Transient ischemic attack presenting as recurrent migratory numbness by seconds: a rare case confirmed by transcranial Doppler micro-emboli monitoring.
Transient ischemic attack (TIA) is a brief episode of cerebral ischemia. However, if a symptom is not presented as drop attack or hemiplegia, and alarming to the patient and the physician, how short of a symptom duration would raise the concern of a physician for TIA? It will be more complicated if the location of the neurological deficit is vagrant. This report highlights a rare TIA case which presented a very short duration of migratory patchy distribution numbness. A middle-aged gentleman was presented with recurrent patchy distribution numbness on the right side of the body for 2 months, with the episode lasting as short as about 10 s. The location of the numbness was erratic and migratory. Magnetic resonance angiography (MRA) revealed mild stenosis on the left middle cerebral artery (MCA). Transcranial Doppler (TCD) micro-emboli monitoring detected positive micro-emboli signals (MES), leading to the confirmation of a TIA diagnosis. After a standard dual antiplatelet treatment combined with enhanced lipid reduction therapy with statins, MES disappeared on dynamic TCD emboli monitoring, and no more episodes of TIA have been noticed on the follow-ups. TIA caused by micro-emboli can display as recurrent migratory neurological deficit within seconds. TCD micro-emboli monitoring is very helpful to differentiate this situation from TIA mimics with follow-ups, as well as to locate unstable plague.


The efficacy and safety of extending the ischemic time with a modified cardioplegic technique for coronary artery surgery.
The need to intermittently discontinue the administration of cardioplegia in order to complete the surgical procedure is a major drawback of antegrade warm blood cardioplegia. An ischemic time of 15 minutes is generally considered safe based on empirical observation. The aim of this study was the evaluation of the efficacy and safety of an intermittent warm blood cardioplegia with intervals between administrations prolonged to 25 minutes. Ninety-seven patients undergoing primary elective coronary artery revascularization were prospectively randomized into two groups. The first, Intermittent Antegrade Warm Blood Cardioplegia (IAWBC) group, comprising 49 patients, received standard intermittent antegrade warm blood cardioplegia repeated every 15 minutes. The second, Modified Intermittent Antegrade Warm Blood Cardioplegia (M-IAWBC) group, comprising 48 patients, received intermittent antegrade warm blood cardioplegia supplemented with magnesium sulfate (MgSO(4)), delivered in volumes proportional to the ventricular mass and repeated every 25 minutes. The clinical outcomes were evaluated. The levels of creatine kinase-MB (CK-MB) isoenzyme, in addition to the echocardiographic assessment of septal dyskinesia and tricuspid annulus plane systolic excursion (TAPSE), have been used as markers of myocardial damage. There were no statistically significant differences in clinical outcomes, need for inotropes and vasodilators, length of stay in the intensive care unit, and postoperative levels of CK-MB between the two groups. Likewise, postoperative echocardiographic assessment showed no relevant differences. Administration of warm antegrade cardioplegic solution supplemented with MgSO(4), delivered in volumes proportional to ventricular mass every 25 minutes, provides adequate myocardial protection for coronary artery surgery.


Genomic sequence of the HLA-B*08:01:71, HLA-B*51:382, and HLA-B*55:01:30 alleles.
The full length sequence of the HLA-B*08:01:71, HLA-B*51:382 and HLA-B*55:01:30 alleles are reported.


Fusimotor neurones can be reflexly influenced by activity in receptor afferents from the posterior cruciate ligament.
Recordings were made simultaneously from 2-4 primary muscle spindle afferents from triceps surae and/or posterior biceps and semitendinosus muscles in cats anaesthetized with alpha-chloralose. It was demonstrated that stretch of the posterior cruciate ligament of the ipsilateral knee could cause changes in dynamic and/or static sensitivity of these afferents to sinusoidal stretching. The changes were due to reflex actions of stretch/tension-sensitive receptors in the cruciate ligaments onto fusimotor neurones. It is concluded that the cruciate ligaments may play an important 'sensory' role and that they may participate, via reflex actions on the gamma-motor-muscle spindle system, in the regulation of muscular stiffness of the knee joint, and thereby of the knee joint stability.


[Treatment of renal calculi with extracorporeal lithotripsy. Experience of the Urology Service at Rennes. Preliminary report on 134 patients].
The results of 134 patients who underwent 150 treatments with the EDAP lithotriptor are reported. The first patients were treated with a frequency of 150 Hz under general anesthesia, with a success rate of 64%. In order to decrease the pain induced by the shocks waves, the frequency was lowered (20 Hz and 10 Hz), so that treatment could be performed under neuroleptic analgesia. The success rate was respectively 84% and 90%. A second treatment was required in 11% of the patients and 9% have undergone auxiliary endoscopic manoeuvres preoperatively. Morbidity was extremely low with only 3% of ureteral obstruction. The gradual reduction of anesthesia constitutes an advance in lowered morbidity and costs; in addition, the possibility to repeat the treatments makes the management of complex lithiasis easier.


Anaplastic carcinoma of the colon: clinicopathologic study of eight cases of a poorly recognized lesion.
Eight cases of a distinctive histological variant of bowel cancer characterized by an anaplastic morphology were identified from 2,650 colonic malignancies (0.3%). The tumors were histologically composed of sheets of anaplastic tumor cells with frequent atypical mitoses, absence of gland formation, and mucicarmine and periodic acid-Schiff (PAS) negativity. Positive immunostaining for cytokeratin and vimentin was observed in eight cases and for epithelial membrane antigen in three; whereas carcinoembryonic antigen, alpha-fetoprotein, S-100 protein, HMB-45 antimelanoma antigen, leukocyte common antigen, and neuroendocrine markers were uniformly negative. Ultrastructural examination demonstrated intercellular tight junctions, focal surface microvilli, and apical terminal webs or long rootlets of microfilaments supporting a colonic derivation. At the time of diagnosis, metastases to regional lymph nodes were found in seven cases and to the liver in six. All patients in this study died of tumor within 9 months. This report emphasizes a poorly recognized variant of colonic carcinoma, characterized by a high degree of anaplasia and malignant behavior. The differential diagnosis for these lesions is discussed.


Increased creativity associated with dopamine agonist therapy: A case report and short review of the literature.
Impulse control disorder (ICD) has been linked to dopamine agonist use in patients with Parkinson's disease. Increased creativity is another cognitive side effect of dopaminergic therapy. While ICD is well recognized in the literature, enhanced creativity as a positive phenomenon is underreported because it does not negatively affect the patients' quality of life. Herein, we report a case of a 49-year-old man with Parkinson's disease who developed enhanced creativity expressed by the acquisition of multiple, new artistic skills with ropinirole treatment. He spent a significant amount of time on painting, carving and axe restoration, selling these artistic products became a source of income. He also reports that these hobbies help him cope with physical limitations caused by Parkinson's disease.


Human hedgehog interacting protein expression and promoter methylation in medulloblastoma cell lines and primary tumor samples.
Medulloblastoma is the most common pediatric brain tumor and its development is affected by genetic and epigenetic factors. In this study we found there is low or no expression of the hedgehog interacting protein (HHIP), a negative regulator of the sonic hedgehog pathway, in most medulloblastoma cell lines and primary samples explored. We proceeded to promoter methylation assays of this gene by MCA-Meth, and found that HHIP was hypermethylated in all medulloblastoma cell lines, but only in 2 out of 14 (14%) primary tumor samples. Methylation correlated with low or unexpressed HHIP in cell lines but not in primary tumor samples. These results suggest the possibility of epigenetic regulation of HHIP in medulloblastoma, similarly to gastric, hepatic and pancreatic cancer. However, HHIP seems to be not only under regulation of promoter methylation, but under other factors involved in the control of its low levels of expression in medulloblastoma.


Online Resources Useful for Plant Cytogenetics and Cytogenomics Research.
The advancements in research in the field of plant cytogenetics and genomics in recent decades have led to a significant increase in publications. To simplify access to the widely dispersed data, there has been a rise in the number of online databases, repositories, and analytical tools. This chapter presents a comprehensive overview of these resources, which can be beneficial to researchers in these areas. It includes, among others, databases on chromosome numbers, special chromosomes (such as B chromosomes or sex chromosomes), some of which are taxon-specific; genome sizes, cytogenetics; and online applications and tools for genomic analysis and visualization.


Pravastatin suppresses the increase in matrix metalloproteinase-2 levels after acute myocardial infarction.
Matrix metalloproteinase (MMP) may contribute to myocardial remodeling after myocardial infarction. The goal of this study was to characterize the effects of pravastatin on circulating levels of MMP and on left ventricular dilatation after acute myocardial infarction (AMI). Thirty-four consecutive patients with successful reperfusion following AMI were assigned to either pravastatin group (group P, n=12) or non-pravastatin group (group NP, n=22). Serum MMP-2 and tissue inhibitor of MMP (TIMP)-2 were measured immediately after reperfusion, on days 2, 3, 7, 30, and at 6 months after MI. Left ventriculography was performed after reperfusion and at 4 weeks and 6 months. MMP-2 levels were higher in patients with MI than control on days 1, 30, and at 6 months. Left ventricular end-diastolic volume index (LVEDVI) at 6 months correlated with MMP-2 levels on day 30 (r=0.47, p<0.01) and at 6 months (r=0.56, p<0.001). MMP-2 levels at 6 months were significantly lower in group P than group NP. Further, LVEDVI at 6 months tended to be smaller and DeltaLVEDVI was significantly smaller in group P when compared with group NP. Serum MMP-2 varied in a time-dependent manner following AMI and correlated with late changes in LVEDVI. Serum MMP-2 levels were significantly lower in treatment group than in non-treatment group and DeltaLVEDVI was significantly smaller in treatment group after long-term pravastatin administration. Use of statins in AMI patients may provide beneficial effects in terms of preventing heart failure over and above its lipid-lowering effects.


The BARD1 Cys557Ser variant and risk of familial breast cancer in a South-American population.
Since the discovery of the BRCA1 and BRCA2 genes, much work has been carried out to identify further breast cancer (BC) susceptibility genes. BARD1 (BRCA1-associated ring domain) was originally identified as a BRCA1-interacting protein but has also been described in tumor-suppressive functions independent of BRCA1. Some association studies have suggested that the BARD1 Cys557Ser variant might be associated with increased risk of BC, but others have failed to confirm this finding. To date, this variant has not been analyzed in Spanish or South-American populations. In this study, using a case-control design, we analyzed the C-terminal Cys557Ser change in 322 Chilean BC cases with no mutations in BRCA1 or BRCA2 and in 570 controls in order to evaluate its possible association with BC susceptibility. BARD1 Cys557Ser was associated with an increased BC risk (P = 0.04, OR = 3.4 [95 % CI 1.2-10.2]) among cases belonging to families with a strong family history of BC. No difference between single cases affected with age <50 years at diagnosis (n = 117) and controls was observed for carriers of Cys/Ser genotype. It is likely that this variant is not involved in BC risk in this group of women. We also analyzed a possible interaction between BARD1 557Ser/XRCC3 241Met variants considering the role of both genes in the maintenance of genome integrity. The combined genotype Cys/Ser-carrier with the XRCC3 241Met allele was associated with an increased BC risk (P = 0.02, OR = 5.01 [95 % CI 1.36-18.5]) among women belonging to families with at least three BC and/or ovarian cancer cases. Our results suggest that BARD1 557Ser and XRCC3 241Met may play roles in BC risk in women with a strong family history of BC. Nevertheless there is no evidence of an interaction between the two SNPs. These findings should be confirmed by other studies and in other populations.


The Role of N6-Methyladenosine in the Promotion of Hepatoblastoma: A Critical Review.
Hepatoblastoma (HB) is a rare primary malignancy of the developing fetal liver. Its course is profoundly influenced by genetics, in the context of sporadic mutation or genetic syndromes. Conventionally, subtypes of HB are histologically determined based on the tissue type that is recapitulated by the tumor and the direction of its differentiation. This classification is being reevaluated based on advances on molecular pathology. The therapeutic approach comprises surgical intervention, chemotherapy (in a neoadjuvant or post-operative capacity), and in some cases, liver transplantation. Although diagnostic modalities and treatment options are evolving, some patients experience complications, including relapse, metastatic spread, and suboptimal response to chemotherapy. As yet, there is no consistent framework with which such outcomes can be predicted. N6-methyladenosine (m6A) is an RNA modification with rampant involvement in the normal processing of cell metabolism and neoplasia. It has been observed to impact the development of a variety of cancers via its governance of gene expression. M6A-associated genes appear prominently in HB. Literature data seem to underscore the role of m6A in promotion and clinical course of HB. Illuminating the pathogenetic mechanisms that drive HB are promising additions to the understanding of the clinically aggressive tumor behavior, given its potential to predict disease course and response to therapy. Implicated genes may also act as targets to facilitate the evolving personalized cancer therapy. Here, we explore the role of m6A and its genetic associates in the promotion of HB, and the impact this may have on the management of this neoplastic disease.


Autoimmune antiphospholipid antibodies impair the inhibition of activated factor X by protein Z/protein Z-dependent protease inhibitor.
The hemostatic process is tightly regulated by several antithrombotic mechanisms. Among them, protein Z (PZ)-dependent protease inhibitor (ZPI) potently inhibits factor (F)Xa in a manner dependent on calcium ions, phospholipids and PZ. Autoimmune antiphospholipid antibodies (aPL) are mainly directed against phospholipid-binding plasma proteins such as beta2-glycoprotein I (beta2GPI) and prothrombin, and are known to interfere with phospholipid-dependent hemostatic pathways. In this study, we investigated whether purified aPL are able to interfere with inhibition of FXa by PZ/ZPI. beta2GPI modestly delayed the FXa inactivation by PZ/ZPI and most isolated aPL-IgGs were found to further increase the inhibitory potential of beta2GPI on PZ/ZPI activity. Without beta2GPI, the PZ/ZPI activity was unaffected by the addition of aPL-IgG. As PZ deficiency is hypothesized to lead to a prothrombotic state, we performed a case-control study to measure plasma levels of PZ and ZPI in 66 patients with autoimmune aPL and 152 normal controls. The prevalence of low PZ levels (below the 5th percentile of controls) was significantly greater in the 37 patients with definite antiphospholipid syndrome (APS) (24.3%) but not in the 29 aPL patients not fulfilling the criteria for APS (10.3%) compared with the normal group (4.6%, P < 0.001 vs. APS). ZPI antigen levels were similar in patients with aPL and normal controls. Concomitant PZ deficiency increased by approximately sevenfold the risk of arterial thrombosis in aPL patients. Taken together, these data suggest that the PZ/ZPI system is commonly impaired in aPL patients thus probably increasing the thrombotic risk.


Measurement of the neutron radius of 208Pb through parity violation in electron scattering.
We report the first measurement of the parity-violating asymmetry A(PV) in the elastic scattering of polarized electrons from 208Pb. A(PV) is sensitive to the radius of the neutron distribution (R(n)). The result A(PV)=0.656±0.060(stat)±0.014(syst) ppm corresponds to a difference between the radii of the neutron and proton distributions R(n)-R(p)=0.33(-0.18)(+0.16) fm and provides the first electroweak observation of the neutron skin which is expected in a heavy, neutron-rich nucleus.


Is there still a role for aprotinin in cardiac surgery?
Cardiac surgery is associated with a systemic inflammatory response and systemic coagulopathy, which can result in significant organ dysfunction and bleeding. Aprotinin, a serine protease inhibitor, can limit systemic inflammation, and has been associated with myocardial, pulmonary and cerebral protection in addition to its proven haemostatic efficacy. Data are currently conflicting regarding the haemostatic efficacy of aprotinin relative to alternative agents including tranexamic acid. Recent studies have demonstrated aprotinin usage is associated with increased rates of thrombotic and renal complications, but these findings are at odds with the majority of studies relating to aprotinin safety to date. The lack of adequately powered, randomised studies evaluating aprotinin and alternative agents limits drawing conclusions about the complete use or disuse of aprotinin presently and requires individualised patient selection based on bleeding risk and co-morbidities for its usage.


Development of intravenous lipid emulsion of α-asarone with significantly improved safety and enhanced efficacy.
Severe adverse events have been frequently associated with taking the commercially available formulation of α-asarone injection (α-asarone-I). Hence, we sought to develop an intravenous lipid emulsion of α-asarone (α-asarone-LE), where we hypothesized that these adverse events could be prevented. Using a central composite design-response surface methodology, we developed and optimized an emulsion formulation of α-asarone-LE that composed of 10.0% (w/v) soybean oil, 0.4% (w/v) α-asarone, 1.2% (w/v) soybean lecithin, 0.3% (w/v) F68, and 2.2% (w/v) glycerol. The mean particle size of α-asarone-LE was 226±11 nm, the ζ-potential was -25.6±1.2 mV, the encapsulation efficiency was 99.2±0.1% and the drug loading efficiency was 3.45%. Stability, safety, and efficacy studies of α-asarone-LE were systematically investigated and compared to those of α-asarone-I. The α-asarone-LE not only showed a desired stability, but also exhibited excellent safety and improved efficacy in vivo, indicating its great potential for clinical application in the future.


Human middle-latency auditory evoked potentials: vertex and temporal components.
We recorded middle-latency (20-70 msec) auditory evoked potentials (MLAEPs) to monaural and binaural clicks in 30 normal adults (ages 20-49 years) at 32 scalp locations all referred to a balanced non-cephalic reference. Our goal was to define the MLAEP components that were present at comparable latencies and comparable locations across the subject population. Group and individual data were evaluated both as topographic maps and as MLAEPs at selected electrode locations. Three major components occurred between 20 and 70 msec, two well-known peaks centered at the vertex, and one previously undefined peak focused over the posterior temporal area. Pa is a 29 msec positive peak centered at the vertex and present with both monaural and binaural stimulation. Pb is a 53 msec positive peak also centered at the vertex but seen consistently only with binaural and right ear stimulation. TP41 is a 41 msec positive peak focused over both temporal areas. TP41 has not been identified in previous MLAEP studies that concentrated on central scalp locations and/or used active reference electrode sites such as ears or mastoids. Available topographic, intracranial, pharmacologic, and lesion studies indicate that Pa, Pb and TP41 are of neural origin. Whether Pa and/or Pb are produced in Heschl's gyrus, primary auditory cortex, remains unclear. TP41 is probably produced by auditory cortex on the posterior lateral surface of the temporal lobe. It should prove of considerable value in experimental and clinical evaluation of higher level auditory function in particular and of cortical function in general.


Exon-1 polymorphism of ctla-4 gene is not associated with systemic sclerosis in Iranian patients.
Although, the cytotoxic T lymphocyte antigen-4 gene polymorphism at position 49 of exon-1 has been strongly elucidated in different autoimmune diseases, but its role in predisposition to systemic sclerosis (SSc) is yet controversial. This study intends to analyze the genetic correlation of the ctla-4 gene locus with diffuse systemic sclerosis (dSSc), as well as to understand the influence of these genotypes in disease expression. Seventy known cases of SSc, and 151 age-matched healthy controls, were participated in this investigation. The frequencies of AA, GG and AG genotypes were found to be 26 (37.1%), 5 (7.2%) and 39 (55.7%) in patients, and 60 (39.7%), 19 (12.6%) and 72 (47.7%) in controls, respectively. As indicated, the differences in genotype and allele frequencies between patients and controls were insignificant (P>0.05). Moreover, the distribution of CTLA-4 polymorphism between patients did not differ significantly according to clinical and serologic features. In Iranian patients, susceptibility to SSc is not influenced by a bi-allelic ctla-4 gene (A49G) polymorphism.


Chromatographic behavior of silica-polymer composite molecularly imprinted materials.
Molecularly imprinted polymers (MIP) have recently been prepared inside the pores of silica based HPLC packing materials. Detailed physical and chromatographic characterization of such a silica-MIP composite material is presented. The chromatographic peak shape obtained with the uniformly sized spherical silica-MIP composite is mainly determined by the nonlinear adsorption isotherm. Comparison of the composite with the conventional sieved and grinded bulk MIP is therefore based on the nonlinear isotherm and not on retention factors and plate numbers.


Different members of the jun proto-oncogene family exhibit distinct patterns of expression in response to type beta transforming growth factor.
Type beta transforming growth factor (TGF-beta) is a multifunctional regulator of cell growth and differentiation. In the BC3H1 muscle cell line, TGF-beta blocks the onset of differentiation when added to undifferentiated myoblasts and causes dedifferentiation when added to fully differentiated myocytes. The goal of the present study was to determine whether TGF-beta-dependent repression of muscle-specific genes was preceded by modulation in expression of members of the jun proto-oncogene family, which function as growth factor-inducible transcription factors. junB mRNA was expressed at a basal level in differentiated BC3H1 myocytes. Within 15 min following exposure of myocytes to TGF-beta, junB mRNA began to accumulate; a peak of expression 20-fold above basal levels was observed after 2 h with a gradual decline thereafter. Nuclear run-on transcription assays showed that induction of junB by TGF-beta occurred at the level of transcription through a mechanism independent of protein synthesis. junB was also induced by 20% fetal bovine serum, platelet-derived growth factor, and insulin, but the maximal level of expression in response to these growth factors was lower and less sustained than in the presence of TGF-beta. In contrast to the dramatic effects of TGF-beta on junB expression, c-jun showed only a 2.5-fold increase in expression in response to TGF-beta. In an effort to identify additional members of the jun family which might be regulated by TGF-beta, a cDNA library was prepared from the poly(A)+ mRNA of TGF-beta-stimulated BC3H1 myocytes and was screened under conditions of reduced stringency with a v-jun DNA probe. From this screen, a new jun-related gene product was identified which shared a high degree of homology with regions of c-jun and junB which have been implicated in transcriptional activation, dimerization, and DNA binding. The transcript for this jun-related gene was expressed constitutively in BC3H1 cells and was not regulated by TGF-beta. Three members of the jun family thus exhibit distinct responses to TGF-beta in BC3H1 cells. The rapid transcriptional induction of junB is among the earliest and most dramatic responses to TGF-beta yet described and suggests that junB may mediate certain of the diverse biological effects of this growth factor.


Modulation of bovine neutrophil antibacterial activities by Pasteurella haemolytica A1 purified capsular polysaccharide.
Preincubation of bovine neutrophils with Pasteurella haemolytica A1 purified capsular polysaccharide markedly diminished their ability to ingest and kill P. haemolytica, but not Escherichia coli, in vitro. Ingestion and killing were impaired even when the P. haemolytica were preopsonized, thus suggesting that the inhibitory effects of the polysaccharide included a direct effect on bovine neutrophils rather than simply competition for serum opsonins. Preincubation of neutrophils with purified polysaccharide did not elicit a chemiluminescence response, nor did it alter the chemiluminescence response of neutrophils to subsequent stimulation with opsonized P. haemolytica or opsonized zymosan. In addition, purified polysaccharide alone was neither chemotactic nor did it induce a shape change in bovine neutrophils. These data suggest that the deposition of capsular polysaccharide in the lung during the onset of pulmonary pasteurellosis might impair the ability of neutrophils to ingest and kill P. haemolytica. The capsular polysaccharide of P. haemolytica, therefore, may contribute in part to the fibrinous pleuropneumonia that characterizes acute pasteurellosis.


Inhibition of Csn3 expression induces growth arrest and apoptosis of hepatocellular carcinoma cells.
Csn3 (or CSN3) encodes the third subunit of an eight-subunit complex, the COP9 signalosome (CSN), which acts as a protein kinase and a deneddylase in mammalian cells. Previous studies have shown that Csn3 is essential for maintenance of cell proliferation in the mouse embryonic epiblast and associated with the tumorigenesis process in osteosarcoma. However, its correlation with hepatocellular carcinoma (HCC) has not been explored yet. The expression of Csn3 in HCC (n = 30), cirrhosis (n = 30), and normal tissues (n = 30) was detected using immunohistochemical analysis. The impacts of lentivirus-mediated inhibition of Csn3 on HCC cells were detected using MTT, BrdU incorporation assay, and flow cytometric analysis. In addition, the colony formation and tumor growth ability in nude mice were detected to define the role of Csn3 in tumorigenesis. Knockdown of Csn3 expression in HCC cell lines (SMMC-7721 and Hep3B) significantly inhibits the tumor growth both in vitro and in vivo. Further investigation indicates that this growth inhibition effect may be mediated through cell cycle arrest in G0/G1 phase and inductions of pro-apoptotic proteins BIK and Caspase-8. In addition, knockdown of Csn3 expression evidently suppresses tumor growth in a xenograft nude mice model. Collectively, this study demonstrates Csn3 as an oncogene that regulates the tumorigenesis process in HCC cells.


Fast numerical algorithms for fitting multiresolution hybrid shape models to brain MRI.
In this paper, we present new and fast numerical algorithms for shape recovery from brain MRI using multiresolution hybrid shape models. In this modeling framework, shapes are represented by a core rigid shape characterized by a superquadric function and a superimposed displacement function which is characterized by a membrane spline discretized using the finite-element method. Fitting the model to brain MRI data is cast as an energy minimization problem which is solved numerically. We present three new computational methods for model fitting to data. These methods involve novel mathematical derivations that lead to efficient numerical solutions of the model fitting problem. The first method involves using the nonlinear conjugate gradient technique with a diagonal Hessian preconditioner. The second method involves the nonlinear conjugate gradient in the outer loop for solving global parameters of the model and a preconditioned conjugate gradient scheme for solving the local parameters of the model. The third method involves the nonlinear conjugate gradient in the outer loop for solving the global parameters and a combination of the Schur complement formula and the alternating direction-implicit method for solving the local parameters of the model. We demonstrate the efficiency of our model fitting methods via experiments on several MR brain scans.


Outpatient Clinical Markers for Laryngopharyngeal Reflux Disease: A Correlational Study.
Laryngopharyngeal reflux disease (LPRD) is the result of retrograde flow of gastric contents to the laryngopharynx which comes in contact with tissues of the upper aerodigestive tract. Due to ill defined criteria for diagnosis & followup, LPRD patients are underdiagnosed & undertreated. Reflux Symptom Index (RSI) and the Reflux Finding Score (RFS) are two clinical methods which can be utilised especially in the outpatient setup. This study was done with the aim to assess various laryngoscopic findings in patients with LPRD diagnosed symptomatically and examine the correlation between the RSI & RFS by comparing these two indices. This prospective analytical study was conducted at a tertiary care centre in Bangalore in the Department of ENT for a period of 24 months between Dec 2020 to Dec 2022. The study included patients aged 18 to 60 years diagnosed with LPRD based on symptoms as per RSI score (> 13). RSI & RFS were assessed on diagnosis and patients were followed up for 1, 3 & 6 months for assessment. Total 96 patients were enrolled, with mean age of be 42.49 ± 11.33 years. Prevalence was found to be more in females (61.5%). The most common symptom according to RSI was frequent throat clearing & globus sensation (sensation of something sticking in throat) and most common finding according to RFS was erythema/hyperemia. The mean score of RSI and RFI was found to reduce with treatment at different intervals in follow-up visits. There was a significant strength of association between the RSI and RFS at baseline, 1st month, 3rd month and 6th month of follow-up (r = 0.568, r = 0.684, r = 0.774, r = 0.736 respectively) (p < 0.001).The RFS and RSI showed statistically significant strong relationships between total scores and sign and symptom characteristics. On follow-up, there was a significant reduction in the RSI which was also correlated with a reduction in RFS.


[Search for optimum composition of radiopharmaceuticals for liver scintigraphy].
The paper considers an opportunity of using a method of design based on a scheme of a complete factor experiment to find an optimum drug composition, citing by way of example, a process of development of a diagnostic agent for liver scintigraphy on the basis of the calcium-phytate complex labelled with 99mTc taking into account biological behavior of drugs of various composition.


Low doses of bisphenol A and diethylstilbestrol impair Ca2+ signals in pancreatic alpha-cells through a nonclassical membrane estrogen receptor within intact islets of Langerhans.
Glucagon, secreted from pancreatic alpha-cells integrated within the islets of Langerhans, is involved in the regulation of glucose metabolism by enhancing the synthesis and mobilization of glucose in the liver. In addition, it has other extrahepatic effects ranging from lipolysis in adipose tissue to the control of satiety in the central nervous system. In this article, we show that the endocrine disruptors bisphenol A (BPA) and diethylstilbestrol (DES), at a concentration of 10(-9) M, suppressed low-glucose-induced intracellular calcium ion ([Ca2+]i) oscillations in alpha-cells, the signal that triggers glucagon secretion. This action has a rapid onset, and it is reproduced by the impermeable molecule estradiol (E2) conjugated to horseradish peroxidase (E-HRP). Competition studies using E-HRP binding in immunocytochemically identified alpha-cells indicate that 17beta-E2, BPA, and DES share a common membrane-binding site whose pharmacologic profile differs from the classical ER. The effects triggered by BPA, DES, and E2 are blocked by the G alpha i- and G alpha o-protein inhibitor pertussis toxin, by the guanylate cyclase-specific inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, and by the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester. The effects are reproduced by 8-bromo-guanosine 3',5'-cyclic monophosphate and suppressed in the presence of the cGMP-dependent protein kinase inhibitor KT-5823. The action of E2, BPA, and DES in pancreatic alpha-cells may explain some of the effects elicited by endocrine disruptors in the metabolism of glucose and lipid.


Mechanical valve prosthesis and anticoagulation regimens in pregnancy: a tertiary centre experience.
This study was undertaken to analyze the maternal and perinatal outcome in women with prosthetic heart valves on different anticoagulant regimens. A retrospective chart review of pregnancies in 40 women with mechanical valve prostheses at a tertiary referral centre from 1997 to 2010. The main outcome measures were major maternal complications and perinatal outcome. The valves replaced were mitral (67.5%), aortic (15.0%), or both (17.5%). Forty-nine pregnancies (72.1%) resulted in live births, 3(4.4%) had stillbirths, and 13(19.1%) had spontaneous abortions and 1(1.4%) underwent therapeutic abortions. The live birth rate was higher in women on heparin (78.3%) compared with those on warfarin (66.9%). There were 2 maternal deaths due to acute mitral valvular thrombosis while on acenocoumarol in the second trimester. Hemorrhagic complications occurred in 3 patients on heparin in the postpartum period, 2 of whom required transfusion. In addition one patient who was on acenocoumarol developed secondary hemorrhage. No anticoagulant regimen can be said to be entirely safe for use during pregnancy as there is a degree of risk with each regimen. Further larger studies are needed to come up with sufficient evidence-based recommendations for the best possible management of such patients to reduce the maternal risks after mechanical heart valve replacement without compromising fetal outcome.


Pancreaticoduodenectomy following total occlusion of the superior mesenteric artery: a case report and literature review.
Patients with chronic occlusion of the celiac artery and superior mesenteric artery (SMA) are often asymptomatic, and occlusion may be caused by arteriosclerosis or median arcuate ligament compression. Pancreaticoduodenectomy (PD) is occasionally performed for patients with celiac artery occlusion; however, reports on patients with SMA occlusion are rare. We report a patient with cholangiocarcinoma and total atherosclerotic occlusion of the SMA without preoperative stenting or bypass. A 73-year-old man suspected to have lower bile duct carcinoma was admitted to our hospital for further treatment. Three-dimensional computed tomography (3DCT) showed a common bile duct tumor and total occlusion of the SMA with collateral circulation of the gastroduodenal artery (GDA) and inferior mesenteric artery (IMA). We performed a PD. During the operation, we used test clamping of the GDA, which revealed no bowel ischemia. The postoperative course was uneventful, and the patient was discharged on postoperative day (POD) 30. 3DCT on POD 98 and POD 307 showed development of collateral circulation between the IMA and SMA. Here, we report the case of a patient with total occlusion of the SMA who subsequently underwent PD. 3DCT was instrumental in gathering vascular collateral information and thus we conclude that the assessment of collateral circulation before surgery is important.


Laparoscopic Bilateral Nephro-Ureterectomy Approach for Complete Urinary Tract Extirpation for the Treatment of Multifocal Urothelial Carcinoma in a Kidney Transplant Patient: A Case Report and Literature Review.
Urothelial carcinoma of the transitional epithelium is the most common malignancy in the Thai kidney transplant population. We report our experience in managing simultaneous upper and lower urinary tract urothelial cancer in a post-kidney transplant recipient through the use of laparoscopic bilateral nephron-ureterectomy and anterior pelvic exenteration with the use of a Studer orthotopic neobladder. A 35-year-old woman with end-stage renal disease underwent living related kidney transplantation in 2009. She presented with gross hematuria 5 years later. Enhanced computer tomography revealed diffuse bladder wall thickening with an intravesical polypoid soft tissue mass at the right ureterovesical junction extending to the right distal ureter. Hydronephrosis of the left native kidney without any demonstrable cause of obstruction was also noted. On trans-urethral resection, the pathological finding was high-grade, non-invasive urothelial cell carcinoma. The operation was successfully performed without intra- or post-operative complications. The patient could ambulate independently on post-operative day 2. The kidney graft function did not change from her pre-operative baseline. At 6 months' follow-up, the patient had no tumor recurrence, returned to normal activities, and was able to void spontaneously without any need of intermittent catheterization. Laparoscopic bilateral nephron-ureterectomy for complete urinary tract extirpation is feasible, safe, and associated with low morbidity. This technique avoids a large abdominal midline incision or a bilateral flank incision for nephron-ureterectomy and is a good alternative surgical technique in post-kidney transplant patients who require complete urinary tract extirpation.


Membrane and nuclear estrogen receptor α collaborate to suppress adipogenesis but not triglyceride content.
Estrogen and estrogen receptor (ER)-α suppress visceral fat development through actions in several organs via unclear mechanisms that we sought to identify. Using mice that express only nuclear ER-α [nuclear-only ER-α (NOER) mice] or plasma membrane ER-α [membrane-only ER-α (MOER) mice], we found that 10-wk-old mice that lacked either receptor pool showed extensive abdominal visceral fat deposition and weight gain compared with wild-type (WT) mice. Differentiation of cultured bone marrow stem cells (BMSCs) into the adipocyte lineage was suppressed by 17-β-estradiol (E2) in WT female mice but not in NOER or MOER mice. This finding correlated with E2 inhibition of prominent differentiation genes in WT BMSCs. In contrast, triglyceride content in differentiated BMSCs or 3T3-L1 cells was suppressed as a result of membrane ER-α signaling through several kinases to inhibit carbohydrate response element-binding protein-α and -β. We concluded that extranuclear and nuclear ER-α collaborate to suppress adipocyte development, but inhibition of lipid synthesis in mature cells does not involve nuclear ER-α.


Aging does not alter cytosolic calcium levels of cortical synaptosomes in Fischer 344 rats.
Several lines of experimental evidence support an association between altered Ca2+ regulation and aging. It has been supposed that free cytosolic Ca2+ concentrations ([Ca2+]i) may decrease or increase in aged animals. In this study, both resting and KCl-stimulated [Ca2+]i were measured in purified cortical synaptosomes from young (3 mo.), middle-aged (12 mo.), and old (24 mo.) Fischer 344 rats. Two additional groups of rats were included, one middle-aged and one old which were trained on a treadmill for 6 months prior to experimentation. The [Ca2+]i was determined using the fluorescent Ca2+ chelator fura-2. Net KCl-dependent changes (delta K) in [Ca2+]i were determined by the difference between stimulatory (100 microM Ca2+/60 mM KCl) and resting (100 microM Ca2+/5 mM KCl buffer) conditions among the 3 age groups. Significant increases in [Ca2+]i were observed in each age group upon depolarization with 60 mM KCl. However, there were no significant age-dependent differences in either resting [Ca2+]i or KCl-stimulated [Ca2+]i.


Imaging of human thrombi in the rabbit jugular vein: I: Comparison of two fibrin-specific monoclonal antibodies.
The development of monoclonal antibodies with a specificity for cross-linked fibrin may have a potential role in the detection and of thrombi and thrombolytic therapy. In this study, two monoclonal antibodies with a specificity for fibrin have been examined. In vitro studies have shown NIBn 123 (which has a high affinity for X-oligomer) and DD-3B6 to bind to immobilised fibrin on PVC plates as well as plasma clots which were incubated in the presence of plasma. The Km values for NIBn 123 and DD-3B6 wre 1.0 x 10(10)/7.7 x 10(8) M and 2.6 x 10(8) M respectively. No significant binding to fibrinogen either immobilised or in solution was found. The binding of these antibodies to a human thrombus in the jugular vein of the rabbit was monitored over a 24 hour period. Preferential binding of each antibody reached a ratio of approximately 1.0 (jugular/heart) at 24 hours and an image was detected.


Genetic and phylogenetic characterization of novel bocaparvovirus infecting chimpanzee.
Primate bocaparvoviruses were first described in 2005, since then further human and gorilla bocaparvoviruses have been identified. To uncover diversity of non-human primates' bocaparvoviruses, their phylogenetic relationship and potential to cross the host species barrier, we tested 153 fecal samples from 17 captive primate species. The only one captive female of central chimpanzee (coded CPZh2) has been identified as bocaparvovirus positive. Based on the full genome phylogenetic analyses, CPZh2 strain shows close relationship to HBoV3 and GBoV. Further recombination analysis confirmed expected mosaic origin of CPZh2 strain. According the phylogenetic position, following the ICTV recommendations, we propose a novel genotype within the Primate bocaparvovirus 1 species infecting chimpanzee.


Non-persisting early foci of altered hepatocytes induced in rats by N-nitrosomorpholine.
Male Sprague-Dawley rats were treated for 7 weeks with 120 mg/l N-nitrosomorpholine in their drinking water. At the end of the treatment period there were large numbers of enzyme-altered foci in the liver. During the following 10 weeks, the number of foci decreased significantly. This decrease in the number of enzyme-altered foci was due to the disappearance of a special type of focus. The typical features of these non-persisting foci were distinct enzyme histochemical and striking morphological alterations as well as the localization in or close to the third zone, as defined by Rappaport. In contrast to the simultaneously appearing persisting foci, the non-persisting foci were always glycogen-poor or totally glycogen-free. Signs of cell death were frequently found in or near this type of focus. After these non-persisting foci had disappeared, the total number of pre-neoplastic lesions obviously remained constant. We conclude that this disappearance of early appearing, severely altered foci is due to cell loss caused by the non-specific toxic effect of the carcinogen.


Airway inflammation phenotype prediction in asthma patients using lung sound analysis with fractional exhaled nitric oxide.
We previously reported the results of lung sound analysis in patients with bronchial asthma and demonstrated that the exhalation-to-inhalation sound pressure ratio in the low frequency range between 100 and 200 Hz (E/I LF) was correlated with the presence of airway inflammation and airway obstruction. We classified asthma patients by airway inflammation phenotype using the induced sputum eosinophil and neutrophil ratio and determined whether this phenotype could be predicted using E/I LF and fractional exhaled nitric oxide values. Steroid-naive bronchial asthma patients were classified into four phenotypes, including "Low inflammation" (35 patients), "Eosinophilic type" (58 patients), "Neutrophilic type" (15 patients), and "Mixed type" (15 patients) based on the results of induced sputum examinations. The E/I LF data and FeNO levels were then evaluated for the four phenotype groups; the prediction powers of these two indices were then analyzed for each phenotype. The median E/I LF value was highest in the "Mixed type" and lowest in the "Low inflammation" group. FeNO differentiated between the "Low inflammation" and "Eosinophilic type" groups, "Low inflammation" and "Neutrophilic type" groups, and "Neutrophilic type" and "Mixed type" (p < 0.0001, p = 0.007, and p = 0.04, respectively). E/I LF differentiated between the "Low inflammation" and "Eosinophilic type" groups (p = 0.006). E/I LF could distinguish the "Mixed type" group from the "Low inflammation" and "Eosinophilic type" groups (p = 0.002). A combination of the E/I LF value and FeNO may be useful for the classification of the airway inflammation phenotype in patients with bronchial asthma.


Exploring direct detection suppressed regions in a simple 2-scalar mediator model of scalar dark matter.
We explore regions of parameter space that give rise to suppressed direct detection cross sections in a simple model of scalar dark matter with a scalar portal that mixes with the standard model Higgs. We found that even this simple model allows considerable room in the parameter space that has not been excluded by direct detection limits. A number of effects leading to this result have been previously noted. Our main new result explores interference effects between different contributions to DM annihilation when the DM mass is larger than the scalar portal mass. New annihilation channels open up and the parameters of the model need to compensate to give the correct DM relic abundance, resulting in smaller direct detection cross sections. We find that even in a very simple model of DM there are still sizeable regions of parameter space that are not ruled out by experiment.


Mean residence time in peripheral tissue.
The published methods for determining the mean residence time for drugs in peripheral tissue are reviewed in terms of assumptions involved, advantages and disadvantages. A method for determining mean transit time in peripheral tissue is proposed; this may be a more useful indicator of the tissue retention properties for drug compounds.


A disposable paper-based hydrophobic substrate for highly sensitive surface-enhanced Raman scattering detection.
Detection of target analytes with high sensitivity and reproducibility remains a challenge for surface-enhanced Raman scattering (SERS) due to the lack of cost-effective and highly sensitive substrates. In this study, a hydrophobic SERS substrate capable of concentrating nanoparticles and analytes was prepared by spin-coating lubricating liquid onto commercial paper. The condensation effect of the paper-based hydrophobic substrate induced aggregation of gold nanoparticles (Au NPs) to generate ''hot spots'' for SERS and to drive analytes to the hot-spot areas for more sensitive detection. The obtained SERS signal intensity was 5-fold higher than that obtained using common paper, and a detection limit (LOD) of 4.3 × 10-10 M for rhodamine 6G (R6G) was achieved. Randomly selected points on the substrate and different batches of substrates all exhibited high reproducibility, and the relative standard deviation (RSD) at 1362 cm-1 is approximately 11%. A further application of the hydrophobic substrate was demonstrated by the detection of cytochrome C within a linear detection range of 3.90 × 10-8 M-1.25 × 10-6 M. In addition, the prepared substrate can obtain identifiable SERS spectra of cancer cells and non-cancer cells because a large number of AuNP or Au NPs clusters can adhere to cells, resulting in the construction of a 3D hotspot matrix. The disposable hydrophobic paper substrate eliminates the problem of solution diffusion, and also provides an effective platform for biomolecular screening detection.


Diaquatetra-kis(μ-3-meth-oxy-benzoato-κ2 O 1:O 1')dicopper(II).
The asymmetric unit of the binuclear title compound, [Cu2(C8H7O3)4(H2O)2], comprises two halves of diaquatetra-kis-(μ-3-meth-oxy-benzoato-κ2 O 1:O 1')dicopper(II) units. The paddle-wheel structure of each complex is completed by application of inversion symmetry, with the inversion centre situated at the midpoint between two CuII atoms in each dimer. The two CuII atoms of each centrosymmetric dimer are bridged by four 3-meth-oxy-benzoate anions resulting in Cu⋯Cu separations of 2.5961 (11) and 2.6060 (12) Å, respectively. The square-pyramidal coordination sphere of each CuII atom is completed by an apical water mol-ecule. Inter-molecular O-H⋯O hydrogen bonds of weak nature link the complexes into layers parallel to (100). The three-dimensional network structure is accomplished by C-H⋯O hydrogen bonds inter-linking adjacent layers.


Is there an association between hypertension and cancer mortality?
Because of suggestions that hypertension may increase the long-term risk of cancer, we assessed the relation between hypertension and malignancy. We conducted a MEDLINE search of English-language articles published between January 1966 and January 2000 using the terms hypertension or blood pressure, and neoplasm or cancer or malignancy. We reviewed prospective studies that reported cancer incidence or mortality in hypertensive and nonhypertensive patients, case-control studies that reported the prevalence of hypertension in cancer patients and controls, and references from identified articles. We identified 10 longitudinal studies that evaluated the association between blood pressure and cancer mortality in 47 119 subjects. Subjects with hypertension experienced an increased rate of cancer mortality during durations of follow-up ranging 9 to 20 years, with an age- and smoking-adjusted pooled odds ratio of 1.23 (95% confidence interval [CI]: 1.11 to 1.36). In 13 case-control studies, including 6964 cases of renal cell cancer and 9181 controls, the adjusted odds ratio for renal cell cancer among hypertensive patients, relative to normotensive counterparts, was 1.75 (95% CI: 1.61 to 1.90). No clear association was found between hypertension and cancer of other sites. Hypertension was associated with an increased risk of mortality from cancer, particularly renal cell carcinoma.


Immediate Effects of Limb Rotational Kinesio Tape Application on Upper Quarter Y-Balance Test Scores.
Rounded shoulder posture is a common problem in the athletic population. Recently Kinesio tape has been utilized to improve balance, proprioception, and posture. However, the literature has been unable to provide definitive answers on the efficacy of Kinesio tape use. To determine the immediate effect of the limb rotational Kinesio tape application on the dynamic balance and proprioception of the shoulder measured by the Y-Balance Upper Quarter Test (YBT-UQ) in male collegiate athletes. Cross-sectional. Sports medicine research laboratory. Nineteen healthy male collegiate National Association of Intercollegiate Athletics athletes (including rodeo, baseball, football, and soccer) with a mean age of 19.8 (1.4) years. Subjects were randomized into Kinesio tape and non-Kinesio tape groups. The limb rotational Kinesio tape application was applied to the Kinesio tape group, while the non-Kinesio tape group received no intervention. Each group performed the YBT-UQ, which requires reaching in 3 directions in a push-up position, before and after the randomized intervention on a single day. The variables of interest included the maximum reach distance in each of the 3 directions and the composite score for both trials between the Kinesio tape and non-Kinesio tape groups. Each score was normalized against the subject's limb length. No statistically significant improvements in any YBT-UQ scores were observed following either the Kinesio tape or non-Kinesio tape intervention. Applying the limb rotational Kinesio tape technique did not improve immediate YBT-UQ scores in a male collegiate athletic population with rounded shoulder posture. The use of Kinesio tape to improve immediate closed kinetic chain function in male collegiate athletes with rounded shoulder posture cannot be supported.


An algorithm for the optimal collection of wet waste.
This work refers to the development of an approach for planning wet waste (food waste and other) collection at a metropolitan scale. Some specific modeling features distinguish this specific waste collection problem from the other ones. For instance, there may be significant differences as regards the values of the parameters (such as weight and volume) characterizing the various collection points. As it happens for classical waste collection planning, even in the case of wet waste, one has to deal with difficult combinatorial problems, where the determination of an optimal solution may require a very large computational effort, in the case of problem instances having a noticeable dimensionality. For this reason, in this work, a heuristic procedure for the optimal planning of wet waste is developed and applied to problem instances drawn from a real case study. The performances that can be obtained by applying such a procedure are evaluated by a comparison with those obtainable via a general-purpose mathematical programming software package, as well as those obtained by applying very simple decision rules commonly used in practice. The considered case study consists in an area corresponding to the historical center of the Municipality of Genoa.


Action of Arthrobacter ureafaciens sialidase on sialoglycolipid substrates. Mode of action and highly specific recognition of the oligosaccharide moiety of ganglioside GM1.
A new bacterial sialidase (N-acetylneuraminate glycohydrolase, EC 22.214.171.124) isolated from the culture filtrate of Arthrobacter ureafaciens was characterized in detail with respect to its action on sialoglycolipids. Strong electrolytes had a reversible inhibitory effect on the action of the enzyme on brain gangliosides in accordance with Debye-Hückel effect of ionic environment on ionic activity, and resulted in an acidic shift and a broadening of the pH optimum. Both ionic and non-ionic detergents markedly enhanced the enzymic activity on the gangliosides, and caused an acidic shift on the pH optimum of this enzyme. Sulfhydryl groups seemed to be involved in its active site. This enzyme had a highly specific action on sialidase-resistant ganglioside GM1, showing about 100-fold higher activity on GM1 than Clostridium perfringens sialidase, the only sialidase so far reported to cleave the lipid substrate in the presence of bile salts. In the absence of detergents, the activity of A. ureafaciens sialidase on GM1 was very low. Ganglioside GM1 in either the monomeric or micelar form was hydrolyzed to asialo-GM1 by A. ureafaciens sialidase most efficiently in the presence of sodium cholate of about three times the GM1 molar concentration. The presence of detergents increased both the Km and Vmax values for ganglioside GM1. The oligosaccharide prepared from GM1 by ozonolysis was cleaved well by this sialidase in the absence of detergents, and no detergent was found to affect the hydrolysis. The Km value for the sugar substrate was about two orders of magnitude greater than that for the corresponding lipid substrate. It is suggested that the hydrophobic ceramide moiety increases affinity of the lipid substrate to the enzyme, but inhibits hydrolysis of the substrate, possibly due to its hydrophobic interaction with hydrophobic portions of the enzyme molecule (resulting in lower Km and Vmax for lipid substrates). This inhibition may be released by detergent due to formation of mixed micelles of sialoglycolipid and detergent molecules. It is also indicated that recognition of the specific saccharide structure of GM1 by individual sialidases is essential for release of the resistant sialyl residue, and that A. ureafaciens sialidase seemed to have an isoenzymic or oligomeric structure.


Selenylation modification can enhance antioxidant activity of Potentilla anserina L. polysaccharide.
Potentilla anserina L. polysaccharide had been selenizingly modified by nitric acid-selenious acid method with microwave-assistant. The optimal reaction parameters on selenylation modification were time 116 min, temperature 63°C, microwave power 190 W and the actual value of selenium content was 2690.1±7.2 μg/g. The scavenging ability of DPPH, OH and superoxide radicals, the metal chelating ability and reducing power in vitro were compared by antioxidant assay taking the non-modified PAP as a control. The results showed that selenylation modification could significantly enhance the antioxidant activity of SePAP and SePAP could be used as a potential antioxidant.


Salivary extracellular heat shock protein 70 (eHSP70) levels increase after 59 min of intense exercise and correlate with resting salivary secretory immunoglobulin A (SIgA) levels at rest.
This study aimed to identify the response of a salivary stress protein, extracellular heat shock protein (eHSP70), to intense exercise and to investigate the relationship between salivary eHSP70 and salivary immunoglobulin A (SIgA) levels in response to exercise. Sixteen healthy sedentary young males (means ± SD 23.8 ± 1.5 years, 172.2 ± 6.4 cm, 68.3 ± 7.4 kg) performed 59 min of cycling exercise at 75% VO2max. Saliva and whole blood samples were collected before (Pre), immediately after (Post), and at 1, 2, 3, and 4 h after completion of the exercise (1, 2, 3, and 4 h). The salivary eHSP70 and SIgA levels were measured by enzyme-linked imunosorbent assay (ELISA), and the secretion rates were computed by multiplying the concentration by the saliva flow rate. White blood cells were analyzed using an automated cell counter with a direct-current detection system. The salivary eHSP70 secretion rates were 1.11 ± 0.86, 1.51 ± 1.47, 1.57 ± 1.32, 2.21 ± 2.04, 3.36 ± 2.72, and 6.89 ± 4.02 ng · min(-1) at Pre, Post, and 1, 2, 3, and 4 h, respectively. The salivary eHSP70 secretion rate was significantly higher at 4 h than that at Pre, Post, 1, and 3 h (p < 0.05). The SIgA secretion rates were 26.9 ± 12.6, 20.3 ± 10.4, 19.6 ± 11.0, 21.8 ± 12.8, 21.5 ± 11.9, and 21.9 ± 11.7 μg · min(-1) at Pre, Post, 1, 2, 3, and 4 h, respectively. The salivary SIgA secretion rate was significantly lower between 1 and 4 h than that at Pre (p < 0.05). There was a positive correlation between salivary eHSP70 and SIgA in both concentration and secretion rates before exercise (p < 0.05). The absolute number of white blood cells significantly increased after exercise, with a maximum at 2 h (p < 0.05). The neutrophil/lymphocyte ratio was significantly increased from 1 to 4 h when compared with that in the Pre samples (p < 0.05). The present study revealed that salivary eHSP70 significantly increased at 4 h after the 59 min of intense exercise in sedentary male subjects. Exercise stress can induce elevated salivary eHSP70 level and upregulate oral immune function partially.


Single-course bleomycin, etoposide, and cisplatin (1xBEP) as adjuvant treatment in testicular nonseminoma clinical stage 1: outcome, safety, and risk factors for relapse in a population-based study.
Clinical stage 1 (CS1) nonseminomatous (NS) germ cell tumors involve a 30% probability of relapse upon surveillance. Adjuvant chemotherapy with one course of bleomycin, etoposide, and cisplatin (1xBEP) can reduce this risk to <5%. However, 1xBEP results are based solely on five controlled trials from high-volume centers. We analyzed the outcome in a real-life population. In a multicentric international study, 423 NS CS1 patients receiving 1xBEP were retrospectively evaluated. Median follow-up was 37 (range, 6-89) months. Primary end points were relapse-free and overall survival evaluated after 5 years. We also looked at associations of relapse with clinico-pathological factors using stratified Kaplan-Meier methods and Cox regression models. Treatment modality and outcome of recurrences were analyzed descriptively. The 5-year relapse-free survival rate was 96.2%. Thirteen patients (3.1%; 95% confidence interval, 1.65-5.04%) relapsed after a median time of 13 months, of which 10 were salvaged (77%). Relapses were mostly confined to retroperitoneal nodes. Three patients succumbed, two to disease progression and one to toxicity of chemotherapy. Pathological stage >pT2 was significantly associated with relapse rate. The relapse rate of 3.1% found in this population of NS CS1 patients treated with 1xBEP at the routine care level was not inferior to the median rate of 2.3% reported from a meta-analysis of controlled trials. Also, the cure rate of relapses of 77% is consistent with the previously reported rate of 80%. This study clearly shows that the 1xBEP regimen represents a safe treatment for NS CS1 patients.


Expression and actions of GnIH and its orthologs in vertebrates: Current status and advanced knowledge.
The physiology of reproduction is very complex and is regulated by multiple factors, including a number of hypothalamic neuropeptides. In last few decades, various neuropeptides have been discovered to be involved in stimulation or inhibition of reproduction. In 2000, Tsutsui and colleagues uncovered gonadotropin-inhibitory hormone (GnIH), a neuropeptide generating inhibitory drive to the reproductive axis, in the brain of Coturnix quail. Afterward, GnIH orthologs were discovered in other vertebrates from fish to mammals including human. In these vertebrates, all the discovered GnIH and its ortholgs have LPXRFamide (X=L or Q) sequence at C-terminus. GnIH orthologs of mammals and primates are also termed as RFamide-related peptide (RFRP)-1 and -3 that too have an LPXRFamide (X=L or Q) motif at their C-terminus. GnIH and its orthologs form a member of the RFamide peptide family. GnIH signals via its canonical G protein coupled receptor 147 (GPR147). Both GnIH and GPR147 are expressed in hypothalamus and other brain regions. Besides actions through the hypothalamic GnRH and kisspeptinergic neurons, GnIH-GPR147 signaling exerts inhibitory effect on the reproductive axis via pituitary gonadotropes and directly at gonadal level. Various factors including availability and quality of food, photoperiod, temperature, social interaction, various stresses and some diseases modulate GnIH-GPR147 signaling. In this review, we have discussed expression and actions of GnIH and its orthologs in vertebrates. Special emphasis is given on the role of GnIH-GPR147 signaling pathway in the regulation of reproduction. We have also reviewed and discussed currently available literature on the participation of GnIH-GPR147 signaling pathway in the stress modulation of reproduction.


Real-space observation of nanoscale inhomogeneities and fluctuations in a phase transition of a surface quasi-one-dimensional system: In/Si(111).
We report direct visualizations of the fluctuation and condensation phenomena in a phase transition of a one-dimensional (1D) In/Si(111) system using scanning tunneling microscopy. The high-temperature (HT) and low-temperature (LT) phases are found to coexist on the nanometer scale near Tc. Above Tc, 1D LT-phase stripes fluctuate in the HT phase and coalesce into 2D islands with decreasing temperature. They condense to make the LT phase below Tc. Small areas of the HT phase also exist below Tc. The observed temperature-dependent evolution of the nanoscale inhomogeneities is consistent with the theoretical predictions for a second-order phase transition.


Photocatalytic transformation of acesulfame: Transformation products identification and embryotoxicity study.
Artificial sweeteners have been recognized as emerging contaminants due to their wide application, environmental persistence and ubiquitous occurrence. Among them, acesulfame has attracted much attention. After being discharged into the environment, acesulfame undergoes photolysis naturally. However, acesulfame photodegradation behavior and identity of its transformation products, critical to understanding acesulfame's environmental impact, have not been thoroughly investigated. The present study aimed to fill this knowledge gap by a laboratory simulation study in examining acesulfame transformation products and pathways under UV-C photolysis in the presence of TiO2. Photodegradation products of acesulfame were isolated and analyzed using the LC-IM-QTOF-MS coupled with LC Ion Trap MS in the MS(n) mode. Our results show six new transformation products that have not been previously identified. The molecular structures and transformation pathways were proposed. Further embryotoxicity tests showed that acesulfame transformation products at the low g L(-1) level produced significant adverse effects in tail detachment, heart rate, hatching rate and survival rate during fish embryo development. The identification of additional transformation products with proposed transformation pathways of acesulfame, the increased toxicity of acesulfame after photolysis, and the fact that the accumulation of acesulfame transformation products is increasingly likely make acesulfame contamination even more important. Water resource control agencies need to consider legislation regarding acesulfame and other artificial sweeteners, while further studies are carried out, in order to protect the safety of this most vital resource.


Epidemiological Surveillance of Rodent-Borne Viruses (Roboviruses).
This article will outline surveillance approaches for rodent-borne viruses (roboviruses). We present a synopsis of the main categories of trapping methods with some notes about their use in fieldwork. We also describe the types of laboratory analysis commonly used in Robovirus surveillance.


In vivo analysis of torsadogenic potential of an antipsychotic drug paliperidone using the acute atrioventricular block rabbit as a proarrhythmia model.
We assessed electrophysiological effects of an atypical antipsychotic drug paliperidone in acute atrioventricular block rabbits. Intravenous administration of paliperidone at a clinically relevant dose (0.06 mg/kg) hardly affected the QT interval or monophasic action potential (MAP) duration, and the higher doses (0.6 and 6 mg/kg) prolonged the QT interval and MAP duration. Meanwhile, premature ventricular contractions with R on T phenomenon were observed in 3 out of 6 animals at the middle dose, and torsades de pointes (TdP) episodes were detected in 2 out of 6 animals at the high dose. Intravenous administration of its chemically related compound risperidone at a clinically relevant dose (0.03 mg/kg) hardly affected the electrophysiological parameters, and the higher doses (0.3 and 3 mg/kg) prolonged the QT interval and MAP duration. Meanwhile, the premature ventricular contractions with R on T were observed in 2 out of 6 animals at the middle dose, and TdP episodes were detected in 4 out of 6 animals at the high dose. These results suggest that paliperidone showed torsadogenic potential at supra-therapeutic doses, whose potency can be estimated to be equal or slightly subordinate in comparison with that of risperidone.


Remodeling of the glycosylation pathway in the methylotrophic yeast Hansenula polymorpha to produce human hybrid-type N-glycans.
As a step forward to achieve the generation of human complex-type N-glycans in the methylotrophic yeast Hansenula polymorpha, we here report the modification of the yeast glycosylation pathway by heterologous expression of the human gene encoding β-1,2-N-acetylglucosaminyltransferase I (GnTI). For the optimal expression of human GnTI in the yeast Golgi compartment, the catalytic domain of the GnTI was fused to various N-terminal leader sequences derived from the yeast type II membrane proteins. The vectors containing GnTI fusion constructs were introduced into the H. polymorpha och1Δ single and och1Δalg3Δ double mutant strains expressing the ER-targeted Aspergillus saitoi α-1,2 mannosidase, respectively. Both of the glycoengineered Hpoch1Δ and Hpoch1ΔHpalg3Δ strains were shown to produce successfully the hybrid-type glycans with a monoantennary N-acetylglucosamine (GlcNAc(1)Man(5)GlcNAc(2) and GlcNAc(1)Man(3)GlcNAc(2), respectively) by N-glycan profile analysis of cell wall proteins. Furthermore, by comparative analysis of byproduct formation and the glycosylation site occupancy, we propose that the Hpoch1Δ strain would be more suitable than the Hpoch1ΔHpalg3Δ strain as a host for the production of recombinant proteins with humanized glycans.


Three-dimensional analysis of the posttreatment displacements of mandibular anterior teeth with rigid and flexible lingual retainers.
The purpose of this study was to analyze any posttreatment changes in the positions of mandibular anterior teeth retained by 2 different fixed retention methods (rigid or flexible) and their effectiveness in minimizing postorthodontic tooth movement. Thirty patients were selected for inclusion in this retrospective study. Group I consisted of 15 patients with 0.032-in stainless steel rigid retainers bonded to canines only. Group II consisted of 15 patients with 0.0215-in twisted stainless steel flexible retainer bonded to all mandibular anterior teeth. Geomagic Control (3DS Systems, Rock Hill, SC) software was used to quantify the changes between selected points. Paired t test was used for intragroup comparisons in all 3 coordinates, and an independent-sample t test was used for intergroup comparison. In the transverse dimension, significant intergroup differences were found in displacements of distoincisal points of the right lateral (P <0.05) and left central incisors (P <0.01). In the sagittal dimension, significant intergroup differences were found in the displacements of mesioincisal point of the right central incisor (P <0.05) and distoincisal point of the left central incisor (P <0.01). Examining total displacement, there were significant intergroup differences in mesioincisal point on the right central incisor, distoincisal point on the left lateral incisor (P <0.05). Our results suggested that central incisor contacts were more likely to shift with the rigid retainers, especially in sagittal and transverse dimensions. However, no statistically or clinically significant changes were noted in the third-order or vertical positions of the teeth with either retention method.


Benchmarking Patient Engagement Capabilities and Preparedness of Drug Development Sponsors.
Consistent implementation and measurement of patient engagement initiatives across the industry have remained aspirational and elusive despite strong interest in adopting patient-centric approaches. One factor contributing to this inertia stems from a lack of standardized implementation of patient engagement activities, which varies widely from company to company, making it difficult to track and measure. Further, empirical evidence mapping the impact of patient engagement capabilities on clinical research outcomes has remained sparse. To address this gap, the Drug Information Association (DIA) and Tufts Center for the Study of Drug Development (Tufts CSDD) at the Tufts University School of Medicine developed and administered an assessment tool that companies can use to not only evaluate their organization's patient engagement capabilities and implementation preparedness but can also measure the impact of such activities on trial outcomes. Results showed that while most organizations are providing logistical support to increase patient engagement in the form of travel stipends, accommodation, and financial incentives, most are not implementing more involved forms of patient engagement such as gathering patient input through patient input panels or patient steering committees. This paper discusses the process for designing and administering this assessment tool, the results of the assessment, and future implications.


Monoethlenic C20 and C22 fatty acids in marine oil and rapeseed oil. Studies on their oxidation and on their relative ability to inhibit palmitate oxidation in heart and liver mitochondria.
1. Carnitine esters of erucic acid (22:1 n-9 cis), cetoleic acid (22:1 n-11 cis), brassidic acid (22:1 n-9 trans), gadoleic acid (20:1 n-9 cis) and oleic acid (18:1 n-9 cis) have been compared as mitochondrial substrates and as inhibitors of palmitoylcarnitine oxidation in heart and liver mitochondria. 2. Both the rate of intramitochondrial-CoA acylation and the rate of beta-oxidation decreases as the chain length increases from C18 to C22. There are no significant differences among the three C22 isomers as oxidizable substrates. 3. All the tested acylcarnitines inhibit palmitoylcarnitine oxidation. The C18 and C20 acylcarnitines inhibit by virtue of being competing substrates; i.e. the respiration is not inhibited. The C22-isomers inhibit also respiration; this shows that the inhibition of palmitolycarnitine oxidation is not compensated for by oxidation of C22-acylcarnitines. Brassidoylcarnitine inhibits the oxidation of palmitoylcarnitine and respiration less than erucoyl-and cetoleoylcarnitine. The different behaviour of the C22-isomers is probably due to the difference in their competitive properties with respect to long-chain acyl-CoA dehydrogenase. 4. All C22 acylcarnitines seem to be relatively better oxidized in the liver than in the heart mitochondria while their inhibitory effect on the usage of the radioactive palmitoylcarnitine is very similar. 5. Palmitoylcarnitine inhibits almost completely the "endogenous" formation of acetyl-CoA presumably from malate via pyruvate in the liver mitochondria while the C22-acylcarnitines cause only a partial inhibiton of this acetyl-CaO formation.


Safety profile of cyclin-dependent kinase (CDK) 4/6 inhibitors with concurrent radiation therapy: A systematic review and meta-analysis.
The cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have become the standard of care for hormone receptor-positive (HR + ) and human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer, improving survival outcomes compared to endocrine therapy alone. Abemaciclib and ribociclib, in combination with endocrine therapy, have demonstrated significant benefits in invasive disease-free survival for high-risk HR+/HER2- early breast cancer patients. Each CDK4/6i-palbociclib, ribociclib, and abemaciclib-exhibits distinct toxicity profiles. Radiation therapy (RT) can be delivered with a palliative or ablative intent, particularly using stereotactic body radiation therapy for oligometastatic or oligoprogressive disease. However, pivotal randomized trials lack information on concomitant CDK4/6i and RT, and existing preclinical and clinical data on the potential combined toxicities are limited and conflicting. As part of a broader effort to establish international consensus recommendations for integrating RT and targeted agents in breast cancer treatment, we conducted a systematic review and meta-analysis to evaluate the safety profile of combining CDK4/6i with palliative and ablative RT in both metastatic and early breast cancer settings.


Herpesvirus infections and allergic sensitization in children of families with anthroposophic and non-anthroposophic lifestyle - the ALADDIN birth cohort.
Growing up in families with an anthroposophic lifestyle has been associated with reduced risk of allergic disease in children. The aim of this report was to assess whether children with this lifestyle are infected earlier with Epstein-Barr virus (EBV), which has been associated with reduced risk of allergic disease, and three other herpesviruses potentially involved in allergy development, namely Human herpesvirus 6 (HHV6), Human herpesvirus 7 (HHV7) and cytomegalovirus (CMV). Within the ALADDIN (Assessment of Lifestyle and Allergic Disease During Infancy), birth cohort study 157 children were categorized according to lifestyle into anthroposophic and non-anthroposophic. IgG-levels for EBV, HHV6, HHV7 and CMV were determined in plasma samples collected at ages 12 and 24 months and from parents. IgE levels against seven common allergens were analyzed at 24 months. No significant differences in seroprevalence of EBV, HHV7 or CMV were detected at any age between the two lifestyle groups. The seroprevalence of HHV6 was significantly lower in the anthroposophic group at 24 months of age (74.6% vs. 87.5%, p-value 0.048). Further, no significant associations between allergic sensitization and seropositivity to any of the viruses were detected; however, an interaction effect of lifestyle could not be ruled out. Our results indicate that there is no strong influence of exposure to the anthroposophic lifestyle on the time for infection with EBV, HHV6, HHV7 or CMV. These infections can therefore not be assumed to be important factors in the allergy-protective effect of this lifestyle.


A Gut Check Explains Improved Glucose Metabolism after Surgery.
Biliopancreatic diversion (BPD) surgery leads to more frequent diabetes remission than Roux-en-Y gastric bypass (RYGB). In this issue, Harris et al. (2019) compare each surgery after careful matching for percentage weight loss and find the gut as a major site of difference between the effects of the two surgeries.


Predictions of blood flow from thermal clearance during regional hyperthermia.
In order to provide a method for estimation of regional blood flow during hyperthermia, a mathematical model has been developed which employs thermal clearance to measure this physiologic parameter. Limbs of mongrel dogs were heated with 2450 megaHertz microwaves to temperatures of 43 degrees C, 45 degrees C, or 47 degrees C and thermal washout was measured at five minute intervals throughout each treatment period. Calculated blood flow indicates that in response to heat challenge, normal tissue compensates by increasing regional blood flow within the treatment volume. This increase in blood flow continues to a maximum value after which the blood flow begins to decrease. Data indicate that the time for maximum increase in blood flow (induction time) decreases as treatment temperature increases. These induction times were 40 minutes, 25 minutes, and 15 minutes for treatment temperatures of 43 degrees, 45 degrees, and 47 degrees C, respectively. The data also show that the calculated value of peak blood flow is directly related to treatment temperature. Calculated peak blood flow values reached 37.8, 59.0, and 183.0 ml/minute/100 grams of tissue during 43 degrees, 45 degrees, and 47 degrees C, hyperthermia, respectively. It is suggested that a therapeutic advantage could be gained by treating tumors for a specific length of time during which the blood flow in adjacent normal tissues continues to increase. This would take maximum advantage of normal tissue's ability to compensate for increased temperature, and would exploit any decreased ability of tumor tissue to perform this same function.


Evaluation of the international phage typing set and some experimental phages for typing of Listeria monocytogenes from poultry in Spain.
The validity of the international phage set and 13 experimental phages for subtyping Listeria monocytogenes strains isolated from poultry in Spain was investigated. Ninety-six L. monocytogenes strains (52 from serogroup 1/2 and 44 from serogroup 4) were phage-typed using the international phage set, 10 experimental phages for typing serogroup 1/2 strains (seven isolated in France: 1313, 9425, 1807, 351, 881, 717 and 586-, and three from Denmark: 5775, 12682 and 6223-) and three experimental phages isolated in France for typing serogroup 4 strains (2425 A, 4286 and 197). Percentages of serogroup 1/2, serogroup 4 and total phage-typeable strains were 57.7%, 52.3% and 55.2%, respectively. Important differences in the behaviour of the phages tested were found. The typeability rate, the specificity index and the percentage of strong reactions were greater in the phages of international set than in the experimental phages. The number of phage typeable strains and the number of phage types (42) were not modified by the use of experimental phages. The phage set used was not effective for typing L. monocytogenes strains from poultry in Spain, because a low typeability rate was found. Our results suggest the importance of the availability of new phages specific to a geographical area in order to improve the typeability of the system.


Ablation of Ventral Midbrain/Pons GABA Neurons Induces Mania-like Behaviors with Altered Sleep Homeostasis and Dopamine D2R-mediated Sleep Reduction.
Individuals with the neuropsychiatric disorder mania exhibit hyperactivity, elevated mood, and a decreased need for sleep. The brain areas and neuronal populations involved in mania-like behaviors, however, have not been elucidated. In this study, we found that ablating the ventral medial midbrain/pons (VMP) GABAergic neurons induced mania-like behaviors in mice, including hyperactivity, anti-depressive behaviors, reduced anxiety, increased risk-taking behaviors, distractibility, and an extremely shortened sleep time. Strikingly, these mice also showed no rebound sleep after sleep deprivation, suggesting abnormal sleep homeostatic regulation. Dopamine D2 receptor deficiency largely abolished the sleep reduction induced by ablating the VMP GABAergic neurons without affecting the hyperactivity and anti-depressive behaviors. Our data demonstrate that VMP GABAergic neurons are involved in the expression of mania-like behaviors, which can be segregated to the short-sleep and other phenotypes on the basis of the dopamine D2 receptors.


Double rupture of interventricular septum and free wall of the left ventricle, as a mechanical complication of acute myocardial infarction: a case report.
Cardiac ruptures following acute myocardial infarction include rupture of the left ventricle free-wall, ventricular septal defects, and papillary muscle rupture. Double myocardial rupture is a rare complication of acute myocardial infarction (0.3 %) and the report of such cases is exclusively limited to a small series of autopsy studies. In this report we present the unusual case of a 70-year-old woman with acute anteroseptal myocardial infarction, which was complicated by a combined rupture of the interventricular septum near the apex, and the free wall of the left ventricle with concomitant formation of a pseudoaneurysm. The double myocardial rupture was accidentally discovered 10 days later with echocardiography, when the patient, complaining only of mild exertional dyspnea, was hospitalized for a scheduled coronary angiography. The patient underwent successful surgical correction of the double myocardial rupture along with by-pass grafting. This report highlights the importance of comprehensive noninvasive predischarge diagnostic evaluation of all postinfarct patients, since serious and potentially life-threatening complications might have not been suspected on clinical grounds.


Neurotrophic-priming of glucocorticoid receptor signaling is essential for neuronal plasticity to stress and antidepressant treatment.
Neurotrophins and glucocorticoids are robust synaptic modifiers, and deregulation of their activities is a risk factor for developing stress-related disorders. Low levels of brain-derived neurotrophic factor (BDNF) increase the desensitization of glucocorticoid receptors (GR) and vulnerability to stress, whereas higher levels of BDNF facilitate GR-mediated signaling and the response to antidepressants. However, the molecular mechanism underlying neurotrophic-priming of GR function is poorly understood. Here we provide evidence that activation of a TrkB-MAPK pathway, when paired with the deactivation of a GR-protein phosphatase 5 pathway, resulted in sustained GR phosphorylation at BDNF-sensitive sites that is essential for the transcription of neuronal plasticity genes. Genetic strategies that disrupted GR phosphorylation or TrkB signaling in vivo impaired the neuroplasticity to chronic stress and the effects of the antidepressant fluoxetine. Our findings reveal that the coordinated actions of BDNF and glucocorticoids promote neuronal plasticity and that disruption in either pathway could set the stage for the development of stress-induced psychiatric diseases.


Multipass optical system equipped with thin films for the study of the spectra of cryogenic solids: measurement of the infrared spectrum of solid H(2).
A multipass optical system external to the optical head of a cryostat has been designed for use with a Bruker IFS 120 HR interferometer. A White cell using mirrors with a focal length of 10 cm is the central feature of the system. Nearly all optical elements, including those in the cryostat, have been optimized with thin-film technology for maximum signal throughput in the 6000 to 7000 cm(-1) range. The extension of the path length of the sample, in a cell limited to 3.8 cm in length, is illustrated with spectra of solid para-H(2) at 12 K. The cell was limited to four passes in this application because of refraction of the infrared radiation at the sample surface. Twelve to 20 passes are possible for a sample with an index of refraction close to 1 and with smaller aperture settings.


Artificial nanozyme based on platinum nanoparticles anchored metal-organic frameworks with enhanced electrocatalytic activity for detection of telomeres activity.
This study reports a new artificial nanozyme based on ultra-small Pt nanoparticles (Pt NPs) grown on nanoscale metalloporphyrin metal organic frameworks (P-MOF(Fe)) (termed as Pt@P-MOF(Fe)) as biomimetic catalysts and redox mediator to detect the telomerase activity. In this system, the P-MOF(Fe) were used as nanocarrier and signal media. The DNA functionalized Pt@P-MOF(Fe) was as signal probe and exhibited enhanced electrochemical signal in the presence of H2O2, owing to the synergistic effect between P-MOF(Fe) and Pt NPs. Upon the addition cell extract, the telomerase primer could extend and then hybridize with assistant DNA2 in the triple-helix, leading to the structure of triple-helix changes and release the hairpin DNA to hybridize with the capture DNA on the surface of Pt@P-MOF(Fe), resulting in the electrochemical signal readout of H2O2 reduction. With the aid of recycling amplification of Exonuclease III, the telomeres sensor exhibited the detection down to 20 Hela cell mL-1. This work supplies a new avenue to design artificial enzyme catalysts and serves as an ideal platform to use metalloporphyrin metal organic frameworks as signal media for detection of analytes.


[Research Progress in Precision Nursing for Enhanced Recovery After Surgery].
With the evolution and development of the concepts of medicine, research concerning precision medicine and precision nursing is constantly expanding and deepening, creating new challenges and opportunities for the nursing practice of enhanced recovery after surgery (ERAS). In this paper, we reviewed the current status of research on precision nursing for ERAS, giving an overview of the application status of precision nursing in ERAS from the perspectives of precision nursing assessment, precision symptom management, precision nutrition support, and precision health education and nursing follow-up. In addition, we analyzed the challenges and their solutions for further promotion and application of precision nursing in ERAS, including strengthening the basic professional knowledge and skills, building a nursing information platform, and actively applying new tools and technologies. In the future, clinical nursing staffs should further utilize the relevant concepts and methods of precision nursing to optimize and improve perioperative patient care strategies, ensure patient safety, enhance the quality of nursing care, improve patient outcomes, and promote a more important role played by precision nursing in ERAS.


The representation of the oral structures in the first somatosensory cortex of the cat.
Applying light mechanical stimulations to the oral structures, multi-unit recordings (MUR) were performed, and receptive fields of neurons were defined in the somatosensory cortex S I of the cat. Oral representation was confirmed in the circumscribed area of the anterior coronal gyrus rostral to the facial area in the following order: the contralateral lips, the contralateral periodontal tissues such as the gingivae and periodontal membranes, the middle and ipsilateral part of the periodontal tissues, and the palate and tongue in a caudorostral direction. The representation of the lip and perioral tissues of the lower jaw was found on the medial side of the coronal gyrus, while the upper one was found on the lateral side. The same oral representation was confirmed by single-unit recording (SUR) analysis in the anterior coronal gyrus. The representation area of the contralateral, middle and ipsilateral site of the non-hairy lips and periodontal tissues was found in cytoarchitectural field, areas 3b and 2; somatic koniocortex.


Cardiac manifestations of graft-versus-host disease.
Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after bone marrow transplantation. Well-documented manifestations of GVHD include dermatologic, gastrointestinal, hepatic, pulmonary, musculoskeletal, and hematologic manifestations and sicca syndrome. To date, the heart has only rarely been reported to be a target of GVHD. We report a series of patients who developed bradycardia, coronary artery disease, or cardiomyolysis in association with acute or chronic GVHD. The severity of these manifestations ranged from asymptomatic to fatal. The bradycardias were responsive to increased immunosuppression. Although they are uncommon, it is important to recognize these cardiac manifestations, because they may reflect GVHD activity and may be reversible by increasing immunosuppression.


Seasonal influenza vaccine dose distribution in 195 countries (2004-2013): Little progress in estimated global vaccination coverage.
Seasonal influenza is an important disease which results in 250,000-500,000 annual deaths worldwide. Global targets for vaccination coverage rates (VCRs) in high-risk groups are at least 75% in adults ≥65 years and increased coverage in other risk groups. The International Federation of Pharmaceutical Manufacturers and Associations Influenza Vaccine Supply (IFPMA IVS) International Task Force developed a survey methodology in 2008, to assess the global distribution of influenza vaccine doses as a proxy for VCRs. This paper updates the previous survey results on absolute numbers of influenza vaccine doses distributed between 2004 and 2013 inclusive, and dose distribution rates per 1000 population, and provides a qualitative assessment of the principal enablers and barriers to seasonal influenza vaccination. The two main findings from the quantitative portion of the survey are the continued negative trend for dose distribution in the EURO region and the perpetuation of appreciable differences in scale of dose distribution between WHO regions, with no observed convergence in the rates of doses distributed per 1000 population over time. The main findings from the qualitative portion of the survey were that actively managing the vaccination program in real-time and ensuring political commitment to vaccination are important enablers of vaccination, whereas insufficient access to vaccination and lack of political commitment to seasonal influenza vaccination programs are likely contributing to vaccination target failures. In all regions of the world, seasonal influenza vaccination is underutilized as a public health tool. The survey provides evidence of lost opportunity to protect populations against potentially serious influenza-associated disease. We call on the national and international public health communities to re-evaluate their political commitment to the prevention of the annual influenza disease burden and to develop a systematic approach to improve vaccine distribution equitably.


Coordination among neighbors improves the efficacy of Zika control despite economic costs.
Emerging mosquito-borne viruses like Zika, dengue, and chikungunya pose a major threat to public health, especially in low-income regions of Central and South America, southeast Asia, and the Caribbean. Outbreaks of these diseases are likely to have long-term social and economic consequences due to Zika-induced congenital microcephaly and other complications. Larval control of the container-inhabiting mosquitoes that transmit these infections is an important tool for mitigating outbreaks. However, metapopulation theory suggests that spatiotemporally uneven larvicide treatment can impede control effectiveness, as recolonization compensates for mortality within patches. Coordinating the timing of treatment among patches could therefore substantially improve epidemic control, but we must also consider economic constraints, since coordination may have costs that divert resources from treatment. To inform practical disease management strategies, we ask how coordination among neighbors in the timing of mosquito control efforts influences the size of a mosquito-borne infectious disease outbreak under the realistic assumption that coordination has costs. Using an SIR (Susceptible-Infectious-Recovered)/metapopulation model of mosquito and disease dynamics, we examine whether sharing surveillance information and coordinating larvicide treatment among neighboring patches reduces human infections when incorporating coordination costs. We examine how different types of coordination costs and different surveillance methods jointly influence the effectiveness of larval control. We find that the effect of coordination depends on both costs and the type of surveillance used to inform treatment. With epidemiological surveillance, coordination improves disease outcomes, even when costly. With demographic surveillance, coordination either improves or hampers disease control, depending on the type of costs and surveillance sensitivity. Our results suggest coordination among neighbors can improve management of mosquito-borne epidemics under many, but not all, assumptions about costs. Therefore, estimating coordination costs is an important step for most effectively applying metapopulation theory to strategies for managing outbreaks of mosquito-borne viral infections.


Association of GIST, breast cancer and schwannoma in a 60-year-old woman affected by type-1 von Recklinghausen's neurofibromatosis.
Neurofibromatosis (NF1 or von Recklinghausen's disease) is a common autosomal dominant disease associated with a higher incidence of neoplasms than in the general population. We report the case of a 60-year-old woman affected by NF1 who was coincidentally diagnosed with a gastrointestinal stromal tumor, a breast carcinoma and a peripheral nervous system tumor.


Management and etiology of the unilateral multicystic dysplastic kidney: a review.
In children, unilateral multicystic dysplastic kidney (MCDK) is one of the most frequently identified urinary tract abnormalities. A variety of proposed etiologies has been associated with the underlying pathogenesis of MCDK. These include genetic disturbances, teratogens, in utero infections, and urinary outflow tract obstruction. From 5-43% of the time, MCDK has associated genito-urinary anomalies, both structural and functional in nature. A review of the literature reveals that involution rates are reported to be 19-73%, compensatory hypertrophy of the contralateral kidney occurs from 24-81% of the time, and estimated glomerular filtration rates (GFRs) (by the Schwartz formula) range from 86-122 ml/min per 1.73 m(2) body surface area. Most authors suggest serial ultrasonography to monitor contralateral growth, routine blood pressure monitoring, and a serum creatinine monitoring algorithm. The risk of hypertension in those with MCDKs does not appear to be greater than that of the general population, and the rates of malignant transformation of MCDK are small, if at all increased, in comparison with those in the general population. If the patient develops a urinary tract infection or has abnormalities of the contralateral kidney, shown on ultrasound, a voiding cystourethrogram is recommended. Finally, the body of literature does not support the routine surgical removal of MCDKs.


Crosslinking of PCR primers reduces unspecific amplification products in multiplex PCR.
The polymerase chain reaction is not only essential for many DNA-based diagnostic methods but is also exploited in other molecular methods that require an upstream amplification step. Multiplex PCRs are especially attractive as they reduce the number of individual reactions. However, the multiplexing efficiency is impaired by primer interactions such as the formation of primer dimers. In this study, covalent crosslinking of primers via their 5'-ends was used to avoid those undesired effects. The specificity of the primers as well as the efficiency of the PCR could be increased upon primer crosslinking in reactions containing up to 34 primer pairs targeting the most important antibiotic resistance genes in a single multiplex reaction.