Val Group Research Articles

Anti-atrial Fibrillatory and Cardiorenal Protective Effects of the Combination of Valsartan and Cilnidipine in Dahl Salt-Sensitive Rats.

The current study aimed to investigate the anti-atrial fibrillatory (AF) effects of a combination of valsartan and a calcium channel blocker (cilnidipine or amlodipine) in Dahl salt-sensitive (Dahl S) rats. Seven-week-old male Dahl S rats were fed an 8% salt diet. Six weeks later, valsartan (60 mg/kg, Val group), cilnidipine + valsartan (10 + 60 mg/kg, CV group), amlodipine + valsartan (3 + 60 mg/kg, AV group), or vehicle was orally administered daily for 5 weeks. Echocardiography and atrial electrophysiological evaluations were performed on the last day of treatment. Blood pressure in each drug treatment group was lower than in the Vehicle group. The duration of AF induced by atrial burst stimulation was shorter in the Val group (3.2 ± 1.6 s) than in the Vehicle group (11.2 ± 6.0 s), which was further shortened in the CV and AV groups (1.1 ± 0.3 and 1.3 ± 0.3 s, respectively). Left ventricular ejection fraction and left ventricular fractional shortening were greater in the CV and AV groups than those in the Vehicle group. Urinary albumin excretion in the CV group was the lowest among the drug-treated groups. The results collectively suggest that the combination of a calcium channel blocker with valsartan could be useful in terms of its anti-AF action as well as for improving cardiac and renal functions.

Characterization and seasonal variation in biofilms attached to leaves of submerged plant.

The microorganisms and functional predictions of leaf biofilms on submerged plants (Vallisneria natans (Val)) and in water samples (surface water (S) and bottom water (B)) in different seasons were evaluated in this study. S and B groups had 3249 identical operational taxonomic units (OTUs) (50.03%), while the Val group only had 1201 (18.49%) unique OTUs. There was significant overlap between microbial communities of S and B groups in the same season, while Val group showed the greater diversity. The dominant microbial clades were Proteobacteria (18.2-47.3%), Cyanobacteria (3.74-39.3%), Actinobacteria (1.64-29.3%), Bacteroidetes (1.31-21.7%), and Firmicutes (1.10-15.72%). Furthermore, there was a significant relationship between total organic carbon and the distribution of microbial taxa (p = 0.047), and TN may have altered the status of Cyanobacteria by affecting its biological nitrogen fixation capacity and reproductive capacity. The correlation network analysis results showed that the whole system consisted of 249 positive correlations and 111 negative correlations, indicating strong interactions between microbial communities. Functional predictions indicated that microbial functions were related to seasonal variation. These findings would guide the use of submerged plants to improve the diversity and stability of wetland microbial communities.

Alteration in social interaction and tactile discrimination of juvenile autistic-like rats following tactile stimulation and whisker deprivation.

Autism spectrum disorder is a developmental disorder that can affect sensory-motor behaviors in the valproic acid (Val) rodent model of autism. Although whisker deprivation (WD) induces plastic changes in the cortical neurons, tactile stimulation (TS) during the neonatal period may reverse it. Here, we investigate the interaction effects of TS and WD on behavioral and histologic features of barrel cortex neurons in juvenile Val-treated. Control (CTL, CTL-TS, CTL-WD, and CTL-TS-WD groups) and Val-treated (Val, Val-TS, Val-WD, and Val-TS-WD groups) rats of both sexes were subjected to behavioral tests of social interaction, and novel texture recognition, and Nissl staining. The TS groups were exposed to sensory stimulation for 15min, three times/day; moreover, all whiskers in the WD groups were trimmed every other day from postnatal days 1 to 21. Both prenatal valproic acid administration and postnatal WD decreased the rats' performance percentage of the Val and CTL-WD groups of both sexes compared with the CTL groups in the social interaction and texture discrimination tests. Following TS, the performance of the Val-TS-WD group increased significantly compared to the Val group (p<.05), whereas the performance of the CTL-TS-WD group rescued to the CTL group. Nissl staining results also revealed the neuron degeneration percentage in the barrel field area of the Val and CTL-WD groups was increased significantly (p<.05) compared with the CTL group. In this regard, TS decreased the neuron degeneration percentage of the Val-TS-WD and the CTL-TS-WD groups, compared with the CTL group, significantly (p<.05). TS in juvenile male and female rats can act as a modulator and compensate for the behavioral and histological consequences of WD and prenatal valproic acid exposure.

Combined Deflection Angle Classification: A Novel Typing System of Adult Femoral Neck Fracture

Femoral neck fracture (FNF) is a common clinical trauma with high mortality and disability rates. Furthermore, its incidence increases exponentially with increasing age. Existing classifications have some disadvantages. Thus, this study aimed to establish a novel typing system for FNF. We retrospectively analyzed all adult patients with FNF admitted to our hospital between December 2015 and November 2017 for cannulated screw internal fixation. The study population was divided into the femoral varus offset group (VAR) and the valgus offset group (VAL). The data collected included sex, age, affected side, injury mode, body mass index, complications, pelvic incidence (PI), hip deflection angle (HDA), combined deflection angle (CDA), and neck shaft angle. Statistical analysis was conducted to determine the correlation between complications and deviation angles. A novel typing system was developed and compared with the Garden classification to detect its superiority. A total of 108 patients were recruited, with 59 patients in the VAR and 49 patients in the VAL groups. The incidence of complications in the VAR group was significantly higher than that in the VAL group (P < 0.05). Moreover, there were more male participants in the VAR group. Compared with the VAL group, the VAR group had significantly higher PI, HDA, and CDA (P < 0.05). The CDA classification (CDAC) was defined, with CDA as the main criterion and HDA as the supplementary criterion. Furthermore, there was a hierarchical correlation between the actual incidence of complications and the typing level, which was increased in CDAC but not in the Garden classification. This showed that CDAC was more accurate. A novel typing system, CDAC, for FNF was established, which was more accurate than the Garden classification. We suggest combining CDAC and Garden classifications for the preoperative diagnosis, treatment selection, and prognostic evaluation for patients with FNF.

P-047 The effects of dietary branched-chain amino acids on mice semen parameters and plasma amino acids profile

Abstract Study question Are there any differences between the effect of each member of the branched-chain amino acids (BCAAs) on sperm parameters and plasma amino acids profile? Summary answer Valine supplementation had destructive effects on sperm parameters and viability. However, blood amino acids profile were similar among treatments. What is known already BCAAs, a group of three essential amino acids, have a crucial role on protein synthesis, besides being strongly associated with impaired glucose and fat metabolism. Although BCAAs supplements are one of the most demanding products for the fitness industry to increase the lean body mass and boost exercise performance, little information exists on the advantages and disadvantages of dietary BCAAs on male fertility. Study design, size, duration Fifty NMRI mature male mice were divided into five groups and were fed diets as follow: Control (CTR): 2.4% Beta-alanine, Leucine (Leu): 1.18% Leu + 1.2% Beta-alanine, Isoleucine (Ile): 0.58% Ile + 1.8% Beta-alanine, Valine (Val): 0.65% + 1.7% Beta-alanine, and BCAAs (Leu:Ile:Val ratio of 2:1:1): 2.4% BCAA: 1.18% Leu + 0.58% Ile + 0.65% Val. After 5 weeks, testes and epididymides were dissected, and sperm parameters and plasma amino acids profile were assessed. Participants/materials, setting, methods Semen parameters were evaluated by a Computer-Aided Semen Analysis (CASA) system. Plasma amino acids concentrations were determined by HPLC. Data were analyzed using SPSS and statistical differences among various groups were determined by ANOVA and Tukey’s post-hoc test. Main results and the role of chance Higher BCAAs intake, particularly Val, increased the destructive mechanisms on sperm viability. The results showed no significant difference on body weight after 40 days. Sperm concentration (8.4 vs. 4.5 ×106), progressive motility (51.5 vs. 27.2 %), and viability (67 vs. 56 % for CTR and Val group, respectively) decreased dominantly in the Val group compared to CTR (p≤0.05). The immotile parameter was significantly higher in the Val group compared to the CTR (p≤0.05). In addition, there were no significant differences on plasma amino acids profile. Limitations, reasons for caution The current study's limitation is that only one level of BCAAs was used. Given the potential role of Val on sperm cell death, further data on different levels of all BCAAs, especially Val administration and evaluation of the related mechanisms are needed. Wider implications of the findings The findings of our study show, for the first time, that individual levels of Ile and Leu have different effects on sperm parameters compared with all BCAAs or Val. More attention should be given to BCAAs supplementation and semen quality that was previously ignored. Trial registration number not applicable

Spatial Cities in the East and South. Gyula Kosice’s Artistic Dialogue with Hungarian and Slovak Artists

The article aims to reveal similarities between the artistic approaches of the Czechoslovakian-born Argentine artist Gyula Kosice and the Slovak art scene. Referencing Polish art historian Piotr Piotrowski’s concept of “horizontal art history”, the article focuses on the artistic dialogue between kinetic and op art artists developed during the Cold War period in the countries of Central Europe and Latin America. The goal of the article is twofold. Firstly, it will expose the specificity of artistic practices and strategies developed in non-Western art scenes. It also aims to reveal certain proximities among artists, especially those engaged in kinetic and geometrical art. Adopting a transnational and transmodern approach, the text will focus on Gyula Kosice’s contact with the Slovak artist Alex Mlynárčik, established through the French art critic Michel Ragon. It will also highlight similarities between Kosice’s hydrospatial cities, Mlynárčik’s architectural proposals realised with the VAL group in the 1970s, and the concept of prospective architecture coined by Michel Ragon.

Sacubitril/valsartan decreases mortality in the rat model of the isoprenaline-induced takotsubo-like syndrome.

AimsTakotsubo syndrome (TTS) is an acute potentially reversible cardiac syndrome characterized by variable regional myocardial akinesia that cannot be attributed to a culprit coronary artery occlusion. TTS is an important differential diagnosis of acute heart failure where brain natriuretic peptides are elevated. Sacubitril/valsartan is a novel and effective pharmacological agent for the treatment of patients with heart failure. Our aim was to explore whether treatment with sacubitril/valsartan could prevent isoprenaline‐induced takotsubo‐like phenotype in rats.Methods and resultsA total number of 186 Sprague–Dawley male rats were randomized to receive pretreatment with water (CONTROL, n = 62), valsartan (VAL, n = 62), or sacubitril/valsartan (SAC/VAL, n = 62) before receiving isoprenaline for induction of TTS. We recorded heart rate and blood pressure invasively. Cardiac morphology and function were evaluated by high‐resolution echocardiography 90 min after the administration of isoprenaline. We documented the survival rate at the time of echocardiography. Compared with the CONTROL group, the SAC/VAL group had less pronounced TTS‐like cardiac dysfunction and lower mortality rate, while the VAL group did not differ. Heart rate and blood pressure were not significantly different between the groups. Analysis of cardiac lipids was performed with mass spectrometry. The VAL and SAC/VAL groups had significantly higher levels of lysophosphatidylcholine (LPC), in particular LPC 18:1 and LPC 16:0.ConclusionsPretreatment with sacubitril/valsartan but not with valsartan reduces mortality and attenuates isoprenaline‐induced apical akinesia in the TTS‐like model in rats. Sacubitril/valsartan could be a potential treatment option in patients with TTS in humans.

BDNF genotype Val66Met interacts with acute plasma BDNF levels to predict fear extinction and recall

Brain-derived neurotropic factor (BDNF) is a potent regulator of memory processes and is believed to influence the consolidation of fear extinction memories. No previous human study has tested the effect of unstimulated BDNF on fear extinction recall, and no study has tested the association between plasma BDNF levels and psychophysiological responding during an extinction paradigm. We tested the association between fear responses during a 2-day differential conditioning, extinction and extinction recall paradigm and Val66Met genotype in a group of healthy participants (N = 191). There were no group differences during habituation or acquisition. Met allele carriers compared to Val homozygotes displayed higher responses to the CS + compared to the CS- during extinction learning and had higher responding to both the CS+ and CS- during extinction recall. Plasma levels of BDNF protein that were collected in a sub-sample of the group (n = 56) moderated the effect of Met allele presence, such that lower BDNF level was associated with higher skin conductance response in the Met but not Val group to the CS+ during extinction learning and to both the CS+ and CS- during extinction recall. The current results extend previous observations of a Val66Met effect during fear extinction learning to extinction recall and show for the first time that these effects are moderated by plasma BDNF level.

Arginase plays an important role in ammonia detoxification of yellow catfish Pelteobagrus fulvidraco

A two-stage study was carried out to test the mechanism of arginase in ammonia detoxification of yellow catfish. At stage 1, fish was injected lethal half concentration ammonium acetate and 0.9% sodium chloride respectively every 12 h in six replicates for 72 h. The result found that no significant different in serum ammonia contents of fish in ammonium acetate group at hours 12, 24, 36, 48, 60 and 72. At stage 2, ammonium acetate group was split in two, one continued to injected with ammonium acetate (NH3 group) and the other with ammonium acetate and valine (an inhibitor of arginase; Val group); Sodium chloride group also was split in two, one continued to injected with sodium chloride (NaCl group) and the other with sodium chloride and valine (NaCl + Val group). The experiment continued for 12 h. Serum ammonia and liver arginine contents of fish in Val group were higher than those of fish in NH3 group; Compared with NaCl group, arginase activity and ARG 1 expression in liver of fish in Val group were lower; Fish in NaCl and NaCl + Val groups had the lowest serum superoxide dismutase activities, malondialdehyde, tumor necrosis factor-α, interleukin 1 and 8 contents, TNF-α, IL-1 and IL-8 expressions than fish in NH3 and Val groups, and had the higher lysozyme activities, complement 3 and 4 contents. This study indicates that ammonia poisoning would lead to oxidative damage, immunosuppression and inflammation in yellow catfish; Arginase may be an important target of ammonia toxicity in yellow catfish; Exogenous arginine supplementation might alleviate the symptoms of ammonia poisoning in yellow catfish.

Interactive effect between dietary valine and isoleucine on growth performance, blood parameters and resistance against low salinity stress of Japanese flounderParalichthys olivaceus

The interaction between dietary valine (Val) and isoleucine (Ile) on growth, blood parameters, and tolerance against low salinity stress of Japanese flounder Paralichthys olivaceus was studied in a 60-day feeding trial. Fish (initial body weight: 3.57 ± 0.05 g) were fed six experimental diets containing different proportions of Ile and Val, two levels of Ile 0% (LI) and 2% diet (HI), combine with three levels of Val 0% (LV), 0.83% (MV), and 2.27% diet (HV), respectively. The results revealed that significant interactive effect of Ile and Val was found on body weight gain and feed conversion ratio, also stimulative effect was found in high Ile groups. Meanwhile, interactive effect of these two amino acids was also observed on high-density lipoprotein (HDL), the maximum of Ile with maximum of Val group has the highest concentration of HDL, which was significantly higher than other groups (p < .05). Moreover, no interaction was found on whole body proximate composition, muscle Ile and Val concentration, and tolerance ability against low salinity stress (reflected by LT50). But high level of Ile combined with high level of Val diet altered tolerance ability against low salinity stress of Japanese flounder. It would be indicated that dietary Ile and Val interacted in the diet of Japanese flounder, and the flounders fed the diet supplemented with 2% Ile and 2.27% Val was superior to the other groups on growth and blood parameters, and tolerance against low salinity stress.

Assignment of the Ile, Leu, Val, Met and Ala methyl group resonances of the DEAD-box RNA helicase DbpA from E. coli

ATP-dependent DEAD-box helicases constitute one of the largest families of RNA helicases and are important regulators of most RNA-dependent cellular processes. The functional core of these enzymes consists of two RecA-like domains. Changes in the interdomain orientation of these domains upon ATP and RNA binding result in the unwinding of double-stranded RNA. The DEAD-box helicase DbpA from E. coli is involved in ribosome maturation. It possesses a C-terminal RNA recognition motif (RRM) in addition to the canonical RecA-like domains. The RRM recruits DbpA to nascent ribosomes by binding to hairpin 92 of the 23S rRNA. To follow the conformational changes of Dbpa during the catalytic cycle we initiated solution state NMR studies. We use a divide and conquer approach to obtain an almost complete resonance assignment of the isoleucine, leucine, valine, methionine and alanine methyl group signals of full length DbpA (49 kDa). In addition, we also report the backbone resonance assignments of two fragments of DbpA that were used in the course of the methyl group assignment. These assignments are the first step towards a better understanding of the molecular mechanism behind the ATP-dependent RNA unwinding process catalyzed by DEAD-box helicases.

Differential Relationship between Microstructural Integrity in White Matter Tracts and Motor Recovery following Stroke Based on Brain-Derived Neurotrophic Factor Genotype.

Objective The relationship between white matter integrity and the brain-derived neurotrophic factor (BDNF) genotype and its effects on motor recovery after stroke are poorly understood. We investigated the values of fractional anisotropy (FA) in the corticospinal tract (CST), the intrahemispheric connection from the primary motor cortex to the ventral premotor cortex (M1PMv), and the interhemispheric connection via the corpus callosum (CC) in patients with the BDNF genotype from the acute to the subacute phase after stroke. Methods The Fugl-Meyer assessment, upper extremity (FMA-UE), and tract-related FA were assessed at 2 weeks (T1) and 3 months (T2) after stroke using diffusion tensor imaging (DTI). Fifty-eight patients diagnosed with ischemic stroke were classified according to the BDNF genotype into a Val (valine homozygotes) or Met (methionine heterozygotes and homozygotes) group. Results The Val group exhibited a larger reduction of FA values in the ipsilesional M1PMv than the Met group from T1 to T2. The FMA-UE at T2 was negatively correlated with FA of the contralesional M1PMv at T2 in the Val group but was positively correlated with FA of the ipsilesional CST and CC at T2 in the Met group. Conclusions The integrity of the intra- and interhemispheric connections might be related to different processes of motor recovery dependent on the BDNF genotype. Thus, the BDNF genotype may need to be considered as a factor influencing neuroplasticity and functional recovery in patients with stroke. This trial is registered with http://www.clinicaltrials.gov: NCT03647787.

Valine acts as a nutritional signal in brain to activate TORC1 and attenuate postprandial ammonia-N excretion in Chinese perch (Siniperca chuatsi).

An emerging concept is that the hypothalamic nutrient sensor can regulate peripheral energy metabolism via a brain-liver circuit. Valine is an essential branched-chain amino acid (BCAA) that drives intracellular signaling cascades by the activation of target of rapamycin complex 1 (TORC1) which is critical to protein metabolism in mammals. However, in teleost fish, it remains scarce in this area especially about how the intraventricular (ICV) injection of valine can mediate the protein metabolism in peripheral organs. This study would tentatively explore the effects of ICV injection of valine on protein metabolism in peripheral organs through evaluating the postprandial ammonia-N excretion rate in Chinese perch. The control group was injected with 5-μL PBS, and the Val group was injected with 20-μgL valine dissolved into 5-μL PBS. The ammonia-N excretion rate of Val group was lower than control group at 4-, 12-, and 24-h postinjection, while the concertation of plasma glucose was increased sharply at 0.5-, 4-, 12-, and 24-h postinjection. We further checked both mRNA level and the enzyme activity of glutamate dehydrogenase (GDH) in the liver and adenosine monophosphate deaminase (AMPD) in muscle, and we found that they were obviously decreased in Val group at 4-, 12-, and 24-h postinjection. The phosphorylation level of ribosomal protein S6, a downstream target protein of TORC1, was markedly enhanced in the liver of Val group at 4-, 12-, and 24-h postinjection. Collectively, these results illustrated that ICV injection of valine can attenuate protein degradation in peripheral organs by depressing the GDH and AMPD enzyme activity; on the other hand, the injected valine can trigger the activation of TORC1 in the liver via a brain-liver circuit and then interdict proteolysis.

Effort-related decision making in humanized COMT mice: Effects of Val158Met polymorphisms and possible implications for negative symptoms in humans

Catechol-o-methyltransferase (COMT) is an enzyme that metabolizes catecholamines, and is crucial for clearance of dopamine (DA) in prefrontal cortex. Val158Met polymorphism, which causes a valine (Val) to methionine (Met) substitution at codon 158, is reported to be associated with human psychopathologies in some studies. The Val/Val variant of the enzyme results in higher dopamine metabolism, which results in reduced dopamine transmission. Thus, it is important to investigate the relation between Val158Met polymorphisms using rodent models of psychiatric symptoms, including negative symptoms such as motivational dysfunction. In the present study, humanized COMT transgenic mice with two genotype groups (Val/Val (Val) and Met/Met (Met) homozygotes) and wild-type (WT) mice from the S129 background were tested using a touchscreen effort-based choice paradigm. Mice were trained to choose between delivery of a preferred liquid diet that reinforced panel pressing on various fixed ratio (FR) schedules (high-effort alternative), vs. intake of pellets concurrently available in the chamber (low-effort alternative). Panel pressing requirements were controlled by varying the FR levels (FR1, 2, 4, 8, 16) in ascending and descending sequences across weeks of testing. All mice were able to acquire the initial touchscreen operant training, and there was an inverse relationship between the number of reinforcers delivered by panel pressing and pellet intake across different FR levels. There was a significant group x FR level interaction in the ascending limb, with panel presses in the Val group being significantly lower than the WT group in FR1–8, and lower than Met in FR4. These findings indicate that the humanized Val allele in mice modulates FR/pellet-choice performance, as marked by lower levels of panel pressing in the Val group when the ratio requirement was moderately high. These studies may contribute to the understanding of the role of COMT polymorphisms in negative symptoms such as motivational dysfunctions in schizophrenic patients.

Genetic polymorphisms for BDNF, COMT, and APOE do not affect gait or ankle motor control in chronic stroke: A preliminary cross-sectional study

ABSTRACT Background: Motor deficits after stroke are a primary cause of long-term disability. The extent of functional recovery may be influenced by genetic polymorphisms. Objectives: Determine the effect of genetic polymorphisms for brain-derived neurotrophic factor (BDNF), catechol-O-methyltransferase (COMT), and apolipoprotein E (APOE) on walking speed, walking symmetry, and ankle motor control in individuals with chronic stroke. Methods: 38 participants with chronic stroke were compared based upon genetic polymorphisms for BDNF (presence [MET group] or absence [VAL group] of a Met allele), COMT (presence [MET group] or absence [VAL group] of a Met allele), and APOE (presence [ε4+ group] of absence [ε4- group] of ε4 allele). Comfortable and maximal walking speed were measured with the 10-m walk test. Gait spatiotemporal symmetry was measured with the GAITRite electronic mat; symmetry ratios were calculated for step length, step time, swing time, and stance time. Ankle motor control was measured as the accuracy of performing an ankle tracking task. Results: No significant differences were detected (p ≥ 0.11) between the BDNF, COMT, or APOE groups for any variables. Conclusions: In these preliminary findings, genetic polymorphisms for BDNF, COMT, and APOE do not appear to affect walking speed, walking symmetry, or ankle motor performance in chronic stroke.

The effects of low dose LCZ 696 on kidney function in Dahl SS rats

Recent reports and our data showed that increasing circulating Atrial Natriuretic Peptide (ANP) levels could be beneficial for attenuating renal disease progression. ANP is a hormone that is known to stimulate salt excretion and vasodilation, thus reducing the blood pressure (BP). Recently, a new drug (LCZ 696, also known as Entresto) was approved by FDA to be used in heart failure; LCZ 696 is a combination of a neprilysin inhibitor (sacubitril), which increases ANP levels, and a known RAAS blocker (valsartan). The goal of this project was to test a low dose of LCZ 696 can be beneficial for the mitigation of renal damage is salt‐sensitive (SS) hypertension.LCZ 696 (sacubitril and/or valsartan) was administered chronically at 75 ug/day to a model of SS hypertension, Dahl SS rats, via an osmotic pump. Animals were fed a 0.4% NaCl (normal salt, NS) diet until 8 weeks of age, and then underwent a high salt (HS) 4% NaCl challenge for 21 days. Vehicle (veh), sacubitril (sac), valsartan (val), or a 1:1 mix of both drugs (sac/val, or LCZ 696) were administered together with the HS diet; metabolic cage studies and GFR measurements were performed. Collection of the renal tissue, blood plasma and urine allowed for examination of electrolyte excretion, glomerular damage, renal damage markers, proteinuria, as well as protein cast and fibrosis formation.Post HS challenge, the endpoint kidney‐to‐body‐weight ratio (indicative of hypertrophy) was similar between groups. Urine flow was elevated in all the HS diet fed groups compared to the NS diet (p&lt;0.001 for all); a trend for a lower urine output as well as water consumption was observed in the sac‐treated group. Urinary electrolyte analysis after 21 days on HS diet showed significant increases for Na+ (0.28±0.04 to 1.12±0.12 mM/day/100g, 0.23±0.02 to 1.26±0.12 mM/day/100g, 0.27±0.02 to 1.21±0.14 mM/day/100g, 0.30±0.03 to 1.29±0.08 mM/day/100g for veh, s/v, sac, and val groups respectively). Cl− excretion increased among all groups in a similar manner. After the HS challenge, GFR decreased in the veh group, and increased in the sac/val and sac groups (this increase was attenuated in the val group). Glomerular damage scoring of Masson trichrome stained slides revealed a pattern for lower damage in the val group. Interestingly, proteinuria was less pronounced in the sac/val and val groups (vs control). In addition, we observed an increase in urinary KIM‐1 and NGAL excretion in the control and sac animals, which was attenuated in the sac/val and val groups. Protein cast formation was also lower in the sac/val and val groups after the HS diet compared to the veh group (s/v: p=0.00331, val: p=0.0228).Our data show attenuation of the SS hypertension progression in the sac/val (LCZ 696) and val treated groups; future studies will be devoted to establishing the effects of a higher dose of LCZ 696 for the alleviation of renal damage and hypertension.Support or Funding InformationThis study was supported by: the National Institutes of Health (NIDDK) R00 DK105160, Dialysis Clinic Inc Reserve Fund, the MUSC SCTR support program via NIH/NCATS UL1TR001450, and the APS Lazaro J Mandel award (to DVI).

Gene polymorphisms and response to transcranial direct current stimulation for auditory verbal hallucinations in schizophrenia.

Recent observations demonstrate a significant ameliorative effect of add-on transcranial direct current stimulation (tDCS) on auditory verbal hallucinations (AVHs) in schizophrenia. Of the many SNPs, NRG1 rs35753505 and catechol-o-methyl transferase (COMT) rs4680 polymorphisms have shown to have a strong association with neuroplasticity effect in schizophrenia. Schizophrenia patients (n=32) with treatment resistant auditory hallucinations were administered with an add-on tDCS. The COMT (rs4680) and NRG1 (rs35753505) genotypes were determined. The COMT genotypes were categorised into Val group (GG; n=15) and Met group (GG/AG; n=17) and NRG1 genotypes were categorised into AA group (n=12) and AG/GG group (n=20). The reduction in auditory hallucination sub-scale score was significantly affected by COMT-GG genotype [Time×COMT interaction: F(1,28)=10.55, p=0.003, ɳ2=0.27]. Further, COMT-GG effect was epistatically influenced by the co-occurrence of NRG1-AA genotype [Time×COMT×NRG1 interaction: F(1,28)=8.09, p=0.008, ɳ2=0.22]. Irrespective of genotype, females showed better tDCS response than males [Time×Sex interaction: F(1,21)=4.67, p=0.04, ɳ2=0.18]. COMT-GG and NRG1-AA genotypes aid the tDCS-induced improvement in AVHs in schizophrenia patients. Our preliminary observations need replication and further systematic research to understand the neuroplastic gene determinants that modulate the effect of tDCS.

Usefulness of valacyclovir prophylaxis for cytomegalovirus infection after anti-thymocyte globulin as rejection therapy.

Background/AimsAnti-thymocyte globulin (ATG) treatment for acute T-cell mediated rejection (TCMR) can increase the risk of cytomegalovirus (CMV) infection. We aimed to evaluate the effect of valacyclovir prophylaxis against CMV infection after ATG administration as anti-rejection therapy.MethodsWe retrospectively analyzed 55 kidney transplant recipients (KTRs) receiving ATG for steroid resistant TCMR. In all KTRs, we used intravenous ganciclovir during ATG injection. In 34 KTRs treated before July 2013, we performed preemptive therapy for CMV infection after ATG therapy. They were regarded as the historic control group (CONT). After July 2013, we used valacyclovir maintenance for 1 month after ATG therapy in 21 patients (VAL). The primary outcome was the incidence of CMV infection, and the secondary outcomes were subsequent acute rejection, and graft and patient outcome.ResultsValacyclovir prophylaxis significantly reduced the incidence of CMV infection (VAL, 9.6% vs. CONT, 67.6%; p < 0.001), and CMV-free survival rate was higher in the VAL group compared to the CONT group (p = 0.009). In the VAL group, two cases of CMV infection were limited to CMV viremia, but CMV disease or syndrome (n = 3) was detected in the CONT group. There was no difference in graft failure (CONT, 70.5% vs. VAL, 47.6%; p = 0.152), incidence of subsequent rejection after ATG treatment (CONT, 41.1% vs. VAL, 33.3%; p = 0.776), and graft or patient survival between the two groups. There were no major adverse events associated with valacyclovir prophylaxis.ConclusionsIn conclusion, valacyclovir prophylaxis is effective in the prevention of CMV infection after ATG treatment for steroid resistant TCMR.

Genetic factors moderate everyday physical activity effects on executive functions in aging: Evidence from the Victoria Longitudinal Study.

Everyday physical activity (EPA) is an important modifiable contributor to age-related variability in executive functioning (EF). However, its role may be moderated by nonmodifiable genetic factors. We tested independent and interactive effects of brain-derived neurotrophic factor (BDNF rs6265) and insulin degrading enzyme (IDE rs6583817) on EF and EPA-EF relationships. The sample consisted of genotyped older adults (N = 577; M age = 70.47 years) over 3 waves (∼9 years) of the Victoria Longitudinal Study. Analyses included (a) confirmatory factor analysis establishing a single latent EF factor from 4 standard EF tasks, (b) latent growth modeling over a 40-year band of aging (ages 53 to 95), and (c) structural regression to investigate the independent and interactive effects of BDNF, IDE, and EPA. First, higher levels of EPA were associated with better EF performance at the centering age (75 years) and less EF decline. Second, IDE G+ (protective) carriers exhibited better EF performance at Age 75 than their G- (nonprotective) peers. Third, within the IDE G+ carrier group, those with higher EPA exhibited better EF performance and slower decline over time than those with lower EPA. Fourth, for the BDNF homozygote Val group, higher EPA was associated with better EF performance and more gradual EF change; however, this beneficial effect was not seen for Met carriers. The effect of modifiable physical health factors on EF is moderated by biological mechanisms associated with risk-protection genetic polymorphisms.

Effect of Valsartan on extracellular matrix remodeling in rats with heart failure after myocardial infarction

Objective To investigate the effect of Valsartan on Disintegrin metalloproteinases (ADAMs10,17) expressions in the process of heart failure (HF) after myocardial infarction (MI).MethodsAdult male Wistar rats weighing (200 ± 30) g were given humane care in compliance with the rules of the Animal Experimentation Committee of the first hospital of Harbin Medical University.And then the left anterior descending coronary artery was ligated.Based on UCG (LVEF ＜ 45％) Results The successfully MI-operated Wistar rats were divided randomly (random number) into three groups:HF group (HF group),placebo group (Pla group) and valsartan group (Val group).The rats in the Pla group and Val group were given the same volume of normal saline and valsartan 50 mg/ (kg · d),provided by Novartis company) by gavage.After 16 weeks,heart function was assessed by hemodynamic evaluation and serum TNF-α from LV cavity was measured by ELISA (R&D,USA).Muscle samples were extracted from the ischemic zone,and then the ADAMs 10,17 expressions were measured by immunoblotting.All the data were expressed by mean ± standard and evaluated by Student' s t test.Results After 16 weeks,the data of LV function including LVdp/dt LVdp/dtmin and LVSP were significantly improved in Val group than the others (P =0.006,P =0.015,P =0.003),and the LVEDP level was decreased (P =0.002).At the same time,the TNF-o level in the Val group was lower than that in the HF group (P =0.023).The ADAM17 and TNF-R1 expressions in the Val group was reduced compared with those in the HF group (P =0.01 1,P =0.022).However,ADAM10 expression is unchangeable in the four groups.Conclusions Valsartan may reduce the ADAM17 and TNF-R1 expressions in the ischemic zone,decrease the TNF-αconcentration and function in LV cavity so as to inhibit cardiac remodeling and improve heart function after MI. Key words: Valsartan ; Myocardial infarction ; Heart failure ; Tumor necrosis factor-α ; Tumor necrosis factor receptor; A disintegrin metalloproteinase; extracellular matrix remodeling; left ventricular function