Lower levels of the glial cell marker TSPO in drug-naive first-episode psychosis patients as measured using PET and [11C]PBR28.

Several lines of evidence are indicative of a role for immune activation in the pathophysiology of schizophrenia. Nevertheless, studies using positron emission tomography (PET) and radioligands for the translocator protein (TSPO), a marker for glial activation, have yielded inconsistent results. Whereas early studies using a radioligand with low signal-to-noise in small samples showed increases in patients, more recent studies with improved methodology have shown no differences or trend-level decreases. Importantly, all patients investigated thus far have been on antipsychotic medication, and as these compounds may dampen immune cell activity, this factor limits the conclusions that can be drawn. Here, we examined 16 drug-naive, first-episode psychosis patients and 16 healthy controls using PET and the TSPO radioligand [11C]PBR28. Gray matter (GM) volume of distribution (VT) derived from a two-tissue compartmental analysis with arterial input function was the main outcome measure. Statistical analyses were performed controlling for both TSPO genotype, which is known to affect [11C]PBR28 binding, and gender. There was a significant reduction of [11C]PBR28 VT in patients compared with healthy controls in GM as well as in secondary regions of interest. No correlation was observed between GM VT and clinical or cognitive measures after correction for multiple comparisons. The observed decrease in TSPO binding suggests reduced numbers or altered function of immune cells in brain in early-stage schizophrenia.

Accelerated wound healing in a diabetic rat model using decellularized dermal matrix and human umbilical cord perivascular cells.

There is an unmet clinical need for novel wound healing strategies to treat full thickness skin defects, especially in diabetic patients. We hypothesized that a scaffold could perform dual roles of a biomechanical support and a favorable biochemical environment for stem cells. Human umbilical cord perivascular cells (HUCPVCs) have been recently reported as a type of mesenchymal stem cell that can accelerate early wound healing in skin defects. However, there are only a limited number of studies that have incorporated these cells into natural scaffolds for dermal tissue engineering. The aim of the present study was to promote angiogenesis and accelerate wound healing by using HUCPVCs and decellularized dermal matrix (DDM) in a rat model of diabetic wounds. The DDM scaffolds were prepared from harvested human skin samples and histological, ultrastructural, molecular and mechanical assessments were carried out. In comparison with the control (without any treatment) and DDM alone group, full thickness excisional wounds treated with HUCPVCs-loaded DDM scaffolds demonstrated an accelerated wound closure rate, faster re-epithelization, more granulation tissue formation and decreased collagen deposition. Furthermore, immunofluorescence analysis showed that the VEGFR-2 expression and vascular density in the HUCPVCs-loaded DDM scaffold treated group were also significantly higher than the other groups at 7days post implantation. Since the rates of angiogenesis, re-epithelization and formation of granulation tissue are directly correlated with full thickness wound healing in patients, the proposed HUCPVCs-loaded DDM scaffolds may fulfil a role neglected by current treatment strategies. This pre-clinical proof-of-concept study warrants further clinical evaluation. STATEMENT OF SIGNIFICANCE: The aim of the present study was to design a novel tissue-engineered system to promote angiogenesis, re-epithelization and granulation of skin tissue using human umbilical cord perivascular stem cells and decellularized dermal matrix natural scaffolds in rat diabetic wound models. The authors of this research article have been working on stem cells and tissue engineering scaffolds for years. According to our knowledge, there is a lack of an efficient system for the treatment of skin defects using tissue engineering strategy. Since the rates of angiogenesis, re-epithelization and granulation tissue are directly correlated with full thickness wound healing, the proposed HUCPVCs-loaded DDM scaffolds perfectly fills the niche neglected by current treatment strategies. This pre-clinical study demonstrates the proof-of-concept that necessitates clinical evaluations.

Efficacy of Crocus sativus L. on reduction of cadmium-induced toxicity on spermatogenesis in adult rats.

Cadmium is a toxic heavy metal element, which probably cause infertility by impairment in spermatogenesis. The present work aimed (i) to study the toxic effect of cadmium on spermatogenesis in rat, as well as (ii) the protective effect of Crocus sativus L. on cadmium-intoxicated rats. Cadmium chloride was administered intraperitoneally during 16 days at intervals of 48 h between subsequent treatments. Crocus sativus L. was pre-treated in both of control and cadmium-injected rats. Animals were sacrificed on day 17 after the first treatment. The left cauda epididymis was removed and immediately immersed into Hank's balanced salt solution for the evaluation of sperm count and viability, and left testis was fixed in 10% formalin for histological evaluation. Following contamination with cadmium, a decrease was observed in the number and viability of cauda epididymis sperm, which were increased by Crocus sativus L. pre-treatment (P < 0.05). In addition, cadmium decreased both cell proliferation and Johnsen Scores in the seminiferous tubules, which were reversed by Crocus sativus pre-treatment (P < 0.05). Furthermore, cadmium-induced decrease in the amount of free serum testosterone as well as an increase in lipid peroxidation activity in the testicular tissue was reversed by Crocus sativus L. (P < 0.05). These findings may support the concept that Crocus sativus L. can improve the cadmium toxicity on spermatogenesis.

Impact of early postoperative platelet count on volumetric liver gain and perioperative outcomes after major liver resection.

BACKGROUND: Although perioperative platelet count has been associated with postoperative morbidity and mortality, its impact on liver regeneration has not been examined directly. This study sought to determine the impact of platelet count on liver regeneration after major liver resection using cross-sectional imaging volumetric assessment. METHODS: Patients who underwent major liver resection between 2004 and 2015 and had available data on immediate postoperative platelet count, as well as preoperative and postoperative CT images, were identified retrospectively. Resected liver volume was subtracted from total liver volume (TLV) to define postoperative remnant liver volume (RLVp ). The liver regeneration index was defined as the relative increase in liver volume within 2 months ((RLV2m - RLVp )/RLVp , where RLV2m is the remnant liver volume around 2 months after surgery). The association between platelet count, liver regeneration and outcomes was assessed. RESULTS: A total of 99 patients met the inclusion criteria. Overall, 25 patients (25 per cent) had a low platelet count (less than 150 × 10(9) /l), whereas 74 had a normal-high platelet count (at least 150 × 10(9) /l). Despite having comparable clinicopathological characteristics and RLVp /TLV at surgery (P = 0·903), the relative increase in liver volume within 2 months was considerably lower in the low-platelet group (3·9 versus 16·5 per cent; P = 0·043). Patients with a low platelet count had an increased risk of postoperative complications (72 versus 38 per cent; P = 0·003), longer hospital stay (8 versus 6 days; P = 0·004) and worse median overall survival (24·5 versus 67·3 months; P = 0·005) than those with a normal or high platelet count. CONCLUSION: After major liver resection, a low postoperative platelet count was associated with inhibited liver regeneration, as well as worse short- and long-term outcomes. Immediate postoperative platelet count may be an early indicator to identify patients at increased risk of worse outcomes.

Test-retest reproducibility of [(11)C]PBR28 binding to TSPO in healthy control subjects.

PURPOSE: The PET radioligand [(11)C]PBR28 binds to the translocator protein (TSPO), a marker of brain immune activation. We examined the reproducibility of [(11)C]PBR28 binding in healthy subjects with quantification on a regional and voxel-by-voxel basis. In addition, we performed a preliminary analysis of diurnal changes in TSPO availability. METHODS: Twelve subjects were examined using a high-resolution research tomograph and [(11)C]PBR28, six in the morning and afternoon of the same day, and six in the morning on two separate days. Regional volumes of distribution (V T) were derived using a region-of-interest based two-tissue compartmental analysis (2TCM), as well as a parametric approach. Metabolite-corrected arterial plasma was used as input function. RESULTS: For the whole sample, the mean absolute variability in V T in the grey matter (GM) was 18.3 ± 12.7 %. Intraclass correlation coefficients in GM regions ranged from 0.90 to 0.94. Reducing the time of analysis from 91 to 63 min yielded a variability of 16.9 ± 14.9 %. There was a strong correlation between the parametric and 2TCM-derived GM values (r = 0.99). A significant increase in GM V T was observed between the morning and afternoon examinations when using secondary methods of quantification (p = 0.028). In the subjects examined at the same time of the day, the absolute variability was 15.9 ± 12.2 % for the 91-min 2TCM data. CONCLUSION: V T of [(11)C]PBR28 binding showed medium reproducibility and high reliability in GM regions. Our findings support the use of parametric approaches for determining [(11)C]PBR28 V T values, and indicate that the acquisition time could be shortened. Diurnal changes in TSPO binding in the brain may be a potential confounder in clinical studies and should be investigated further.

Clinical and morphometric parameters of frailty for prediction of mortality following hepatopancreaticobiliary surgery in the elderly.

BACKGROUND: Although frailty is a known determinant of poor postoperative outcomes, it can be difficult to identify in patients before surgery. The authors sought to develop a preoperative frailty risk model to predict mortality among patients aged 65 years or more. METHODS: Clinical and morphometric data including total psoas area (TPA), total psoas volume (TPV) and psoas density (Hounsfield unit average calculation, HUAC) were collected for patients undergoing hepatopancreaticobiliary (HPB) surgery between 2012 and 2014. Multivariable Cox proportional hazards regression was used to identify preoperative risk factors associated with 1-year mortality. RESULTS: The median age of the 518 patients included in the study was 72 (i.q.r. 68-76) years; 55·6 per cent of patients were men, and half of the cohort had multiple co-morbidities (Charlson co-morbidity index (CCI) of 4 or more, 55·6 per cent). TPA cut-offs to define sarcopenia were 552·7 mm(2) /m(2) in women and 702·9 mm(2) /m(2) in men; cut-offs for TPV were 18·2 cm(3) /m(2) in women and 26·2 cm(3) /m(2) in men, whereas HUAC cut-offs were 31·1 HU in women and 33·3 HU in men. The overall 1-year mortality rate was 14·1 per cent. In multivariable analysis, risk factors associated with 1-year mortality included CCI of 4 or above (hazard ratio (HR) 2·91, 95 per cent c.i. 1·47 to 5·77; P = 0·002), malignant disease (HR 3·94, 1·17 to 13·30; P = 0·027) and sarcopenia by HUAC (HR 1·85, 1·10 to 3·10; P = 0·021). A weighted 25-point composite score was developed to stratify patients at risk of 1-year postoperative mortality. The 1-year mortality rate was noted to be 2·5 per cent among patients scoring 0-10 (low risk), 17·3 per cent among patients scoring 11-20 (intermediate risk) and 29·2 per cent among those scoring between 21 and 25 (high risk) (P < 0·001). CONCLUSION: Clinical and morphometric measures of frailty accurately predict the risk of 1-year mortality following HPB surgery in elderly patients, and can be used to risk-stratify patients appropriately.

Compared therapeutic efficacy between intralesional bleomycin and cryotherapy for common warts: a randomized clinical trial.

UNLABELLED: In spite of many available studies on bleomycin and cryotherapy in treating warts, little head to head research is done to compare efficacy of these treatments. Our aim was to compare the therapeutic effects of intralesional bleomycin and cryotherapy on common warts of the hands and feet. In this clinical trial 44 patients above 12 years of age referred to the dermatology clinic of Bouali University Hospital were enrolled. The patients were required to have warts on at least two symmetric limbs (hands or feet). The warts located on right and left limbs of each patient were examined and counted. Each patient received both cryotherapy and intralesional bleomycin on his or her warts. The two treatment types were randomly allocated to either right sided or left sided warts. Each patient was evaluated at 2 week intervals and retreated if necessary up to three times. Data were analyzed by SPSS 11 and EPI Info 2002 statistical packages. The mean number of warts was 5.2 on upper limbs and 4.6 on lower limbs. In 86.4 percent of the cases all warts on the limb side treated by intralesional bleomycin were cleared compared with 68.2 % for cryotherapy (P<0.05). Relative risk for the effect of bleomycin compared to cryotherapy in this regard was 1.27 (1