Among simple non-invasive scores, Pro-C3 and ADAPT best exclude advanced fibrosis in Asian patients with MAFLD.
With metabolic dysfunction-associated fatty liver disease (MAFLD) incidence and prevalence increasing, it is necessary to identify patients with advanced fibrosis (F3-F4 stages). We evaluated the performance of new biomarkers and algorithms for diagnosing advanced fibrosis in an Asian population. Data from two Asian cohorts (including 851 biopsy-proven MAFLD [578 from Wenzhou, 273 from Hong Kong]) were studied. The association between N-terminal propeptide of type 3 collagen (PRO-C3) and the histologic stage of liver fibrosis was analyzed by multivariable linear regression. The area under the receiver operating characteristic curve (AUROC) was used to test the diagnostic performance of serum PRO-C3 and the ADAPT score for advanced fibrosis and compared them to other established non-invasive tests. Serum PRO-C3 levels increased progressively across liver fibrosis stages and correlated with advanced fibrosis (P < 0.001). The ADAPT score had an AUROC of 0.865 (95% confidence interval 0.829-0.901) for advanced fibrosis; the accuracy, sensitivity and negative predictive values were 81.4%, 82.2% and 96.1%, respectively. This result was better compared to that of PRO-C3 alone or other non-invasive fibrosis biomarkers (aspartate aminotransferase-to-platelet ratio index, Fibrosis-4, BARD, and NAFLD fibrosis score). In subgroup analyses (including sex, age, diabetes, NAFLD activity score, body mass index or serum alanine aminotransferase levels), the ADAPT score had good diagnostic performance. PRO-C3 and the ADAPT score reliably exclude advanced fibrosis in MAFLD patients and reduce the need for liver biopsy.


Multidisciplinary management of acromegaly: A consensus.
The 13th Acromegaly Consensus Conference was held in November 2019 in Fort Lauderdale, Florida, and comprised acromegaly experts including endocrinologists and neurosurgeons who considered optimal approaches for multidisciplinary acromegaly management. Focused discussions reviewed techniques, results, and side effects of surgery, radiotherapy, and medical therapy, and how advances in technology and novel techniques have changed the way these modalities are used alone or in combination. Effects of treatment on patient outcomes were considered, along with strategies for optimizing and personalizing therapeutic approaches. Expert consensus recommendations emphasize how best to implement available treatment options as part of a multidisciplinary approach at Pituitary Tumor Centers of Excellence.


Release of homocysteic acid from rat thalamus following stimulation of somatosensory afferents in vivo: feasibility of glial participation in synaptic transmission.
The sulphur-containing amino acid homocysteic acid (HCA) is present in and released in vitro from nervous tissue and is a potent neuronal excitant, predominantly activating N-methyl-d-aspartate (NMDA) receptors. However, HCA is localised not in neurones but in glial cells [Eur J Neurosci 3 (1991) 1370], and we have shown that it is released from astrocytes in culture upon glutamate receptor activation [Neuroscience 124 (2004) 377]. We now report the in vivo release of HCA from ventrobasal (VB) thalamus following natural stimulation of somatosensory afferents arising from the facial vibrissae of the rat. Simultaneously with multi-unit recording, [35S]-methionine, a HCA precursor, was perfused through a push-pull cannula in VB thalamus of anaesthetized rats. Perfusates were collected before, during and after 4 min stimulation of the vibrissal afferents with an air jet. A marked release of radiolabeled HCA was observed during and after the stimulation. Furthermore, the beta-adrenoreceptor agonist isoproterenol, which is known to evoke HCA release from glia in vitro, was found to increase the efflux of HCA in the perfusate in vivo. In separate experiments, the excitatory actions of iontophoretically applied HCA on VB neurones were inhibited by the NMDA receptor antagonist CPP, but not by the non-NMDA antagonist CNQX. These results suggest a possible "gliotransmitter" role for HCA in VB thalamus. The release of HCA from glia might exert a direct response or modulate responses to other neurotransmitters in postsynaptic neurons, thus enhancing excitatory processes.


Considering zooplankton as a black box in determining PAH concentrations could result in misjudging their bioaccumulation.
Zooplankton play an important role in energy transfer in the marine food web and form the dietary basis for the size of important fish stocks and the maintenance of their resources. Although zooplankton include numerous taxa with significantly different ecological characteristics and the interspecific differences in optimum body size and taxonomic specificity in fish feeding on zooplankton are remarkable, they are always considered as a whole (like a "black box") in current studies about the transport of persistent organic pollutants through the food chain. This approach might result in misjudgment of their bioaccumulation. In this study, the distribution properties of each taxa of zooplankton community were discerned using data from two cruise surveys conducted in the northern South China Sea. Twelve groups of zooplankton were identified, all of which had distinct ecological and functional characteristics. The carbon-based community structure of zooplankton could explain their variability with respect to polycyclic aromatic hydrocarbons (PAHs). Smaller-sized zooplankton (smaller calanoids and cyclopoids) were more likely to accumulate low molecular weight PAHs (LMW-PAHs), while larger-sized zooplankton (larger calanoids) were more likely to accumulate high molecular weight PAHs (HMW-PAHs). The bioaccumulation capacity of the zooplankton community for LMW-PAHs was negatively correlated with the proportion of omnivores and carnivores, while the opposite was true for HMW-PAHs. These results suggested that the effects of complex community structure within plankton communities should be taken into account when assessing the transfer and bioaccumulation effects of PAHs in the marine food chain.


Antioxidant gene expression analysis and evaluation of total phenol content and oxygen-scavenging system in tea accessions under normal and drought stress conditions.
Abiotic and biotic stresses induce oxidative processes in plant cells that this process starts with the production of ROSs which cause damage to the proteins. Therefore, plants have increased their antioxidant activity to defend against this oxidative stress to be able to handle stress better. In this research, 14 different tea accessions in a randomized complete block design with two replications were evaluated in two normal and drought stress conditions, and their antioxidant activity was measured by DPPH-free radicals' assay and gene expression analysis. The results of gene expression analysis showed that the 100 and 399 accessions and Bazri cultivar had high values for most of the antioxidant enzymes, ascorbate peroxidase, superoxide dismutase, catalase, and peroxidase under drought stress conditions while the 278 and 276 accessions had the lowest amount of antioxidant enzymes in the same situation. Results showed that the IC50 of the BHT combination was 90.12 μg/ ml. Also, The IC50 of accessions ranged from 218 to 261 μg/ml and 201-264 μg/ml at normal and drought stress conditions, respectively. The 100 and 399 accessions showed the lowest IC50 under normal and drought stress conditions, while 278 and 276 accessions had the highest value for IC50. The antioxidant activity of tea accession extracts under normal conditions was ranged from 25 to 69% for accessions 278 and 100, respectively. While, the antioxidant activities of extracts under drought stress condition was 12 to 83% for accessions 276 and 100, respectively. So, according to the results, 100 and 399 accessions exhibited the least IC50 and more antioxidant activity under drought stress conditions and were identified as stress-tolerant accessions. However, 278 and 276 accessions did not show much antioxidant activity and were recognized as sensitive accessions under drought stress conditions. These results demonstrate that total phenol content, antioxidant activity, and the oxygen-scavenging system can be used as a descriptor for identifying drought-tolerant accessions.


Association of Facial Paralysis With Perceptions of Personality and Physical Traits.
Facial paralysis has a significant effect on affect display, with the most notable deficit being patients' the inability to smile in the same way as those without paralysis. These impairments may result in undesirable judgements of personal qualities, thus leading to a significant social penalty in those who have the condition. To quantify the association of facial paralysis with the way smiling patients are perceived by others with respect to personality traits, attractiveness, and femininity or masculinity and to evaluate the potential association of facial palsy-related patient-reported outcome measures with how patients are perceived by others. This retrospective cross-sectional study used 20 images of smiling patients with facial paralysis evaluated between January 1, 2014, and December 31, 2016. Using photograph editing software, the photographs were edited to create a simulated nonparalysis smiling facial appearance. A total of 40 photographs were split into 4 groups of 10 photographs, each with 5 altered and 5 unaltered photographs. The surveys were designed such that altered and unaltered photographs of the same patient were not placed in the same survey to avoid recall bias. Anonymous raters used a 7-point Likert scale to rate their perception of each patient's personality traits (ie, aggressiveness, likeability, and trustworthiness), attractiveness, and femininity or masculinity based on photographs in their assigned survey. Raters were blinded to study intent. Scores from the Facial Clinimetric Evaluation questionnaire were included to assess self-perception. Data were analyzed from November 11, 2019, to February 20, 2020. Ratings of personality traits, attractiveness, and femininity or masculinity. Social function domain scores and overall scores were analyzed from the Facial Clinimetric Evaluation questionnaire. This study included photographs of 20 patients with facial paralysis (mean [range] age, 54 [28-69] years; 15 [75%] women). A total of 122 respondents completed the survey (71 [61%] women). Most respondents were between the ages of 25 and 34 years (79 participants [65%]). Overall, smiling photos of patients with facial paralysis were perceived as significantly less likeable (difference, -0.29; 95% CI, -0.43 to -0.14), trustworthy (difference, -0.25; 95% CI, -0.39 to -0.11), attractive (difference, -0.47; 95% CI, -0.62 to -0.32), and feminine or masculine (difference, -0.21; 95% CI, -0.38 to -0.03) compared with their simulated preparalysis photographs. When analyzed by sex, smiling women with facial paralysis experienced lower ratings for likeability (difference, -0.34; 95% CI, -0.53 to -0.16), trustworthiness (difference, -0.24; 95% CI, -0.43 to -0.06), attractiveness (difference, -0.74; 95% CI, -0.94 to -0.55), and femininity (difference, -0.35; 95% CI, -0.58 to -0.13). However, smiling men with facial paralysis only received significantly lower ratings for likeability (difference, -0.24; 95% CI, -0.47 to -0.01) and trustworthiness (difference, -0.30; 95% CI, -0.53 to -0.07). As patients' self-reported social function and total Facial Clinimetric Evaluation scores increased, there was an increase in perceived trustworthiness (rs[480] = 0.11; P = .02) and attractiveness (rs[478] = 0.10; P = .04) scores by raters. In this study, photographs of patients with facial paralysis received lower ratings for several personality and physical traits compared with digitally edited images with no facial paralysis. These findings suggest a social penalty associated with facial paralysis.


Effects of chronic treatment with valproate and oxcarbazepine on ovarian folliculogenesis in rats.
We aimed to define the morphologic effects of valproate (VPA) and oxcarbazepine (OXC) on ovarian folliculogenesis in rats. Forty female wistar rats (21-24 days old and weighted between 46.4 and 55.3 g) were divided equally into 4 experimental groups, which were applied tap water (control group), 300 mg/kg/day VPA, 100 mg/kg/day OXC, and both VPA and OXC via gavage for 90 days. Ovaries of the rats on proestrous and diesterous phase of estrous cycle according to daily vaginal smear were taken out and placed in a fixation solution. Immunohistochemical and apoptosis (TUNEL) staining protocols were applied. The number of follicles decreased and that of corpora lutea increased significantly in OXC, VPA, and OXC+VPA treated groups compared with control group (p < 0.05). The number of TUNEL positive ovarian follicles was 1.40 +/- 0.52 in control group, but it significantly increased to 3.50 +/- 0.53, 3.50 +/- 0.53, and 4.90 +/- 0.88 in VPA, OXC, and VPA+OXC groups (p < 0.0001). The increase in the number of TUNEL positive granulosa cells was also significant for OXC and VPA+OXC groups (p < 0.0001). Immunohistochemical HSCORE decreased for TGF beta 1 and IGF1 staining and increased for P53 staining in all drug groups compared with control group (p < 0.001). Intensity of P53 labeling increased, while intensity of TGF beta 1, IGF-1, and GDF-9 immunoreactivity decreased significantly in all drug groups compared with control group (p < 0.001). Long-term treatment with VPA or OXC from prepuberty to adulthood causes apoptosis and deterioration of folliculogenesis in rat ovarian follicles.


Recombinant Lactococcus lactis expressing porcine insulin-like growth factor I ameliorates DSS-induced colitis in mice.
Insulin-like growth factor I (IGF-I) is one important family of growth factors, which plays key role in intestinal growth, regeneration, and damage repair. However, the low natural abundance of IGF-I limits its research opportunities and practical application in the fields of medicine and animal husbandry. In this study, a tandem repeat strategy was used to express three copies of the same pIGF-I3 protein in L. lactis. The activity of recombinant pIGF-I3 (rpIGF-I3) was further examined by a mouse model of dextran sulfate sodium (DSS)-induced colitis. In addition, the potential of recombinant L. lactis expressing pIGF-I3 to reduce inflammatory disease was evaluated. pIGF-I3 could be expressed in L. lactis by the detection of SDS-PAGE and Western blot. Experimental colitis was induced in BALB/c mice by administration of 5 % DSS in drinking water, and the clinical symptoms were observed in DSS-treated mice. Oral administration of recombinant L. lactis expressing pIGF-I3 improved the colonic architecture, and significantly reduced the increase of colonic damage score (P < 0.05). Furthermore, recombinant L. lactis expressing pIGF-I3 treatment significantly reduced serum DAO activity and colonic MPO level, and elevated colonic occludin level compared to the DSS group (P < 0.05). The pIGF-I3 expressed in L. lactis has good biological activity, and oral administration of recombinant L. lactis expressing pIGF-I3 attenuated the symptoms and development of DSS-induced colitis in mice. These suggested that L. lactis could be a potential host bacterium for production and delivery of IGF-I against intestinal diseases.


The effect of refreezing previously frozen-deglycerolized red blood cells.
Frozen red blood cells, once thawed and washed, must be used within 24 hours or discarded. In this study, three units of blood underwent two freeze-thaw cycles. It was shown that red blood cell survival, ATP, and 2,3-DPG were not adversely effected. The data suggest that previously frozen red blood cells should be refrozen, rather than discarded, if not used within 24 hours of deglycerolization.


VMAT partial arc technique decreases dose to organs at risk in whole pelvic radiotherapy for prostate cancer when compared to full arc VMAT and IMRT.
Whole pelvic radiotherapy (WPRT) can sterilize microscopic lymph node metastases in treatment of prostate cancer. WPRT, compared to prostate only radiotherapy (PORT), is associated with increased acute gastrointestinal, and hematological toxicities. To further explore minimizing normal tissue toxicities associated with WPRT in definitive IMRT for prostate cancer, this planning study compared dosimetric differences between static 9-field-IMRT, full arc VMAT, and mixed partial-full arc VMAT techniques. In this retrospective study, 12 prostate cancer patients who met the criteria for WPRT were randomly selected for this study. The initial volume, PTV46, included the prostate, seminal vesicles, and pelvic nodes with margin and was prescribed to 4600 cGy. The cone-down volume, PTV78, included the prostate and proximal seminal vesicles with margin to a total dose of 7800 cGy. For each CT image set, 3 plans were generated for each of the PTVs: an IMRT plan, a full arc (FA) VMAT plan, and a mixed partial-full arc (PFA) VMAT plan, using 6MV photons energy. According to RTOG protocols none of the plans had a major Conformity Index (CI) violation by any of the 3 planning techniques. PFA plan had the best mean CI index of 1.00 and significantly better than IMRT (p = 0.03) and FA (p = 0.007). For equivalent PTV coverage, the average composite gradient index of the PFA plans was better than the IMRT and the FA plans with values 1.92, 2.03, and 2.01 respectively. The defference was statistically significant between PFA/IMRT and PFA/FA, with p- values of < 0.001. The IMRT plans and the PFA plans provided very similar doses to the rectum, bladder, sigmoid colon, and femoral heads, which were lower than the dose in the FA plans. There was a significant decrease in the mean dose to the rectum from 4524 cGy with the FA to 4182 cGy with the PFA and 4091 cGy with IMRT (p < 0.001). The percent of rectum receiving 4000 cGy was also the highest with FA at 66.1% compared to 49.9% (PFA) and 47.5% (IMRT). There was a significant decrease in the mean dose to the bladder from 3922 cGy (FA) to 3551 cGy (PFA) and 3612 cGy (IMRT) (p < 0.001). The percent of bladder receiving 4000 cGy was also the highest with FA at 45.4% compared to 36.6% (PFA) and 37.4% (IMRT). The average mean dose to the sigmoid colon decreased from 4177 cGy (FA) to 3893 cGy (PFA) and 3819 cGy (IMRT). The average mean dose to the femoral heads decreased from 2091 cGy (FA) to 2026 cGy (PFA) and 1987 cGy (IMRT). Considering the improvement in plan quality indices recorded in this study including the dose gradient and the dose to organs at risk, mixed partial-full arc plans may be the preferred VMAT treatment technique over full arc plans for prostate cancer treatments that include nodal volumes.


Snacking for a reason: detangling effects of socio-economic position and stress on snacking behaviour.
As snacking can be considered a cornerstone of an unhealthy diet, investigating psychological drivers of snacking behaviour is urgent, and therefore the purpose of this study. Socio-economic position (SEP) and stress are known to affect many behaviours and outcomes, and were therefore focal points in the study. In a cross-sectional survey study, we examined whether Socio-economic position (SEP) would amplify associations between heightened stress levels and self-reported negative-affect related reasons for snacking. Next, we investigated whether Socio-economic position (SEP) predicted frequency of snacking behaviour, and how stress and other reasons for snacking could explain this association. Outcome measures were reasons people indicated for snacking, and frequency of snacking behaviour. Analyses revealed that people seem to find more reasons to snack when they are stressed, and that this association was more pronounced for people with a high compared to low socio-economic position. Furthermore, a higher socio-economic position was associated with a higher frequency of snacking, and both snacking to reward oneself and snacking because of the opportunity to do so remained significant mediators. Whereas low socio-economic position was associated with higher stress levels, this did not translate into increased snacking. Contrarily, those with higher socio-economic position could be more prone to using 'reasons to snack', which may result in justification of unhealthy snacking behaviour.


A randomized comparison of fixed power and temperature monitoring during slow pathway ablation in patients with atrioventricular nodal reentrant tachycardia.
Temperature monitoring may be helpful for ablation of accessory pathways, however its role in ablation of atrioventricular nodal reentrant tachycardia (AVNRT) using the slow pathway approach is unclear. Therefore, the purpose of this study was to prospectively compare slow pathway ablation for AVNRT using fixed power or temperature monitoring. The study included 120 patients undergoing ablation for AVNRT. Patients were randomly assigned to receive either fixed power at 32 watts, or to temperature monitoring with a target temperature of 60 degrees C. The primary success rate was 72% in the fixed power group and 95% in the temperature monitoring group (p = 0.001). The ablation procedure duration (35 +/- 29 min vs 35 +/- 30 min; p = 0.9), fluoroscopic time (32 +/- 17 vs 35 +/- 19 min; p = 0.4), mean number of applications (10.2 +/- 8.1 vs 8.4 +/- 7.9; p = 0.2), and coagulum formation per application (0.2% vs 0.5%; p = 0.6) were statistically similar in the fixed power and temperature monitoring groups, respectively. The mean temperature (47.3 +/- 4.8 degrees C vs 48.6 +/- 3.8 degrees C; p < 0.01), and the temperature associated with junctional ectopy (48.2 +/- 3.8 degrees C vs 49.3 +/- 3.6 degrees C, p < 0.01) were less for the fixed power than the temperature monitoring group. In the temperature monitoring group, only 31% of applications achieved an electrode temperature of 60 degrees C. During follow up of 6.6 +/- 3.6 months there were two recurrences in the fixed power group and one in the temperature monitoring group (p = 1.0). In summary, power titration directed by temperature monitoring was associated with an improved primary procedural success rate. Applications of energy were associated with a temperature of approximately 50 degrees C with both techniques, suggesting that there is a low efficiency of heating in the posterior septum.


Repeat length of C9orf72-associated glycine-alanine polypeptides affects their toxicity.
G4C2 hexanucleotide repeat expansions in a non-coding region of the C9orf72 gene are the most common cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). G4C2 insertion length is variable, and patients can carry up to several thousand repeats. Dipeptide repeat proteins (DPRs) translated from G4C2 transcripts are thought to be a main driver of toxicity. Experiments in model organisms with relatively short DPRs have shown that arginine-rich DPRs are most toxic, while polyGlycine-Alanine (GA) DPRs cause only mild toxicity. However, GA is the most abundant DPR in patient brains, and experimental work in animals has generally relied on the use of low numbers of repeats, with DPRs often tagged for in vivo tracking. Whether repeat length or tagging affect the toxicity of GA has not been systematically assessed. Therefore, we generated Drosophila fly lines expressing GA100, GA200 or GA400 specifically in adult neurons. Consistent with previous studies, expression of GA100 and GA200 caused only mild toxicity. In contrast, neuronal expression of GA400 drastically reduced climbing ability and survival of flies, indicating that long GA DPRs can be highly toxic in vivo. This toxicity could be abolished by tagging GA400. Proteomics analysis of fly brains showed a repeat-length-dependent modulation of the brain proteome, with GA400 causing earlier and stronger changes than shorter GA proteins. PolyGA expression up-regulated proteins involved in ER to Golgi trafficking, and down-regulated proteins involved in insulin signalling. Experimental down-regulation of Tango1, a highly conserved regulator of ER-to Golgi transport, partially rescued GA400 toxicity, suggesting that misregulation of this process contributes to polyGA toxicity. Experimentally increasing insulin signaling also rescued GA toxicity. In summary, our data show that long polyGA proteins can be highly toxic in vivo, and that they may therefore contribute to ALS/FTD pathogenesis in patients.


A (GATA)(7) motif located in the 5' boundary area of the human beta-globin locus control region exhibits silencer activity in erythroid cells.
A 40-bp DNA, consisting of seven tandem GATA repeats, is located near the HS5 site in the 5' boundary area of the locus control region (LCR) of human beta-globin gene. This (GATA)(7) motif, named 5a, exhibits silencer activity in erythroid cells. In transfected, recombinant plasmids containing the chloramphenicol acetyltransferase (CAT) reporter gene, 5a repressed the activity of the cis-linked housekeeping phosphoglycerate kinase (pgk) promoter; 5a also repressed the activity of the cis-linked HS2 enhancer regardless of whether the CAT gene was driven by the pgk or the epsilon-globin promoter. Repression by 5a was most severe when 5a was spliced upstream of HS2 at a distance of less than 200 bases from the HS2 enhancer core. The silencer activity of 5a was independent of whether the component GATA motifs were in head to tail orientation as in the wild type 5a or in head to head or tail to tail orientation as in a mutant 5a. Band shift experiments show that the GATA-1 protein binds to both 5a and the mutant 5a and forms a large protein complex. Together, the results suggest that GATA-1 bound at 5a is a strong, proximal repressor of HS2 enhancer activity.


Prolonged expiratory apnoea with cyanosis in Arnold Chiari II malformation.
Apnoea associated with Arnold Chiari malformation is a known entity and can be obstructive or central. Differentiating between two types is vital to deciding management pathway and prognosticating disease process.


Impact of Preoperative Exclusive Enteral Nutrition on Postoperative Complications and Recurrence After Bowel Resection in Patients with Active Crohn's Disease.
The impact of preoperative enteral nutrition (EN) on postoperative complications and recurrence in Crohn's disease (CD) has not been investigated to date. The purpose of the present study was to determine the effect of preoperative exclusive EN on postoperative complications and recurrence after bowel resection in patients with active CD. Patient data were obtained from a prospectively maintained database. 81 patients who received bowel resection for ileal or ileocolonic CD were studied. Before operation, 42 CD patients received exclusive EN for 4 weeks, and the other patients had no nutritional therapy. All patients were followed up regularly for 2 years after surgery, and ileocolonoscopy was performed every 6 months after bowel resection. Patients receiving exclusive EN had a dramatic improvement of nutritional (BMI, albumin, pre-albumin, and Hb) and inflammatory (CRP and CDAI) status compared with baseline after the EN therapy for 4 weeks (P < 0.05). Furthermore, significantly lower incidence of both infectious and non-infectious complications was observed in patients receiving exclusive EN compared with those received no nutritional therapy (P < 0.05). Exclusive EN therapy for 4 weeks significantly reduced endoscopic recurrence rates after resection for CD 6 months after operation. However, during the 2-year follow-up, incidence of clinical recurrence was similar in both groups (P > 0.05). Preoperative exclusive EN therapy for 4 weeks reduced postoperative complications, which may be associated with improvement of nutritional and inflammatory status in patients with active CD.


Magnetic resonance imaging and clinical findings in adults with tick-borne encephalitis.
Magnetic resonance imaging (MRI) in tick-borne encephalitis (TBE) is often performed for differential diagnosis, but only a few reports on the morphologic changes in TBE patients and their relation to the disease severity exist. We retrospectively searched for all TBE patients who were admitted to the Departments of Neurology of the Medical University of Graz (Austria) and the Paracelsus Medical University of Salzburg (Austria) between 2003 and 2014. We recorded the clinical and demographic variables and rated overall disease severity as mild, moderate, severe or leading to death due to TBE. MRI scans were screened for morphologic abnormalities. Of an initial cohort of 88 patients with TBE, 45 patients with an available MRI of the brain were included in this study (median age 58.0years, range: 18-80; men n=28). Their median time spent in the hospital was 18days (range: 4-174days). 16 patients had a mild, 18 a moderate and 10 a severe disease course. One patient died due to TBE. TBE related brain abnormalities could be identified in 4 cases. They consisted of diffuse areas of T2-signal hyperintensity, which were located in the crura cerebri in three patients and in the right centrum semiovale in one patient. No contrast enhancement was observed in any of the lesions and their presence was not related to specific clinical findings or the severity of TBE. MRI brain lesions in TBE are rare and do not correlate with the course of the disease. Diffuse areas of signal hyperintensity in the crura cerebri appear suggestive of TBE.


[Surgical and local treatment in a case of fungal sinusitis in a patient with bone marrow aplasia].
We report a clinical case of severe medullary aplasia complicated by fungal antritis. The treatment adopted for this patient consists in a clean operation of the infective focus and the local instillation of Amfotericina B during the post operative period. In this way the systemic circulation is not interested by the use of Amfotericina B, which is extremely important to avoid the inevitable onset of several unwanted side-effects; besides, we avoid the progression of the infective focus and its systemic diffusion.


Isotope tracer study of hydrogen spillover on carbon-based adsorbents for hydrogen storage.
A composite material comprising platinum nanoparticles supported on molecular sieve templated carbon was synthesized and found to adsorb 1.35 wt % hydrogen at 298 K and 100 atm. The isosteric heat of adsorption for the material at low coverage was approximately 14 kJ/mol, and it approached a value of 10.6 kJ/mol as coverage increased for pressures at and above 1 atm. The increase in capacity is attributed to spillover, which is observed with the use of isotopic tracer TPD. IRMOF-8 bridged to Pt/C, a material known to exhibit hydrogen spillover at room temperature, was also studied with the hydrogen-deuterium scrambling reaction for comparison. The isotherms were reversible. For desorption, sequential doses of H2 and D2 at room temperature and subsequent TPD yield product distributions that are strong indicators of the surface diffusion controlled reverse spillover process.


Metabolic disorders and gastroenteropancreatic-neuroendocrine tumors (GEP-NETs): How do they influence each other? An Italian Association of Medical Oncology (AIOM)/ Italian Association of Medical Diabetologists (AMD)/ Italian Society of Endocrinology (SIE)/ Italian Society of Pharmacology (SIF) multidisciplinary consensus position paper.
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of malignancies derived from neuroendocrine cells that can occur anywhere along the gastrointestinal tract. GEP-NETs incidence has been steadily increasing over the past decades, in parallel with the increasing incidence of the metabolic syndrome (MetS). It is not yet fully known whether the MetS components (such as obesity, dyslipidemia and type 2 diabetes) could be involved in the etiology of GEP-NETs or could influence their outcomes. In this review, a panel of experts of the Italian Association of Medical Oncology (AIOM), Italian Association of Medical Diabetologists (AMD), Italian Society of Endocrinology (SIE), and Italian Society of Pharmacology (SIF) provides a critical view of the experimental and clinical evidence about the association of GEP-NETs risk, outcomes, and therapies with the metabolic disorders typical of MetS. The potential therapeutic strategies for an optimal management of patients with both GEP-NETs and MetS are also discussed.


Use of CPAP and surfactant therapy in newborns with respiratory distress syndrome.
Respiratory distress syndrome (RDS) is a major disease burden in the developing countries. Current evidence supports early continuous positive airway pressure (CPAP) use and early selective surfactant administration as the most efficacious interventions in the management of RDS, both in developed and developing countries. In developing countries, it is recommended to increase institutional deliveries and increase the coverage of antenatal steroids in women in preterm labor as preventive measures. Establishing intervention of CPAP and surfactant therapies in the Level II special care newborn units (SCNUs) and Level III units requires focus on training nursing staff and pediatricians across the board. These approaches would pave the way in optimizing the care of the preterm infants with RDS and decrease their mortality and morbidity significantly.


Retinal Vessel Pulsatile Characteristics Associated With Vascular Stiffness Can Predict the Rate of Functional Progression in Glaucoma Suspects.
Tissue stiffening and alterations in retinal blood flow have both been suggested as causative mechanisms of glaucomatous damage. We tested the hypothesis that retinal blood vessels also stiffen, using laser speckle flowgraphy (LSFG) to characterize vascular resistance. In the longitudinal Portland Progression Project, 231 eyes of 124 subjects received LSFG scans of the optic nerve head (ONH) and automated perimetry every 6 months for six visits. Eyes were classified as either "glaucoma suspect" or "glaucoma" eyes based on the presence of functional loss on the first visit. Vascular resistance was quantified using the mean values of several instrument-defined parameterizations of the pulsatile waveform measured by LSFG, either in major vessels within the ONH (serving the retina) or in capillaries within ONH tissue, and age-adjusted using a separate group of 127 healthy eyes of 63 individuals. Parameters were compared against the severity and rate of change of functional loss using mean deviation (MD) over the six visits, within the two groups. Among 118 "glaucoma suspect" eyes (average MD, -0.4 dB; rate, -0.45 dB/y), higher vascular resistance was related to faster functional loss, but not current severity of loss. Parameters measured in major vessels were stronger predictors of rate than parameters measured in tissue. Among 113 "glaucoma" eyes (average MD, -4.3 dB; rate, -0.53 dB/y), higher vascular resistance was related to more severe current loss but not rate of loss. Higher retinal vascular resistance and, by likely implication, stiffer retinal vessels were associated with more rapid functional loss in eyes without significant existing loss at baseline.


Pulsating Microbubble in a Micro-vessel and Mechanical Effect on Vessel Wall: A Simulation Study.
Microbubbles are widely used in diagnostic ultrasound applications as contrast agents. Recently, many studies have shown that microbubbles have good potential for the use in therapeutic applications such as drug and gene delivery and opening of blood- brain barrier locally and transiently. When microbubbles are located inside an elastic microvessel and activated by ultrasound, they oscillate and induce mechanical stresses on the vessel wall. However, the mechanical stresses have beneficial therapeutic effects, they may induce vessel damage if they are too high. Microstreaming-induced shear stress is one of the most important wall stresses. The overall aim of this study is to simulate the interaction between confined bubble inside an elastic microvessel and ultrasound field and investigate the effective parameters on microstreaming-induced shear stress. In this Simulation study, we conducted a 2D finite element simulation to study confined microbubble dynamics, also we investigated both acoustical and bubble material parameters on microbubble oscillation and wall stress. Based on our results, for acoustic parameters in the range of therapeutic applications, the maximum shear stress was lower than 4 kPa. Shear stress was approximately independent from shell viscosity whereas it decreased by increasing the shell stiffness. Moreover, shear stress showed an increasing trend with acoustic pressure. Beside the acoustical parameters, bubble properties have important effects on bubble behavior so that the softer and larger bubbles are more appropriate for therapeutic application as they can decrease the required frequency and acoustic pressure while inducing the same biological effects.


Ophthalmic artery changes in type 2 diabetes with and without acute coronary syndrome.
Ocular blood flow provides a new perspective for studying the effects of diabetes and ischemic heart disease on systemic blood flow, pathological mechanisms, and prognosis. Previous studies have analyzed the hemodynamic changes of the ophthalmic artery (OA) in patients with diabetes and ischemic heart disease, but the results remain controversial due to limited observation methods. We aimed to explore the morphological and hemodynamic features in the OA in patients with type 2 diabetes (T2D) with and without acute coronary syndrome (ACS). In total, 134 participants, including 30 control participants, 34 with ACS only, 34 with T2D only, and 36 with both ACS and T2D, undergoing computed tomography angiography were enrolled. Three-dimensional OA models were reconstructed, and morphological parameters of the OA were measured. In addition, numerical simulations using computational fluid dynamics were used to acquire hemodynamic parameters of the OA. In this study, 134 OA models were reconstructed. Morphological measurements revealed a smaller initial OA diameter in the T2D group than in the other two ACS groups. A hemodynamic simulation showed a significantly lower OA blood velocity in patients with ACS and T2D than that in controls (P < 0.001). The mass flow ratios in all disease groups were lower than those in the control group (P < 0.001, P = 0.020, and P < 0.001, respectively). The ACS and T2D groups had higher OA pressure levels than those of the control group (P = 0.013). The OA blood velocity and mass flow ratio were correlated with several clinical parameters. This study revealed morphological and hemodynamic differences in the OA between patients with T2D with and without ACS. Furthermore, the hemodynamic characteristics of the OA correlated with clinical prognostic biomarkers, suggesting the potential predictive ability of the OA.


[Synchronous renal clear-cell carcinoma and ipsilateral transitional-cell carcinoma: case report and bibliographic review].
We report a new case of simultaneous renal cell adenocarcinoma and ipsilateral multifocal transitional cell carcinoma. 73-year-old man with initial diagnosis of transitional cell carcinoma of the urinary tract whose pathological report showed a asynchronous renal cell carcinoma. We present microphotographs of both tumors after radical surgery. The presentation of both tumors in the same kidney is unusual, although there are around 47 cases in the bibliography worldwide, 8 of them in Spanish. Presentation of both tumors altogether does not worsen prognosis.


3D TOF MR angiography to depict pituitary bright spot and to detect posterior pituitary lobe cyst: Original description at 3T MR imaging.
There is no detailed description of the pituitary bright spot (PBS) at 3T in the literature. This study assesses detection of PBS on axial source images of 3D TOF sequence at 3T, and reports cysts in this location for the first time. We retrospectively studied 250 consecutive patients who underwent brain 3T MRI with high resolution 3D TOF angiogram and thin axial T2-weighted sequences. On the axial source images of the 3F TOF, we assessed the presence, location and shape of the PBS. A cyst was diagnosed within the PBS in cases with central sharply defined low-TOF signal intensity surrounded by a rim of hyperintense signal. High T2 signal intensity corresponding precisely with the low T1 signal was also necessary for the diagnosis of such cysts. Evolution of these cysts was assessed on follow-up MRI. PBS was depicted in 83% of patients. Prevalence was significantly higher in women than in men (89% vs 70%, P<0.01). Patients with PBS were significantly younger than those without (mean age 54.1 years vs 59.4 years, P<0.05). A cyst within the PBS was depicted in six patients (2.9%). Mean size was 1.9 mm. These cysts were asymptomatic and remained stable during follow-up. Axial source images of 3D TOF angiogram can be used to assess the posterior pituitary lobe as the PBS was detected in 83% of our cohort. When cysts are seen within, they may be considered incidental findings that remained stable at follow-up.


Differential effect of thermal stress on HSP70 expression, nitric oxide production and cell proliferation among native and crossbred dairy cattle.
In a tropical country like India, thermal stress is one of the major factors which significantly affects the productivity of dairy cattle. The present study was aimed to identify the effect of heat and cold stress on cell viability, mitogen stimulation indices, nitric oxide production and HSP70 expression in Sahiwal and Holstein crossbred (Frieswal) population in India. The results indicated that the Sahiwal breed can better withstand the effect of heat and cold stress significantly (P<0.05) when compared to the crossbred cattle due to the higher survivability of the Peripheral Blood Mononuclear Cells (PBMCs) and Phytohemagglutinin (PHA-P) mitogen based stimulation indices. The study also revealed the significant differences (P<0.05) in the level of nitric oxide (µM) production amongst the pre and post thermal stressed samples of Sahiwal and Frieswal crossbred samples. Further, the expression of HSP70 was significantly (P<0.05) higher in Sahiwal compared to Frieswal immediately after heat/cold shock to 6h of recovery as indirect ELISA analysis showed gradual rise in the Hsp70 protein concentration (ng/ml) immediately after heat and cold stress (0h) and reached the peak at 6h of recovery. Western blot and immune fluorescent assay results were also corroborated with the findings of indirect ELISA. In Sahiwal cattle the mRNA expression of HSP70 and its protein concentration were higher (P<0.05) during peak summer (44°C) and winter (10°C) as compared to Frieswal cattle. This investigation supports the earlier information on the higher adaptability of indigenous cattle breeds to hot and humid conditions compared to the crossbreds of temperate cattle breeds.


Mining and design of biosensors for engineering microbial cell factory.
Improving the yield of target product is the purpose in the construction and optimization of microbial cell factory. Conferring biosensor-based intelligence on the strains is an important way to solve the engineering problems such as imbalance of metabolic flux and accumulation of toxic intermediates. In recent years, genetically encoded biosensors for both metabolites and environmental signals are rapidly created and developed via rational design, directed evolution or machine learning. In addition to being a rapid detection method for high-throughput screening, biosensors are more and more applied for directed evolution of strains and dynamic regulation of metabolic pathway. Biosensor-based intelligence will play more important role in the construction of microbial cell factory.


Vaginal hysterectomy in women with history of previous cesarean delivery.
This study aimed to compare surgical outcomes with vaginal hysterectomy between women who have had >/=1 cesarean delivery and those who have not had a cesarean delivery. A secondary objective was to analyze the effect of previous vaginal birth on the complication rate of vaginal hysterectomy. A retrospective analysis was performed on 221 women undergoing vaginal hysterectomy. Women were separated into those who had a history of previous cesarean deliveries (N = 35) and those who did not (N = 186). The groups were analyzed for the indications for surgery, perioperative hemoglobin loss, operative time, length of hospitalization, and complications. Trends in the complication rate for women in the previous cesarean group were also studied from the perspectives of numbers of previous cesarean deliveries and of vaginal delivery history. The 95% confidence intervals for the difference between proportions as well as P values for probability tests were calculated. P <.05 was considered significant. Previous cesarean delivery experience did not affect hemoglobin change, hospital stay, or operative time among women undergoing vaginal hysterectomy. A total of 11.3% of women in the previous cesarean group had complications, versus 4.3% for the noncesarean group (P =.10, 95% confidence interval -3.8% to 18.0%). Complications did not increase with increasing number of previous cesarean deliveries (U = 1020.5, P =.28). Also, a trend toward fewer complications among patients with a history of cesarean delivery who had also had a vaginal delivery was demonstrated (U = 836, P =.05). Overall, women who were undergoing vaginal hysterectomy who had a history of >/=1 previous vaginal delivery had a complication rate of 3.2%, versus 17.6% for women who had not had a previous vaginal birth (P =.004, 95% confidence interval -27.5% to -1.3%). In this study women who had a history of previous cesarean delivery were not at higher risk for greater hemoglobin loss, longer hospital stay, more prolonged operative time, or significantly more perioperative complications when undergoing vaginal hysterectomy than were those women who had no history of previous cesarean delivery. Likewise, increasing the number of previous cesarean deliveries did not have an adverse impact on the complication rate. Previous vaginal delivery lowered the risk of complications from vaginal hysterectomy.


Generation of Venus reporter knock-in mice revealed MAGI-2 expression patterns in adult mice.
The membrane-associated guanylate kinase inverted 2 (MAGI-2) protein, which is known to localize at the tight junction of epithelial cells, contains multiple copies of the PDZ and WW domains in its structure. Although the expression pattern of Magi2 mRNA in representative organs has been previously published, its detailed cellular distribution at the histological level remains unknown. Such detailed information would be useful to clarify the biological function of MAGI-2. Here, we report the generation of Venus reporter knock-in mice for Magi2 in which exon 6 of the gene was substituted by the Venus-encoding sequence. We detected the expression of the Venus reporter protein in kidney podocytes from these knock-in mice. We also detected Venus reporter protein expression in spermatids within the testes and within neurons in various regions of the brain. Detection of the reporter protein from these diverse locations indicated the endogenous expression of MAGI-2 in these tissues. Our data suggested a potential function of MAGI-2 in the glomerular filtration process and sperm cell maturation. These data indicate that the Venus reporter knock-in mouse for Magi2 is a useful model for the further study of Magi2 gene function.


Motility and oxidative stress of common carp Cyprinus carpio sperm during short-term storage.
Short-term storage of semen is a simple and inexpensive procedure to deal with logistics of large-scale hatchery operations but can lead to oxidative stress and a significant decrease in sperm motility and velocity. To better understand the mechanisms responsible for the association of poor sperm quality with oxidative stress, in the present study we investigated the effect of refrigerated storage for 0, 24, 48, 72, and 144 h on sperm motility and curvilinear velocity and oxidant/antioxidant balance of common carp Cyprinus carpio. Percentage of motile sperm was significantly (p < 0.05) reduced stored for 72 h storage compared to that of fresh sperm. Sperm stored 144 h showed < 40% motility with an average velocity of 91.12 ± 10.4 µm s-1. A time-dependent increase in the level of the oxidative stress indices lipid peroxidation and carbonyl derivatives of proteins was observed. Increase (p > 0.05) in total superoxide dismutase was detected after 48 h, and glutathione reductase and glutathione peroxidase activity demonstrated a significant increase after 72 h. These results provide an additional tool for the development and improvement of short-term sperm preservation procedures commonly applied in aquaculture.


Inhibitory effect of quinidine on plasma pseudocholinesterase activity in pregnant women.
The effect of quinidine at therapeutic and subtherapeutic concentrations on pseudocholinesterase activity in the plasma of 16 normal pregnant women was studied. The mean plasma pseudocholinesterase activity in the absence of quinidine (control) was 0.67 +/- 0.11 U/ml. The mean pseudocholinesterase activity in the presence of quinidine at concentrations of 0.5, 1.0, 2.0, and 5.0 micrograms/ml 0.48 +/- 0.09, 0.38 +/- 0.09, 0.29 +/- 0.10, and 0.19 +/- 0.09 U/ml, respectively. At therapeutic concentrations needed to treat cardiac arrhythmias (2 to 5 micrograms/ml), quinidine inhibited pseudocholinesterase activity by 60% to 70%. All the plasma samples had a normal dibucaine number (78 to 85). We recommend caution when succinylcholine and/or ester-type local anesthetics are used in pregnant women receiving quinidine.


[Comparison of CT findings between gastric cancer and gastric lymphoma].
It is difficult to discriminate progressive gastric cancer and gastric lymphoma by CT imaging, because incrassate gastric wall, lump in gastric cavity, confined gastric cavity, intumescent lymph node, and distant metastasis can be displayed in both of them. This study was to compare the CT findings between gastric cancer and gastric lymphoma to improve diagnosis of gastric tumors, especially for gastric lymphoma. CT images of 27 patients with pathologically proved progressive gastric cancer and 25 patients with pathologically proved gastric lymphoma were reviewed. Tumor location, appearance, scope of involvement, gastric wall thickness, mucous membrane, mucosal fold, serosa membrane, necrosis, enhancement degree and uniformity, involvement of other organs, and abdominal lymph nodes were observed. White line sign was observed in 23 cases (85.2%) of gastric cancer, but not in the 25 cases of gastric lymphoma. The extent of white line sign in gastric cancers was larger in portal vein phase than in arterial phase. Enhancement degree outside the white line was higher in portal vein phase than in arterial phase in 13 cases (48.1%) of gastric cancer. The extent of involved gastric wall was smaller than 50% of the whole gastric wall in all the 27 cases of gastric cancer, while it was larger than 75% in 23 cases (85.2%) of gastric lymphoma. Gastric mucous membrane ulcer was found in all of the 27 cases (100%) of gastric cancer, while it was found in only 1 case (4.0%) of gastric lymphoma. Intumescent lymph nodes in two or more areas were found in 11 cases (40.0%) of gastric lymphoma, but not in gastric cancer. Intumescent lymph nodes in the retroperitoneal space below renal hilum were found in 8 cases (32%) of gastric lymphoma, but not in gastric cancer. There are some different CT features between gastric cancer and gastric lymphoma, such as white line sign, gastric mucous membrane ulcer, extent of involved gastric wall, location of intumescent lymph nodes surrounding the stomach and in retroperitoneal space below renal hilum, and so on, which could be helpful in differential diagnosis of these two diseases.


Anti-mycobacterial activities of some cationic and anionic calix[4]arene derivatives.
Various polycharged calix[4]arenes were assayed as anti-mycobacterial agents against Mycobacterium tuberculosis, H(37)Rv strain. The sulfonate, carboxylate and phosphonate anionic species displayed no activity. Cationic derivatives integrating four aminoethyl groups at the upper rim and two 6,6'-dimethyl-2,2'-bipyridyl- or 4,4'-dimethyl-2,2'-bithiazolyl subunits at the lower rim were also found inactive against M. tuberculosis, while the unsubstituded and the 5,5'-dimethyl-2,2'-bipyridyl-analogues exhibited MIC values of 3.2 and 0.8μM respectively. Introduction of guanidinoethyl groups at the upper rim resulted, except for the 6,6'-dimethyl-2,2'-bipyridyl-derivative, in high anti-mycobacterial activities for the unsubstituted, the 5,5'-dimethyl-2,2'-bipyridyl- and the 4,4'-dimethyl-2,2'-bithiazolyl analogues, with MIC values of 0.8, 0.8 and 1.6μM, respectively, similar to those of current commercial anti-tuberculosis agents. The five more active substances were also evaluated against the isoniazid-resistant strain MYC5165, resulting in highly interesting micromolar or sub-micromolar MIC and IC(50), ca. 4-125 times more active than isoniazid. These preliminary results are attractive for the development of new anti-TB agents.


Lysosomal responses to heat-shock of seasonal temperature extremes in Cd-exposed mussels.
The present study was aimed at determining the effect of temperature extremes on lysosomal biomarkers in mussels exposed to a model toxic pollutant (Cd) at different seasons. For this purpose, temperature was elevated 10°C (from 12°C to 22°C in winter and from 18°C to 28°C in summer) for a period of 6h (heat-shock) in control and Cd-exposed mussels, and then returned back to initial one. Lysosomal membrane stability and lysosomal structural changes in digestive gland were investigated. In winter, heat-shock reduced the labilisation period (LP) of the lysosomal membrane, especially in Cd-exposed mussels, and provoked transient lysosomal enlargement. LP values recovered after the heat-shock cessation but lysosomal enlargement prevailed in both experimental groups. In summer, heat-shock induced remarkable reduction in LP and lysosomal enlargement (more markedly in Cd-exposed mussels), which recovered within 3 days. Besides, whilst heat-shock effects on LP were practically identical for Cd-exposed mussels in winter and summer, the effects were longer-lasting in summer than in winter for control mussels. Thus, lysosomal responsiveness after heat-shock was higher in summer than in winter but recovery was faster as well, and therefore the consequences of the heat shock seem to be more decisive in winter. In contrast, inter-season differences were attenuated in the presence of Cd. Consequently, mussels seem to be better prepared in summer than in winter to stand short periods of abrupt temperature change; this is, however, compromised when mussels are exposed to pollutants such as Cd.


Acute effects of mechanical shocks on finger blood flow: influence of shock repetition rate and shock magnitude.
Finger blood flow is reduced by hand-transmitted vibration but there has been little study of the peripheral vascular response to repetitive mechanical shocks. This study investigated how reductions in finger blood flow depend on shock repetition rate and the peak and rms magnitude of acceleration. Subjects attended seven sessions: six with repetitive mechanical shocks and a control session with no shocks. Each session comprised five successive 5-min periods: (1) no force and no vibration, (2) force and no vibration, (3) force and vibration, (4) force and no vibration and (5) no force and no vibration. During the second-fourth periods, the palm of the right hand applied 2-N force to a vibrator. During the third period, a 125-Hz mechanical shock was applied with one of four repetition rates (1.3, 5.3, 21 or 83.3/s) and one of three acceleration magnitudes (2.5, 5 or 10 ms(-2) rms, unweighted). Finger blood flow was measured every 30 s in the middle and little fingers of the right (exposed) hand and the left (unexposed) hand. Different repetition rates (1.3-83.3 s(-1)) and different peak magnitudes (10-88 ms(-2) peak) but the same rms acceleration (10 ms(-2) rms) caused similar decreases in blood flow in fingers on exposed and unexposed hands. Shocks with a 83.3 s(-1) repetition rate, peak magnitude of 10 ms(-2) and rms acceleration of 10 ms(-2) provoked greater reduction in finger blood flow than shocks with the same peak magnitude but lower repetition rate (21 or 5.3 s(-1)) and lower rms acceleration (5 or 2.5 ms(-2)). For shocks similar to those based on 125-Hz oscillations with repetition rates between 1.3 and 83.3 s(-1), acute reductions in finger blood flow can be predicted from the rms acceleration.


Vasopressin infusion in children with catecholamine-resistant septic shock.
To describe use of vasopressin infusion for catecholamine-refractory septic shock in children. We report successful use of vasopressin infusion in three children with septic shock, in whom hypotension and poor perfusion persisted despite use of multiple infusions of vasopressors and inotropes. All three had a rapid improvement in hypotension and perfusion after starting vasopressin infusion, allowing tapering of other infusions. Two children recovered completely. Vasopressin appears to be useful in treatment of catecholamine-refractory septic shock in children.


MRTFB suppresses colorectal cancer development through regulating SPDL1 and MCAM.
Myocardin-related transcription factor B (MRTFB) is a candidate tumor-suppressor gene identified in transposon mutagenesis screens of the intestine, liver, and pancreas. Using a combination of cell-based assays, in vivo tumor xenograft assays, and Mrtfb knockout mice, we demonstrate here that MRTFB is a human and mouse colorectal cancer (CRC) tumor suppressor that functions in part by inhibiting cell invasion and migration. To identify possible MRTFB transcriptional targets, we performed whole transcriptome RNA sequencing in MRTFB siRNA knockdown primary human colon cells and identified 15 differentially expressed genes. Among the top candidate tumor-suppressor targets were melanoma cell adhesion molecule (MCAM), a known tumor suppressor, and spindle apparatus coiled-coil protein 1 (SPDL1), which has no confirmed role in cancer. To determine whether these genes play a role in CRC, we knocked down the expression of MCAM and SPDL1 in human CRC cells and showed significantly increased invasion and migration of tumor cells. We also showed that Spdl1 expression is significantly down-regulated in Mrtfb knockout mouse intestine, while lower SPDL1 expression levels are significantly associated with reduced survival in CRC patients. Finally, we show that depletion of MCAM and SPDL1 in human CRC cells significantly increases tumor development in xenograft assays, further confirming their tumor-suppressive roles in CRC. Collectively, our findings demonstrate the tumor-suppressive role of MRTFB in CRC and identify several genes, including 2 tumor suppressors, that act downstream of MRTFB to regulate tumor growth and survival in CRC patients.


Towards the Big History of information. Approaching the origins of information behaviour.
A palaeontological analysis of the evolutionary steps of Metazoa is tracing back the appearance and first steps of information behaviour as far as the Proterozoic Eon. Either the neural cell or the nervous system or the eyesight did not trigger the appearance of the information behaviour, but it did a novel way of diet. Carnivorous diet appeared on Earth slightly before the information behaviour as a completely new way of feeding - and what is more important: the application of light into the behavioural complexes as a radically innovative survival supporting tool. A genetic toolkit was ready for Metazoa, and the combination of the neural system, eyesight and carnivorous diet initiated the information behaviour. We provide an answer for this simple question: why did the carnivorous diet result in the first disruptive innovation in information behaviour? The junction of Big History, palaeontology and information history provides many challenging new aspects for further research.


Novel and versatile superfusion system. Its use in the evaluation of some spasmogenic and spasmolytic agents using guinea-pig isolated tracheal smooth muscle.
We have developed a novel, eight-chamber superfusion system that is suitable for a variety of applications involving the study of both contraction and relaxation of smooth muscle preparations, and the effect of agents that interfere with these actions. The system allows electrical stimulation of preparations, and thus neuronally mediated responses and agents that interfere with neurotransmission may also be studied. To demonstrate some of the applications of the system, we have evaluated both spasmogenic and spasmolytic agents on the guinea-pig isolated tracheal strip preparation. The potency and the times for onset and offset of action of the spasmogens, acetylcholine, histamine, and prostaglandin F2 alpha, and the spasmolytics, isoprenaline, clenbuterol, salbutamol, papaverine, N-ethylcarboxamide adenosine, theophylline, and verapamil, have been investigated. The spasmolytic agents have been tested against both prostaglandin F2 alpha-induced tone and electrically induced contractile responses of the guinea-pig trachea. This superfusion system has several advantages over previously described superfusion or immersion techniques. It is compact and allows simultaneous study of up to eight preparations. It is suitable for a wide range of tissues, and the use of this system avoids the necessity of repeatedly washing drugs from organ baths. However, one of the most important applications of the system is its use in the study of rates of onset and offset of drug action. We believe, therefore, that this system represents an important alternative to the classical organ bath for in vitro pharmacological experimentation.


Patellar instability: treatment by arthroscopic electrosurgical lateral release.
We reviewed the results of arthroscopic lateral release using electrosurgery in 39 patients (45 knees) with a history of recurrent patellar subluxation or dislocation. The average follow-up time was 28 months (range, 24-36). At follow-up, the patients had decreased swelling, instability, and pain. There was an improvement in flexion activities, sports participation, and overall functional ability. Only 20% of the knees had completely normal physical findings: 11.1% of the knees were rated as excellent; 64.4% were improved; and 24.5% were poor. Dislocators had more frequent poor results. The complication rate was 4.4%. There were no postoperative hemathroses. One patient was considered a surgical failure. The technique yields results comparable with those of open extensor realignment procedures and avoids the complications inherent to lateral release in general. The place for this procedure in patellar instability is well-documented.


Use of Taguchi design for optimization of diesel-oil biodegradation using consortium of Pseudomonas stutzeri, Cellulosimicrobium cellulans, Acinetobacter baumannii and Pseudomonas balearica isolated from tarball in Terengganu Beach, Malaysia.
A consortium of bacteria capable of decomposing oily hydrocarbons was isolated from tarballs on the beaches of Terengganu, Malaysia, and classified as Pseudomonas stutzeri, Cellulosimicrobium cellulans, Acinetobacter baumannii and Pseudomonas balearica. The Taguchi design was used to optimize the biodegradation of diesel using these bacteria as a consortium. The highest biodegradation of diesel-oil in the experimental tests was 93.6%, and the individual n-alkanes decomposed 87.6-97.6% over 30 days. Optimal settings were inoculum size of 2.5 mL (1.248 OD600nm); 12% (v/v) the initial diesel-oil in a minimal salt medium of pH 7.0, 30.0 gL-1 NaCl and 2.0 gL-1 NH4NO3 concentration, incubated at 42 °C temperature and 150 rpm agitation speed. Parameters significantly improved diesel-oil removal by consortium as shown by the model determination coefficient (R2 = 90.89%; P < 0.001) with a synergistic effect of agitation speed significantly contributing 81.03%. Taguchi design determined the optimal settings for the parameters under study, which significantly improved diesel-oil removal by consortium. This can be used to design a novel bioremediation strategy that can achieve optimal decontamination of oil pollution in a shorter time. The online version contains supplementary material available at 10.1007/s40201-022-00812-3.


[Prevalence of neurocognitive disorders in a rural area of Argentina]
To carry out a cognitive screening to detect cases of Neurocognitive Disorders (NCD) 60 and over years adults and estimate its prevalence in the eastern area of Tucumán. A neuropsychological assessment was carried out. Groups were formed according to the presence and severity of NCD. 257 subjects participated in the study (X = 69.9 years, SD = 7.2; 60.7% of female gender). The prevalence of neurocognitive disorders was estimated at 51.17% with 90% confidence and a precision (d) of 4%. The prevalence exceeded the estimation for Argentina. From the tests it was observed that the lower the educational level and the older the age, the risk of developing neurocognitive disorders would increase. This work demonstrated the ability to develop large-scale epidemiological studies in public health, articulating the activity of the different healthcare centers, given the lack of studies about the matter in our country.


Recent advances in the development of inhibitors targeting KRAS-G12C and its related pathways.
The RAS gene, also known as the mouse sarcoma virus, includes three genes (KRAS, HRAS, and NRAS) that are associated with human tumors. Among them, KRAS has the highest incidence of mutations in cancer, accounting for around 80% of cases. At the molecular level, the RAS gene plays a regulatory role in transcription and translation, while at the cellular level, it affects cell proliferation and migration, making it crucial for cancer development. In 2021, the FDA approved AMG510, the first direct inhibitor targeting the KRAS-G12C mutation, which has shown tumor regression, prolonged survival, and low off-target activity. However, with the increase of drug resistance, a single inhibitor is no longer sufficient to achieve the desired effect on tumors. Therefore, a large number of other highly efficient inhibitors are being developed at different stages. This article provides an overview of the mechanism of action targeting KRAS-G12C in the KRASGTP-KRASGDP cycle pathway, as well as the structure-activity relationship, structure optimization, and biological activity effects of inhibitors that target the upstream and downstream pathways, or combination therapy.


The role of tumor necrosis factor-alpha in stress-induced worsening of cerebral ischemia in rats.
Whereas stress is known to be one of the risk factors of stroke, few experimental studies have examined the possible mechanisms by which stress may affect stroke outcome. Most of the knowledge on the effects of stress on cerebrovascular disease in humans is restricted to catecholamines and glucocorticoids effects on blood pressure and/or development of atherosclerosis. By using an experimental paradigm consisting of the exposure of Fischer rats to repeated immobilization sessions (1 h daily during seven consecutive days) prior to permanent middle cerebral artery occlusion (MCAO), we have found that stress worsens behavioral outcome and increases infarct size after MCAO. These changes occur concomitantly to an increase in inducible nitric oxide synthase (iNOS) expression and to the accumulation of lipid peroxidation markers in brain tissue. The possible regulatory role of TNFalpha was studied by looking at the mechanisms of release of this cytokine as well as to the expression of its receptors (TNFR1 and 2). The results of the present study suggest an increase in TNFalpha expression and release after stress, as well as an increase in the expression of TNFR1. Pharmacological blockade of TNFalpha with anti-TNFalpha led to a decrease in the infarct size as well as in the oxidative/nitrosative biochemical parameters seen after ischemia. In summary, our results indicate that TNFalpha accounts, at least partly, for the worsening of MCAO consequences in brain of rats exposed to stress. Furthermore, the data presented here provide evidence that stress can increase brain ischemic damage and support a possible protective effect of treatment of stressful situations before and during the development of the brain ischemia.


No SEVI-mediated enhancement of rectal HIV-1 transmission of HIV-1 in two humanized mouse cohorts.
Amyloid fibrils from semen-derived peptide (SEVI) enhance HIV-1 infectivity in vitro but the ability of SEVI to mediate enhancement of HIV infection in vivo has not been tested. In this study we used immunodeficient mice reconstituted with human immune systems to test for in vivo enhancement of HIV-1 transmission. This mouse model supports mucosal transmission of HIV-1 via the intrarectal route leading to productive infection. In separate experiments with humanized mouse cohorts reconstituted with two different donor immune systems, high dose HIV-1JR-CSF that had been incubated with SEVI amyloid fibrils at physiologically relevant concentrations did not show an increased incidence of infection compared to controls. In addition, SEVI failed to enhance rectal transmission with a reduced concentration of HIV-1. Although we confirmed potent SEVI-mediated enhancement of HIV infectivity in vitro, this model showed no evidence that it plays a role in the much more complex situation of in vivo transmission.


A controlled study of ischemic stroke risk in migraine patients.
To help resolve the uncertain relationship between migraine headache and ischemic stoke, we performed a hospital-based, case-control study. Eighty-nine cases ages 15-65 with a head computed tomography (CT) scan supported diagnosis of ischemic stroke were matched to 178 control subjects. Using information obtained by telephone interview, the patients were placed into three categories according to explicit criteria: classic migraine; common migraine; and no migraine headache. Overall, the association between migraine and ischemic stroke is significantly increased only in patients with classic migraine [odds ratio (OR) = 2.6, 95% confidence interval (CI) 1.1-6.6]. In addition, classic migraine does not appear to increase ischemic stroke when hypertension, diabetes or smoking are present; however, when these other risk factors are absent, classic migraine is strongly and significantly associated with the risk of ischemic stroke [no hypertension, OR = 5.7 (95% CI 1.6-20.2); no diabetes, OR = 3.4 (95% CI 1.2-9.3); non-smoker OR = 4.3 (95% CI 1.2-15.0)]. Since none of the migraine patients in our study had a migrainous stroke, an underlying disorder other than prolonged vasospasm may be responsible for the observed increased risk. Our data suggest that classic migraine may be a marker for patients at increased risk for ischemic stroke unrelated to a migraine attack.


Ties between Stress and Lipid Droplets Pre-date Seeds.
Seeds were a key evolutionary innovation. These durable structures provide a concerted solution to two challenges on land: dispersal and stress. Lipid droplets (LDs) that act as nutrient storage reservoirs are one of the main cell-biological reasons for seed endurance. Although LDs are key structures in spermatophytes and are especially abundant in seeds, they are found across plants and algae, and increase during stress. Further, the proteins that underpin their form and function often have deep homologs. We propose an evolutionary scenario in which (i) the generation of LDs arose as a mechanism to mediate general drought and desiccation resilience, and (ii) the required protein framework was co-opted by spermatophytes for a seed-specific program.


Calmodulin-stimulated dephosphorylation of p-nitrophenyl phosphate and free phosphotyrosine by calcineurin.
Calcineurin, a calmodulin-binding protein from brain, has been shown to possess a metal ion-dependent and calmodulin-stimulated phosphatase activity towards phosphorylase kinase and inhibitor-1 (Stewart, A. A., Ingebritsen, T. S., Manalan, A., Klee, C. B., and Cohen, P. (1982) FEBS Lett. 137, 80-84). In this report, we show that calcineurin can also dephosphorylate p-nitrophenyl phosphate and free phosphotyrosine. However, calcineurin does not show significant activity towards phosphothreonine, phosphoserine, or several other low molecular weight phosphocompounds tested. As we have found with phosphorylase kinase and phosphocasein, the dephosphorylation of p-nitrophenyl phosphate and free phosphotyrosine is stimulated by calmodulin and is metal ion-dependent with the order of efficiency being Mn2+ much greater than Co2+ greater than Ca2+. The dephosphorylation of these substrates appears to be an intrinsic property of calcineurin and is not due to contamination by alkaline phosphatases since the pH optimum for calcineurin activity occurs at a neutral rather than an alkaline pH. The dephosphorylation of p-nitrophenyl phosphate provides an easy, rapid, and accurate method for the quantification of calcineurin activity as well as permitting insight into reaction kinetics. The dephosphorylation of free phosphotyrosine by calcineurin suggests that this compound may be a physiological substrate of calcineurin.


The size of lipid rafts: an atomic force microscopy study of ganglioside GM1 domains in sphingomyelin/DOPC/cholesterol membranes.
Atomic force microscopy has been used to study the distribution of ganglioside GM1 in model membranes composed of ternary lipid mixtures that mimic the composition of lipid rafts. The results demonstrate that addition of 1% GM1 to 1:1:1 sphingomyelin/dioleoylphosphatidylcholine/cholesterol monolayers leads to the formation of small ganglioside-rich microdomains (40-100 nm in size) that are localized preferentially in the more ordered sphingomyelin/cholesterol-rich phase. With 5% GM1 some GM1 microdomains are also detected in the dioleoylphosphatidylcholine-rich phase. A similar preferential localization of GM1 in the ordered phase is observed for bilayers with the same ternary lipid mixture in the upper leaflet. The small GM1-rich domains observed in these experiments are similar to the sizes for lipid rafts in natural membranes but considerably smaller than the ordered bilayer domains that have been shown to be enriched in GM1 in recent fluorescence microscopy studies of lipid bilayers. The combined data from a number of studies of model membranes indicate that lateral organization occurs on a variety of length scales and mimics many of the properties of natural membranes.


Structure and function of the bacterial communities during rhizoremediation of hexachlorobenzene in constructed wetlands.
Vertical flow constructed wetlands (VF CWs) are considered to be effective for treating organic pollutants. The rhizosphere of macrophytes such as Phragmites sp., Typha sp. serves as an active and dynamic zone for the microbial degradation of organic pollutants. However, it is still not clear how soil bacterial communities respond to macrophytes and pollutants during the process. For this purpose, the seedlings of Phragmites australis and Typha angustifolia were planted respectively in the VF CWs added with HCB at a dose of 2 mg/kg. During 96 days of cultivation, we monitored hexachlorobenzene (HCB) removal efficiency by GC/MS and the structure of the rhizosphere bacterial communities in the different VF CWs by denaturing gradient gel electrophoresis (DGGE), and constructed bacterial clone library based on PCR-amplified 16S rRNA gene. As expected, the rhizosphere bacterial communities also remained insensitive to HCB exposure in the wetland soil. The diversity of these microbes presented two stages, from the varied up and down to equilibrium in the entire experimental period. Molecular analysis revealed that the phylum Firmicutes dominated over the bacterial communities. The genera that increased under HCB stress included the well-known HCB-degrading bacteria (Pseudomonas sp. and Alcaligenes sp.) and other common bacteria found in contaminated soil but with lesser known practical functions (Burkholderia sp., Lysinibacillus fusiformis, and Bacillus cereus). Furthermore, there was a certain variance in the relative abundances of the bacterial phyla and HCB removal efficiency among different VF CW treatments. The degradation of HCB in T. angustifolia microcosms was faster than that in P. australis and unvegetated wetlands, and the highest bacterial diversity and richness was found in the VF CWs comprising T. angustifolia.


Health and Well-Being Outcomes of Adolescents Conceived Through In Vitro Fertilization and Intracytoplasmic Sperm Injection.
What is the perception of health and well-being of adolescents from an assisted reproductive technology (ART) cohort? We conducted a survey, from September 2015 to June 2016, through self-completion questionnaires, on 487 singleton or twin ART-conceived 11- to 15-year-old adolescents, followed up since 1994, as part of an ART cohort. Collected data concerned perinatal characteristics, health indicators and perception, eating habits, behavior, and living standards. A total of 60.6% of the questionnaires were returned and could therefore be analyzed. This concerned 295 adolescents who were representative of the 788 remaining adolescents of our cohort, in terms of type of ART, maternal and perinatal characteristics, but not gender (sex ratio = 0.77). Overall, 15.3% reported chronic diseases, and only 13.3% of them considered that their chronic disease had an impact on their school life. Moreover, 94.2% of adolescents perceived that their health was "excellent" or "good"; 97.3% adolescents had normal weight or were underweight; onset of menstruation was 12 years old (± 1) for girls, age usually reported for puberty in girls; 51.9% declared having regular physical activity, boys more frequently than girls. Moreover, 70.6% of the boys had a sedentary behavior compared to 44.8% of the girls. A total of 73.5% of the adolescents were stressed at school, but school demand was considered high only in 12.2% of cases. Finally, 90% declared to have high life satisfaction. Overall, ART does not appear to have particular effect on the health indicators and behavior of adolescents who participated in the survey except for higher family affluence scale.


Inhibition of surgically induced ischemia/reperfusion injury by oxygen free radical scavengers.
Recent experimental work implicates oxygen free radicals as mediators of ischemia/reperfusion injury. A simple cardioplegic solution was designed to scavenge superoxide anion and hydroxyl free radical with superoxide dismutase (10 micrograms/ml), mannitol (325 mOsm/L), and KCl 25 mEq/L (FRS). Hemodynamic and subcellular functions were studied in seven in situ canine models of hypothermic global ischemia receiving FRS, compared to a group (n = 7) receiving hyperosmolar, hyperkalemic saline (HSK) and to a standard model of topical hypothermia (TH, n = 5). Following 60 minutes of ischemia (10 degrees to 15 degrees C), hearts were reperfused and rewarmed. After 45 minutes of reperfusion, left ventricular peak systolic pressure (LVPSP), developed pressure (LVDP), dP/dt max, -dP/dt max, compliance, and elastic stiffness constant (K) were improved in the FRS group and not significantly different from control. Sarcoplasmic reticulum (SR) calcium transport in the FRS group was significantly improved (control = 1.077 +/- 0.022, TH = 0.754 +/- 0.018, HSK = 0.725 +/- 0.05, and FRS = 0.966 +/- 0.05 mumol/mg-min). Calcium adenosine triphosphatase (ATPase) activity did not differ significantly from control at pH 7.0. In this model of hypothermic global ischemia and reperfusion, free radical scavengers provide significant protection of mechanical and subcellular function. These findings support the hypothesis that oxygen free radicals are important mediators of myocardial ischemia and reperfusion injury.


GABA triggers a Cl- efflux from cultured mouse oligodendrocytes.
gamma-Aminobutyric acid (GABA) has been shown to depolarize the membranes of astrocytes and oligodendrocytes taken from different tissues and species. The mechanism mediating this depolarization was identified, in cultured rat brain astrocytes, as an activation of GABA receptor-linked Cl- channels. A subpopulation of cultured oligodendrocytes from mouse spinal cord also responded to GABA with a membrane depolarization. In the present study we demonstrate that, in oligodendrocytes, the depolarization was accompanied by a decrease in intracellular Cl- activity [( Cl-]i) as measured with ion-selective microelectrodes. At rest, [Cl-]i was elevated above the passive distribution, and upon application of GABA, [Cl-]i decreased towards the level of passive distribution. Furosemide blocked the Cl- inward carrier which led to a passive Cl- distribution; in the presence of furosemide, GABA no longer elicited a membrane depolarization or a change in [Cl-]i. We conclude that oligodendrocytes, which were depolarized by GABA, expressed GABA-activated Cl- channels. Oligodendrocytes which were unresponsive to GABA demonstrated a non-passive Cl- distribution indicating that they did express inward-directed Cl- carriers, but no GABA-activated Cl- channels.


Proximal junctional fractures after long-segment instrumented fusion: comparisons between upper instrumented vertebrae and upper instrumented vertebrae + 1.
Proximal junctional failure (PJF) is a well-known complication after long-segment (at least 4 vertebral levels) instrumented fusion. The etiologies of PJF include degenerative processes or are fracture induced. The fracture type of PJF includes vertebral fractures developed at the upper instrumented vertebrae (UIV) or UIV + 1. The purpose of this study was to investigate clinical and radiographic features of these two subtypes of PJF and to analyze risk factors in these patients. In total, forty-two patients with PJF who underwent revision surgery were included. Twenty patients suffered fractures at the UIV, and the other 22 cases had fractures at UIV + 1. The weighted Charlson Comorbidity Index (CCI) and bone mineral density (BMD) T scores for these patients were recorded. Surgery-related data of index surgery and complications were collected. Radiographic parameters including pelvic tilt (PT), pelvic incidence (PI), sagittal vertical axis (SVA), lumbar lordosis (LL), and PI-LL were recorded in both groups before and after the revision surgery. Both groups had severe osteoporosis and comorbidities. The interval between the index surgery and revision surgery was shorter in the UIV group than in the UIV + 1 group (8.2 months vs. 35.9 months; p < 0.001). The analysis for radiographic parameters in UIV and UIV + 1 group demonstrated no significant change before and after the revision surgery. However, the preoperative radiographic analysis showed a larger PT (31.5° vs. 23.2°, p = 0.013), PI (53.7° vs. 45.3°, p = 0.035), and SVA (78.6° vs. 59.4°, p = 0.024) in the UIV group compared to the UIV + 1 group. The postoperative radiographic analysis showed a larger PI-LL (27.8° vs. 18.1°, p = 0.016) in the UIV group compared to the UIV + 1 group. PJF in the UIV group tends to occur earlier than in the UIV + 1 group. Moreover, more severe global sagittal imbalances were found in the UIV group than in UIV + 1 group.


Geriatric trauma: a case study.
Major advances in health care have made it possible for a greater number of people to live to advanced age and thereby be exposed to the same risk of injury as the younger segment of the population. Elderly trauma victims, however, possess unique needs that must be addressed. Comorbidity, the aging process, and its relationship to the response to injury, as well as ethical and moral dilemmas such as "do not resuscitate" decisions and cost of care, need to be investigated. Although advanced age clearly predisposes one to an increase in mortality, mortality has also been correlated with complications that develop during the hospital stay. Trauma, especially involving the elderly, is a rich area for nursing research, and a refined knowledge base contributes to improving the quality of trauma care.


Autoregulation remains intact during stable xenon inhalation in the baboon.
To test the possible effect of 32% end-tidal Xe concentration upon autoregulation, 5 baboons, Papio anubis/cynocephalus, were anesthetized/paralyzed with propranolol 0.02, diazepam 0.1, morphine sulfate 0.1, and pancuronium 0.2 (mg/(h.kg)). The animals were subjected to a servocontrolled blood infusion-withdrawal program to control central aortic blood pressure (CAP). PaCO2 was held to 30 to 35 torr, with individual variation less than 3 torr by control of ventilation and by including CO2 in the Xe/O2 mixture. Three to six CBF measurements were made in each subject over the above range. In four animals the CAP was varied between 18 and 150 torr, with corresponding CBF measurements. The CAP range was extended to 196 torr in the 5th animal by IV administration of phenylephrine. Significant lowering of global blood flow did not occur above 40 torr mean CAP. While regulated flow persists to about 150 torr at the high end, there is a breakaway between 150 and 190 torr where flow increased 90%. A 4th order polynomial fit of the data has the characteristic appearance of the familiar autoregulation curve. We conclude that autoregulation is preserved even in the presence of FIXe of 32% in the breathing mixture.


Design, synthesis and bioevaluation of new vanillin hybrid as multitarget inhibitor of α-glucosidase, α-amylase, PTP-1B and DPP4 for the treatment of type-II diabetes.
Diabetes mellitus (DM) is a real challenge to the recent era and is one of the major diseases for initiating life-threatening disorders. In current research, a compound was designed by combining vanillin, thiazolidinedione and morpholine. The goal of our designed work is to demonstrate the ability of our design compound (9) to modulate more than one target responsible for hyperglycemia at the same time. The synthesized compound was able to show good to moderate inhibition potential against α-glucosidase, α-amylase and protein tyrosine phosphatase 1B. However, it exhibited excellent in-vitro inhibition of Dipeptidyl peptidase-4 (DPP-4) with IC50 value of 0.09 µM. Antioxidant activity by using DPPH assay also showed its good antioxidant potential. In in-vivo experiments, the compound 9 was proved to be safe in experimental mice. The activity profile of the compound was observed for 21 days which showed that the compound was also effective in experimental mice. Binding orientations and Interactions with key amino acid residues of the selected targets were also studied by using docking studies. Overall, we were successful in synthesizing multitarget preclinical therapeutic by combining three pharmacophoric moieties into a single chemical entity that can modulate more than one target at the same time.


[A study of anterior segment structures in primary infantile glaucoma eyes by ultrasound biomicroscopy].
To investigate anterior segment structures in primary infantile glaucoma (PIG) eyes by ultrasound biomicroscopy (UBM) in vivo. UBM high frequency transducer (50 mHz) was used to measure and observe the anterior segment of 38 PIG cases (58 eyes). No matter the severity of the disease or the age at onset, the most significant characteristics of the diseased eyes are relative positional changes between scleral spur and angle apex. In three forth of the eyes, the scleral spur lay in the lateral or posterior-lateral site of the angle apex and in one forth of the eyes the site of the tip of scleral spur was parallel with the iris root insertion. The thickness and length of ciliary processes in the eyes of PIG were greater than that of the normal infantile eyes. The ciliary processes were anteriorly displaced, pulled towards the lens, and part of them got into contact with the iris. The relative positional changes between scleral spur and angle apex in diseased eyes indicate that the poor development of scleral spur and the iris anterior insertion are the basic pathogenesis in PIG.


Individual and binary exposure of embryonic zebrafish (Danio rerio) to single-walled and multi-walled carbon nanotubes in the absence and presence of dissolved organic matter.
The available toxicological information was inadequate to assess the potential ecological risk of a mixture of different nanostructured carbon nanotubes (CNTs) to aquatic organisms, especially for the co-existence of mixed CNTs with dissolved organic matter (DOM). Herein, we investigated individual and binary exposure of zebrafish (Danio rerio) embryos to single-walled (SWCNTs) and multi-walled carbon nanotubes (MWCNTs) in the absence and presence of DOM. Results indicated that embryonic chorions were more resistant to mixed-type CNTs than to single-type CNTs, yet the addition of DOM decreased this resistance. The mixed-type CNTs increased the antioxidant capacity of zebrafish embryos by increasing superoxide dismutase activity in comparison to the single-type CNTs. Furthermore, the mixed-type CNTs caused oxidative damage to the zebrafish embryos, characterized by an increase in malondialdehyde level. Nevertheless, the activation of the antioxidant defense system was modulated by the presence of DOM. Transcriptome sequencing analysis showed that the number of unique genes (UGs) and differentially expressed genes (DEGs) between the mixed-type CNTs and control groups was significantly enhanced compared to the single-type CNTs. DOM increased the number of UGs and up-regulated DEGs, but decreased the number of down-regulated DEGs. GO classification analysis revealed that the mixed-type CNTs mainly altered the cellular component process of single-type CNTs to induce joint effects. DOM generally enhanced the GO enrichment of DEGs in D. rerio embryos exposed to the mixed-type CNTs during the biological process. KEGG pathway enrichment analysis for the mixed-type CNTs showed enrichment of DEGs encoding ether lipid metabolism, glycerophospholipid metabolism, glycerolipid metabolism, citrate cycle, and biosynthesis of nucleotide sugars. However, DOM allowed more specific KEGG pathways towards the mixed-type CNTs to be identified. Despite the mixed-type CNTs exhibiting differential expression of functional genes compared to the control and single-type CNTs, DOM could regulate the expression of these functional genes associated with oxidative stress response, carbohydrate metabolism, endoplasmic reticulum stress, neuroendocrine, osmotic stress, and DNA damage and repair. Our study thus paves a solid way for exploring the molecular mechanism of aquatic toxicity of multiple nanomaterials under field-relevant conditions.


[The research of Valeriana amurensis seed germination characteristics].
To study the effect of different treatments on the Valeriana amurensis seed germination rate. Used different chemical reagents and seed soakings on the routine germination test and the orthogonal test of the Valeriana amurensis seed, calculated the germination rate under different germination condition. Valeriana amurensis treated with different chemical reagends had different germination rate. The suitable immersion time could enhance Valeriana amurensis seed germination rate. Different treatment time, different disposal temperature, different germination temperature would have an impact on the Valeriana amurensis seed germination rate. In order to raise the Valeriana amurensis seed germination rate, use appropriate treatment on the seed before plant seeds; The seed growing must under suitable time and temperature.


A new presynchronization system (Double-Ovsynch) increases fertility at first postpartum timed AI in lactating dairy cows.
This study evaluated a novel presynchronization method, using Ovsynch prior to the Ovsynch-timed AI protocol (Double-Ovsynch) compared to Presynch-Ovsynch. Lactating Holstein (n=337) cows, were assigned to two treatment groups: (1) Presynch (n=180), two injections of PGF 14 d apart, followed by the Ovsynch-timed AI protocol 12 d later; (2) Double-Ovsynch (n=157), received GnRH, PGF 7 d later, and GnRH 3 d later, followed by the Ovsynch-timed AI protocol 7 d later. All cows received the same Ovsynch-timed AI protocol: GnRH (G1) at 68+/-3 DIM (mean+/-SEM), PGF 7 d later, GnRH (G2) 56h after PGF, and AI 16 to 20h later. Pregnancy was diagnosed 39-45 d after timed AI. Double-Ovsynch increased the pregnancies per AI (P/AI) compared to Presynch-Ovsynch (49.7% vs 41.7%, P=0.03). Surprisingly, Double-Ovsynch increased P/AI only in primiparous (65.2% vs 45.2%; P=0.02) and not multiparous (37.5% vs 39.3%) cows. In a subset of 87 cows, ovarian ultrasonography and progesterone (P4) measurements were performed at G1 and 7 d later. Double-Ovsynch decreased the percentage of cows with low P4 (<1ng/mL) at G1 (9.4% vs 33.3%) and increased the percentage of cows with high P4 (> or =3ng/mL) at PGF (78.1% vs 52.3%). Thus, presynchronization of cows with Double-Ovsynch increased fertility in primiparous cows compared to a standard Presynch protocol, perhaps due to induction of ovulation in non-cycling cows and improved synchronization of cycling cows. Future studies are needed, with a larger number of cows, to further test the hypothesis of higher fertility with Double-Ovsynch, and to elucidate the physiological mechanisms that underlie apparent changes in fertility with this protocol.


Influence of the humidification device during acute respiratory distress syndrome.
To evaluate the effects of the humidification device on respiratory, hemodynamic and gas exchange parameters in acute respiratory distress syndrome (ARDS) patients. A prospective open study. A medical intensive care unit of a university hospital. Acute respiratory distress syndrome patients, with hypercapnia (PaCO(2)>60 mmHg). A progressive reduction of the humidification system dead space (DSh). The following five conditions were tested sequentially: (1). heat and moisture exchanger (internal volume=95 ml) with a tracheal closed-suction system (internal volume=25 ml; total DSh=120 ml), (2). heat and moisture exchanger (internal volume=45 ml) with the closed-suction system (DSh=70 ml), (3). heat and moisture exchanger (internal volume=25 ml) with the closed-suction system (DSh=50 ml), (4). heated humidifier with the closed-suction system (DSh=25 ml) and (5). heated humidifier alone (DSh=0 ml). Recordings were performed at baseline and every 30 min after each artificial dead-space reduction. All ventilatory settings remained constant during the measurement periods. Ten ARDS patients were included. A significant PaCO(2) decrease was observed at each humidification system dead-space reduction, compared to baseline: PaCO(2 )=80.3+/-20 mmHg at DSh(120) compared to PaCO(2 )=63.6+/-13 mmHg at DSh(0) ( p<0.05). No changes were observed for hemodynamic and ventilatory parameters between the different humidification devices. Artificial airway dead-space reduction allows a significant PaCO(2) reduction. Independently of any respiratory mechanical changes, this very simple maneuver may be of importance when low tidal volume ventilation is used in ARDS patients, and when PaCO(2) lowering is warranted.


Middle third femoral fractures treated with medullary nailing or AO compression plates.
Fifty-eight medullary nailings and 46 internal fixations with AO plates were performed on fractures of the middle third of the femur. The complication rate was 21-2%, infections accounting for 7-7% and implant failures for another 7-7%. Critical descriptions of the failures are given, 6 of 8 implant failures being biomechanical. Follow-up results were excellent or satisfactory in 95% of cases in both groups. At follow-up after 3 1/2 years, there was no difference in results between the two methods of treatment.


Bicarbonate is required for the peroxidase function of Cu, Zn-superoxide dismutase at physiological pH.
Cu,Zn-superoxide dismutase (SOD1) acts as a peroxidase in the presence of H2O2 at high pH (pH > 9). The high pH species of H2O2, HO2-, was previously implicated as the reactive species. However, recent EPR studies of the enzyme performed in the physiological pH range 7.4-7.6 with the spin trap 5,5'-dimethyl-1-pyrolline-N-oxide attributed the intense EPR signal of 5, 5'-dimethyl-1-pyrolline-N-oxide-OH obtained from SOD1 and H2O2 to the peroxidase activity of the enzyme. The present study establishes that this intense signal is obtained only in the presence of bicarbonate. To explore the critical role of HCO3-, a comprehensive EPR investigation of the radical production and redox state of the active site copper was performed. The results indicate that HCO3- competes with other anions for the anion-binding site of SOD1 (Arg141) but does not bind directly to the copper. Structurally different anions that bind to Arg141 did not stimulate, but rather blocked, peroxidase function, ruling out an effect due to mere anion binding. However, the structurally similar anions HSeO3- and HSO3- mimic HCO3- in stimulating peroxidase function. These data suggest that HCO3- bound to Arg141 anchors the neutral H2O2 molecule at the active site copper, enabling its redox cleavage. Thus, SOD1 acquires peroxidase activity at physiological pH only in the presence of HCO3- or structurally similar anions. Alterations in pH that shift the HCO3-/CO2 equilibrium as occur in disease processes such as ischemia, sepsis, or shock would modulate the peroxidase function of SOD1.