iron are well documented for neurodegenerative diseases but have not been associated with methamphetamine (METH). In this study, vervet monkeys that received two doses of METH (2 mg/kg, intramuscularly, 6 h apart) showed at 1 month, iron increases in substantia nigra pars reticulata and globus pallidus, with concurrent increases of ferritin-immunoreactivity and decreases of tyrosine hydroxylase-immunoreactivity in substantia nigra. At 1.5 years, substantia nigra tyrosine hydroxylase-immunoreactivity had recovered while iron and ferritin-immunoreactivity increases persisted. Globus pallidus and substantia nigra iron levels of the adult METH-exposed animals (age 5-9 years) were now comparable with those of drug-naive, aged animals (19-22 years), suggesting an aging-related condition that might render those regions more vulnerable to oxidative stress.

Phosphorylation of the NF2 tumor suppressor in Schwann cells is mediated by Cdc42-Pak and requires paxillin binding.

Mutations in the Neurofibromatosis type 2 tumor suppressor gene that encodes Schwannomin causes formation of benign schwannomas. Schwannoma cells lose their characteristic bipolar shape and become rounded with excessive ruffling membranes. Schwannomin is phosphorylated at serine 518 (S518) by p21 activated kinase (Pak). Unphosphorylated schwannomin is associated with growth inhibition but little is known about the function of the phosphorylated form, or the molecular events leading to its phosphorylation. Here, we report in SCs that schwannomin S518 phosphorylation requires binding to paxillin and targeting to the plasma membrane. Phospho-S518-schwannomin is enriched in the peripheral-most aspects of membrane specializations where paxillin, activated Pak, Cdc42 but not Rac are highly expressed. Schwannomin and Pak phosphorylation levels are not reduced in response to lowering Rac-GTP levels with NSC23766. Expression of schwannomin S518A/D-GFP variants each distinctively altered Schwann cell shape and polarity. These results are consistent with tight spatial regulation of S518 phosphorylation at the plasma membrane in a paxillin and Cdc42-Pak dependent manner that leads to local reorganization of the SC cytoskeleton.

Reduction meatoplasty with a post-auricular island flap.

The importance of an adequate meatoplasty is often emphasised in mastoid surgery. However, bigger is not always better, as an excessively widened external meatus can be cosmetically unacceptable, provide little extra benefit for cleaning, be an obstacle to the good fitting of hearing aids and expose the mastoid cavity to exaggerated caloric effect. The problems created by an overly large meatus can occasionally be difficult to manage, prompting consideration of reduction of the meatus. We describe the use of a pedicled, post-auricular skin flap to achieve reduction of an excessively large meatus.

Free tensor fasciae latae musculofasciocutaneous flap in reconstructive surgery: a series of 85 cases.

The use of tensor fasciae latae was first described as a rotation or island flap and evolved into a free flap in the late 1970s. This series of 85 patients undergoing free tensor fasciae latae transfer includes complex head and neck, abdominal wall and lower limb reconstruction. The overall success rate was 93% (79 patients), partial flap loss, 5% (four cases), and flap failure, 2% (two patients). Twelve patients (14%) required unplanned return to theatre for exploration resulting in a 75% salvage rate. We believe this series demonstrates the great versatility of this flap and highlights particular indications for its use.

The use of the Siamese combined free flap to reconstruct challenging defects: twin and triplet variants.

The reconstruction of large and intricate defects may need the use of combined flaps due to either the size or requirement for multiple surfaces. The combination may be between free and pedicled tissue transfer, and combined or connected free flaps classified by Koshima. We will discuss the use of the Siamese combined free flap as a method of the reconstructing challenging cases, including one of the largest free tissue transfer reported.

Malignancies of the external auditory canal and temporal bone: a review.

BACKGROUND: Malignancies of the external auditory canal and temporal bone are uncommon. A retrospective review was conducted of a large series treated at the Prince of Wales hospital between 1974 and 1995. METHODS: Retrospective review of 59 cases of ear canal and temporal bone malignancies. These were analysed according to histopathology, disease extent, surgery, margin status and survival. A TNM-type staging system was applied to 51 cases and Kaplan-Meier survival analysis applied to this group. RESULTS: The 5-year cancer-specific survival (CSS) for the series was 54%. For stages 1, 2, 3 and 4 disease, the CSS were 90, 45, 40 and 19%, respectively. Survival was significantly higher where clear surgical margins were achieved (80 vs 35%). CONCLUSIONS: Carcinoma of the external ear canal is rare and, in Australia, is often related to recurrence of periauricular cutaneous malignancy. Surgical extirpation with clear margins provides the best survival.