Computer Simulation and Field Experiment for Downlink Multiuser MIMO in Mobile WiMAX System.
The transmission performance for a downlink mobile WiMAX system with multiuser multiple-input multiple-output (MU-MIMO) systems in a computer simulation and field experiment is described. In computer simulation, a MU-MIMO transmission system can be realized by using the block diagonalization (BD) algorithm, and each user can receive signals without any signal interference from other users. The bit error rate (BER) performance and channel capacity in accordance with modulation schemes and the number of streams were simulated in a spatially correlated multipath fading environment. Furthermore, we propose a method for evaluating the transmission performance for this downlink mobile WiMAX system in this environment by using the computer simulation. In the field experiment, the received power and downlink throughput in the UDP layer were measured on an experimental mobile WiMAX system developed in Azumino City in Japan. In comparison with the simulated and experimented results, the measured maximum throughput performance in the downlink had almost the same performance as the simulated throughput. It was confirmed that the experimental mobile WiMAX system for MU-MIMO transmission successfully increased the total channel capacity of the system.


Histopathological effects of dietary Fusarium graminearum on rat duodenum.
Microscopic pathology of duodenum in rats exposed to Fusarium graminearum, a fungus infecting small-grain cereals, was investigated. Intestinal haemorrhage was observed macroscopically in one of the rats. Light microscopy demonstrated detachments between the surface epithelium and the lamina propria and severe interstitial oedema in the lamina propria in the test group. Electron microscopy identified epithelial absorptive cells with highly expanded endoplasmic reticulum tubules, abundant cytoplasmic vesicles containing electronlucent materials, swollen mitochondria with spongiform appearance, and prominent cellular swelling. Other observations included opening of junctional complexes between epithelial cells lining the duodenum, highly enlarged intercellular spaces in duodenal epithelium, and numerous eosinophilic granulocytes and mast cells in the lamina propria. These findings indicate that dietary F. graminearum causes epithelial cell and connective tissue damage in rat duodenum. This is the first histopathological study showing that F. graminearum ingestion is associated with duodenal damage.


Acute dyslipoproteinemia induced by interleukin-2: lecithin:cholesteryl acyltransferase, lipoprotein lipase, and hepatic lipase deficiencies.
Recombinant human interleukin-2 (rIL-2) is used to treat refractory cancers. During such treatment, patients develop severe hypocholesterolemia along with striking alterations in the concentration and composition of the circulating lipoproteins. The present study was undertaken to gather information about the pathogenesis of these abnormalities. Patients were studied before-, during- and after a 5-day course of high dose i.v. rIL-2. Whole plasma cholesterol was markedly reduced by rIL-2 administration (52%; P < 0.001), whereas the triglyceride concentration did not change. Thus, the lipoproteins became triglyceride enriched (P = 0.004). Low density lipoprotein cholesterol, apolipoprotein B (apoB), high density lipoprotein cholesterol, and apoA-I concentrations all decreased. Esterified cholesterol levels were markedly reduced. Total plasma apoE increased markedly, and two kinds of abnormal particles appeared: 1) beta-migrating, very low density lipoproteins; and 2) discoidal, apoE- and phospholipid-containing particles with abnormal density and electrophoretic mobility. The activities of two lipoprotein triglyceride hydrolases, lipoprotein lipase and hepatic lipase, fell significantly during treatment and returned promptly to pretreatment levels after rIL-2 was discontinued. Lecithin:cholesteryl acyltransferase (LCAT) activity also decreased significantly (64%) during treatment, but in contrast to the lipases, remained low for at least 5 days after the last dose of rIL-2 (P < 0.001). High dose i.v. rIL-2 induces severe dyslipidemia with deficiencies of both postheparin lipases and acute LCAT deficiency. Most, if not all, of the lipoprotein changes observed are explained by the LCAT deficiency that follows IL-2-induced hepatocellular injury and cholestasis.


Implications of the 21-gene recurrence score assay (Oncotype DX) on adjuvant treatment decisions in ER-positive early-stage breast cancer patients: experience of Kuwait Cancer Control Center.
The Oncotype DX is a quantitative assay of the expression of 16 tumor-related genes and 5 reference genes that predicts the potential of adjuvant chemotherapy benefit in estrogen receptor (ER)-positive early breast cancer patients. The study aims to evaluate the impact of Oncotype DX as a tool for adjuvant treatment decision of ER-positive, HER2-negative, N0/N1 early-stage breast cancer patients and to determine which clinicopathological criteria derived the greatest advantage. A hundred patients at a median age of 50 years were included. TNM stage distribution was 34, 63, and 3 patients for stages I, II, and IIIA respectively. Fifty-four patients had luminal A and 46 had luminal B tumors. The recurrence score (RS) results were low, intermediate, and high risk in 54, 34, and 12 patients respectively. Before the test results, adjuvant chemoendocrine therapy (CET) was recommended for 46 patients while 54 were advised for endocrine therapy (ET). After getting the test results, 25 patients received CET (1, 12, and12 patients in the low-, intermediate-, and high-risk groups respectively) and 75 received ET. Treatment change was documented in 37 patients (8 patients from ET to CET and 29 from CET to ET; p = 0.001, McNemar test). Treatment change was significant among patients ≤ 50 years, luminal B tumors, stage II and IIIA disease, and node-positive disease. Oncotype DX testing resulted in significant changes in the adjuvant treatment decisions in ER-positive, HER2-negative early breast cancer particularly in the case of young, luminal B, N1, and stage II-IIIA disease.


Encoded Silicon-Chip-Based Platform for Combinatorial Synthesis and Screening.
Solid-supported chemical libraries have proven useful for the rapid and cost-effective discovery of bioactive compounds. However, traditional on-bead screening involves time-intensive chemical characterization of hit compounds and high false positive rates. Herein, we report a new platform for encoded chemical synthesis and solid-supported screening using p-Chips, microsized silicon microtransponders capable of storing and emitting unique numerical identifiers (IDs). By encoding the structures of library members using p-Chip IDs, we can track compound identities throughout both split-and-pool synthesis and protein binding assays without destructive cleavage. Thanks to the numerical IDs, our p-Chip platform can provide binding constants for library members simply by stripping and reprobing with different protein concentrations, unlike traditional on-bead assays. To showcase these features, we synthesized a library of 108 hemagglutinin (HA) peptide variants using split-and-pool approach, and measured EC50s for each variant directly on p-Chips. On-chip EC50s obtained from these studies showed excellent correlation (80%) with those obtained using traditional ELISA methods. Our screen also yielded a false positive rate of 14%, markedly superior to that reported for conventional bead-based binding studies (66-96%).1-9 On the basis of these results, we believe the p-Chip platform has the potential to improve the effectiveness of solid-supported high-throughput screening by a significant margin.


Dopaminergic dysbalance in distinct basal ganglia neurocircuits: implications for the pathophysiology of Parkinson's disease, schizophrenia and attention deficit hyperactivity disorder.
The basal ganglia form a forebrain system that collects signals from a large part of the neocortex, redistributes these cortical inputs both with respect to one another and with respect to inputs from the limbic system, and then focuses the inputs of this redistributed, integrated signals into particular regions of the frontal lobes and brainstem involved in aspects of motor planning and motor memory. Movement disorders associated with basal ganglia dysfunction comprise a spectrum of abnormalities that range from the hypokinetic disorder (from which Parkinson's disease, PD, is the best-known-example) at one extreme to the hyperkinetic disorder (exemplified by Huntington's disease and hemiballism) at the other. In addition to disorders of movement, major mental disorders including schizophrenic-like states and attention deficit hyperactivity disorder (ADHD) have been linked to abnormalities in the basal ganglia and their allied nuclei. In this paper we discuss recent evidence indicating that a dopamine-induced dysbalance of basal ganglia neurocircuitries may be an important pathophysiological component in PD, schizophrenia and ADHD. According to our model, the deprivation of dopaminergic nigro-striatal input, as in PD, reduces the positive feedback via the direct system, and increases the negative feedback via the indirect system. The critical consequences are an overactivity of the basal ganglia output sites with the resulting inhibition of thalamo-cortical drive. In schizophrenia the serious cognitive deficits might be partly a result of a hyperactivity of the inhibitory dopamine D(2) transmission system. Through this dysinhibition, the thalamus exhibits hyperactivity that overstimulates the cortex resulting in dysfunctions of perception, attention, stimulus distinction, information processing and affective regulation (inducing hallucinations and delusions) and motor disabilities. Recent studies have strongly suggested that a disturbance of the dopaminergic system is also involved in the pathophysiology of ADHD. The most convincing evidence comes from the demonstration of the efficacy of psychostimulants such as the dopamine transporter (DAT) blocker methylphenidate in the symptomatic treatment of ADHD. Genetic studies have shown an association between ADHD and genes involved in dopaminergic neurotransmission (for example the dopamine receptor genes DRD4 and DRD5, and the DAT gene DAT1). DAT knockout mice display a phenotype with increased locomotor activity, which is normalized by psychostimulant treatment. Finally, imaging studies demonstrated an increased density of DAT in the striatum of ADHD patients. Which system is disturbed and whether this system is hyper- or hypoactive is not unambiguously known yet.


All-optical phase-preserving multilevel amplitude regeneration.
The possibility of all-optical phase-preserving amplitude regeneration for star-8QAM is demonstrated using a modified nonlinear optical loop mirror. Experiments show a reduction in amplitude noise on both amplitude levels simultaneously, considering two different types of signal distortions: deterministic low-frequency amplitude modulation and broadband amplitude noise. Furthermore, using this amplitude regeneration, the robustness against nonlinear phase noise from fiber nonlinearity in a transmission line is increased. The scheme suppresses the conversion of amplitude noise to nonlinear phase noise. This is shown for simultaneous amplitude regeneration of the two amplitude states as well as for amplitude regeneration of the high-power states only. If the transmission is limited by nonlinear phase noise, single-level operation at the more critical higher-power state will benefit because of the wider plateau region. Numerical simulations confirm the experimental results.


Neurohumoral and metabolic effects of short-term dietary NaCl restriction in men. Relationship to salt-sensitivity status.
Published observations suggest that not everyone benefits from severe dietary NaCl restriction, since blood pressure responses appear heterogeneous and adverse metabolic effects may occur. We studied the cardiovascular, neurohumoral, and metabolic effects of 7 day periods of 20 v 200 mEq/day NaCl diets in 27 men. Twelve subjects were salt sensitive (SS), defined as mean intraarterial pressure (MAP, mm Hg) during high NaCl greater than or equal to 5% above MAP on low NaCl. Eleven subjects were salt resistant (SR), defined as MAP during the low NaCl phase greater than or equal to MAP during the high NaCl phase. The SR subset had a tendency to greater neurohumoral activity, assessed by changes in mean values for plasma norepinephrine (NE, P = .12) and plasma renin activity (PRA, P less than .001) on the low v high NaCl diet. In SR subjects the low v high NaCl diet also raised mean values for creatinine (P = .03), uric acid (P = .001), and low density cholesterol (LDL-C, P = .03), but not fasting insulin (P = .15). In SS subjects, the low v high NaCl diet did not raise NE (P = .35), although the PRA was greater (P = .002). Among SS subjects, mean values for uric acid (P = .005) and insulin (P = .02) were greater during the low v high NaCl phase, while creatinine (P = .15) and LDL-C (P = .67) were not different. The data suggest that severe, short-term NaCl restriction can be undesirable, especially in SR subjects, since potentially adverse neurohumoral and metabolic changes are not counterbalanced by the benefits of a lower MAP.


[The relationship of quality of life (QOL) with physical fitness, competence and stress response in elderly in Japan].
In order to evaluate the relationship of quality of life (QOL) with physical fitness, competence and stress response in the elderly population in Japan, a cross sectional field survey of elderly subjects was conducted. This survey was taken in Naguri village, Saitama. The data collected included physical fitness, competence, stress response and QOL in addition to demographic variables. As for physical fitness indexes, grip strength (GS), single leg balance with eyes closed (SLB), bar grip ping reaction time (RT), trunk flexion (RF), ten-meter walking time (WT) and vital capacity (VC) were measured. The SF-36 was used for QOL assessment. A total of 120 elderly subjected participated to the survey. There were 42 males (73.5 +/- 5.74 years) and 78 females (74.2 +/- 6.17 years). The associations between physical health parameters in SF-36 and WT were highly significant: physical functioning (beta = -2.96, p < 0.001), role physical (beta = -3.64, p < 0.001), bodily pain (beta = -3.27, p < 0.001) and general health (beta = -3.14, p = 0.001). Psychological stress response had a negative correlation with social functioning (beta = -0.74, p = 0.024), role-emotional (beta = -2.34, p < 0.007) and mental health (beta = -0.97, p = 0.024) as determined by multiple regression analysis. The goodness-of-fit indexes of the structural equation model describing the relationships among physical fitness, competence, stress response and QOL indicated excellent fit to the data with GFI = 0.95 and AGFI = 0.88. Stress response showed relatively stronger influence on QOL than physical fitness or competence. Although there were slight differences in degree of influence, physical fitness, stress response and competence were found to be clearly related to QOL in elderly subjects. To keep good QOL status, it is important to maintain good physical fitness and level of competence and to reduce stress response.


Geometrical and conformational properties of ganglioside GalNAc-GD1a, IV4GalNAcIV3Neu5AcII3Neu5AcGgOse4Cer.
The aggregative properties of GalNAc-GD1a ganglioside, in comparison with those of GD1a, have been investigated and correlated to the intrinsic conformation and mobility of the oligosaccharide chain of the molecules. Micellar parameters in aqueous solution (molecular mass, hydrodynamic radius as well as the surface area at the lipid/water interface and the packing parameter of the monomer inserted in the aggregate) are measured by the laser light-scattering technique. The presence of a further GalNAc residue causes a 22% increase in molecular mass, contrary to expectation. Oligosaccharide moiety three-dimensional structures have been modeled using molecular mechanics and dynamics calculations, based on NOE interactions observed for native gangliosides dissolved in deuterated dimethylsulfoxide or, as mixed micelles with fully deuterated dodecylphosphocholine, in D2O. Compared with GD1a the GalNAc-GD1a is less mobile, thus influencing the surface area, this lower mobility together with the GalNAc-GD1a conformation leads to a larger number of monomers participating in the formation of the micelle. The results further substantiate the model in which the three-dimensional structure and the intrinsic dynamic properties of the oligosaccharide chain affect the geometrical properties of the aggregate.


The determination and characterisation of 2-naphthyloxycarbonyl chloride derivatised biogenic amines in pet foods.
The need to monitor biogenic amines levels is essential for many areas of the food industry for two main reasons: the caustic nature and potential toxicity of these amines, and the potential to use amine levels as markers for freshness and quality in foodstuffs. Optimised analysis conditions used for the determination of biogenic amines derivatised with 2-napthyloxycarbonyl chloride has been applied to different pet food samples to assess the effectiveness of this method for complex sample matrices. Further to this, the use of high-resolution mass spectrometry has enabled the previously unconfirmed derivatised form of seven biogenic amines to be established. The derivatised forms identified include as mono substituted (tryptamine and histamine), bisubstituted (putrescine, cadaverine and tyramine), trisubstituted (spermidine) and tetrasubstituted (spermine). The methodology of biogenic amine determination was performed successfully to a range of pet food products highlighting the applicability to a variety of complex sample matrices.


Physiological skin changes during pregnancy.
Physicians may often mistake normal physiological skin changes in pregnancy for pathologic changes, so being able to recognize the skin manifestations unique to pregnancy is of the utmost importance to avoid unnecessary testing and stress for the obstetric patient. Most physiological skin changes will resolve postpartum, so reassurance and expectant management is indicated in almost all cases.


[Therapeutic effect of massage on denervated skeletal muscle atrophy in rats and its mechanism].
To investigate the therapeutic effects of massage on denervated skeletal muscle atrophy in rats and its mechanism. Forty-eight male SD rats were randomly divided into model group (n=24) and massage group (n=24). Gastrocnemius muscle atrophy model was established by transecting the right tibial nerve of rat. On the second day after operation, the gastrocnemius muscle of the rats in the massage group was given manual intervention and the model group was not intervened. Six rats were sacrificed at the four time points of 0 d, 7 d, 14 d and 21 d. The gastrocnemius of the rats were obtained and measured the wet mass ratio after weighing. Cross-sectional area and diameter of the muscle fiber were measured after HE staining. The relative expressions of miR-23a, Akt, MuRF1 and MAFbx mRNA were tested with qPCR. Compared with 0 d, the wet weight ratio, cross-sectional area and diameter of gastrocnemius muscle showed a progressive decline in the model group and massage group. The wet weight ratio, cross-sectional area and diameter of gastrocnemius muscle in the massage group were higher than those in the model group on 7 d, 14 d and 21 d (P<0.05, P<0.01). Compared with 0 d, the expressions of MuRF1, MAFbx and Akt mRNA were increased first and then were decreased in the model group and massage group. The expression of MuRF1 mRNA in massage group was lower than that in model group on 7 d and 21 d (P<0.05, P<0.01). The expression of MAFbx mRNA in massage group was lower than that in model group on 7 d, 14 d and 21 d (P<0.01, P<0.05, P<0.01). The expression of Akt mRNA in massage group was higher than that in model group on 7 d, 14 d and 21 d (P<0.05, P<0.01). Compared with 0 d, the expression of miR-23a mRNA was increased in the model group and massage group on 21 d, and the expression of miR-23a mRNA in massage group was higher than that in model group (P< 0.05). Massage can delay the atrophy of denervated skeletal muscle. The mechanism may be related to up-regulation of the expression of miR-23a and Akt mRNA, down-regulation of the expressions of MuRF1 and MAFbx mRNA, inhibition of protein degradation rate, and reduction of skeletal muscle protein degradation.


Impact of portal versus systemic venous drainage on acute rejection of simultaneous pancreas-kidney transplantation in pig.
The immunological benefits of portal venous drainage (PVD) in pancreas transplantation remain debated clinically. We established simultaneous pancreas-kidney transplantation (SPK) models with portal venous drainage and systemic venous drainage to compare the impact of venous drainage site on acute rejection in pig. Forty-eight nonrelated, first hybrid landrace pigs were divided into PE (portal-enteric drainage) and SE (systemic-enteric drainage) groups. Type I diabetes mellitus was induced by whole pancreatectomy, and right-side nephrectomy was also performed in the recipients. The donor portal vein was anastomosed to superior mesenteric vein of the recipients in PE group or to the inferior hepatic cava vena of the recipients in SE group. Graft tissue specimens were obtained with laparotomy on Day 3 and 7 after transplant, and the severity of acute rejection was scored according to Nakhleh and Banff criteria. The cold ischemia time, fasting plasma glucose and urine creatinine of the 2 groups had no statistic difference between 2 groups at Day 1, 3, 5, and 7 after transplant (P>0.05). The occurrence of both pancreas and kidney acute rejections in PE group was significant later and slighter than SE group (P<0.05). PVD, compared with SVD, could ameliorate and delay acute rejection in pig SPK. It might become a tolerance inducing method of pancreas transplantation, decrease the cost and improve the quality of SPK, if further confirmed by clinical trials.


Information transfer and nontrivial collective behavior in chaotic coupled map networks.
The emergence of nontrivial collective behavior in networks of coupled chaotic maps is investigated by means of a nonlinear mutual prediction method. The resulting prediction error is used to measure the amount of information that a local unit possesses about the collective dynamics. Applications to locally and globally coupled map systems are considered. The prediction error exhibits phase transitions at critical values of the coupling for the onset of ordered collective behavior in these networks. This information measure may be used as an order parameter for the characterization of complex behavior in extended chaotic systems.


A new test of advanced theory of mind: The "Strange Stories Film Task" captures social processing differences in adults with autism spectrum disorders.
Real-life social processing abilities of adults with autism spectrum disorders (ASD) can be hard to capture in lab-based experimental tasks. A novel measure of social cognition, the "Strange Stories Film task' (SSFt), was designed to overcome limitations of available measures in the field. Brief films were made based on the scenarios from the Strange Stories task (Happé) and designed to capture the subtle social-cognitive difficulties observed in ASD adults. Twenty neurotypical adults were recruited to pilot the new measure. A final test set was produced and administered to a group of 20 adults with ASD and 20 matched controls, alongside established social cognition tasks and questionnaire measures of empathy, alexithymia and ASD traits. The SSFt was more effective than existing measures at differentiating the ASD group from the control group. In the ASD group, the SSFt was associated with the Strange Stories task. The SSFt is a potentially useful tool to identify social cognitive dis/abilities in ASD, with preliminary evidence of adequate convergent validity. Future research directions are discussed. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1120-1132. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.


Free energy of translocating an arginine-rich cell-penetrating peptide across a lipid bilayer suggests pore formation.
The molecular mechanism and energetics of the translocation of arginine-rich, cell-penetrating peptides through membranes are still under debate. One possible mechanism involves the formation of a water pore in the membrane such that the hydrophilic residues of the peptide are solvated throughout the translocating process. In this work, employing two different order parameters, we calculate the free energies of translocating a cyclic Arg(9) peptide into a lipid bilayer along one path that involves a water-pore formation and another path that does not form a separate pore. The free-energy barrier of translocating the peptide along a pore path is 80 kJ/mol lower than along a pore-free path. This suggests that the peptide translocation is more likely associated with a water-pore formation.


[Comparison of in vitro activity of 4 oral beta-lactams on microorganisms responsible for broncho-pulmonary infections in children].
MIC 90 and MBC 90 of amoxicillin, cefaclor, cefadroxil and cefuroxime axetil have been determined by the microdilution method against 48 organisms responsible of acute respiratory tract infections in children: 17 E. coli, 15 K. pneumoniae, 16 H. influenzae. An inoculum effect and an inhibitory index in blood and bronchial secretions were determined. An inoculum effect was more important for amoxicillin and cefadroxil than for cefuroxime axetil and cefaclor. Against H. influenzae, cefuroxime axetil and cefaclor have a similar activity. Against Enterobacteria, cefuroxime axetil has the lowest MIC 90 and MBC 90 and the highest inhibitory index.


Concurrent vs sequential chemoradiotherapy for patients with advanced non-small-cell lung cancer: A meta-analysis of randomized controlled trials.
Chemotherapy in combination with thoracic radiotherapy yields significant results in patients with advanced non-small-cell lung cancer (NSCLC) compared with thoracic radiotherapy alone. However, whether concurrent or sequential delivery of chemotherapy combined with thoracic radiotherapy is optimal remains unclear. Herein, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of concurrent vs sequential chemoradiotherapy in patients with NSCLC. PubMed, EmBase, and Cochrane Library were systematically searched for RCTs focusing on concurrent and sequential chemoradiotherapy for patients with NSCLC. The pooled-effect estimate was calculated using the random-effects model. Sensitivity, subgroup, and publication biases were also evaluated. A total of 14 RCTs (2634 patients with NSCLC) were selected for the final meta-analysis. Compared with sequential chemoradiotherapy, concurrent chemoradiotherapy did not increase the 1-year survival rates; however, concurrent chemoradiotherapy significantly increased the 2-, 3-, 4-, and 5-year survival rates. Moreover, although there were no significant differences between concurrent and sequential chemoradiotherapy in terms of distant relapse and locoregional plus distant relapse, concurrent chemoradiotherapy significantly reduced the risk of locoregional relapse. Furthermore, concurrent chemoradiotherapy yielded positive results with respect to overall response rates. Unfortunately, concurrent chemoradiotherapy could result in esophagitis, nausea/vomiting, and reduced leukocyte and platelet counts in patients with NSCLC. Compared with sequential chemoradiotherapy, concurrent chemoradiotherapy may be significantly beneficial in terms of long-term survival and locoregional relapse, although it increases the risk of grade 3 (or greater) adverse events.


Remodelling of early axonal projections through the selective elimination of neurons and long axon collaterals.
Studies using neuroanatomical techniques have shown that the connections characteristic of the mature vertebrate brain are brought about by a considerable refinement of the projections initially established during development. The selective loss of neurons and long axon collaterals plays a major role in this remodeling process as illustrated in the development of the retina and cortex of the rat. In the retina, two-thirds of the initial population of ganglion cells (RGCs) die early. This loss serves to remove selectively RGCs that make erroneous axonal projections, including those which project to an incorrect target, to an inappropriate part of a correct target, or to the wrong side of the brain. Studies using the sodium channel blocker, tetrodotoxin, suggest that in rats the selective elimination of erroneously projecting RGCs is based, in part, on patterns of impulse activity. In the cortex a different mechanism is illustrated. All neocortical areas initially give rise to callosal and pyramidal tract axons but through a process of selective collateral elimination not involving cell death these projections assume the limited distributions seen in adult rats. Manipulations resulting in the maintenance of such long collaterals suggest that their removal is functionally and locally determined. In contrast to error elimination, this phenomenon of collateral elimination may be a developmental strategy for generating connectional diversity while limiting the amount of information required for the regional specification of the cortex.


The role of substituents on functionalized 1,10-phenanthroline in controlling the emission properties of cationic iridium(III) complexes of interest for electroluminescent devices.
The photophysical and electrochemical properties of the novel complexes [Ir(ppy)(2)(5-X-1,10-phen)][PF(6)] (ppy = 2-phenylpyridine, phen = phenanthroline, X = NMe(2), NO(2)), [Ir(pq)(2)(5-X-1,10-phen)][PF(6)] (pq = 2-phenylquinoline, X = H, Me, NMe(2), NO(2)), [Ir(ppy)2(4-Me,7-Me-1,10-phen)][PF(6)], [Ir(ppy)2(5-Me,6-Me-1,10-phen)][PF(6)], [Ir(ppy)(2)(2-Me,9-Me-1,10-phen)][PF(6)], and [Ir(pq)2(4-Ph,7-Ph-1,10-phen)][PF(6)] have been investigated and compared with those of the known reference complexes [Ir(ppy)(2)(4-Me or 5-H or 5-Me-1,10-phen)][PF(6)] and [Ir(ppy)(2)(4-Ph,7-Ph-1,10-phen)][PF(6)], showing how the nature and number of the phenanthroline substituents tune the color of the emission, its quantum yield, and the emission lifetime. It turns out that the quantum yield is strongly dependent on the nonradiative decay. The geometry, ground state, electronic structure, and excited electronic states of the investigated complexes have been calculated on the basis of density functional theory (DFT) and time-dependent DFT approaches, thus substantiating the electrochemical measurements and providing insight into the electronic origin of the absorption spectra and of the lowest excited states involved in the light emission process. These results provide useful guidelines for further tailoring of the photophysical properties of ionic Ir(III) complexes.


3-[N,N-Bis(sulfonyl)amino]isoxazolines with Spiro-Annulated or 1,2-Annulated Cyclooctane Rings Inhibit Reproduction of Tick-Borne Encephalitis, Yellow Fever, and West Nile Viruses.
Spirocyclic compounds containing heterocyclic moieties represent promising 3D scaffolds for modern drug design. In the search for novel anti-flaviviral agents, we have obtained a series of 3-[N,N-bis(sulfonyl)amino]isoxazolines containing spiro-annulated cyclooctane rings and assessed their antiviral activity against tick-borne encephalitis (TBEV), yellow fever (YFV), and West Nile (WNV) viruses. The structural analogs of spirocyclic compounds with a single sulfonyl group or 1,2-annulated cyclooctane ring were also investigated. Almost all the studied 3-[N,N-bis(sulfonyl)amino]isoxazolines revealed antiviral activity against TBEV and WNV. The most active against TBEV was spiro-isoxazoline derivative containing p-nitrophenyl groups in the sulfonyl part (EC50 2.0 ± 0.5 μM), while the highest potency against WNV was found for the compounds with lipophilic substituents in sulfonyl moiety, naphtyl being the most favorable one (EC50 1.3 ± 0.5 μM). In summary, two novel scaffolds of anti-flaviviral agents based on N,N-bis(sulfonyl)amino]isoxazoline were proposed, and the compounds of this type demonstrated activity against TBEV and WNV.


Hypotony Following Intravitreal Silicone Oil Removal in a Patient With a Complex Retinal Detachment With Giant Retinal Tear.
Postoperative ocular hypotony after silicone oil removal in complex cases of retinal detachment is a complication that can occur in about 20% of cases and can prevent the successful management of retinal detachments. Thus, it is critical to understand the mechanisms of hypotony and the potential interventions that can be done in order to avoid irreversible tissue damage. We present a case of a 35-year-old man who underwent intraocular surgery for removal of silicone oil tamponade following a combined scleral buckling and pars plana vitrectomy (PPV) surgery for a rhegmatogenous retinal detachment associated with a giant retinal tear. On Day 1 after the operation, the patient was found to have hypotony with optic disc edema, chorioretinal folds, and visual acuity of 'hand movement' perception. Two weeks postop, the patient's condition stabilized, with a visual acuity of 0.38 logMAR, an intraocular pressure (IOP) of 12 mmHg, and the absence of macular edema.


Experimental demonstration of a time-domain digital-coding metasurface for a Doppler cloak.
By generating an artificial Doppler shift, a Doppler cloak can compensate for the Doppler shift from a moving object. An object covered by a Doppler cloak will be detected as a static object, even if it is actually moving. Herein, we experimentally demonstrate the Doppler cloak in a radar system using a time-domain digital-coding metasurface. We theoretically illustrate an active metasurface with a modulated reflection phase that can imitate the motion of moving, thereby generating an artificial Doppler shift for a Doppler cloak. Moreover, a reflective metasurface composed of voltage-controlled varactor diodes with a 3-bit reflection phase was designed and fabricated. Finally, we experimentally demonstrate that an artificial Doppler shift for a Doppler cloak is obtained from the proposed metasurface using a discrete time-varying bias voltage. Simulation and measurement results show that the proposed time-domain digital-coding metasurface can cancel the Doppler shift and serve as a Doppler cloak. The proposed metasurface may have potential applications in a Doppler radar illusion, Doppler cancellation in vehicle-to-vehicle communications, and wireless communications.


Identification and characterization of an amphipathic leucine zipper-like motif in Escherichia coli toxin hemolysin E. Plausible role in the assembly and membrane destabilization.
Hemolysin E (HlyE) is a 34 kDa protein toxin, recently isolated from a pathogenic strain of Escherichia coli, which is believed to exert its toxic activity via formation of pores in the target cell membrane. With the goal of understanding the involvement of different segments of hemolysin E in the membrane interaction and assembly of the toxin, a conserved, amphipathic leucine zipper-like motif has been identified. In order to evaluate the possible structural and functional roles of this segment in HlyE, a 30-residue peptide (H-205) corresponding to the leucine zipper motif (amino acid 205-234) and two mutant peptides of the same size were synthesized and labeled by fluorescent probes at their N termini. The results show that the wild-type H-205 binds to both zwitterionic (PC/Chol) and negatively charged (PC/PG/Chol) phospholipid vesicles and also self-assemble therein. Detailed membrane-binding experiments revealed that this synthetic motif (H-205) formed large aggregates and inserted into the bilayer of only negatively charged lipid vesicles but not of zwitterionic membrane. Although both the mutants bound to zwitterionic and negatively charged lipid vesicles, neither of them inserted into the lipid bilayers nor assembled in any of these lipid vesicles. Furthermore, H-205 adopted a significant helical structure in membrane mimetic environments and induced the permeation of monovalent ions and release of entrapped calcein across the phospholipid vesicles more efficiently than the mutant peptides. The results presented here indicate that this H-205 (amino acid 205-234) segment may be an important structural element in hemolysin E, which could play a significant role in the binding and assembly of the toxin in the target cell membrane and its destabilization.


A multicentre comparative evaluation of catheter valves.
Catheter valves are an alternative to leg bags for urine drainage, but no studies have yet been published which have compared the performance of different valves. This study was undertaken to evaluate the performance of the seven catheter valves available on the UK market in April 1996. The study was carried out by the Continence Products Evaluation (CPE) Network funded by the Medical Devices Agency (Department of Health). Each valve type was tested for 1 week by 19-36 cognitively unimpaired and manually dextrous subjects recruited from 11 test centres. At the end of each week, subjects completed an evaluation form (based on a three-point rating scale) to record product performance. The same catheter valves were also tested for ease of opening/closing by 33 subjects (mostly catheter users) who had some manual impairment. Performance scores varied widely between products. It was found that, to be successful, a valve needs to be easy to manipulate, leak-free, comfortable and inconspicuous. Prescribers need to be aware of the strengths and limitations of different valves for appropriate product selection.


Sperm transport to and survival in the human fallopian tube.
A review is given on sperm migration to and sperm survival within the human Fallopian tube. Sperm migration from the external os can be very fast. The survival time of spermatozoa in the oviduct has been demonstrated to be 85 h. Spermatozoa normally enter the abdominal cavity through the open fimbriated end. Laterally closed oviducts retain spermatozoa resulting in a larger number of spermatozoa than in the normal oviduct, where the number of sperm at the site of fertilization is very low. The morphology of spermatozoa reaching the ampulla of the oviduct is mostly normal, which seems to be based on the correlation between normal morphology and good motility. Spermatozoa within the abdominal cavity do not cause antibody formation of any importance for the fertility of the woman.


General mechanism involved in subwavelength optics of conducting microstructures: charge-oscillation-induced light emission and interference.
Interactions between light and conducting microstructures or nanostructures can result in a variety of novel phenomena, but their underlying mechanisms have not been completely understood. From calculations of surface charge density waves on conducting gratings and by comparing them with classical surface plasmons, we revealed a general yet concrete picture regarding the coupling of light to free electron oscillation on structured conducting surfaces that can lead to oscillating subwavelength charge patterns (i.e., structured surface plasmons). New wavelets emitted from these light sources then destructively interfere to form evanescent waves. This principle, usually combined with other mechanisms, is mainly a geometrical effect that can be universally involved in light scattering from all periodic and non-periodic structures containing free electrons. This picture may provide clear guidelines for developing conductor-based nano-optical devices.


Swelling, Mechanics, and Thermal/Chemical Stability of Hydrogels Containing Phenylboronic Acid Side Chains.
We report here studies of swelling, mechanics, and thermal stability of hydrogels consisting of 20 mol % methacrylamidophenylboronic acid (MPBA) and 80 mol % acrylamide (AAm), lightly crosslinked with methylenebisacrylamide (Bis). Swelling was measured in solutions of fixed ionic strength, but with varying pH values and fructose concentrations. Mechanics was studied by compression and hold. In the absence of sugar or in the presence of fructose, the modulus was mostly maintained during the hold period, while a significant stress relaxation was seen in the presence of glucose, consistent with reversible, dynamic crosslinks provided by glucose, but not fructose. Thermal stability was determined by incubating hydrogels at pH 7.4 at room temperature, and 37, 50, and 65 °C, and monitoring swelling. In PBS (phosphate buffered saline) solutions containing 9 mM fructose, swelling remained essentially complete for 50 days at room temperature, but decreased substantially with time at the higher temperatures, with accelerated reduction of swelling with increasing temperature. Controls indicated that over long time periods, both the MPBA and AAm units were experiencing conversion to different species.


Alignment of a vector magnetometer to an optical prism.
A method for alignment of a vector magnetometer to a rigidly attached prism is presented. This enables optical comparison of the magnetometer axes to physical surfaces in the apparatus, and thus an absolute determination of the magnetic field direction in space. This is in contrast with more common techniques, which focus on precise determination of the relative angles between magnetometer axes, and so are more suited to measuring differences in the direction of magnetic fields. Here we demonstrate precision better than 500 μrad on a fluxgate magnetometer, which also gives the coil orthogonality errors to a similar precision. The relative sensitivity of the three axes is also determined, with a precision of about 5 × 10-4.


Dissecting aneurysm of the femoral and popliteal arteries.
Dissecting aneurysms of peripheral arteries within the extremities are very rare. We report a case of dissection of the superficial femoral and popliteal arteries, in which the preoperative arteriography was diagnostic and surgical treatment was undertaken before the onset of severe ischaemia. It is recommended that the diagnosis of dissecting aneurysm of a major artery should be considered when limb ischaemia occurs in a younger patient.


Construction of a Prognostic Nomogram Model for Patients with Mucinous Breast Cancer.
The objective of the study is to develop a nomogram for estimating three- and five-year survival rates in mucinous breast cancer patients. Between 2010 and 2016, the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) were searched as a data source for patients associated with mucinous breast cancer (MBC). A total of 3964 patients were recruited after screening. The multivariate Cox model and the univariate Kaplan-Meier (KM) approach were employed to evaluate the independent prognostic markers, followed by developing a nomogram for estimating three- and five-year survival rates in MBC patients. Consequently, the consistency index (C-index) was employed to assess the predictive accuracy of the generated nomogram. Age, race, T stage, M stage, surgery, and radiotherapy were all independent predictive biomarkers for the MBC patients (P < 0.05). The nomogram was finally developed based on the underlined factors. Furthermore, the C-index of 0.803 and reliable calibration curves were obtained in the nomogram's assessment. In patients with mucinous breast cancer, the proposed nomogram provides a viable tool for accurate prognostic prediction. In clinical practice, it could serve as a personalized diagnosis tool, estimate prognosis, and help in suggesting treatment plans for patients with MBC.


Hypoglycemic Mechanism of the Berberine Organic Acid Salt under the Synergistic Effect of Intestinal Flora and Oxidative Stress.
Both alterations to the intestinal microflora and chronic systemic inflammation predispose towards type 2 diabetes (T2D). Changes in the composition of the intestinal microflora are associated with glucose metabolism changes in rats with T2D. Here, we demonstrate that a berberine fumarate (BF) has a hypoglycemic effect by regulating the intestinal microflora and metabolism of diabetic rats. The T2D rats had disorders of glucose and lipid metabolism, an abnormal intestinal microflora, fewer butyrate-producing and probiotic-type bacteria, larger numbers of potentially pathogenic and sulfate-reducing bacteria, and tissue inflammation. Administration of berberine fumarate significantly ameliorated the metabolic disorder; increased the populations of Bacteroidetes, Clostridia, Lactobacillales, Prevotellaceae, and Alloprevotella; and reduced those of Bacteroidales, Lachnospiraceae, Rikenellaceae, and Desulfovibrio. In addition, it reduced inflammation, inhibiting the overexpression of TLR4 and p-JNK and increasing the expression of PI3K, GLUT2, and other proteins, which are closely related to oxidative stress, thereby promoting the metabolism of glucose.


Comparing the dynamical effects of symmetric and antisymmetric stretch excitation of methane in the Cl+CH4 reaction.
The effects of two nearly isoenergetic C-H stretching motions on the gas-phase reaction of atomic chlorine with methane are examined. First, a 1:4:9 mixture of Cl(2), CH(4), and He is coexpanded into a vacuum chamber. Then, either the antisymmetric stretch (nu(3)=3019 cm(-1)) of CH(4) is prepared by direct infrared absorption or the infrared-inactive symmetric stretch (nu(1)=2917 cm(-1)) of CH(4) is prepared by stimulated Raman pumping. Photolysis of Cl(2) at 355 nm generates fast Cl atoms that initiate the reaction with a collision energy of 1290+/-175 cm(-1) (0.16+/-0.02 eV). Finally, the nascent HCl or CH(3) products are detected state-specifically via resonance enhanced multiphoton ionization and separated by mass in a time-of-flight spectrometer. We find that the rovibrational distributions and state-selected differential cross sections of the HCl and CH(3) products from the two vibrationally excited reactions are nearly indistinguishable. Although Yoon et al. [J. Chem. Phys. 119, 9568 (2003)] report that the reactivities of these two different types of vibrational excitation are quite different, the present results indicate that the reactions of symmetric-stretch excited or antisymmetric-stretch excited methane with atomic chlorine follow closely related product pathways. Approximately 37% of the reaction products are formed in HCl(v=1,J) states with little rotational excitation. At low J states these products are sharply forward scattered, but become almost equally forward and backward scattered at higher J states. The remaining reaction products are formed in HCl(v=0,J) and have more rotational excitation. The HCl(v=0,J) products are predominantly back and side scattered. Measurements of the CH(3) products indicate production of a non-negligible amount of umbrella bend excited methyl radicals primarily in coincidence with the HCl(v=0,J) products. The data are consistent with a model in which the impact parameter governs the scattering dynamics.


Therapeutic potential of endothelin receptor antagonists for chronic proteinuric renal disease in humans.
Diabetes and arterial hypertension continue to be the main causes of chronic renal failure in 2010, with a rising prevalence in part due to the worldwide obesity epidemic. Proteinuria is a main feature of chronic renal disease and mediated by defects in the glomerular filtration barrier and is as a good predictor of cardiovascular events. Indeed, chronic renal disease due to glomerulosclerosis is one of the important risk factors for the development of coronary artery disease and stroke. Glomerulosclerosis develops in response to inflammatory activation and increased growth factor production. Preclinical and first preliminary clinical studies provide strong evidence that endogenous endothelin-1 (ET-1), a 21-amino-acid peptide with strong growth-promoting and vasoconstricting properties, plays a central role in the pathogenesis of proteinuria and glomerulosclerosis via activation of its ET(A) subtype receptor involving podocyte injury. These studies have not only shown that endothelin participates in the disease processes of hypertension and glomerulosclerosis but also that features of chronic renal disease such as proteinuria and glomerulosclerosis are reversible processes. Remarkably, the protective effects of endothelin receptors antagonists (ERAs) are present even on top of concomitant treatments with inhibitors of the renin-angiotensin system. This review discusses current evidence for a role of endothelin for proteinuric renal disease and podocyte injury in diabetes and arterial hypertension and reviews the current status of endothelin receptor antagonists as a potential new treatment option in renal medicine.


Thrombolytic treatment and complement activation.
Details of possible complement activation in acute myocardial infarction (AMI) and the in vivo effects of fibrinolytic agents on this activation are not yet known. We measured complement activation in 40 patients with AMI: 20 were treated with streptokinase, and 20 did not receive any fibrinolytic agent. Anaphylatoxin C4a, C3a and membrane attack complexes SC5b-9 increased about 10-fold (p < 0.0001) during streptokinase infusion. There were no increases in complement catabolic products in AMI patients not treated with streptokinase. Significant transient leukopenia (-29.5%, 7.0 SEM, p = 0.001) and a drop in systolic pressure (-29%, 3.4 SEM, p < 0.0001) occurred after 15 min of streptokinase infusion simultaneously with the peak of anaphylatoxins in plasma.


Assembly of fibronectin into extracellular matrix.
The results summarized above suggest that assembly of fibronectin is a fundamental biological process and that knowledge of the process of assembly may reveal new ways by which cells interact with extracellular molecules. Deposition of a fibronectin matrix seems to be regulated as tightly as synthesis of fibronectin or expression of adhesion receptors for fibronectin and is influenced profoundly by two products of blood coagulation--TGF-beta released from platelets and factor XIII activated by thrombin. Fibronectin assembly may be important in all sorts of physiological and pathophysiological processes. Cell A--for instance, a stromal cell--can influence the behavior of cell B--for instance, a lymphocyte--by assembling fibronectin made by cell C--for instance, a hepatocyte. We hope that the testable models of assembly presented in this paper will lead to new understanding of the process of assembly and suggest new modalities for treatment of diseases that result in fibrosis, damaged tissues, and neoplastic growth.


Robust, Stretchable, and Self-Healable Supramolecular Elastomers Synergistically Cross-Linked by Hydrogen Bonds and Coordination Bonds.
Polymeric elastomers integrated with high mechanical toughness and excellent self-healing ability can find attractive applications in electronic skin, soft robotics, and electrical devices. However, simultaneously enhancing the mechanical and self-healing properties of elastomers is still a great challenge because it is difficult to balance the effects between strong and weak cross-linking bonds. Here, a novel self-healing elastomer is developed via a one-pot polycondensation reaction between bis(3-aminopropyl)-terminated poly(dimethylsiloxane) and 2,4'-tolylene diisocyanate, followed by being coordinated with Al(III) ions by metal-coordination bonds. In this elastomer system, the quadruple hydrogen bonds not only are able to achieve rapid reformation after fracture but also can dissipate strain energy as a weak dynamic bond, endowing the elastomer with excellent self-healing ability and high stretchability, while the treble Al-coordination bonds acting as a strong dynamic bond contribute to the robust molecular networks, leading to the significantly improved robustness and elasticity of the self-healing elastomer. Owing to the accuracy design, the synthesized elastomer exhibits all the desired properties, including high tensile stress (2.6 MPa), exceptional toughness (∼14.7 MJ m-3), high stretchability (∼1700%), and excellent self-healing ability (90%). The robust self-healing elastomer enables the easy fabrication of flexible electronic skin, which will open a new avenue for next-generation electrical devices.


Topical delivery of therapeutic agents in the treatment of inflammatory bowel disease.
For targeting local and systemic inflammatory processes in inflammatory bowel disease (IBD) therapeutic agents of first choice (e.g. aminosalicylates, corticosteroids) have been developed in special galenic forms to accomplish the topical delivery of the active compounds to the terminal ileum (Crohn's disease) and/or the colon (Crohn's disease and ulcerative colitis). However, it has to be realized that intestinal physiology (e.g. motility, intraluminal pH profiles), extent and pattern of IBD as well as drug disposition demonstrate large interindividual differences resulting in variable clinical response rates between about 35% and 75%. 5-Aminosalicylate (5-AS) can be delivered to the colon either by azo-prodrugs (e.g. sulfasalazine, olsalazine or balsalazide) or by direct rectal administration of 5-AS in form of enemas, foam or suppositories. Such formulations will be only effective in patients with ulcerative colitis (UC). Various slow/controlled release preparations of 5-AS have been developed for oral use. Some of them (e.g. Pentasa, Salofalk) release sufficient 5-AS already in the small bowel which could provide some additional benefit in Crohn's disease (CD). As urinary and faecal recoveries of total 5-AS are similar for all oral formulations, no major clinical differences can be expected. Extent of the disease, profile of adverse effects and patient's acceptance provide some guidance for selection of the particular agent. Rectal installation of several glucocorticosteroids has been employed for many years. More recently scientific and clinical interest has been focused on budesonide which is extensively presystemically metabolized in the intestinal wall and the liver. Therefore, its systemic availability is low (10-15%) independent whether budesonide is administered orally as controlled release formulation in patients with CD or rectally as enema in patients with UC. Numerous pharmacokinetic and clinical studies have documented the anticipated topical delivery and clinical efficacy of this corticosteroid without serious side effects such as cushingoid features. It can be assumed that for any novel therapeutic principle in IBD the approach of topical delivery will be also tried.


Fluorinated Unsymmetrical N,N'-Diaryl Imidazolium Salts-New Functionalized NHC-Ligand Precursors.
An efficient and scaled-up synthesis of the imidazol-2-ylidene-based unsymmetrical NHC precursors bearing the sterically demanding hexafluoroisopropylalkoxy group [(CF3 )2 (OR)C-] at the ortho position of the N-aryl substituent was developed. The key step of the method involved the transformation of a Mes-substituted oxazolinium tetrafluoroborate salt through the reaction with the corresponding binucleophilic fluoroalkyl-substituted aniline. The subsequent post-modification of the resulting hydroxyl-containing salt through a simple one-step O-alkylation protocol provided access to a new family of unsymmetrical fluorinated NHC precursors. These compounds were successfully utilized for the preparation of several novel metal complexes. The molecular structures of some NHC precursors and their metal complexes have been unambiguously characterized by single-crystal X-ray diffraction analysis. A preliminary evaluation of the catalytic activity of the palladium complexes was performed on a Buchwald-Hartwig amination reaction. As a result, two PEPPSI-type (PEPPSI=pyridine-enhanced pre-catalyst preparation stabilization and initiation) Pd complexes have demonstrated promising activity in alkane solvents.


Federated Robustness Propagation: Sharing Adversarial Robustness in Heterogeneous Federated Learning.
Federated learning (FL) emerges as a popular distributed learning schema that learns a model from a set of participating users without sharing raw data. One major challenge of FL comes with heterogeneous users, who may have distributionally different (or non-iid) data and varying computation resources. As federated users would use the model for prediction, they often demand the trained model to be robust against malicious attackers at test time. Whereas adversarial training (AT) provides a sound solution for centralized learning, extending its usage for federated users has imposed significant challenges, as many users may have very limited training data and tight computational budgets, to afford the data-hungry and costly AT. In this paper, we study a novel FL strategy: propagating adversarial robustness from rich-resource users that can afford AT, to those with poor resources that cannot afford it, during federated learning. We show that existing FL techniques cannot be effectively integrated with the strategy to propagate robustness among non-iid users and propose an efficient propagation approach by the proper use of batch-normalization. We demonstrate the rationality and effectiveness of our method through extensive experiments. Especially, the proposed method is shown to grant federated models remarkable robustness even when only a small portion of users afford AT during learning. Source code will be released.


A Tale from TGF-β Superfamily for Thymus Ontogeny and Function.
Multiple signaling pathways control every aspect of cell behavior, organ formation, and tissue homeostasis throughout the lifespan of any individual. This review takes an ontogenetic view focused on the large superfamily of TGF-β/bone morphogenetic protein ligands to address thymus morphogenesis and function in T cell differentiation. Recent findings on a role of GDF11 for reversing aging-related phenotypes are also discussed.


Whole-brain N-acetylaspartate as a surrogate marker of neuronal damage in diffuse neurologic disorders.
Proton MR spectroscopy (1H-MR spectroscopy) is a quantitative MR imaging technique often used to complement the sensitivity of conventional MR imaging with specific metabolic information. A key metabolite is the amino acid derivative N-acetylaspartate (NAA), which is almost exclusive to neurons and their processes and is, therefore, an accepted marker of their health and attenuation. Unfortunately, most 1H-MR spectroscopy studies only account for small 1- to 200-cm volumes of interest (VOI), representing less than 20% of the total brain volume. These VOIs have at least 5 additional restrictions: 1) To avoid contamination from subcutaneous and bone marrow lipids, they must be placed away from the skull, thereby missing most of the cortex. 2) They must be image-guided onto MR imaging-visible pathology, subjecting them to the implicit assumption that metabolic changes occur only there. 3) They encounter misregistration errors in serial studies. 4) The time needed to accumulate sufficient signal-intensity quality is often restrictive, and 5) they incur (unknown) T1- and T2-weighting. All these issues are avoided (at the cost of specific localization) by measuring the nonlocalized average NAA concentration over the entire brain. Indeed, whole-brain NAA quantification has been applied to several diffuse neurodegenerative diseases (where specific localization is less important than the total load of the pathology), and the results are presented in this review.


Metal-dioxygen and metal-dinitrogen complexes: where are the electrons?
Transition-metal complexes of O(2) and N(2) play an important role in the environment, chemical industry, and metalloenzymes. This Perspective compares and contrasts the binding modes, reduction levels, and electronic influences on the nature of the bound O(2) or N(2) group in these complexes. The charge distribution between the metal and the diatomic ligand is variable, and different models for describing the adducts have evolved. In some cases, single resonance structures (e.g. M-superoxide = M-O(2)(-)) are accurate descriptions of the adducts. Recent studies have shown that the magnetic coupling in certain N(2)(2-) complexes differs between resonance forms, and can be used to distinguish experimentally between resonance structures. On the other hand, many O(2) and N(2) complexes cannot be described well with a simple valence-bond model. Defining the situations where ambiguities occur is a fertile area for continued study.


Bedside monitoring of nutritional metabolism in the persistent vegetative state.
The basal metabolism and daily energy consumption of eight cases of the persistent vegetative state were low. Some received excessive energy and inappropriate essential nutrient infusions.


THE OCULAR SEQUELAE OF THIRD CRANIAL NERVE PALSY.
The ocular sequelae in nineteen patients who had suffered from a complete paralysis of the third cranial nerve were analyzed. In eleven of these patients, the paralysis was associated with an aneurysm of the internal carotid artery system. None of the cases in this group showed complete recovery of the third nerve function; however, six recovered sufficiently to permit binocular single vision in most fields of gaze. Two cases of aberrant regeneration of the third nerve were diagnosed.Trauma accounted for four cases of third nerve paralysis. One of these recovered completely and one showed features of aberrant regeneration. Of the cases of oculomotor paralysis associated with herpes zoster ophthalmicus, encephalitis, or an obscure etiology (two cases), all recovered completely.


Incorporation of Smooth Muscle Cells Derived from Human Adipose Stem Cells on Poly(Lactic-co-Glycolic Acid) Scaffold for the Reconstruction of Subtotally Resected Urinary Bladder in Athymic Rats.
The urinary tract can be affected by both congenital abnormalities as well as acquired disorders, such as cancer, trauma, infection, inflammation, and iatrogenic injuries, all of which may lead to organ damage requiring eventual reconstruction. As a gold standard, gastrointestinal segment is used for urinary bladder reconstruction. However, one major problem is that while bladder tissue prevents reabsorption of specific solutes, gastrointestinal tissue actually absorbs them. Therefore, tissue engineering approach had been attempted to provide an alternative tissue graft for urinary bladder reconstruction. Human adipose-derived stem cells isolated from fat tissues were differentiated into smooth muscle cells and then seeded onto a triple-layered PLGA sheet to form a bladder construct. Adult athymic rats underwent subtotal urinary bladder resection and were divided into three treatment groups (n = 3): Group 1 ("sham") underwent anastomosis of the remaining basal region, Group 2 underwent reconstruction with the cell-free scaffold, and Group 3 underwent reconstruction with the tissue-engineered bladder construct. Animals were monitored on a daily basis and euthanisation was performed whenever a decline in animal health was detected. All animals in Groups 1, 2 and 3 survived for at least 7 days and were followed up to a maximum of 12 weeks post-operation. It was found that by Day 14, substantial ingrowth of smooth muscle and urothelial cells had occurred in Group 2 and 3. In the long-term follow up of group 3 (tissue-engineered bladder construct group), it was found that the urinary bladder wall was completely regenerated and bladder function was fully restored. Urodynamic and radiological evaluations of the reconstructed bladder showed a return to normal bladder volume and function.Histological analysis revealed the presence of three muscular layers and a urothelium similar to that of a normal bladder. Immunohistochemical staining using human-specific myocyte markers (myosin heavy chain and smoothelin) confirmed the incorporation of the seeded cells in the newly regenerated muscular layers. Implantation of PLGA construct seeded with smooth muscle cells derived from human adipose stem cells can lead to regeneration of the muscular layers and urothelial ingrowth, leading to formation of a completely functional urinary bladder.


Effect of sensitization and non-antibody IgE on 48/80 induced histamine release from isolated rat mast cells.
Histamine release from isolated rat mast cells from non-immunized and immunized Hooded Lister rats was induced by compound 48/80. The histamine release was decreased with a lower maximum at the optimal concentration of 48/80 when using cells from immunized rats compared to non-immunized control rats. The stimulation of IgE antibody production, after immunization using B. pertussis as an adjuvant was also accompanied by an elevation of total serum IgW. The 48/80 induced histamine release from Sprague Dawley mast cells was not inhibited by immunization. Non-antibody IgE showed a non-competitive inhibition of 48/80 induced histamine release when myeloma IgE was incubated with mast cells from both Hooded Lister and Sprague Dawley rats. The results indicate the existence of different receptors for IgE and 48/80.


Ischemia right ventricular dysfunction.
For many years ischemic heart disease involving the right ventricle had received little attention. During the last 15 years, the initial works of Cohn, Isner, and others spawned a number of clinical and experimental studies that extended the understanding of the pathophysiology of ischemia in the right ventricle. Most of the work has been done in the setting of acute myocardial infarction, and information is still lacking in other conditions, such as chronic ischemic heart disease and perioperative right ventricular dysfunction. Acute right ventricular infarction rarely occurs in the absence of left ventricular necrosis and in most cases is the extension of an inferior left ventricular infarct. The majority of patients with right ventricular infarction only exhibit subtle signs of ischemic dysfunction. Elevated right atrial pressure is found only in the typical syndrome of elevated venous pressure; low output syndrome can be found only in 20% of the cases, and cardiogenic shock secondary to right ventricular necrosis is found only in 10%. It is also important to note that there is not a clear correlation between the severity of ischemic right ventricular dysfunction and the necrotic area. The discrepancy may be due to ischemia without necrosis of the right ventricular wall (stunned myocardium), but the intact pericardium and the necrosis of the interventricular septum may also play an important role. In the most severe form of ischemic right ventricular dysfunction, the entire right ventricular wall is akinetic. Right atrial, right ventricular, and pulmonary artery pressures become similar in magnitude and shape, and the pulmonary valve is opened during diastole, demonstrating a passive blood flow from the right atrium to the left ventricle through the low resistance pulmonary capillary bed. Volume loading, administration of dopamine or dobutamine, and careful use of vasodilators under hemodynamic monitoring are the therapeutic measures to control the severe forms of acute ischemic right ventricular dysfunction. The use of thrombolytic agents has decreased the incidence of right ventricular dysfunction after acute myocardial infarction. Mortality is high in the severe forms of acute ischemic right ventricular dysfunction, but after discharge from hospital the prognosis is good and right heart failure is unusual, even in those patients with shock during the first days of evolution of the infarct.


Acute and one-year clinical outcomes of pre-stenting intravascular ultrasound: a patient-level meta-analysis of randomised clinical trials.
Pre-stenting intravascular ultrasound (IVUS) assessment is helpful for appropriate stent sizing and determination of the stent landing zone during percutaneous coronary intervention. The aim of this meta-analysis was to investigate the effect of pre-stenting IVUS evaluation on procedural and clinical outcomes for diffuse lesions treated with drug-eluting stents (DES). In four randomised trials comparing IVUS- and angiography-guided DES placement, a total of 1,396 patients who underwent DES implantation with IVUS guidance were identified. Pre-stenting IVUS assessment was performed in 905 patients along with post-stenting IVUS (65%; pre-stenting IVUS(+) group). Post-stenting IVUS evaluation alone was conducted on 491 patients (35%; pre-stenting IVUS(-) group). The pre-stenting IVUS(+) group had a larger angiographic minimal lumen diameter and IVUS-derived minimal stent area (MSA) than did the pre-stenting IVUS(-) group. After adjusting, these findings were consistent. The one-year composite of cardiac death, myocardial infarction, and target vessel revascularisation did not differ between the groups. In subgroup analysis, the pre-IVUS(+) group was significantly favoured over the pre-IVUS(-) group in the subset of patients with acute myocardial infarction and lesions with small vessels in terms of larger MSA, and in the subset of patients with chronic total occlusions in terms of better clinical outcomes. Pre-stenting IVUS assessment prior to DES placement was associated with better acute procedural outcomes, though this did not translate into one-year clinical outcomes in the context of post-stenting IVUS assessment. Visual summary. Acute and one-year outcomes of pre-stenting intravascular ultrasound: a meta-analysis of randomised clinical trials.


Rethinking regenerative medicine: a macrophage-centered approach.
Regenerative medicine, a multi-disciplinary approach that seeks to restore form and function to damaged or diseased tissues and organs, has evolved significantly during the past decade. By adapting and integrating fundamental knowledge from cell biology, polymer science, and engineering, coupled with an increasing understanding of the mechanisms which underlie the pathogenesis of specific diseases, regenerative medicine has the potential for innovative and transformative therapies for heretofore unmet medical needs. However, the translation of novel technologies from the benchtop to animal models and clinical settings is non-trivial and requires an understanding of the mechanisms by which the host will respond to these novel therapeutic approaches. The role of the innate immune system, especially the role of macrophages, in the host response to regenerative medicine based strategies has recently received considerable attention. Macrophage phenotype and function have been suggested as critical and determinant factors in downstream outcomes. The constructive and regulatory, and in fact essential, role of macrophages in positive outcomes represents a significant departure from the classical paradigms of host-biomaterial interactions, which typically consider activation of the host immune system as a detrimental event. It appears desirable that emerging regenerative medicine approaches should not only accommodate but also promote the involvement of the immune system to facilitate positive outcomes. Herein, we describe the current understanding of macrophage phenotype as it pertains to regenerative medicine and suggest that improvement of our understanding of context-dependent macrophage polarization will lead to concurrent improvement in outcomes.


Ophthalmic manifestations in IgG4-related disease: Clinical presentation and response to treatment in a French case-series.
IgG4-related disease (IgG4-RD) is characterized by variable tissue or organ involvements sharing common pathological findings. Orbital or orbital adnexa involvement of the disease has been reported in a few case series. The aim of our study was to characterize and analyze ophthalmic manifestations from a nationwide French case-series.Patients with IgG4-RD and orbital or orbital adnexa involvement included in the French multicentric IgG4-RD case-registry were identified. Only patients fulfilling "modified" comprehensive diagnostic criteria with pathological documentation were retained for the study. Clinical, biological, pathological, radiological findings and data regarding the response to treatment were retrospectively analyzed.According to our data registry, the frequency of IgG4-related ophthalmic disease (IgG4-ROD) was 17%. Mean age at diagnosis was 55.1 ± 7.1 years with a male/female ratio of 2.2. The 19 cases of IgG4-ROD consisted of lacrimal gland (68.4%), soft tissue (57.9%), extra-ocular muscles (36.8%), palpebral (21.1%), optical nerve (10.5%), orbital bone (10.5%), and mononeuritis (V1 and/or V2, 10.5%) involvements. IgG4-ROD was bilateral in 57.9% of cases. Extra-ophthalmic manifestations were reported in 78.9% of cases. All patients responded to prednisone but two-thirds of patients relapsed within a mean (SD) of 9.8 (3.5) months and 72.2% required long-term glucocorticoids and/or immunosuppressive agents. Eight patients were treated by rituximab with a favorable response in 87.5% of cases.Lacrimal involvement is the most frequent ophthalmic manifestation of IgG4-RD and is frequently associated with extra-orbital manifestations. Despite initial favorable response to steroids, the long-term management of relapsing patients needs to be improved.


AICAR-Induced AMPK Activation Inhibits the Noncanonical NF-κB Pathway to Attenuate Liver Injury and Fibrosis in BDL Rats.
To evaluate the AMP-activated protein kinase- (AMPK-) mediated signaling and NF-κB-related inflammatory pathways that contribute to cholestatic diseases in the bile duct ligation (BDL) rat model of chronic cholestasis and verify the protective role of 5-Aminoimidazole-4-carboxamide1-β-D-ribofuranoside (AICAR) against hepatic injury and fibrosis triggered by cholestasis-related inflammation. Animals were randomly divided into three groups: sham-operated group, BDL group, and BDL+ AICAR group. Cholestatic liver injury was induced by common BDL. Two weeks later, rats in BDL+AICAR group started receiving AICAR treatment. Hepatic pathology was examined by haematoxylin and eosin (H&E) and sirius red staining and hydroxyproline assay was performed in evaluating the severity of hepatic cirrhosis. Real-time PCR and Western blot were performed for RNA gene expression of RNA and protein levels, respectively. The BDL group showed liver injury as evidenced by histological changes and elevation in serum biochemicals, ductular reaction, fibrosis, and inflammation. The mRNA expression of canonical NF-κB inflammatory cytokines such as TNF-α, IL-1β, TGF-β, and the protein of noncanonical NF-κB, P100, and P52 was upregulated in the livers of BDL rats. The BDL rats with the administration of AICAR could induce AMPK activation inhibiting the noncanonical NF-κB pathway to attenuate liver injury and fibrosis in BDL rats. The BDL model of hepatic cholestatic injury resulting in activation of Kupffer cells and recruitment of immune cells might initiate an inflammatory response through activation of the NF-κB pathway. The AMPK activator AICAR significantly alleviated BDL-induced inflammation in rats by mainly inhibiting the noncanonical NF-κB pathway and thus protecting against hepatic injury and fibrosis triggered by BDL.


Self-reported health bias: the role of daily affective valence and arousal.
The present study addresses gaps in the literature on affect-biased health perceptions by (a) investigating health bias while considering both valence and arousal components of affect; (b) establishing the presence of, and variability in, affective health bias at the daily level; and (c) exploring daily health bias in a non-clinical, community sample of adults. Participants were 477 adults (aged 33-80 years) who reported daily health events, health satisfaction and affect for up to 56 days. Health bias was present when the effect of a given day's health events on that day's health satisfaction was significantly moderated by that day's affect. Multilevel modelling was used to investigate fixed and random within-day effects. Daily health satisfaction. Significant interaction effects indicated the presence of health bias on the daily level: positively valenced affect buffered the negative impact of health events on health satisfaction, whereas negatively valenced affect exacerbated this association; additionally, valence emerged as the most salient characteristic of positive affect, whereas arousal was a differentiating factor for negative affect. The results provide evidence that both valence and arousal components of affect are important to consider when investigating day-level health bias, and that these effects can be detected using a general population of adults.


Investigation on photo-induced mechanistic activity of GO/TiO2 hybrid nanocomposite against wound pathogens.
Pathogenic microorganism delays wound-healing process by causing infection. In recent years, researchers have developed various kinds of photo-active nanomaterials with enhanced antibacterial properties. This work focus on the preparation of graphene oxide and TiO2 nanocomposites (GO/TiO2) as a visible light-induced high efficiency antibacterial material. The hydrothermal method was used for the synthesis of GO/TiO2 nanocomposites at 180 oC for 3 h with different loading percentages of GO (10, 20, 30, 40 and 50 wt. %). The systematic characterization tools including X-ray diffraction analysis, FT-IR, UV-vis, Raman and TEM which were used to understand the physicochemical properties of the prepared GO/TiO2 nanocomposites. Furthermore, GO/TiO2 nanocomposites were used as photocatalytic active materials against wound infection-causing bacteria in the presence of visible light irradiation. The possible antibacterial mechanism under presence and absence of light were depicted. The antibacterial mechanism of the GO/TiO2 nanocomposite was investigated on wound infection-causing bacteria such as Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Enterococcus faecalis. The high hemocompatibility and the cellular biocompatibility of the nanocomposite aids in using it for wound-healing application. Overall, the results suggest that the GO/TiO2 nanocomposite could be developed as a photo-active nanomaterial against pathogenic microorganisms that are present in wound.


Effects of single nucleotide polymorphisms of the folylpolyglutamate synthase gene on pemetrexed administration-induced nephropathy.
Long-term administration of pemetrexed (PEM) in patients with lung cancer can cause renal damage, leading to treatment discontinuation. Previous reports have suggested that specific single nucleotide polymorphisms (SNPs) in the folylpolyglutamate synthase (FPGS) gene affect therapeutic efficacy; however, whether the FPGS SNPs affect renal function is unclear. Identifying SNPs related to renal damage during PEM administration may help predict the decrease in renal function caused by PEM. We retrospectively examined age, sex, body weight, total administered PEM, combined platinum, estimated glomerular filtration rate (eGFR) and serum creatinine (SCr) levels before and after PEM administration in patients with non-small cell lung cancer and searched for the alleles of FPGS SNPs (rs1544105 and rs10106) using DNA extracted from whole blood samples of patients. Renal function decreased after PEM administration in 26 cases overall. The SCr and eGFR indices showed decreased renal function irrespective of concomitant cisplatin use. Based on promoter activity and miRNA binding predictions, rs1544105-C and rs10106-T were hypothesized to increase FPGS expression. Single SNP analyses showed no significant differences in renal function between groups with and without each SNP. Multiple regression analysis revealed that the most significant factors for decreased renal function were sex on SCr and the number of SNPs on eGFR. In subgroup analyses, the patients with rs10106-T showed a decline in renal function in the older group. The number of FPGS SNPs may contribute to PEM-induced renal impairment. Detecting FPGS SNPs may help predict PEM-induced renal damage.


Kinetics and product studies of the reaction of Br, Cl, and NO with ClOOCl using discharge-flow mass spectrometry.
The kinetics of the reactions Cl + ClOOCl --> products, Br + ClOOCl --> products (7), and NO + ClOOCl --> products have been studied as a function of temperature at 1 Torr total pressure using a discharge-flow mass spectrometric technique. The measured rate coefficients, expressed in Arrhenius form, are k5 = (7.60 +/- 0.56) x 10(-11)exp((65.4 +/- 17.9)/T) cm3 s(-1) for 217 K < T < 298 K, and k7 = (5.88 +/- 0.50) x 10(-12) exp(-173 +/- 20/T) cm3 s(-1) for 223 K < T< 298 K. The observed temperature dependencies of these rate coefficients indicate a common direct halogen atom abstraction mechanism. Mass spectral product studies indicate that BrCl is the only major Br-containing product from reaction. Extensive product studies were used to estimate that the peroxide form of the ClO-dimer is formed in > 90% yield from the ClO self-reaction. No evidence for the formation of ClOClO and ClClO2 was observed. No reaction between NO and ClOOCl was observed and an upper limit of k8 < 1 x 10(-15) cm3 s(-1) for 220 K < T < 298 K was determined.


Neutrophils in cancer: neutral no more.
Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets.


The responsiveness of the anterior pituitary gland to luteinizing hormone releasing factor in rats exposed to constant light.
The responsiveness of the anterior pituitary gland to synthetic luteinizing hormone releasing factor (LH-RF) was tested in rats exposed to constant light. At a dosage of 50 ng LH-RF/100 g body wt the mean maximal increments in plasma LH and FSH were similar to those at 10.00 h of pro-oestrus. The increments in the plasma gonadotrophins at dosages of 500 and 1000 ng LH-RF/100 g body wt did not differ significantly from those at 250 ng LH-RF/100 g body wt. These findings suggest that, in contrast to rats which exhibit regular oestrous cycles, the preovulatory (post-coital) release of LH in rats exposed to constant light may depend almost entirely on the release of a relatively large amount of LH-RF into hypophysial portal vessel blood. Whereas in pro-oestrous animals a relatively small fraction of the readily releasable pool of LH is released during the spontaneous preovulatory surge, in rats exposed to constant light most releasable LH appears to be discharged during the reflex preovulatory surge of this hormone. The concentrations of radioimmunoassayable FSH in blood samples withdrawn before the injection of LH-RF support the view that FSH secretion in the rat is increased by constant exposure to light.


Quantification of Chemical and Mechanical Effects on the Formation of the G-Quadruplex and i-Motif in Duplex DNA.
The formation of biologically significant tetraplex DNA species, such as G-quadruplexes and i-motifs, is affected by chemical (ions and pH) and mechanical [superhelicity (σ) and molecular crowding] factors. Because of the extremely challenging experimental conditions, the relative importance of these factors on tetraplex folding is unknown. In this work, we quantitatively evaluated the chemical and mechanical effects on the population dynamics of DNA tetraplexes in the insulin-linked polymorphic region using magneto-optical tweezers. By mechanically unfolding individual tetraplexes, we found that ions and pH have the largest effects on the formation of the G-quadruplex and i-motif, respectively. Interestingly, superhelicity has the second largest effect followed by molecular crowding conditions. While chemical effects are specific to tetraplex species, mechanical factors have generic influences. The predominant effect of chemical factors can be attributed to the fact that they directly change the stability of a specific tetraplex, whereas the mechanical factors, superhelicity in particular, reduce the stability of the competing species by changing the kinetics of the melting and annealing of the duplex DNA template in a nonspecific manner. The substantial dependence of tetraplexes on superhelicity provides strong support that DNA tetraplexes can serve as topological sensors to modulate fundamental cellular processes such as transcription.


Frequency of limb salvage after infra-inguinal bypass for chronic limb-threatening ischaemia in diabetics: A retrospective study.
A study was conducted to assess the number of limbs salvaged among diabetic patients with chronic limb-threatening ischaemia after infra-inguinal bypass surgeries at a low- to middle-income country (LMIC) hospital. It was a retrospective chart review of diabetic patients who underwent infra-inguinal bypass for lower leg revascularisation for chronic limb-threatening ischaemia at the Section of Vascular Surgery, Aga Khan University Hospital, Karachi (Pakistan) from January 2008 till April 2019. Diabetic patients with chronic limb-threatening ischaemia had a salvage rate of 90.5%(29/32) after infra-inguinal bypass surgery in our set up which is comparable to those described in the literature.


Evaluation of 80 children with prolonged fever.
Several studies have been published regarding the etiology and evaluation of a child with prolonged fever, however, the reasons for the prolonged fever have changed during the years. The present study aims to determine the causes of prolonged fever, to investigate the relationship of fever using some basic laboratory tests, and to establish guidelines for the approach in those children. The charts of 80 out of 17490 hospitalized children who were seen between 1996 and 2001 with prolonged fever of longer than 2 weeks and unknown origin were reviewed in the university hospital of Izmir, Turkey. Their charts were evaluated in respect of age, sex, growth curves, educational level of their families, the duration and the magnitude of fever, causes of fever, and basic laboratory investigations such as white blood cell, blood smear, hemoglobin, erythrocyte sedimentation rate, and C-reactive protein. Forty-four (55.00%) were boys and 36 (45.00%) were girls. Forty-four children (55.00%) were aged between 1 month and 2 years, 21 (26.25%) were aged 3-6 years, seven (8.75%) were aged 7-10 years, and eight (10.00%) were older than 10 years. The mean age was 3.87 +/- 4.17 years (range 3 months-17 years). Forty-six children (57.50%) had a prolonged fever that had lasted from 15-30 days, 18 (22.50%) from 31-60 days, and 16 (20.00%) had fever lasting more than 60 days. Final diagnosis had been reached in 70 of the 80 children (87.50%). The most common causes were infection (47/80), followed by immune deficiency (6/80), collagen tissue disorder (5/80), neoplasia (2/80), and miscellaneous (10/80) such as central fever in three, diabetes insipidus in two, familial Mediterranean fever in two, Kawasaki disease, foreign body in the respiratory system, and Crohn disease in one patient each. Among the laboratory tests white blood cell count, hemoglobin level and blood smear distribution of infection group were statistically significant. The most common cause of fever of unknown origin remains infection. The proportion of collagen tissue disorders and neoplasia have been found to be decreased. Unusual reasons such as diabetes insipidus and foreign body in the respiratory system in the miscellaneous group have been detected. Age plays important role in the diagnosis of prolonged fever, while some basic laboratory tests might give clues in the evaluation and may suggest a diagnosis.


Dietary predictors of arterial stiffness in a cohort with type 1 and type 2 diabetes.
To determine the dietary predictors of central blood pressure, augmentation index and pulse wave velocity (PWV) in subjects with type 1 and type 2 diabetes. Participants were diagnosed with type 1 or type 2 diabetes and had PWV and/or pulse wave analysis performed. Dietary intake was measured using the Dietary Questionnaire for Epidemiological Studies Version 2 Food Frequency Questionnaire. Serum lipid species and carotenoids were measured, using liquid chromatography electrospray ionization-tandem mass spectrometry and high performance liquid chromatography, as biomarkers of dairy and vegetable intake, respectively. Associations were determined using linear regression adjusted for potential confounders. PWV (n = 95) was inversely associated with reduced fat dairy intake (β = -0.01; 95% CI -0.02, -0.01; p = 0 < 0.05) in particular yoghurt consumption (β = -0.04; 95% CI -0.09, -0.01; p = 0 < 0.05) after multivariate adjustment. Total vegetable consumption was negatively associated with PWV in the whole cohort after full adjustment (β = -0.04; 95% CI -0.07, -0.01; p < 0.05). Individual lipid species, particularly those containing 14:0, 15:0, 16:0, 17:0 and 17:1 fatty acids, known to be of ruminant origin, in lysophosphatidylcholine, cholesterol ester, diacylglycerol, phosphatidylcholine, sphingomyelin and triacylglycerol classes were positively associated with intake of full fat dairy, after adjustment for multiple comparisons. However, there was no association between serum lipid species and PWV. There were no dietary predictors of central blood pressure or augmentation index after multivariate adjustment. In this cohort of subjects with diabetes reduced fat dairy intake and vegetable consumption were inversely associated with PWV. The lack of a relationship between serum lipid species and PWV suggests that the fatty acid composition of dairy may not explain the beneficial effect.


Metabolic Mechanism of Sulfadimethoxine Biodegradation by Chlorella sp. L38 and Phaeodactylum tricornutum MASCC-0025.
Antibiotic resistance is one of the most important environmental challenges. Microalgae has been considered as a promising green media for environmental purification. In this work, sulfadimethoxine (SDM) biodegradation potential of Chlorella sp. L38 and Phaeodactylum tricornutum MASCC-0025 is investigated. Experimental results indicated that the tested freshwater and marine microalgae strains presented stress response to SDM addition. For Chlorella sp. L38, it has a good adaptability to SDM condition via antioxidant enzyme secretion (SOD, MDA, and CAT up to 23.27 U/mg, 21.99 μmol/g, and 0.31 nmol/min/mg) with removal rate around 88%. P. tricornutum MASCC-0025 exhibited 100% removal of 0.5 mg/L SDM. With increasing salinity (adding a certain amount of NaCl) of cultivation media, the removal rate of SDM by microalgae increased. Although its adaptive process was slower than Chlorella sp. L38, the salinity advantage would facilitate enzyme accumulation. It indicated that microalgae could be used to remove SDM from freshwater and marine environment via suitable microalgae strain screening.


The medicalisation of male menopause in America.
The topic of male menopause occupied space on the medical radar screen from the late 1930s through the mid-1950s, then virtually disappeared for the next four decades, until the late 1990s. By contrast, articles on this subject appeared in American popular magazines and newspapers at a consistent, if low-level, rate throughout the same period. This essay describes how the male menopause became medicalised, not by the driving forces of academic researchers and influential clinicians, but instead by a model perpetuated by lay people and medical popularisers. A medicalised conceptualisation of the body and the life-cycle had become widespread by the second half of the twentieth century, as Americans grew accustomed to regarding their lives through the lens of medicine. People came to expect medicine to provide a cure for any ailment; in the wake of the development of the so-called wonder drugs, no affliction seemed beyond medical and pharmaceutical intervention. A medicalised model had also been effectively produced for understanding and treating the menopause in women; a parallel, if not identical, stage in the life-course of men seemed reasonable. This framework, rather than persuasive evidence from the research laboratory or clinic, helped to medicalise male menopause and provided the basis for its eventual pharmaceuticalisation at the end of the twentieth century.


Toward TeV conformality.
We study the chiral properties of an SU(3) gauge theory with N{f} massless Dirac fermions in the fundamental representation when N{f} is increased from 2 to 6. For N{f}=2, our lattice simulations lead to a value of psi psi/F{3}, where F is the Nambu-Goldstone-boson decay constant and psi psi is the chiral condensate, which agrees with the measured QCD value. For N{f}=6, this ratio shows significant enhancement, presaging an even larger enhancement anticipated as N{f} increases further, toward the critical value for transition from confinement to infrared conformality.


Itaconic Acid as A Differential Transcription Regulator of Apoptosis and Autophagy Pathways Genes: A Rat Adipose Mesenchymal Stem Cells Model.
Itaconate, a novel regulatory immunometabolite, is synthesized by inflammatory macrophage. It acts as an anti-inflammatory mediator and regulates several metabolic and signaling pathways particularly Nrf2 pathway. The immunometabolites can affect the stemness potency, differentiation ability and viability of stem cells, but little is known about the critical function of Itaconate on the stem cell fate. The objective of the present study was to determine the regulatory effects of Itaconic acid on the cell viability and transcription of apoptosis and autophagy pathways genes in the rat adipose derived mesenchymal stem cells (ADMSCs). In this experimental study, the ADMSCs were incubated with 125 μM and 250 μM dimethyl itaconate (DMI) for 24 hours or 48 hours. The expression of apoptosis pathway genes (Bax, Bcl2, Caspase 3, Fas, Fadd and Caspase 8) and autophagy pathway genes (Atg12, Atg5, Beclin, Lc3b and P62) were determined using real time polymerase chain reaction (PCR) assay. Using the ELISA method, cellular level of phospho-NRF2 protein was measured. The results indicated that DMI increased the expression of NRF2 protein, altered the expression of some apoptosis genes (Fadd, Bax and Bcl2), and changed the expression of some autophagy related genes (Lc3b, Becline and P62) in ADMSCs. DMI had no obvious effect on the transcription of caspases enzymes. Because autophagy activation and apoptosis suppression can protect stem cells against environmental stress, it seems Itaconate can affect the functions and viability of ADMSCs via converse regulation of these pathways.


2009 pandemic H1N1 influenza virus replicates in human lung tissues.
The replication activity of 2009 pandemic H1N1 influenza virus in human lung cells was evaluated in this study. Twenty-two surgically removed human lung tissue samples were infected ex vivo with pandemic H1N1 influenza virus (A/California/04/2009), seasonal human H1N1 influenza virus (A/Shantou/92/09), or a highly pathogenic H5N1 influenza virus (A/Vietnam/1194/04). Examination of nucleoprotein expression and viral RNA replication in the infected human lung tissue samples showed that whereas the replication of pandemic H1N1 influenza virus varied between tissue samples, overall this virus replicated more efficiently than seasonal H1N1 influenza virus but less efficiently than H5N1 influenza virus. Double-immunostaining for viral antigens and cellular markers indicated that pandemic H1N1 influenza virus replicates in type 2 alveolar epithelial cells.


Unraveling the Potential of Orange Pulp for Improving Laying Rate, Egg Quality, Oxidative Stability, Fatty Acids Composition, and Reproductive Tract Morphology of Laying Hens.
The current study aimed to demonstrate the effects of dietary dried orange pulp (DOP) on the laying performance, egg quality, antioxidant status, yolk fatty acid composition, serum biochemistry, and reproductive tract morphology of laying hens. A total of 200 Lohman Brown Lite laying hens were randomly allotted into 4 dietary treatments with 10 replicates each. The experimental treatment groups were the control group, a basal diet containing 50 g DOP/kg feed (DOP5%), a basal diet containing 70 g DOP/kg feed (DOP7%), and a basal diet containing 100 g DOP/kg feed (DOP10%). Data were statistically analyzed by one-way ANOVA following a completely randomized design, and the incremental levels of dietary DOP were tested by orthogonal polynomial contrasts. The body weight gain, feed intake, egg production%, egg weight, egg mass, and feed conversion ratio of laying hens fed the DOP7% and DOP10% diets were greater (p < 0.01) than those fed the control diet. Eggs obtained from the DOP7% and DOP10% groups had a heavier shell weight% and shell thickness, as well as a greater yolk color score (p < 0.01; linear, p < 0.01). Dietary DOP improved the egg yolk concentrations of PUFA, n-3 PUFA, and n-6 PUFA (linear, p < 0.001; quadratic, p < 0.05), whereas the content of SFA was reduced (p < 0.001; linear, p < 0.001). The egg yolk cholesterol and triglyceride levels were linearly decreased (p < 0.001) with the inclusion of DOP in the diets of hens. After storage for 40 days, the malondialdehyde (MDA) contents in the egg yolk were reduced, whereas the glutathione peroxidase content was increased (p < 0.01) due to dietary DOP. The DOP7% and DOP10% hens had an obvious reduction in the levels of serum total lipids, total cholesterol, triglycerides, low-density lipoprotein, and MDA, whereas high-density lipoprotein and GPx levels were increased (p < 0.01) compared with those fed the control diet. The relative weights of the ovary, oviduct, uterus, and follicle of hens receiving diets containing 7% and 10% DOP were heavier (p < 0.01) than those of the control hens. Moreover, the number of large yellow follicles was increased (p < 0.001; linear, p < 0.001) in the hens-fed diets containing 7% and 10% DOP. In conclusion, dietary DOP at up to 100 g/kg of feed improves laying performance, health status, antioxidant capacity, egg nutritive value, and egg shelf life in laying hens.