Oral supplementation with carbohydrate- and branched-chain amino acid-enriched nutrients improves postoperative quality of life in patients undergoing hepatic resection

The long-term outcomes of branched-chain amino acid (BCAA) administration in patients undergoing hepatic resection remain unclear. The aim of this study is to assess the impact of oral supplementation with BCAA-enriched nutrients on postoperative quality of life (QOL) in patients undergoing liver resection. A prospective randomized clinical trial was conducted in 96 patients undergoing hepatic resection. Patients were randomly assigned to receive BCAA supplementation (AEN group, n = 48) or a conventional diet (control group, n = 48). Postoperative QOL and short-term outcomes were regularly and continuously evaluated in all patients using a short-form 36 (SF-36) health questionnaire and by measuring various clinical parameters. This study demonstrated a significant improvement in QOL after hepatectomy for liver neoplasm in the AEN group based on the same patients’ preoperative SF-36 scores (P < 0.05). Perioperative BCAA supplementation preserved liver function and general patient health in the short term for AEN group patients compared to those not receiving the nutritional supplement. BCAA supplementation improved postoperative QOL after hepatic resection over the long term by restoring and maintaining nutritional status and whole-body kinetics. This study was registered at (registration number: NCT00945568).     

Increased serum HSP70 levels are associated with the duration of diabetes

The evolutionary conserved family of heat shock proteins (HSP) is responsible for protecting cells against different types of stress, including oxidative stress. Although the levels of HSPs can be readily measured in blood serum, the levels of HSP70 in patients with different durations of diabetes have not been studied before. We quantified serum HSP70 levels in a healthy control group (n = 36) and two groups of type 2 diabetic patients, defined as newly diagnosed diabetes (n = 36) and patients with diabetes duration of more than 5 years (n = 37). The clinical characteristics and biochemical parameters were evaluated in the studied population. We found that serum HSP70 levels were significantly higher in patients with diabetes when compared with controls (p < 0.001) and it was higher in patients with disease for more than 5 years than in newly diagnosed patients (p < 0.001). Serum HSP70 was inversely correlated with fasting blood sugar in patients with diabetes for more than 5 years (r = −0.500, p = 0.002), positively correlated with the history of hypertension in newly diagnosed patients (p < 0.001), and positively correlated with age in patients with diabetes (r = 0.531, p = 0.001). Serum level of HSP70 is significantly higher in patients with diabetes and correlates with the duration of disease. Higher HSP70 in prolonged diabetes versus newly diagnosed diabetes may be an indicator of metabolic derangement in the course of diabetes.     

Switch to checkpoint inhibition after targeted therapy at time of progression or during ongoing response: A retrospective single‐centre experience in patients with BRAF‐mutated melanoma

BRAF + MEK inhibition is preferentially applied as first‐line therapy in BRAF V600‐mutated melanoma patients with unfavourable prognostic features, due to the ability of targeted therapy (TT) to induce rapid symptom control, decrease tumour burden and normalize lactate dehydrogenase (LDH) levels. In addition, short‐term TT transiently increases tumour antigen presentation and tumour influx of T cells. Therefore, it might be favourable to switch TT to checkpoint inhibition (CPI) before progression (PD). We retrospectively analysed melanoma patients treated first line with TT (TT1) and who subsequently switched to CPI during response to TT (sDR group) or at progression upon TT (sPD group). We identified 74 patients (n = 37 sDR group and n = 37 sPD group). ORR to CPI was 27.0% in the sDR group versus 24.3% in the sPD group (p = .790). Median was PFS 2.5 months versus 1.2 months (p = .145), and median OS was 30.6 versus 14.1 months (p = .007). After adjusting for baseline differences and known prognostic factors, hazard ratios (HRs) favouring sDR were 0.89 for PFS upon CPI (p = .956) and 0.48 for OS (p = .055). Thus, patients switching to CPI during ongoing clinical benefit from TT do not have an inferior outcome. Due to baseline imbalances and small patient population, a favourable trend for the sDR group can be hypothesized only.     

A potential role of TNFR gene polymorphisms in autoimmune thyroid diseases in the Tunisian population

Autoimmune thyroid diseases (AITDs) including Graves disease (GD) and autoimmune hypothyroidism (AH) are associated with TNF genes polymorphisms. TNF molecules bind to TNFRI and TNFRII. No genetic association was reported between TNFR and AITDs. In this study, we have analysed two polymorphisms in TNFRI gene (TNFRI+36A/G SNP and a microsatellite (GT)₁₇ (GA)_n) and one polymorphism in TNFRII gene (TNFRII +676 T/G). All these polymorphisms were studied in a large Tunisian family with high prevalence of AITDs, and on a case-control sample of 91 GD patients and 165 controls. The present study was undertaken to investigate the genetic association of these polymorphisms with AITDs development. We reported the implication of TNFRIA3 allele in AITDs pathogenesis in familial and case control studies, respectively (χ² = 4.13, p = 0.042; χ² = 9.26, p_c = 0.005). In addition, Case-control study has revealed for the first time that TNFRII+676G allele was associated with GD (χ² = 11.53; p = 0.0007). Two TNFRI haplotypes were found to be associated with GD: TNFRI+36G-A8, TNFRI+36A-A3 (χ² = 88.07; p = 6.32 × 10⁻²¹, χ² = 16.78; p = 4.2 × 10⁻⁵, respectively). Our data showed that TNFRI polymorphisms have an important role in AITDs pathogenesis in both familial and case-control samples and that TNFRII was rather implicated in GD development in the Tunisian population.     

Treadmill exercise suppresses muscle cell apoptosis by increasing nerve growth factor levels and stimulating p-phosphatidylinositol 3-kinase activation in the soleus of diabetic rats

We investigated the effects of treadmill exercise performed regularly for 6 weeks on the levels of nerve growth factor (NGF), tyrosine kinase A and p75 receptors, phosphatidylinositol 3-kinase (PI3-K), mitogen-activated protein kinase/extracellular signal-regulated kinase (Erk) 1,2, cyclic AMP response element-binding protein (CREB), and caspase-3 in the soleus of rats with streptozotocin (STZ)-induced diabetes. Thirty-two male Sprague–Dawley rats were divided into the following four groups: (1) normal control group (NCG; n = 8), (2) normal exercise group (NEG; n = 8), (3) diabetes control group (DCG; n = 8), and (4) diabetes exercise group (DEG; n = 8). Diabetes was induced by intraperitoneal injection of STZ (55 mg/kg dissolved in 0.05 M citrate buffer, pH 4.5). Rats were subjected to treadmill exercise 5 days a week for 6 weeks. The protein level of NGF significantly increased in the NEG and DEG (p < 0.001), whereas the levels of tyrosine kinase A and p75 receptors significantly increased in the NEG (p < 0.001). The levels of t-PI3-K, p-PI3-K, and p-CREB, and the p-CREB/t-CREB ratio significantly increased in the NEG (p < 0.001, respectively). The p-PI3-K/t-PI3-K ratio significantly increased in the DEG (p < 0.001). The p-Erk1/t-Erk1 ratio significantly increased in the NEG (p < 0.001), whereas the p-Erk2/t-Erk2 ratio significantly decreased in the DCG and DEG (p < 0.001). The caspase-3 level significantly increased in the DCG compared with that in the DEG (p < 0.001). These results suggest that treadmill exercise increases NGF levels and accelerates p-PI3-K activation in order to suppress apoptotic cell death in the soleus muscle of diabetic rats.     

Elevated endogenous testosterone concentrations potentiate muscle androgen receptor responses to resistance exercise

The purpose of this study was to determine the influence of endogenous circulating testosterone (T) on muscle androgen receptor (AR) responses to acute resistance exercise (RE). Six healthy men (26 ± 4 years; 176 ± 5 cm; 75.8 ± 11.4 kg) performed a knee extension exercise protocol on two occasions separated by 1–3 weeks. Rest preceded one trial (i.e., control [CON] trial) and a high-volume upper-body RE protocol designed to increase circulating T preceded the other trial (i.e., high T [HT] trial). Serial blood samples were obtained throughout each trial to determine circulating T concentrations. Biopsies of the vastus lateralis were obtained pre-RE (REST), 10-min post-RE (+10), and 180-min post-RE (+180) to determine muscle AR content. Circulating T concentrations remained stable during CON. Alternately, HT significantly (p ≤ 0.05) increased T concentrations above resting values (+16%). Testosterone area-under-the-time curve during HT exceeded CON by 14%. AR content remained stable from REST to +10 in both trials. Compared to the corresponding +10 value, muscle AR content at +180 tended to decrease during CON (−33%; p = 0.10) but remained stable during HT (+40%; p = 0.17). Muscle AR content at +180 during the HT trial exceeded the corresponding CON value. In conclusion, acute elevations in circulating T potentiated muscle AR content following RE.     

Proteomic profiling of epicardial fat in heart failure with preserved versus reduced and mildly reduced ejection fraction

In order to explore the proteomic signatures of epicardial adipose tissue (EAT) related to the mechanism of heart failure with reduced and mildly reduced ejection fraction (HFrEF/HFmrEF) and heart failure (HF) with preserved ejection fraction (HFpEF), a comprehensive proteomic analysis of EAT was made in HFrEF/HFmrEF (n = 5) and HFpEF (n = 5) patients with liquid chromatography–tandem mass spectrometry experiments. The selected differential proteins were verified between HFrEF/HFmrEF (n = 20) and HFpEF (n = 40) by ELISA (enzyme-linked immunosorbent assay). A total of 599 EAT proteins were significantly different in expression between HFrEF/HFmrEF and HFpEF. Among the 599 proteins, 58 proteins increased in HFrEF/HFmrEF compared to HFpEF, whereas 541 proteins decreased in HFrEF/HFmrEF. Of these proteins, TGM2 in EAT was down-regulated in HFrEF/HFmrEF patients and was confirmed to decrease in circulating plasma of the HFrEF/HFmrEF group (p = 0.019). Multivariate logistic regression analysis confirmed plasma TGM2 could be an independent predictor of HFrEF/HFmrEF (p = 0.033). Receiver operating curve analysis indicated that the combination of TGM2 and Gensini score improved the diagnostic value of HFrEF/HFmrEF (p = 0.002). In summary, for the first time, we described the proteome in EAT in both HFpEF and HFrEF/HFmrEF and identified a comprehensive dimension of potential targets for the mechanism behind the EF spectrum. Exploring the role of EAT may offer potential targets for preventive intervention of HF.     

Comparison of escitalopram alone and combined with zolpidem in treating major depression and related sleep impairments

Escitalopram has been shown to be effective for treating major depression (MDD); however, research is lacking regarding its effect on treating MDD-related sleep impairments. The purpose of this study was to assess the efficacy of escitalopram monotherapy and investigate changes in insomnia, depressive symptoms, and quality of life (QOL). Participants were 14 patients with MDD who enrolled in a clinical trial at Jikei University Katsushika Medical Center. Escitalopram monotherapy was used, and hypnotics were administered three times per week for individuals suffering from sleep impairments. The following variables were assessed: (1) sleep quality [Pittsburgh sleep quality index (PSQI)], (2) depression [Zung self-rating depression scale (ZSRDS)], and (3) quality of life (QOL) as determined by the Sheehan disability scale (SDISS) and short form (36) health survey (SF-36). These assessments were conducted prior to any treatment (pre-test) and again 8–12 weeks after treatment (post-test). Monotherapy (E = escitalopram alone; n = 6) and combination therapy (E+ = escitalopram + zolpidem; n = 8) groups were compared. All participants completed the full protocol (average 9.4 ± 1.8 weeks). Regardless of treatment group, participants improved on all assessments (including sleep impairment). However, groups did not differ in their level of improvement. A two-factor ANOVA revealed that the E+ group showed particular improvements in QOL. In treating MDD and associated sleep impairments, zolpidem did not confer additional benefits. Thus, clinicians should consider E monotherapy for patients with MDD-related sleep impairments before prescribing combination therapies.

     

Increased survival and reproductive success associated with stereotypical behaviours in laboratory-bred bank voles (Clethrionomys glareolus)

The aim of this study was to examine whether voles performing stereotypic behaviours (Ster) differed in physical welfare from voles, which did not develop stereotypies (N-Ster). The chosen variables were reproductive success and capacity to survive barren housing conditions. Furthermore, effect of weight on proneness to develop stereotypic behaviours were examined. Singly housed Ster (n = 62) in barren cages showed superior survival when compared to similar housed N-Ster (n = 38; p = 0.002). Furthermore, Ster females (n = 25) gave birth to both a first and second litter faster than N-Ster females (n = 14; p ≤ 0.019). Litter size, number of weanlings and proportion of barren females did not differ between Ster and N-Ster, but pups from Ster experienced a higher pre-weaning mortality in the second litter (p = 0.0095). Voles classed as Ster within age 6 month (n = 55) weighed less than same aged N-Ster (n = 45) already from weaning (21 days; p = 0.0204). However, weight at weaning, whether LIGHT (weight ≤ median; n = 47) or HEAVY (weight > median; n = 53), had no effect on subsequent development of stereotypies in terms of either onset age or fraction which developed stereotypies. The results suggested that Ster had better physical welfare, as reflected in better survival, than N-Ster when housed singly and a higher reproductive success when used as breeders.     

Acupuncture at Both ST25 and ST37 Improves the Pain Threshold of Chronic Visceral Hypersensitivity Rats

Previous studies demonstrated the efficacy of electro-acupuncture (EA) in relieving chronic visceral hypersensitivity (CVH) in IBS rats. However, ST25 which is a key acupoint for patients with IBS has not been reported in these experiments. Eight CVH rats were treated by EA at both ST25 and ST37 for 20 min, once daily for seven consecutive days, model rats (n = 8) and normal rats (n = 8) as controls. After the first EA treatment, the abdominal withdrawal reflex scores were investigated to evaluate the pain threshold. After seven EA treatments, the concentrations of 5-hydroxytryptamine (5-HT), 5-HT3 receptor (5-HT3R) and 5-HT4 receptor (5-HT4R) in colon tissue were assayed quantitatively by enzyme-linked immunosorbent assay. The results showed that EA improved the pain threshold of CVH rats, reduced the 5-HT concentration and increased the 5-HT4R concentration, but had no effect on the 5-HT3R concentration. Further studies are needed to optimize the choice of two-matching points for EA in the treatment of CVH rats.     

Microstructural and biomechanical alterations of the human aorta as a function of age and location

While it is known that the aorta stiffens with location and age, little is known about the underlying mechanisms that govern these alterations. The purpose of this study was to investigate the relationship between the anisotropic biomechanical behavior and extracellular matrix microstructure of the human aorta and quantify how each changes with location and age. A total of 207 specimens were harvested from 5 locations (ascending n = 33, arch n = 38, descending n = 54, suprarenal n = 52, and abdominal n = 30) of 31 autopsy donor aortas (aged 3 days to 93 years). Each specimen underwent planar biaxial testing in order to derive quantitative biomechanical endpoints of anisotropic stiffness and compliance. Quantitative measures of fiber alignment and degree of fiber alignment were also generated on the same samples using a small-angle light scattering (SALS) technique. Circumferential and axial stiffening occurred with age and increased from the proximal to distal aorta, and the abdominal region was found to be more stiff than all others (p ≤ 0.006). Specimens from donors aged 61 and above were drastically more stiff than younger specimens (p < 0.001) and demonstrated greater circumferential compliance and axial stiffening (p < 0.001). Fiber direction for all ages and locations was predominantly circumferential (p < 0.001), and the degree of fiber alignment was found to increase with age (p < 0.001). Our results demonstrate that the aorta becomes more biomechanically and structurally anisotropic after age 60; with significant changes occurring preferentially in the abdominal aorta, these changes may play an important role in the predisposition of disease formation (e.g., aneurysm) in this region with age.     

Are San Jose scale (Hom., Diaspididae) pheromone trap captures predictive of crawler densities?

Abstract: Abundance of San Jose scale (SJS), Quadraspidiotus perniciosus (Comstock), adult males and crawlers were monitored with pheromone traps checked weekly and associated sticky tape traps monitored biweekly, respectively, in commercial almond orchards in Kern County, California, USA, during 1999 and 2000. Regression analysis was used to determine if SJS crawler abundance could be predicted from SJS males captured on pheromone traps. No significant relationship (P > 0.05) was indicated for any generation or for all SJS captured for the season in 1999. With greater replication in 2000, statistically significant relationships were indicated for the first generation (r = 0.727; F = 25.712; P < 0.0001; n = 25) and for all generations (r = 0.777; F = 63.239; P < 0.0001; n = 25). An additional orchard in 2000 was divided into 18 1.21‐ha plots with different treatments applied. A statistically significant relationship was indicated for the first generation (r = 0.507; F = 11.769; P = 0.0016; n = 36) and second generation (r = 0.436; F = 7.972; p = 0.0079; n = 36). These results suggest that relative densities of SJS crawlers on sticky tapes can be estimated using SJS male trap captures for the first generation, and that this approximation is appropriate for whole orchards or for subplots within orchards as small as 1.21‐ha.     

Ten-year survival analysis for renal carcinoma patients treated with an autologous tumour lysate vaccine in an adjuvant setting

About 30% of renal cell carcinomas (RCC) will develop recurrence after surgery. Despite evidence for a significantly improved survival by autologous tumour cell vaccination therapy, the procedure has not become standard. Between August 1993 and December 1996, 1,267 RCC patients undergoing radical nephrectomy in 84 German hospitals were subsequently treated by autologous tumour cell vaccination therapy. The study group comprised 692 patients with complete follow-up (stages pT2-3, pNx-2, M0 based on the TNM classification, 4th edition). Subsequent propensity-score matching according to 7 defined criteria with 861 control patients undergoing nephrectomy alone without adjuvant treatment at the Carl-Thiem-Hospital Cottbus, resulted in 495 matched pairs. Overall and stage-specific survival rates were analysed after a median follow-up of 131 months. The 5- and 10-year overall survival (OS) rates were 80.6 and 68.9% in the vaccine group and 79.2 and 62.1% in the control group (p = 0.066). Patients with pT3 stage RCC revealed 5- and 10-year OS rates of 71.3 and 53.6% in the study group and 65.4 and 36.2% in the control group (p = 0.022). In multivariable analysis, patients in the vaccine group showed a significantly improved survival both in the whole study group (HR = 1.28, p = 0.030) and in the subgroup presenting with pT3 stage tumours (HR = 1.67, p = 0.011). Adjuvant treatment with autologous vaccination therapy resulted in a significantly improved overall survival in pT3 stage RCC patients, suggesting benefit especially in this subgroup. However, controlled clinical trials integrating the recent TNM classification and further risk constellations are required to define additional patient groups that may derive benefit from this treatment.     

Copper and Zinc in the Serum,Urine, and Hair of Patients with Wilson’s Disease Treated with Penicillamine and Zinc

The purpose of this study was to determine the different levels of copper and zinc in the serum, urine, and scalp hair of patients with Wilson’s disease receiving different, currently accepted methods of treatment to reduce the copper load (penicillamine—group 1, n = 8; zinc—group 2, n = 8; penicillamine+zinc—group 3, n = 8). Blood, urine, and hair samples were collected from the patients. All three treatments resulted in a significant decrease of the serum copper levels. Significantly increased levels of zinc in the serum were detected in the patients in groups 2 and 3 (19.1 and 18.8 μmol/l, respectively; p < 0.05). Copper excretion in the urine significantly increased during its administration to groups 1 and 3 (11.5 and 7.94 μmol/24 h respectively; p < 0.001) due to the effect of penicillamine. The administration of zinc as monotherapy (group 2) or in combination with penicillamine (group 3) led to an increase of its excretion (25.3 and 22.4 μmol/24 h, respectively; p < 0.01). Only an insignificant rise of the copper content in the hair was found in all three groups of patients. The content of zinc in the hair did not differ significantly in any of the groups in comparison with the control group.     

Heterogeneity of Hippo signalling activity in different histopathologic subtypes of renal cell carcinoma

This study aimed to reveal the prognostic role of the Hippo pathway in different histopathological subtypes of renal cell carcinoma (RCC). The TCGA-KIRC (n = 537), TCGA-KIRP (n = 291) and TCGA-KICH (n = 113), which contain data about clear cell (ccRCC), papillary (pRCC) and chromophobe RCC (chRCC), respectively, were investigated. Gene Set Variation Analysis was used to compare the activity of many pathways within a single sample. Oncogenic pathway-related expression differed between cases of ccRCC involving low and high Hippo pathway activity. There were two subsets of ccRCC, in which the cancer exhibited lower and higher Hippo signalling activity, respectively, compared with normal tissue. In the ccRCC cohort, lower Hippo pathway activity was associated with a higher clinical stage (p < 0.001). The Hippo pathway (HR = 0.29; 95% CI = 0.17–0.50, p < 0.001), apoptosis (HR = 6.02; 95% CI = 1.47–24.61; p = 0.013) and the p53 pathway (HR = 0.09; 95% CI = 0.02–0.36; p < 0.001) were identified as independent prognostic factors for ccRCC. The 5-year overall survival of the ccRCC patients with low and high Hippo pathway activity were 51.9% (95% CI = 45.0–59.9) and 73.6% (95% CI = 67.8–79.9), respectively. In conclusion, the Hippo pathway plays an important role in the progression of ccRCC. Low Hippo pathway activity is associated with poor outcomes in ccRCC, indicating the tumour suppressor function of this pathway.     

Monocyte chemoattractant protein-1 (MCP-1) gene polymorphism as a potential risk factor for cardiovascular disease in hemodialyzed patients

Aim: Polymorphism in the monocyte chemoattractant protein-1 (MCP-1) gene (A-2518G) has been associated with functional effects. The aim of the present study was to assess the effect of this polymorphism on end-stage renal disease (ESRD) and cardiovascular disease (CVD) in hemodialyzed patients. Methods: A total of 720 patients with ESRD treated with hemodialysis (450 patients with CVD) and 325 healthy control subjects were genotyped for the MCP-1 -2518 polymorphism by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) procedure. Results: There was a significant difference in genotype frequencies between entire group of hemodialyzed patients and controls (p < 0.01). The odds ratio for the risk allele was 1.85, 95% CI 1.49–2.32 (p < 0.01). Hemodialyzed patients were divided into subgroups with CVD (n = 450) and without CVD (n = 270). The G allele carriers occurred with significantly higher frequency in patients with CVD (62% vs. 38% in patients without CVD and 36% in controls). The odds ratio for the risk allele for patients with CVD vs. those without CVD was 2.17, 95% CI 1.71–2.79. There was no statistically significant difference in the distribution of MCP-1 genotypes between ESRD patients without CVD and healthy controls. Conclusion: Our results demonstrate for the first time an association between the polymorphism in the regulatory region of the MCP-1 gene and susceptibility to CVD in hemodialyzed patients.     

Neuro-protective effects of carbamazepine on sleep patterns and head and body shakes in kainic acid-treated rats

The aim of this work was to analyze the effect of carbamazepine (CBZ) on sleep patterns and on “head and body shakes” and to determine the role of serotonin (5-HT) in a model of kainic-induced seizures. Thirty male Wistar rats (280–300 g) were used for polygraphic sleep recording. After a basal recording, the rats were allocated into three groups: kainic acid-treated animals (KA; 10 mg/kg; n = 10), carbamazepine-treated animals (CBZ; 30 mg/kg; n = 10) and animals injected with KA 30 min after pretreatment with CBZ (CBZ + KA; n = 10). Polygraphic recordings were performed for 10 h for 3 days, with the exception of the CBZ group, which were observed for 1 day. In order to measure the head and body shakes that occurred over that time, a behavioral assessment was performed in two additional groups of KA (n = 10) and CBZ + KA (n = 10) animals. After 10 h of behavioral assessment, the rats were sacrificed, and the levels of 5-HT and 5-hydroxy-indol-acetic acid (5-HIAA) were analyzed. We compared these findings with the results from a group of rats without pharmacological intervention (n = 10). All of the recordings were performed from 08:00 to 18:00 h. Data analysis: the electrographic parameters, head and body shake counting and monoamine concentrations were analyzed by an ANOVA test. Differences of *p ≤ 0.01 and **p ≤ 0.001 were considered statistically significant. Our results showed that CBZ exerted a protective effect on sleep pattern alterations induced by KA, which when administered alone caused a complete inhibition of sleep for the first 10 h after administration. Although there was a reduction in the amount of sleep after the administration of KA in CBZ-pretreated animals, sleep inhibition was incomplete. In addition, CBZ decreased the frequency of head and body shakes by 60% as compared to KA. The 5-HT and 5-HIAA levels in the pons were increased in the KA and KA + CBZ groups. Our conclusion is that in addition to decreasing seizure intensity, CBZ facilitates the partial recovery of sleep. These results suggest that CBZ provides neuro-protective effects on sleep and against seizures.     

Differences exist in bird communities using restored and natural wetlands in the Parkland region,Alberta, Canada

Wetland restoration is used to compensate for historic and ongoing wetland losses. We compared bird community composition in 24 restored wetlands and 36 natural wetlands in the Parkland region of Alberta. Natural wetlands ranged in exposure to agricultural activity and were binned into three classes (low, medium, and high disturbance). Although the abundance and average species richness of birds were similar between restored and natural wetlands (analysis of variance: p > 0.22), the avian community composition differed significantly among wetland types (multiresponse permutation procedure [MRPP]: A = 0.05, p < 0.001). The avifauna using restored wetlands was distinct from the avifauna using natural wetlands spanning a range of disturbance levels (A = 0.02–0.06; p ≤ 0.006). Notably, restored wetlands were surrounded by less shrub/forest cover and more open water than low‐disturbance, natural wetlands. The majority (58%) of species using the surveyed wetlands were not classified as wetland‐dependent. Interestingly, if only wetland‐dependent species are considered, the avifauna using restored wetlands is no longer distinctive (MRPP: A < 0.01, p = 0.187), although the abundance of wetland‐dependent birds was marginally higher in restored wetlands (n = 24) than in low‐disturbance, natural wetlands (n = 10; Tukey's honestly significant difference test: p = 0.041). Overall, restored wetlands had reduced beta diversity compared to natural wetlands, regardless of whether the avifauna were restricted to wetland‐dependent species or considered comprehensively. This draws into question the legitimacy of the assumption that restoration can fully offset continued losses of natural wetlands.     

Excitatory and inhibitory neuron imbalance in the intrauterine growth restricted fetal guinea pig brain: Relevance to the developmental origins of schizophrenia and autism

Neurodevelopmental disorders such as schizophrenia and autism are thought to involve an imbalance of excitatory and inhibitory signaling in the brain. Intrauterine growth restriction (IUGR) is a risk factor for these disorders, with IUGR onset occurring during critical periods of neurodevelopment. The aim of this study was to determine the impact of IUGR on excitatory and inhibitory neurons of the fetal neocortex and hippocampus. Fetal brains (n = 2) were first collected from an unoperated pregnant guinea pig at mid-gestation (32 days of gestation [dg]; term ∼67 dg) to visualize excitatory (Ctip2) and inhibitory (calretinin [CR] and somatostatin [SST]) neurons via immunohistochemistry. Chronic placental insufficiency (CPI) was then induced via radial artery ablation at 30 dg in another cohort of pregnant guinea pigs (n = 8) to generate IUGR fetuses (52 dg; n = 8); control fetuses (52 dg; n = 7) were from sham surgeries with no radial artery ablation. At 32 dg, Ctip2- and CR-immunoreactive (IR) cells had populated the cerebral cortex, whereas SST-IR cells had not, suggesting these neurons were yet to complete migration. At 52 dg, in IUGR versus control fetuses, there was a reduction in SST-IR cell density in the cerebral cortex (p = .0175) and hilus of the dentate gyrus (p = .0035) but not the striatum (p > .05). There was no difference between groups in the density of Ctip2-IR (cortex) or CR-IR (cortex, hippocampus) neurons (p > 0.05). Thus, we propose that an imbalance in inhibitory (SST-IR) and excitatory (Ctip2-IR) neurons in the IUGR fetal guinea pig brain could lead to excitatory/inhibitory dysfunction commonly seen in neurodevelopmental disorders such as autism and schizophrenia.     

Urinary Peptidomic Analysis Identifies Potential Biomarkers for Acute Rejection of Renal Transplantation

Introduction  Human urine is a complex matrix of proteins, endogenous peptides, lipids, and metabolites. The level of any or all of these components can reflect the pathophysiological status of an individual especially of the kidney at the time of urine collection. The naturally occurring endogenous urinary peptides which are thought to be the product of several proteolytic and degradation processes may provide clinically useful biomarkers for different renal and systemic diseases. Materials and Methods  To examine if specific differences in the urinary peptidome (<10 kDa) occur at the time of acute renal transplant rejection (AR), we undertook a study of urine samples collected from biopsy-proven AR (n = 10), stable graft function (n = 10), and healthy normal control (n = 10). The peptides (<10 kDa) were extracted and fractionated with high-performance liquid chromatography followed by matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometric (MS) analysis. Results  We identified 54 endogenous peptides, including multiple peptides for Tamm–Horsfall protein (UMOD). A panel of peptides are identified which discriminate renal transplant patients with AR from stable graft. We have shown that liquid chromatography followed by MALDI is a useful tool to identify potential biomarkers, which after verification with larger patient cohort can be used as a non-invasive monitoring tool for renal transplant rejection.