Dietary Prebiotics and Bioactive Milk Fractions Improve NREM Sleep, Enhance REM Sleep Rebound and Attenuate the Stress-Induced Decrease in Diurnal Temperature and Gut Microbial Alpha Diversity.

Severe, repeated or chronic stress produces negative health outcomes including disruptions of the sleep/wake cycle and gut microbial dysbiosis. Diets rich in prebiotics and glycoproteins impact the gut microbiota and may increase gut microbial species that reduce the impact of stress. This experiment tested the hypothesis that consumption of dietary prebiotics, lactoferrin (Lf) and milk fat globule membrane (MFGM) will reduce the negative physiological impacts of stress. Male F344 rats, postnatal day (PND) 24, received a diet with prebiotics, Lf and MFGM (test) or a calorically matched control diet. Fecal samples were collected on PND 35/70/91 for 16S rRNA sequencing to examine microbial composition and, in a subset of rats; Lactobacillus rhamnosus was measured using selective culture. On PND 59, biotelemetry devices were implanted to record sleep/wake electroencephalographic (EEG). Rats were exposed to an acute stressor (100, 1.5 mA, tail shocks) on PND 87 and recordings continued until PND 94. Test diet, compared to control diet, increased fecal Lactobacillus rhamnosus colony forming units (CFU), facilitated non-rapid eye movement (NREM) sleep consolidation (PND 71/72) and enhanced rapid eye movement (REM) sleep rebound after stressor exposure (PND 87). Rats fed control diet had stress-induced reductions in alpha diversity and diurnal amplitude of temperature, which were attenuated by the test diet (PND 91). Stepwise multiple regression analysis revealed a significant linear relationship between early-life Deferribacteres (PND 35) and longer NREM sleep episodes (PND 71/72). A diet containing prebiotics, Lf and MFGM enhanced sleep quality, which was related to changes in gut bacteria and modulated the impact of stress on sleep, diurnal rhythms and the gut microbiota

Stakeholder Perceptions of Point-of-Care Ultrasound Implementation in Resource-Limited Settings

Nearly half of the world lacks access to diagnostic imaging. Point of care ultrasound (POCUS) is a versatile and relatively affordable imaging modality that offers promise as a means of bridging the radiology gap and improving care in low resource settings. Methods: We performed semi-structured interviews of key stakeholders at two diverse hospitals where POCUS implementation programs had recently been conducted: one in a rural private hospital in Haiti and the other in a public referral hospital in Malawi. Questions regarding the clinical utility of POCUS, as well as barriers and facilitators of its implementation, were asked of study participants. Using the Framework Method, analysis of interview transcripts was guided by the WHO ASSURED criteria for point of care diagnostics. Results: Fifteen stakeholders with diverse roles in POCUS implementation were interviewed. Interviewees from both sites considered POCUS a valuable diagnostic tool that improved clinical decisions. They perceived barriers to adequate training as one of the most important remaining barriers to POCUS implementation. Conclusions: In spite of the increasing affordability and portability of ultrasounds devices, there are still important barriers to the implementation of POCUS in resource-limited settings

Cathelicidin suppresses lipid accumulation and hepatic steatosis by inhibition of the CD36 receptor.

Background and objectivesObesity is a global epidemic which increases the risk of the metabolic syndrome. Cathelicidin (LL-37 and mCRAMP) is an antimicrobial peptide with an unknown role in obesity. We hypothesize that cathelicidin expression correlates with obesity and modulates fat mass and hepatic steatosis.Materials and methodsMale C57BL/6 J mice were fed a high-fat diet. Streptozotocin was injected into mice to induce diabetes. Experimental groups were injected with cathelicidin and CD36 overexpressing lentiviruses. Human mesenteric fat adipocytes, mouse 3T3-L1 differentiated adipocytes and human HepG2 hepatocytes were used in the in vitro experiments. Cathelicidin levels in non-diabetic, prediabetic and type II diabetic patients were measured by enzyme-linked immunosorbent assay.ResultsLentiviral cathelicidin overexpression reduced hepatic steatosis and decreased the fat mass of high-fat diet-treated diabetic mice. Cathelicidin overexpression reduced mesenteric fat and hepatic fatty acid translocase (CD36) expression that was reversed by lentiviral CD36 overexpression. Exposure of adipocytes and hepatocytes to cathelicidin significantly inhibited CD36 expression and reduced lipid accumulation. Serum cathelicidin protein levels were significantly increased in non-diabetic and prediabetic patients with obesity, compared with non-diabetic patients with normal body mass index (BMI) values. Prediabetic patients had lower serum cathelicidin protein levels than non-diabetic subjects.ConclusionsCathelicidin inhibits the CD36 fat receptor and lipid accumulation in adipocytes and hepatocytes, leading to a reduction of fat mass and hepatic steatosis in vivo. Circulating cathelicidin levels are associated with increased BMI. Our results demonstrate that cathelicidin modulates the development of obesity

Extracellular Hsp72 concentration relates to a minimum endogenous criteria during acute exercise-heat exposure

Extracellular heat-shock protein 72 (eHsp72) concentration increases during exercise-heat stress when conditions elicit physiological strain. Differences in severity of environmental and exercise stimuli have elicited varied response to stress. The present study aimed to quantify the extent of increased eHsp72 with increased exogenous heat stress, and determine related endogenous markers of strain in an exercise-heat model. Ten males cycled for 90 min at 50% O2peak in three conditions (TEMP, 20°C/63% RH; HOT, 30.2°C/51%RH; VHOT, 40.0°C/37%RH). Plasma was analysed for eHsp72 pre, immediately post and 24-h post each trial utilising a commercially available ELISA. Increased eHsp72 concentration was observed post VHOT trial (+172.4%) (P<0.05), but not TEMP (-1.9%) or HOT (+25.7%) conditions. eHsp72 returned to baseline values within 24hrs in all conditions. Changes were observed in rectal temperature (Trec), rate of Trec increase, area under the curve for Trec of 38.5°C and 39.0°C, duration Trec ≥ 38.5°C and ≥ 39.0°C, and change in muscle temperature, between VHOT, and TEMP and HOT, but not between TEMP and HOT. Each condition also elicited significantly increasing physiological strain, described by sweat rate, heart rate, physiological strain index, rating of perceived exertion and thermal sensation. Stepwise multiple regression reported rate of Trec increase and change in Trec to be predictors of increased eHsp72 concentration. Data suggests eHsp72 concentration increases once systemic temperature and sympathetic activity exceeds a minimum endogenous criteria elicited during VHOT conditions and is likely to be modulated by large, rapid changes in core temperature

Clinical intervals and diagnostic characteristics in a cohort of prostate cancer patients in Spain: a multicentre observational study

Background: Little is known about the healthcare process for patients with prostate cancer, mainly because hospital-based data are not routinely published. The main objective of this study was to determine the clinical characteristics of prostate cancer patients, the diagnostic process and the factors that might influence intervals from consultation to diagnosis and from diagnosis to treatment. Methods: We conducted a multicentre, cohort study in seven hospitals in Spain. Patients' characteristics and diagnostic and therapeutic variables were obtained from hospital records and patients' structured interviews from October 2010 to September 2011. We used a multilevel logistic regression model to examine the association between patient care intervals and various variables influencing these intervals (age, BMI, educational level, ECOG, first specialist consultation, tumour stage, PSA, Gleason score, and presence of symptoms) and calculated the odds ratio (OR) and the interquartile range (IQR). To estimate the random inter-hospital variability, we used the median odds ratio (MOR). Results: 470 patients with prostate cancer were included. Mean age was 67.8 (SD: 7.6) years and 75.4 % were physically active. Tumour size was classified as T1 in 41.0 % and as T2 in 40 % of patients, their median Gleason score was 6.0 (IQR:1.0), and 36.1 % had low risk cancer according to the D'Amico classification. The median interval between first consultation and diagnosis was 89 days (IQR:123.5) with no statistically significant variability between centres. Presence of symptoms was associated with a significantly longer interval between first consultation and diagnosis than no symptoms (OR:1.93, 95%CI 1.29-2.89). The median time between diagnosis and first treatment (therapeutic interval) was 75.0 days (IQR:78.0) and significant variability between centres was found (MOR:2.16, 95%CI 1.45-4.87). This interval was shorter in patients with a high PSA value (p = 0.012) and a high Gleason score (p = 0.026). Conclusions: Most incident prostate cancer patients in Spain are diagnosed at an early stage of an adenocarcinoma. The period to complete the diagnostic process is approximately three months whereas the therapeutic intervals vary among centres and are shorter for patients with a worse prognosis. The presence of prostatic symptoms, PSA level, and Gleason score influence all the clinical intervals differently

Tianeptine: An Antidepressant with Memory-Protective Properties

The development of effective pharmacotherapy for major depression is important because it is such a widespread and debilitating mental disorder. Here, we have reviewed preclinical and clinical studies on tianeptine, an atypical antidepressant which ameliorates the adverse effects of stress on brain and memory. In animal studies, tianeptine has been shown to prevent stress-induced morphological sequelae in the hippocampus and amygdala, as well as to prevent stress from impairing synaptic plasticity in the prefrontal cortex and hippocampus. Tianeptine also has memory-protective characteristics, as it blocks the adverse effects of stress on hippocampus-dependent learning and memory. We have further extended the findings on stress, memory and tianeptine here with two novel observations: 1) stress impairs spatial memory in adrenalectomized (ADX), thereby corticosterone-depleted, rats; and 2) the stress-induced impairment of memory in ADX rats is blocked by tianeptine. These findings are consistent with previous research which indicates that tianeptine produces anti-stress and memory-protective properties without altering the response of the hypothalamic-pituitary-adrenal axis to stress. We conclude with a discussion of findings which indicate that tianeptine accomplishes its anti-stress effects by normalizing stress-induced increases in glutamate in the hippocampus and amygdala. This finding is potentially relevant to recent research which indicates that abnormalities in glutamatergic neurotransmission are involved in the pathogenesis of depression. Ultimately, tianeptine’s prevention of depression-induced sequelae in the brain is likely to be a primary factor in its effectiveness as a pharmacological treatment for depression

PERMISSIVE INFLUENCE OF STRESS IN THE EXPRESSION OF A U-SHAPED RELATIONSHIP BETWEEN SERUM CORTICOSTERONE LEVELS AND SPATIAL MEMORY ERRORS IN RATS

The relationship between glucocorticoids (GCs) and memory is complex, in that memory impairments can occur in response to manipulations that either increase or decrease GC levels. We investigated this issue by assessing the relationship between serum corticosterone (the primary rodent GC) and memory in rats trained in the radial arm water maze, a hippocampus-dependent spatial memory task. Each day, rats learned a new location of the hidden escape platform and then 30 min later their memory of the location of the platform was tested. Under control conditions, well-trained rats had excellent spatial memory and moderately elevated corticosterone levels (~26 μg/dl versus a baseline of ~2 μg/dl). Their memory was impaired when corticosterone levels were either reduced by metyrapone (a corticosterone synthesis inhibitor) or increased by acute stress (predator exposure), forming an overall U-shaped relationship between corticosterone levels and memory. We then addressed whether there was a causal relationship between elevated corticosterone levels and impaired memory. If elevated corticosterone levels were a sufficient condition to impair memory, then exogenously administered corticosterone, alone, should have impaired performance. However, we found that spatial memory was not impaired in corticosterone-injected rats that were not exposed to the cat. This work demonstrates that an intermediate level of corticosterone correlated with optimal memory, and either a decrease or an increase in corticosterone levels, in conjunction with strong emotionality, impaired spatial memory. These findings indicate that fear-provoking conditions, which are known to engage the amygdala, interact with stress levels of corticosterone to influence hippocampal functioning

Postoperative complications and waiting time for surgical intervention after radiologically guided drainage of intra-abdominal abscess in patients with Crohn’s disease

Postoperative complications; DrainageComplicacions postoperatòries; DrenatgeComplicaciones postoperatorias; DrenajeBackground In patients with active Crohn’s disease (CD), treatment of intra-abdominal abscess usually comprises antibiotics and radiologically guided percutaneous drainage (PD) preceding surgery. The aim of this study was to investigate the risk of postoperative complications and identify the optimal time interval for surgical intervention after PD. Methods A multicentre, international, retrospective cohort study was carried out. Details of patients with diagnosis of CD who underwent ultrasonography- or CT-guided PD were retrieved from hospital records using international classification of disease (ICD-10) diagnosis code for CD combined with procedure code for PD. Clinical variables were retrieved and the following outcomes were measured: 30-day postoperative overall complications, intra-abdominal septic complications, unplanned intraoperative adverse events, surgical-site infections, sepsis and pathological postoperative ileus, in addition to abscess recurrence. Patients were categorized into three groups according to the length of the interval from PD to surgery (1–14 days, 15–30 days and more than 30 days) for comparison of outcomes. Results The cohort comprised 335 CD patients with PD followed by surgery. Median age was 33 (i.q.r. 24–44) years, 152 (45.4 per cent) were females, and median disease duration was 9 (i.q.r. 3.6–15) years. Overall, the 30-day postoperative complications rate was 32.2 per cent and the mortality rate was 1.5 per cent. After adjustment for co-variables, older age (odds ratio 1.03 (95 per cent c.i. 1.01 to 1.06), P < 0.012), residual abscess after PD (odds ratio 0.374 (95 per cent c.i. 0.19 to 0.74), P < 0.014), smoking (odds ratio 1.89 (95 per cent c.i. 1.01 to 3.53), P = 0.049) and low serum albumin concentration (odds ratio 0.921 (95 per cent c.i. 0.89 to 0.96), P < 0.001) were associated with higher rates of postoperative complications. A short waiting interval, less than 2 weeks after PD, was associated with a high incidence of abscess recurrence (odds ratio 0.59 (95 per cent c.i. 0.36 to 0.96), P = 0.042). Conclusion Smoking, low serum albumin concentration and older age were significantly associated with postoperative complications. An interval of at least 2 weeks after successful PD correlated with reduced risk of abscess recurrence

The Immune System in Stroke

Stroke represents an unresolved challenge for both developed and developing countries and has a huge socio-economic impact. Although considerable effort has been made to limit stroke incidence and improve outcome, strategies aimed at protecting injured neurons in the brain have all failed. This failure is likely to be due to both the incompleteness of modelling the disease and its causes in experimental research, and also the lack of understanding of how systemic mechanisms lead to an acute cerebrovascular event or contribute to outcome. Inflammation has been implicated in all forms of brain injury and it is now clear that immune mechanisms profoundly influence (and are responsible for the development of) risk and causation of stroke, and the outcome following the onset of cerebral ischemia. Until very recently, systemic inflammatory mechanisms, with respect to common comorbidities in stroke, have largely been ignored in experimental studies. The main aim is therefore to understand interactions between the immune system and brain injury in order to develop novel therapeutic approaches. Recent data from clinical and experimental research clearly show that systemic inflammatory diseases -such as atherosclerosis, obesity, diabetes or infection - similar to stress and advanced age, are associated with dysregulated immune responses which can profoundly contribute to cerebrovascular inflammation and injury in the central nervous system. In this review, we summarize recent advances in the field of inflammation and stroke, focusing on the challenges of translation between pre-clinical and clinical studies, and potential anti-inflammatory/immunomodulatory therapeutic approaches

Stakeholder Perceptions of Point-of-Care Ultrasound Implementation in Resource-Limited Settings

Nearly half of the world lacks access to diagnostic imaging. Point of care ultrasound (POCUS) is a versatile and relatively affordable imaging modality that offers promise as a means of bridging the radiology gap and improving care in low resource settings. Methods: We performed semi-structured interviews of key stakeholders at two diverse hospitals where POCUS implementation programs had recently been conducted: one in a rural private hospital in Haiti and the other in a public referral hospital in Malawi. Questions regarding the clinical utility of POCUS, as well as barriers and facilitators of its implementation, were asked of study participants. Using the Framework Method, analysis of interview transcripts was guided by the WHO ASSURED criteria for point of care diagnostics. Results: Fifteen stakeholders with diverse roles in POCUS implementation were interviewed. Interviewees from both sites considered POCUS a valuable diagnostic tool that improved clinical decisions. They perceived barriers to adequate training as one of the most important remaining barriers to POCUS implementation. Conclusions: In spite of the increasing affordability and portability of ultrasounds devices, there are still important barriers to the implementation of POCUS in resource-limited settings