More than one third of candidates for bariatric surgery suffer with clinical depression. Significant reduction in depression following bariatric surgery has been shown, but this is not consistent for all patients. The biological mechanisms behind the association between obesity and depression and behind persistent/remitted depression post-surgery remain unclear. This study aimed to identify potential biological mechanisms involved in this association. As part of the longitudinal observational bariatric surgery and depression (BARIDEP) study, blood samples were collected from individuals prior to bariatric surgery. For this study we selected n = 29 subjects (from the original sample of n = 85 participants) based on their Hamilton Depression (HAM-D) scale scores at baseline and at 6 months post-surgery and grouped them as controls (n = 10), persistent depression (n = 7) or remission (n = 12). Participants were selected to be matched for age, sex and BMI. RNA was extracted and bulk RNAseq was performed. Data were analysed for differential expression and gene set enrichment across the 3 groups of interest. Analysis of the differential gene expression showed seven genes differentially expressed across the three groups, with genes mainly involved in immune activation or synaptic function. The greatest differences were found between the persistent and remitting depression groups, despite both experiencing clinical depression at the time of sample collection. Our data show distinct baseline gene expression and gene enrichment suggesting different immune and metabolic mechanisms possibly involved in persistent vs remitting depression post-bariatric surgery.

Obesity and lack of physical activity (PA) are suggested to contribute to development of depression, seemingly ameliorated by integration of regular PA in post-bariatric surgery care. Effects of pre-surgery PA on depressive symptoms and weight loss remain unclear in long-term follow-up post-surgery. We examined associations between PA and depressive symptoms and weight loss over 3-years in obese bariatric surgery patients with and without major depressive disorder (MDD). Data obtained from a sub-group of participants from the bariatric surgery and depression (BARIDEP) study reported PA at baseline, 6-months, and 3-years post-surgery follow-up; 23 MDD (age=45.82±2.61; BMI=48.01±1.49 kg/m2) and 25 controls (age(±se)=44.28±2.08; BMI=49.75±2.33 kg/m2). PA measured using International Physical Activity Questionnaire (IPAQ) and depressive symptoms with Hamilton Depression Scale (HAM- D-17). Metabolic equivalent (MET) scores (weighted sum of walking, moderate, and vigorous PA) were lower in MDD than controls, before (W=354.5, p<0.01), 6-months (W=405.5, p<0.05), but not 3-years post-surgery. The total sample, baseline HAM-D-17 was correlated with baseline MET score (r=-0.361, p=0.016), PA days (r=-0.310, p=0.032), and time walking (r=- 0.422, p=0.004). 3-year HAM-D-17 was not correlated with any 3-year IPAQ domain. No baseline IPAQ domains predicted 3-year HAM-D-17 score. Weight loss post-surgery was not correlated with baseline or 3-year followup IPAQ scores in (MDD, controls, total) groups. We found gradual improvement in PA levels in patients with MDD 3-years following bariatric surgery, but no association with depressive symptom improvement nor weight loss

We recruited obese individuals with or without comorbid depression before undergoing bariatric surgery for the longitudinal bariatric surgery and depression (BARIDEP) study. Participants were followed-up 3-years post-surgery with blood samples and depressive symptom assessment. Based on Hamilton Depression (HAM-D) scale scores participants were classed as controls (HAM-D<8), persistent depression (HAM-D≥8), remission (HAM-D≥8 at baseline and <8 at follow-up), or new depression (HAM-D<8 at baseline and ≥8 at follow-up). Inflammatory cytokines were measured in serum using Meso Scale Discovery immunoassay. Participants who had depression at baseline had significantly higher serum tumour necrosis factor (TNF) and interleukin 6 (IL-6) at 3-year follow-up compared with controls. Those with persistent depression had significantly higher TNF compared with participants with newly diagnosed depression. IL-6 levels were correlated with body mass index (BMI) only in the control group. Our data show persistent higher levels of inflammation in individuals with persistent depression which is not present in individuals who developed depression post-surgery, suggesting a difference in the mechanisms leading to depression between these two groups. Furthermore, pro-inflammatory cytokine levels are not correlated with BMI in individuals with depression indicating the inflammation may be independent of weight.

BACKGROUND Research implicates inflammation in the vicious cycle between depression and obesity, yet few longitudinal studies exist. The rapid weight loss induced by bariatric surgery is known to improve depressive symptoms dramatically, but preoperative depression diagnosis may also increase the risk for poor weight loss. Therefore, we investigated longitudinal associations between depression and inflammatory markers and their effect on weight loss and clinical outcomes in bariatric patients. METHODS This longitudinal observational study of 85 patients with obesity undergoing bariatric surgery included 41 cases with depression and 44 controls. Before and 6 months after surgery, we assessed depression by clinical interview and measured serum high-sensitivity C-reactive protein (hsCRP) and inflammatory cytokines, including interleukin (IL)-6 and IL-10. RESULTS Before surgery, depression diagnosis was associated with significantly higher serum hsCRP, IL-6, and IL-6/10 ratio levels after controlling for confounders. Six months after surgery, patients with pre-existing depression still had significantly higher inflammation despite demonstrating similar weight loss to controls. Hierarchical regression showed higher baseline hsCRP levels predicted poorer weight loss (β = -0.28, p = 0.01) but had no effect on depression severity at follow-up (β = -0.02, p = 0.9). Instead, more severe baseline depressive symptoms and childhood emotional abuse predicted greater depression severity after surgery (β = 0.81, p < 0.001; and β = 0.31, p = 0.001, respectively). CONCLUSIONS Depression was significantly associated with higher inflammation beyond the effect of obesity and other confounders. Higher inflammation at baseline predicted poorer weight loss 6 months after surgery, regardless of depression diagnosis. Increased inflammation, rather than depression, may drive poor weight loss outcomes among bariatric patients.

AbstractBackgroundDepression and overweight are each associated with abnormal immune system activation. We sought to disentangle the extent to which depressive symptoms and overweight status contributed to increased inflammation and abnormal cortisol levels.MethodsParticipants were recruited through the Wellcome Trust NIMA Consortium. The sample of 216 participants consisted of 69 overweight patients with depression; 35 overweight controls; 55 normal-weight patients with depression and 57 normal-weight controls. Peripheral inflammation was measured as high-sensitivity C-Reactive Protein (hsCRP) in serum. Salivary cortisol was collected at multiple points throughout the day to measure cortisol awakening response and diurnal cortisol levels.ResultsOverweight patients with depression had significantly higher hsCRP compared with overweight controls (p = 0.042), normal-weight depressed patients (p < 0.001) and normal-weight controls (p < 0.001), after controlling for age and gender. Multivariable logistic regression showed that comorbid depression and overweight significantly increased the risk of clinically elevated hsCRP levels ⩾3 mg/L (OR 2.44, 1.28–3.94). In a separate multivariable logistic regression model, overweight status contributed most to the risk of having hsCRP levels ⩾3 mg/L (OR 1.52, 0.7–2.41), while depression also contributed a significant risk (OR 1.09, 0.27–2). There were no significant differences between groups in cortisol awakening response and diurnal cortisol levels.ConclusionComorbid depression and overweight status are associated with increased hsCRP, and the coexistence of these conditions amplified the risk of clinically elevated hsCRP levels. Overweight status contributed most to the risk of clinically elevated hsCRP levels, but depression also contributed to a significant risk. We observed no differences in cortisol levels between groups.

Background: Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been suggested to play a role in the association between depression and obesity. The study aimed to investigate differences in cortisol levels in in-dividuals with obesity with and without depression and the role of perceived stress on these differences.Methods: Saliva samples were collected at awakening, 15-, 30-and 60-minutes post-awakening from 66 in-dividuals with obesity (30 with major depressive disorder and 36 without major depressive disorder). Salivary cortisol was analysed using ELISA technique. Linear Mixed Models were used for group differences in cortisol awakening response (CAR) with adjustment for socio-demographic confounders and binge eating.Results: Individuals with obesity and depression had lower CAR compared with individuals with obesity without depression (8 =-0.44; p = 0.036). When controlling for perceived stress, CAR was no longer influenced by depression (8 =-0.09; p = 0.75), but individuals with moderate/high stress had lower CAR compared with those with low stress (8 =-0.63; p = 0.036).Conclusions: Our results suggest that differences in CAR between individuals with obesity with and without depression could be due to higher levels of perceived stress in the depressed subjects.

Background: Inflammation is a well-known risk factor for depression. Specifically, patients who do not respond to antidepressant treatment show higher levels of inflammatory biomarkers compared with responders. Thus, several studies have investigated the efficacy of anti-inflammatory add-on treatment in this population. However, major depressive disorder is more prevalent in females than in males, with sex differences present in antidepressant treatment response and in immune system regulation. To explore sex differences in inflammatory profiles and treatment responses, we investigated a cohort of patients with treatment resistant depression (TRD), for which they received an adjunctive, anti-inflammatory treatment with minocycline - the Minocycline in Depression (MINDEP) study. Methods: The MINDEP study is a 4-week double-blind, randomised, placebo-controlled clinical trial (stratified by sex) with 39 TRD participants, which demonstrated the efficacy of minocycline, an antibiotic with antiinflammatory properties, in TRD patients with major depressive disorder (MDD) and evidence of low-grade inflammation measured with C-reactive protein (CRP) >= 3 mg/L. In these secondary analyses, we investigated the differential effects of minocycline in females (N = 22, 10 randomised to minocycline and 12 randomised to placebo) and in males (N = 17, 8 randomised to minocycline and 9 randomised to placebo) on changes in depressive symptoms (Delta-Hamilton Rating Scale for Depression (HAMD)-17), taking also into consideration CRP levels (CRP >= 3 mg/L vs. CRP <3 mg/L). Additionally, we investigated the role of serum IL-6 in predicting treatment response to minocycline, using sex-specific medians of IL-6, in novel exploratory analyses. Results: Sex differences in Delta-HAMD-17 indicate that only females (F =10.49, p = 0.005), but not males (F = 1.64, p = 0.22), presented an effect of CRP levels on the response to minocycline. Also, we detected sex differences in the relationship between serum CRP and IL-6 levels: CRP was strongly correlated with IL-6 in females (Spearman's rho = 0.658, P < 0.001) but not in males (rho = 0.007, p = 0.979). Exploratory analyses found that IL-6 was indeed a better predictor of response than minocycline than CRP, as we found an interaction between study arms and IL-6 groups (above and below the IL-6 sex-specific median) in females (F = 4.435 p = 0.050) and, at trend statistical level, in males (F = 4.258 p = 0.060). Moreover, Delta-HAMD-17 was numerically comparable in the two high-IL-6 group taking minocycline (females, mean 9.20 +/- SD 7.80; males, mean 8.80 +/- SD 5.97), confirming that high IL-6, differently from high CRP, identified responders to minocycline both in males and females. Conclusion: Our findings highlight the need of sex-specific inflammatory biomarkers in predicting antidepressant response to anti-inflammatories in TRD patients, with the possibility of CRP being a relevant predictor of treatment response only for females, and IL-6 being relevant for both sexes.

Processing-in-memory (PIM) proposes to move computational components inside memory units to alleviate the high cost of data movement in big data processing. This approach has been recently utilized to reach high performance and energy-efficiency in large-scale graph processing. This paper analyzes a state-of-the-art PIM accelerator for graph processing and identifies message queue management as a significant bottleneck for system efficiency. Two metrics were introduced for representing the waiting time and processor utilization. We then present a lightweight solution for reducing waiting time caused by the message queue while increasing resource utilization in the system. Our simulation results on a set of real-world graph examples indicate that the enhanced graph processing system achieves 40% reduction in the overall execution time and 15% system energy savings over the baseline PIM based accelerator.

To characterize features and outcomes of intravenous drug use (IVDU)-associated endophthalmitis.Retrospective cross-sectional study.A retrospective chart review of all cases of endophthalmitis seen between September 2006 and November 2014 at a single academic referral center was performed. All cases of IVDU-associated endophthalmitis were identified and characterized.Ophthalmic examination findings, microbial results, visual outcomes, and secondary ocular sequelae.Thirty patients (32 eyes) with IVDU-associated endophthalmitis were identified, which represented 9% of all endophthalmitis patients (n = 338) and 44% of all endogenous endophthalmitis patients (n = 68). Mean follow-up was 11 months. All eyes had vitritis, 6 had hypopyon, and 2 had subretinal abscesses. Twenty eyes had macular involvement, 8 eyes had no macular involvement, and media opacities precluded macular assessment in 4 eyes. Initial treatment was needle vitreous biopsy with intravitreal antibiotics ("tap and inject") in 25 eyes (78%) and pars plana vitrectomy (PPV) in 6 eyes (19%); 1 patient refused ocular treatment. An organism was identified from at least 1 source in 75% of eyes (24/32): 59% fungal, 16% bacterial, 22% negative cultures, and 3% refused ocular cultures. Mean visual acuity improved significantly between initial examination and final follow-up (1.64 logMAR to 0.91 logMAR, P < 0.0001). At final follow-up, 90% of eyes had improved vision compared with presentation, 31% of eyes had 20/40 or better vision, and 25% of eyes had 20/200 or worse vision. Twenty-one eyes (66%) required PPV for their infection—6 initially and 15 secondarily after tap and inject. Sixty-nine percent of eyes (9/13) that had cultures sent from a secondary PPV had positive cultures, despite almost all receiving appropriate intravitreal antibiotic therapy at the time of the tap and inject. Eight patients (27%) had extraocular signs of infection. Twenty eyes (63%) suffered secondary ocular sequelae.This represents the largest series of IVDU-associated endophthalmitis. Bacterial etiologies constitute an important share of cases. A majority of patients eventually required PPV and there was frequent culture positivity even after tap and inject with appropriate antibiotics; therefore, early PPV may have an important role in management.

The corneal endothelium state is verified on the basis of an in vivo specular microscope image from which the shape and density of cells are exploited for data description. Due to the relatively low image quality resulting from a high magnification of the living, non-stained tissue, both manual and automatic analysis of the data is a challenging task. Although, many automatic or semi-automatic solutions have already been introduced, all of them are prone to inaccuracy.This work presents a comparison of four methods (fully-automated or semi-automated) for endothelial cell segmentation, all of which represent a different approach to cell segmentation; fast robust stochastic watershed (FRSW), KH method, active contours solution (SNAKE), and TOPCON ImageNET. Moreover, an improvement framework is introduced which aims to unify precise cell border location in images pre-processed with differing techniques. Finally, the influence of the selected methods on clinical parameters is examined, both with and without the improvement framework application.The experiments revealed that although the image segmentation approaches differ, the measures calculated for clinical parameters are in high accordance when CV (coefficient of variation), and CVSL (coefficient of variation of cell sides length) are considered. Higher variation was noticed for the H (hexagonality) metric. Utilisation of the improvement framework assured better repeatability of precise endothelial cell border location between the methods while diminishing the dispersion of clinical parameter values calculated for such images. Finally, it was proven statistically that the image processing method applied for endothelial cell analysis does not influence the ability to differentiate between the images using medical parameters.

We have corrected this Article post-publication, because Dr. Cattaneo's affiliation details were originally incorrect (she was affiliated with three institutions but is in fact only linked to one: Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia). These changes reflect in both the PDF and HTML versions of this Article.

An increasing body of evidence suggests alterations in immune and inflammatory signaling in depression, with higher levels of pro-inflammatory cytokines in depressed patients as compared with controls. Importantly, we and other groups have also demonstrated an association between high inflammation and poor treatment response. Here we aimed to investigate a broader range of inflammatory genes in a group of depressed patients, who have been characterized for treatment response. Clinical data and blood samples from PaxGene tubes have been collected from 132 patients with depression (36 untreated, 60 treatment resistant and 36 treatment responsive) and from 40 healthy controls, as part of BIODEP, a multicenter study investigating immune biomarkers in depression within the NIMA Consortium. Using qPCR, we have measured mRNA levels of P2X7R and those of other genes involved in inflammation (IL-1b, TNF-alpha, MIF) and stress response (NR3C1, SGK1 and FKBP5). We have found that, compared with controls, untreated and treatment resistant patients had higher levels of P2X7R (+23% and +17%, p