An anoikis-related gene signature for prediction of the prognosis in prostate cancer.
This study presents a novel approach to predict postoperative biochemical recurrence (BCR) in prostate cancer (PCa) patients which involves constructing a signature based on anoikis-related genes (ARGs). In this study, we utilised data from TCGA-PARD and GEO databases to identify specific ARGs in prostate cancer. We established a signature of these ARGs using Cox regression analysis and evaluated their clinical predictive efficacy and immune-related status through various methods such as Kaplan-Meier survival analysis, subject work characteristics analysis, and CIBERSORT method. Our findings suggest that these ARGs may have potential as biomarkers for prostate cancer prognosis and treatment. To investigate the biological pathways of genes associated with anoikis, we utilised GSVA, GO, and KEGG. The expression of ARGs was confirmed by the HPA database. Furthermore, we conducted PPI analysis to identify the core network of ARGs in PCa. Based on analysis of the TCGA database, a set of eight ARGs were identified as prognostic signature genes for prostate cancer. The reliability and validity of this signature were well verified in both the TCGA and GEO codifications. Using this signature, patients were classified into two groups based on their risk for developing BCR. There was a significant difference in BCR-free time between the high and low risk groups (P < 0.05).This signature serves as a dependable and unbiased prognostic factor for predicting biochemical recurrence (BCR) in prostate cancer (PCa) patients. It outperforms clinicopathological characteristics in terms of accuracy and reliability. PLK1 may play a potential regulatory role as a core gene in the development of prostate cancer. This signature suggests the potential role of ARGs in the development and progression of PCa and can effectively predict the risk of BCR in PCa patients after surgery. It also provides a basis for further research into the mechanism of ARGs in PCa and for the clinical management of patients with PCa.


[Paradoxical worsening of cavernous sinus dural arteriovenous fistula: case report with serial angiograms].
We report, with serial angiograms, a case worsening of dural arteriovenous fistulae (DAVFs) located at the hypoplastic right cavernous sinus and draining into the left superior ophthalmic vein across the inter-cavernous sinus. The patient presented with sudden onset of external ophthalmoplegia and deterioration of visual acuity on the left. An imaging work-up at the day of admission included contrast-enhanced computed tomography and conventional catheter angiography, which demonstrated complete thrombosis of the left cavernous sinus. There was no strong evidence to suggest DAVFs other than small faint opacification of the posterior cavernous sinus on the right at the late arterial phase. For this reason a diagnosis of left cavernous sinus thrombosis was made, followed by aggressive anticoagulation therapy with intravenous administration of antibiotics. Although the patient's eye symptoms improved significantly after the anticoagulation therapy, the follow-up angiogram obtained 5 days after admission demonstrated small right cavernous sinus DAVFs, which drained into the left superior ophthalmic vein. The patient was followed up conservatively at the out-patient clinic. Three-month follow up angiograms demonstrated spontaneous cure of the DAVF. Also noted was a complete recovery of external ophthalmoplegia with significant improvement of left visual acuity. The alternation of clinical and angiographic findings in this case may help to understand the etiology of paradoxical worsening of cavernous sinus DAVF. In selected cases, anticoagulation therapy may help to improve the prognosis of paradoxical worsening.


Optical development in the foetal bovine lens.
The refractive index variations along the optic axes of nine foetal bovine lenses were measured using an optic fibre reflectometer. The device measures refractive index directly, using the principle of Fresnel reflectance. These results show that lenses with a wet weight >0.7 g (corresponding to 4.5 months gestational age), have a refractive index profile which approximates a parabolic shape, akin to that found in post-natal and adult bovine lenses. In lenses of wet weight below 0.7 g, the refractive index distributions show irregularities. These findings suggest that the refractive index profile in the bovine lens starts to form into a parabolic distribution, as seen in adult lenses, about half-way through gestation. The trigger for this formation is not known.


Three-Dimensionally Conformal Porous Microstructured Fabrics via Breath Figures: A Nature-Inspired Approach for Novel Surface Modification of Textiles.
Breath figures (BFs) are a kind of water droplet arrays that can be formed by condensing aqueous vapor onto a cold surface, such as dewy phenomenon on a spider web. This study developed a BF-inspired approach for direct introduction of desired materials onto the textile surfaces with three-dimensionally conformal porous microstructures by the evaporation of solution-coated fabric under high humidity environment, which brings a brand-new kind of modified textiles, three-dimensionally conformal porous microstructured fabrics (CPMFs). Such kind of CPMFs can possess customized multifunctional properties of introduced materials, and meanwhile maintain the inherent properties and unique texture features of fabrics. This nature-inspired BF approach is robust and versatile for customized preparation of CPMFs based on different fabrics with different common polymers. Moreover, it is also feasible for one-step functionalization of CPMFs by the incorporation of nanoparticles (such as titanium dioxide nanoparticles, TiO2 NPs) into the porous microstructures during the BF process. Comparing to the sample modified without porous microstructures, the resultant TiO2 NPs-incorporated CPMFs show an obviously enhanced performance on photocatalytic degradation of pollutants under the same ultraviolet irradiation conditions.


An Association of Morphological Characteristics of Palatal Rugae and Dental Malocclusion in an Adult Indian Population: A Cross-Sectional Study.
Introduction The formation of palatal rugae is completed in the early intrauterine stage, and because of their unique and permanent pattern in each individual, they can be utilized in forensics to identify a person. Objective The primary objective of this study was to determine an association between the rugae pattern and the dental malocclusion system described by Angle. Materials and methods A prospective cross-sectional, observational study was conducted on pretreatment dental casts of 400 subjects in an age range of 18-40 years. The samples were divided according to Angle's system of classification of malocclusion into Class I, Class II, and Class III. The number, length, pattern, and orientation of the three anterior-most primary rugae on both sides of the palatal region were studied. Results Significant differences were noted in the mean number of palatal rugae and mean lengths of rugae 1 and 2 on the right side (p < 0.001) and rugae 3 on the left (p < 0.001) side among the different malocclusion groups. Curved and wavy patterns were predominant, and significant differences were found among the groups (p < 0.05), whereas non-significant differences were observed in the rugae orientation between the groups on the right and left sides. Conclusions The current study showed significant differences in the length, number, and pattern of the palatal rugae among Angle's classes of malocclusion. Clinical implications Palatal rugae can be effectively used to identify dental malocclusion at an early stage and can, therefore, help intercept the developing malocclusion.


Artificial compound eye zoom camera.
We demonstrate a highly compact image capturing system with variable field of view but without any mechanically moving parts. The camera combines an ultra-thin artificial apposition compound eye with one variable focal length liquid lens. The change of optical power of the liquid lens when applying a voltage results in a change of the magnification of the microlens array imaging system. However, its effect on focusing of the individual microlenses can be neglected due to their small focal length.


Seroprevalence of antibodies against Toxoplasma gondii among recently immigrating Ethiopian Jews.
Sera from 144 Ethiopian immigrants who arrived in Operation Solomon, 1991, living in three absorption centers in the Jezreel Valley were tested for antibodies against Toxoplasma gondii. Antibodies were found in 34% of the test group, with a rise in prevalence with age from 0% in the first decade to 46% in the > 40 age-groups. The prevalence in the Ethiopians was higher than in Jewish kibbutz members (22.8%) and lower than in Arab villagers (55.8%). During the reproductive years (age 20-39) the rate of seroconversion is 1% per year, and screening of pregnant Ethiopian women for antibodies to T. gondii should be considered.


Ultrasound of the prostate. Analysis of tissue texture and abnormalities.
Thirty-nine patients with benign prostatic hypertrophy, prostatic carcinoma, or prostatitis underwent ultrasonography using a transabdominal suprapubic approach. In both benign hypertrophy and prostatitis, the gland was enlarged and exhibited a homogeneous echo pattern, being hypoechoic in prostatitis and either hypo- or hyperechoic in hypertrophy. Carcinoma was characterized by focal areas of increased or decreased echogenicity with irregular margins. The various sonographic appearances are explained by correlation with the histological findings, and the advantages of the transabdominal approach are discussed. The authors suggest that widespread application of this technique will improve early detection of prostatic carcinoma.


Seasonal variations on serum glucose and lipid profile in a male poikilotherm vertebrate, Uromastyx hardwickii.
Uromastyx hardwickii, a local lacertilian species, is widely distributed in the Indo-Pak subcontinent and inhabits mostly the arid regions of the country. This study was carried out to assess the seasonal variations on glucose, cholesterol and triacylglycerol (TAG) levels in a poikilotherm vertebrate species and to develop an experimental model for the study of lipid metabolism in higher vertebrates including mammals. This cross-sectional study was carried out on male Uromastyx hardwickii. Sixty animals were bled and sacrificed within 48 hrs of their arrival in the laboratory. Blood samples were collected by anterior abdominal venepuncture from conscious animals using a heparinised syringe. Mean serum TAG levels were significantly higher in summer, while no significant changes were seen in cholesterol level during different parts of the year. Mean serum glucose levels were significantly higher in summer. Lipid metabolism in Uromastyx hardwickii undergoes significant seasonal alteration. There is significant (p < 0.05) increase in serum triglycerides during summer. Similarly, serum glucose also exhibits seasonal variation.


TFE3-rearranged hepatic epithelioid hemangioendothelioma-a case report with immunohistochemical and molecular study.
A recurrent YAP1-TFE3 gene fusion has been identified in WWTR1-CAMTA1-negative epithelioid hemangioendotheliomas arising in soft tissue, bone, and lung, but not in liver. We present the first case of TFE3-rearranged hepatic epithelioid hemangioendothelioma in a 39-year-old Taiwanese woman. Computed tomography scan revealed multifocal, ill-defined nodules involving both hepatic lobes. She then underwent deceased donor liver transplantation. Histologically, the tumors in the liver explant showed a biphasic growth pattern. One component was composed of dilated and well-formed blood vessels lined by epithelioid cells with abundant eosinophilic cytoplasm, mimicking an alveolar pattern, whereas the other component was composed of cords and single cells, featuring intracytoplasmic vacuoles, separated by a myxoid stroma. The tumor cells showed vesicular nuclei and small indistinct nucleoli with mild to moderate cytologic atypia. Most tumor cells showed factor VIII, CD34, CD31, and TFE3 positivity in immunohistochemical study. Fluorescence in situ hybridization analysis for the tumor cells exhibited TFE3 gene rearrangement. The patient is currently alive, and no post-operative tumor recurrence developed during a 13-year follow-up. Awareness of this rare vasoformative variant and identification of the gene rearrangement would be helpful on differential diagnosis with other high-grade carcinoma and angiosarcoma of liver.


N-terminal acylation of the SV40 nuclear localization signal peptide enhances its oligonucleotide binding and membrane translocation efficiencies.
Octanoyl and palmitoyl groups were coupled to the N-terminus of an analog of the SV40 nuclear localization signal peptide, SV126-133(Ser128), to study the effect of the fatty acid chain length on the complex formation with a single-stranded antisense oligodeoxynucleotide (ODN) and on the cellular uptake of the complex. The strongest binding affinity was observed for the palmitoylated peptide, indicating the better accessibility of the positively charged lysyl and arginyl side-chains to the phosphate groups due to the turn structures stabilized by the palmitoyl group. On increase of the peptide to ODN molar ratio (rM), gradual unstacking of the bases was observed, the maximal rate being reached at rM=10. At rM>10 restacking of the nucleotide bases was detected and the ODN was completely encapsulated in a liposome-like structure made up of palmitoylated peptides. Cell translocation experiments revealed a highly efficient cell transport of the ODN by palmitoylated SV40 peptide at rM>10.


Magnetic resonance imaging in the oncology patient: evaluation of the extrahepatic abdomen.
In the oncology patient MR imaging provides excellent depiction of all forms of extrahepatic tumor. Rapid breath-hold imaging techniques are combined with intravenous and intraluminal contrast material to demonstrate tumors of the solid visceral organs, the gastrointestinal tract, peritoneum, mesentery, omentum, bile ducts, lymph nodes, and osseous structures. The unmatched soft tissue contrast of MR imaging allows one to depict subtle tumors involving all of these extrahepatic sites. MR imaging has become an integral and essential element in the management of oncology patients.


Modular characteristics and mechanism of action of herbs for vascular calcification treatment in Chinese medicine: a data mining and network pharmacology-based identification.
The aim of this study was to investigate the modular characteristics and mechanism of action of Chinese herbs for vascular calcification (VC) treatment. Network pharmacology coupled with literature data mining was utilized to assess the Chinese herbal clinical performance as well as its similarity, characteristics, ingredient, target, and Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and network construction. The top 15 medications from the literature, according to the usage, and 190 active chemicals, 183 common targets between medication and VC-related targets were weeded out. Analysis of the relationships between the active ingredients, pharmacological targets, and signaling pathways helped to clearly define the therapeutic effect of Traditional Chinese Medicine (TCM). Importantly, we discovered seven most hub proteins (AKT1, CTNNB1, TNF, EGFR, TP53, JUN and IL-6) and two of the herbs' most fundamental ingredients (Formononetin and Luteolin) in TCM-mediated VC suppression. Mechanistically, the metabolic pathways [AGE-RAGE pathway, interleukin-17 (IL-17) pathway, and p53 pathway] as well as smooth muscle adaptation (functional remodeling) and oxidoreductase activity (redox homeostasis modulating) are also crucially implicated. Our work, accomplished by network pharmacology and data mining, increases our understanding of TCM in VC therapy and may offer insightful information for future drug discovery investigations.


Propagation of RML prions in mice expressing PrP devoid of GPI anchor leads to formation of a novel, stable prion strain.
PrP(C), a host protein which in prion-infected animals is converted to PrP(Sc), is linked to the cell membrane by a GPI anchor. Mice expressing PrP(C) without GPI anchor (tgGPI⁻ mice), are susceptible to prion infection but accumulate anchorless PrP(Sc) extra-, rather than intracellularly. We investigated whether tgGPI⁻ mice could faithfully propagate prion strains despite the deviant structure and location of anchorless PrP(Sc). We found that RML and ME7, but not 22L prions propagated in tgGPI⁻ brain developed novel cell tropisms, as determined by the Cell Panel Assay (CPA). Surprisingly, the levels of proteinase K-resistant PrP(Sc) (PrP(res)) in RML- or ME7-infected tgGPI⁻ brain were 25-50 times higher than in wild-type brain. When returned to wild-type brain, ME7 prions recovered their original properties, however RML prions had given rise to a novel prion strain, designated SFL, which remained unchanged even after three passages in wild-type mice. Because both RML PrP(Sc) and SFL PrP(Sc) are stably propagated in wild-type mice we propose that the two conformations are separated by a high activation energy barrier which is abrogated in tgGPI⁻ mice.


Recruitment to online therapies for depression: pilot cluster randomized controlled trial.
Raising awareness of online cognitive behavioral therapy (CBT) could benefit many people with depression, but we do not know how purchasing online advertising compares to placing free links from relevant local websites in increasing uptake. To pilot a cluster randomized controlled trial (RCT) comparing purchase of Google AdWords with placing free website links in raising awareness of online CBT resources for depression in order to better understand research design issues. We compared two online interventions with a control without intervention. The pilot RCT had 4 arms, each with 4 British postcode areas: (A) geographically targeted AdWords, (B) adverts placed on local websites by contacting website owners and requesting links be added, (C) both interventions, (D) control. Participants were directed to our research project website linking to two freely available online CBT resource sites (Moodgym and Living Life To The Full (LLTTF)) and two other depression support sites. We used data from (1) AdWords, (2) Google Analytics for our project website and for LLTTF, and (3) research project website. We compared two outcomes: (1) numbers with depression accessing the research project website, and then chose an onward link to one of the two CBT websites, and (2) numbers registering with LLTTF. We documented costs, and explored intervention and assessment methods to make general recommendations to inform researchers aiming to use similar methodologies in future studies. Trying to place local website links appeared much less cost effective than AdWords and although may prove useful for service delivery, was not worth pursuing in the context of the current study design. Our AdWords intervention was effective in recruiting people to the project website but our location targeting "leaked" and was not as geographically specific as claimed. The impact on online CBT was also diluted by offering participants other choices of destinations. Measuring the impact on LLTTF use was difficult as the total number using LLTTF was less than 5% of all users and record linkage across websites was impossible. Confounding activity may have resulted in some increase in registrations in the control arm. Practitioners should consider online advertising to increase uptake of online therapy but need to check its additional value. A cluster RCT using location targeted adverts is feasible and this research design provides the best evidence of cost-effectiveness. Although our British pilot study is limited to online CBT for depression, a cluster RCT with similar design would be appropriate for other online treatments and countries and our recommendations may apply. They include ways of dealing with possible contamination (buffer zones and AdWords techniques), confounding factors (large number of clusters), advertising dose (in proportion to total number of users), record linkage (landing within target website), and length of study (4-6 months). clinicaltrials.gov (Registration No. NCT01469689); http://clinicaltrials.gov/ct2/show/NCT01469689 (Archived by WebCite at http://www.webcitation.org/6EtTthDOp).


Functional characteristics of idiopathic hydronephrosis.
The functional characteristics of idiopathic hydronephrosis were studied in 171 patients. Conventional renography and measurement of the glomerular filtration rate were performed in all subjects, 137 (79%) of whom had normal parenchymal function despite severely reduced drainage function. Proximal tubular function, measured by determination of beta 2-microglobulin excretion was not reduced. Distal tubular function, evaluated as the maximum concentration ability, was not reduced in 35 of the 89 patients studied. During urography and diuresis renography were both useful tools for verifying the presence of obstruction in doubtful cases. Intrapelvic pressure was measured during constant perfusion at a rate of 7.5 ml/min and during furosemide-induced diuresis. The basal intrapelvic pressure varied from 6 to 10 cm H2O and was not increased in any kidney regardless of the degree of duration of obstruction. During perfusion, the pressure increased and varied from 28 to 52 cm H2O. During diuresis, an increase in pressure above 20 cm H2O was registered only in obstructed kidneys with a normal urinary concentrating ability. The pressure rise never exceeded 20 cm H2O during diuresis in obstructed kidneys with complications such as calculi of previous episodes of upper urinary tract infection. From these studies it is concluded that, besides cases with complications such as urinary tract infection and renal calculi, surgery should be offered to patients with idiopathic hydronephrosis with reduced urinary concentrating ability. In doubtful cases with wide pelves, renography and urography during increased diuresis can be used provided kidney function is not reduced. When kidney function is reduced, a pressure increase above 20 cm H2O during constant perfusion at a rate of 7.5 ml/min indicates obstruction.


The use of immunodeficient male (CBA/N x BALB/c) F1 mice to produce monoclonal antibodies directed to proteins of Leptospira interrogans rather than to immunodominant lipopolysaccharides.
A method, using an immunodeficient mouse strain, for the production of monoclonal antibodies directed exclusively against the proteins in an antigen mixture also containing immunodominant LPS, is described. Male (CBA/N x BALB/c) F1 mice were immunized with an outer envelope antigen mixture from Leptospira interrogans strain Wijnberg containing both lipopolysaccharides and proteins. The immune response in these mice was shown to be predominantly directed against protein antigens. Hybridoma cell lines were generated by fusing spleen cells from a (CBA/N x BALB/c) F1 mouse with BALB/c Sp2/0 plasmacytoma cells. Hybridoma cell lines producing monoclonal antibodies reacting with the outer envelope preparation were identified by ELISA. All epitopes recognized by the monoclonal antibodies are sensitive to proteinase K degradation and resistant to oxidation by periodate indicating that they are located on proteins. All epitopes are located on a 35 kDa protein and specific for the pathogenic L. interrogans species.


COMPARATIVE EVOLUTIONARY ANALYSIS OF METABOLISM IN NINE DROSOPHILA SPECIES.
To attain balanced and efficient metabolism, the genes encoding enzymes involved in intermediary metabolism must be coordinately regulated. Gross misregulation of these genes can result in deleterious metabolic imbalances, as seen in transgenic laboratory organisms with altered gene dosage. By quantifying the expression of enzymes in nine related species of Drosophila, we hoped to see patterns of coordinated changes that could be related to evolutionary constraints on regulation. The storage pools of triacylglycerols and glycogen were measured, and the activities of 12 enzymes in intermediary metabolism were also quantified. When these phenotypes were placed on the phylogeny of the Drosophila species, quantitative cladistic hypotheses could be tested. The method of independent phylogenetic contrasts provides a formal statistical test of the null hypothesis that phenotypic changes of pairs of characters on a phylogenetic tree are independent. For example, G6PD and 6PGD exhibited a wide range of activity variation among species, and interspecific comparisons suggested significant coregulation. Significant coordinated changes among clades of the Drosophila phylogeny were also seen for 6PGD-malic enzyme, glycogen synthase-fatty acid synthase, G6PD-GPDH, and 6PGD-glycogen synthase, which in most cases exhibited positive intraspecific genetic correlation. This was to be contrasted with the relation between fatty-acid synthesis and fat storage, which exhibits a strong positive correlation within D. melanogaster but no significant interspecific correlation. Limitations of inferring evolutionary constraints by contrasting intraspecific phenotypic variation to interspecific divergence are briefly discussed.


Computational identifying and characterizing circular RNAs and their associated genes in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is currently still a major factor leading to death, lacking of reliable biomarkers. Therefore, deep understanding the pathogenesis for HCC is of great importance. The emergence of circular RNA (circRNA) provides a new way to study the pathogenesis of human disease. Here, we employed the prediction tool to identify circRNAs based on RNA-seq data. Then, to investigate the biological function of the circRNA, the candidate circRNAs were associated with the protein-coding genes (PCGs) by GREAT. We found significant candidate circRNAs expression alterations between normal and tumor samples. Additionally, the PCGs associated with these candidate circRNAs were also found have discriminative expression patterns between normal and tumor samples. The enrichment analysis illustrated that these PCGs were predominantly enriched for liver/cardiovascular-related diseases such as atherosclerosis, myocardial ischemia and coronary heart disease, and participated in various metabolic processes. Together, a further network analysis indicated that these PCGs play important roles in the regulatory and the PPI network. Finally, we built a classification model to distinguish normal and tumor samples by using candidate circRNAs and their associated genes, respectively. Both of them obtained satisfactory results (~ 0.99 of AUC for circRNA and PCG). Our findings suggested that the circRNA could be a critical factor in HCC, providing a useful resource to explore the pathogenesis of HCC.


Biological differences between in vitro produced bovine embryos and parthenotes.
Parthenotes may represent an alternate ethical source of stem cells, once biological differences between parthenotes and embryos can be understood. In this study, we analyzed development, trophectoderm (TE) differentiation, apoptosis/necrosis, and ploidy in parthenotes and in vitro produced bovine embryos. Subsequently, using real-time PCR, we analyzed the expression of genes expected to underlie the observed differences at the blastocyst stage. In vitro matured oocytes were either fertilized or activated with ionomycin +6-DMAP and cultured in simple medium. Parthenotes showed enhanced blastocyst development and diploidy and reduced TE cell counts. Apoptotic and necrotic indexes did not vary, but parthenotes evidenced a higher relative proportion of apoptotic cells between inner cell mass and TE. The pluripotence-related POU5F1 and the methylation DNMT3A genes were downregulated in parthenotes. Among pregnancy recognition genes, TP-1 was upregulated in parthenotes, while PGRMC1 and PLAC8 did not change. Expression of p66(shc) and BAX/BCL2 ratio were higher, and p53 lower, in parthenotes. Among metabolism genes, SLC2A1 was downregulated, while AKR1B1, PTGS2, H6PD, and TXN were upregulated in parthenotes, and SLC2A5 did not differ. Among genes involved in compaction/blastulation, GJA1 was downregulated in parthenotes, but no differences were detected within ATP1A1 and CDH1. Within parthenotes, the expression levels of SLC2A1, TP-1, and H6PD, and possibly AKR1B1, resemble patterns described in female embryos. The pro-apoptotic profile is more pronounced in parthenotes than in embryos, which may differ in their way to channel apoptotic stimuli, through p66(shc) and p53 respectively, and in their mechanisms to control pluripotency and de novo methylation.


[Osteotomy of the base of the first metatarsal bone in the treatment of hallux valgus].
Authors performed in 1979 through 1991 in the Orthopaedic Department of the Semmelweis University of Medicine 47 osteotomies on the base of the first metatarsal bone in 37 patients. After the operation the intermetatarsal angle was in average under 10 and the metatarsophalangeal angle under 20 degrees. In chosen cases and with careful surgical technique good result can be obtained from the osteotomy of the base of the first metatarsal bone. The technique is not complicated, the osteotomy is healed quickly and well and the internal fixation makes early mobilization possible. It can and should be carried out in cases in which the intermetatarsal angle exceeds 10 degrees. After its performance, if necessary, operation beside the metatarsophalangeal joint may also be carried out.


Anti-Müllerian hormone levels are associated with skeletal maturity in adolescent girls in the Fels Longitudinal Study.
The role of anti-Müllerian hormone (AMH), a potential marker of the hypothalamic-pituitary-ovarian axis, is not well established in adolescent females. Most studies use secondary sexual characteristics or chronological age as predictors for AMH. Skeletal maturity, an indicator of bone development, has not been examined to predict AMH. This study sought to examine patterns of change in AMH in relation to skeletal maturity. Demographics, anthropometry, hand-wrist radiographs, and cardiometabolic risk factors from 88 females (212 observations), between the ages of 8 to 18 years from the Fels Longitudinal Study were used in this study. AMH was analyzed using ELISA from stored frozen serum samples. Generalized linear mixed effect modeling was used. In the stepwise regression models, log-transformed AMH (AMHlog) was regressed on relative skeletal age as the skeletal maturity indicator (calculated as chronological age minus skeletal age) and adjusted for chronological age, adiposity, and cardiometabolic risk factors. Skeletal maturity significantly predicted lower AMHlog (β= -0.073, SE=0.032, p=0.023). Glucose was significantly associated with decreases in AMHlog (β= -0.008, SE=0.004, p=0.044). Chronological age modeled as a cubic function was not significant. AMH and skeletal maturity may provide correlated information on growth and pubertal status in adolescent females.


Alzheimer's Type Neuropathological Changes in a Patient with Depression and Anxiety: A Case Report and Literature Review of Neuropathological Correlates of Neuropsychiatric Symptoms in Alzheimer's Disease.
Alzheimer's disease (AD) is classified as a tauopathy and is the most common neuropathological correlate of dementia/cognitive impairment. AD is neuropathologically characterized by the presence of beta-amyloid immunoreactive senile plaques and tau positive neurofibrillary tangles. Neuropsychiatric symptoms of AD however continue to be underscored, and therefore, neuropathological correlates of these neuropsychiatric symptoms are not readily studied. Presented here is a case of 60-year-old female who initially presented with anxiety and depression, and continued to be the predominant symptoms although mild cognitive impairment was noted as per the available clinical notes. Postmortem examination of the brain revealed severe Alzheimer's type neuropathological changes, which included significant tau and beta-amyloid pathology in limbic regions, which were thought to represent correlates of the patient's depression and anxiety. This case report illustrates the possible neuropathological correlates of neuropsychiatric symptoms in patients with AD. The author hopes that such a case will promote more in-depth studies into the pathophysiology of neuropsychiatric manifestations in AD.


Psychosocial factors in teenagers and young adults with myelomeningocele and clean intermittent catheterization.
The aim was to analyse the psychosocial factors of teenagers and young adults with myelomeningocele with at least 5 years' experience of clean intermittent catheterization (CIC). A qualitative interview technique with semi-structured questions was used in 22 participants aged 13-26 years (median 17) and issues addressed were information given to others, integrity, attitudes to other disabilities, friendship, partnership and sexuality. The participants wanted to inform their peers about the disability but often did not have the courage. Ignorance of the principle of self-CIC among medical staff was confusing. Urinary incontinence after the introduction of the self-CIC regimen was not seen as a problem in comparison with other major disabilities. Half of the participants had peers that they could call a best friend. The subjects wanted more specific information regarding their own sexual function. Finding a partner and becoming a parent were strongly desired but considered problematic. The participants wished to acquire more knowledge about CIC as a bladder-emptying method from the medical staff and also to have the respect to perform self-CIC at examinations. This study did not find any negative psychosocial factors associated with CIC.


Studies on microbiologically influenced corrosion of SS304 by a novel manganese oxidizer, Bacillus flexus.
A manganese oxidizing bacterium was isolated from the surface of steel scraps and biochemical tests and 16S rRNA sequencing analysis confirmed the isolate as Bacillus flexus. Potentiodynamic polarization curves showed ennoblement of open circuit potential, increased passive current, a lowering of breakdown potential, active re-passivation potential and enhanced cathodic current in the presence of B. flexus. Adhesion studies with B. flexus on SS304 specimens with different surface treatments demonstrated decreased adhesion on passivated and FeCl(3) treated specimens due to the removal of MnS inclusions. The present study provides evidence that surface treatment of stainless steels can reduce adhesion of this manganese oxidizing bacterium and decrease the probability of microbiologically influenced corrosion.


Class 1 antiarrhythmic drugs--characteristic electrocardiographic differences when assessed by atrial and ventricular pacing.
Class 1 antiarrhythmic drugs have been subdivided into 1a, 1b and 1c according to their effect on the action potential duration. The effects on the surface electrocardiogram of one drug from each subgroup were investigated in nine patients. Electrocardiographic recordings were taken during sinus rhythm and at identical atrial and ventricular paced rates. Disopyramide (1a) significantly prolonged the QT interval during sinus rhythm and at the identical paced rates, by increasing both the QRS duration and JT interval. Lignocaine (1b) significantly reduced the QT interval during sinus rhythm and at the identical paced rates, by reducing the JT interval. Lignocaine had no effect on the QRS duration. Flecainide (1c) significantly prolonged the QRS duration during sinus rhythm, but not the QTc. However the QT interval at the paced rates prolonged significantly, due entirely to an increase of the QRS duration. Flecainide had no effect on the JT interval. These characteristic electrocardiographic differences support the differentiation of class 1 drugs into three separate subgroups.


Age-associated changes in microRNAs affect the differentiation potential of human mesenchymal stem cells: Novel role of miR-29b-1-5p expression.
Age-associated osteoporosis is widely accepted as involving the disruption of osteogenic stem cell populations and their functioning. Maintenance of the local bone marrow (BM) microenvironment is critical for regulating proliferation and differentiation of the multipotent BM mesenchymal stromal/stem cell (BMSC) population with age. The potential role of microRNAs (miRNAs) in modulating BMSCs and the BM microenvironment has recently gained attention. However, miRNAs expressed in rapidly isolated BMSCs that are naïve to the non-physiologic standard tissue culture conditions and reflect a more accurate in vivo profile have not yet been reported. Here we directly isolated CD271 positive (+) BMSCs within hours from human surgical BM aspirates without culturing and performed microarray analysis to identify the age-associated changes in BMSC miRNA expression. One hundred and two miRNAs showed differential expression with aging. Target prediction and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the up-regulated miRNAs targeting genes in bone development pathways were considerably enriched. Among the differentially up-regulated miRNAs the novel passenger strand miR-29b-1-5p was abundantly expressed as a mature functional miRNA with aging. This suggests a critical arm-switching mechanism regulates the expression of the miR-29b-1-5p/3p pair shifting the normally degraded arm, miR-29b-1-5p, to be the dominantly expressed miRNA of the pair in aging. The normal guide strand miR-29b-1-3p is known to act as a pro-osteogenic miRNA. On the other hand, overexpression of the passenger strand miR-29b-1-5p in culture-expanded CD271+ BMSCs significantly down-regulated the expression of stromal cell-derived factor 1 (CXCL12)/ C-X-C chemokine receptor type 4 (SDF-1(CXCL12)/CXCR4) axis and other osteogenic genes including bone morphogenetic protein-2 (BMP-2) and runt-related transcription factor 2 (RUNX2). In contrast, blocking of miR-29b-1-5p function using an antagomir inhibitor up-regulated expression of BMP-2 and RUNX2 genes. Functional assays confirmed that miR-29b-1-5p negatively regulates BMSC osteogenesis in vitro. These novel findings provide evidence of a pathogenic anti-osteogenic role for miR-29b-1-5p and other miRNAs in age-related defects in osteogenesis and bone regeneration.


Hematological and Biochemical Assessment of Two Species of Freshwater Mussels, Quadrula quadrula and Amblema plicata, Following Translocation.
Nondestructive, sublethal, and sensitive health monitoring tools are needed to assess the health of freshwater mussels (family Unionidae). Recent developments to standardize hemocyte characterization have assisted in the hematologic assessment of wild and captive freshwater mussels. In this study, preliminary baseline hematological reference ranges were established for wild mapleleaf mussels Quadrula quadrula (n = 14) and threeridge mussels Amblema plicata (n = 20) collected from the Muskingum River in Devola, Ohio. Mussels were collected from the wild, and hemolymph was sampled from each mussel in the field upon capture (baseline sample). They were then transported live to a propagation facility. Subsequent hemolymph samples were collected at 2 and 4 weeks and quarterly thereafter for 11 months following translocation. Hemocyte counts, hemocyte morphology, and hemolymph chemistry (Na+ , Cl- , Mg2+ , P3- , K+ , Ca2+ , glucose, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase]) were measured from each sample on each sampling occasion. Hemocyte counts were consistently greater in Q. quadrula than in A. plicata following transfer to captivity. Baseline hemocyte morphology and hemolymph chemistry varied between species. This study provides a foundation of reference ranges for hemocyte characterization for Q. quadrula, and A. plicata and a preliminary understanding of how hemocyte character might be expected to change when wild mussels are translocated into captivity, and thus be a useful technique for monitoring the health of freshwater mussels.


3D augmented reality mirror visual feedback therapy applied to the treatment of persistent, unilateral upper extremity neuropathic pain: a preliminary study.
Objective: We assessed whether or not pain relief could be achieved with a new system that combines 3D augmented reality system (3DARS) and the principles of mirror visual feedback. Methods: Twenty-two patients between 18 and 75 years of age who suffered of chronic neuropathic pain. Each patient performed five 3DARS sessions treatment of 20 mins spread over a period of one week. The following pain parameters were assessed: (1) visual analogic scale after each treatment session (2) McGill pain scale and DN4 questionnaire were completed before the first session and 24 h after the last session. Results: The mean improvement of VAS per session was 29% (p < 0.001). There was an immediate session effect demonstrating a systematic improvement in pain between the beginning and the end of each session. We noted that this pain reduction was partially preserved until the next session. If we compare the pain level at baseline and 24 h after the last session, there was a significant decrease (p < 0.001) of pain of 37%. There was a significant decrease (p < 0.001) on the McGill Pain Questionnaire and DN4 questionnaire (p < 0.01). Conclusion: Our results indicate that 3DARS induced a significant pain decrease for patients who presented chronic neuropathic pain in a unilateral upper extremity. While further research is necessary before definitive conclusions can be drawn, clinicians could implement the approach as a preparatory adjunct for providing temporary pain relief aimed at enhancing chronic pain patients' tolerance of manual therapy and exercise intervention. Level of Evidence: 4.


Anodic electrochemiluminescence of CdTe quantum dots and its energy transfer for detection of catechol derivatives.
This work reported for the first time the anodic electrochemiluminescence (ECL) of CdTe quantum dots (QDs) in aqueous system and its analytical application based on the ECL energy transfer to analytes. The CdTe QDs were modified with mercaptopropionic acid to obtain water-soluble QDs and stable and intensive anodic ECL emission with a peak value at +1.17 V (vs Ag/AgCl) in pH 9.3 PBS at an indium tin oxide (ITO) electrode. The ECL emission was demonstrated to involve the participation of superoxide ion produced at the ITO surface, which could inject an electron into the 1Se quantum-confined orbital of CdTe to form QDs anions. The collision between these anions and the oxidation products of QDs led to the formation of the excited state of QDs and ECL emission. The ECL energy transfer from the excited CdTe QDs to quencher produced a novel methodology for detection of catechol derivatives. Using dopamine and L-adrenalin as model analytes, this ECL method showed wide linear ranges from 50 nM to 5 microM and 80 nM to 30 microM for these species. Both ascorbic acid and uric acid, which are common interferences, did not interfere with the detection of catechol derivatives in practical biological samples.


(Vinylaryloxy)acetic acids. A new class of diuretic agents. 4. Various ((2-substituted and 2,2-disubstituted vinyl)aryloxy)acetic acids.
A variety of [(2-substituted and 2,2-disubstituted vinyl)aryloxy]acetic acids was synthesized in which the substituents were primarily electron-withdrawing groups. These compounds were tested in dogs for their saluretic and diuretic properties. Many of the compounds exhibited significant activity; however, they were generally less potent than those reported in the three earlier papers in this series.


The chronic illness problem inventory: problem-oriented psychosocial assessment of patients with chronic illness.
Two studies are presented which describe the development of a problem-oriented psychosocial screening instrument for use in health care settings. Reliability and validity data are presented on the Chronic Illness Problem Inventory (CIPI) which demonstrate its ability to document accurately patient's specific problems in areas of physical limitations, psychosocial functioning, health care behaviors and marital adjustment. A study is also presented which compares the problems of patients with three distinct chronic illnesses: pain, obesity, and respiratory ailments. Results indicate a significantly greater severity of problems for pain patients and especially patients with multiple pain complaints. Problem areas common to all three illness groups are discussed in the context of providing better comprehensive treatment for chronically ill patients.


The stiff elastographic change of submandibular glands rapidly improves after the introduction of glucocorticoid treatment in patients with IgG4-related dacryoadenitis and sialoadenitis.
In three patients with immunoglobulin G4-related dacryoadenitis and sialoadenitis (IgG4-DS), we assessed the changes in the hardness of affected submandibular glands by the real-time tissue elastography at baseline and 2 weeks after the initiation of treatment with oral glucocorticoids. Elastography revealed "blue" meaning to be a hard tissue matched the hypoechoic areas inside the enlarged submandibular glands before treatment. The stiff elastographic changes rapidly improved after 2 weeks. This may relate with the reversibility of salivary function by glucocorticoid treatment in patients with IgG4-DS.


[Puncture methods of the diagnosis and treatment under the control of US, CT and X-ray video image].
Exploratory and therapeutical punctures were made in 454 patients under the control of ultrasound, CT, and X-ray teleimage. Diagnostic biopsies established the cytological and histological nature of diseases in 67.6% of cases, positive ultrasound-, CT-, and X-ray teleimage-controlled biopsies being 76.3, 64.9, and 71.4%, respectively. Beneficial effects of therapeutical interventions were obtained in 89.5% of patients.


Selectivity of N170 for visual words in the right hemisphere: Evidence from single-trial analysis.
Neuroimaging and neuropsychological studies have identified the involvement of the right posterior region in the processing of visual words. Interestingly, in contrast, ERP studies of the N170 typically demonstrate selectivity for words more strikingly over the left hemisphere. Why is right hemisphere selectivity for words during the N170 epoch typically not observed, despite the clear involvement of this region in word processing? One possibility is that amplitude differences measured on averaged ERPs in previous studies may have been obscured by variation in peak latency across trials. This study examined this possibility by using single-trial analysis. Results show that words evoked greater single-trial N170s than control stimuli in the right hemisphere. Additionally, we observed larger trial-to-trial variability on N170 peak latency for words as compared to control stimuli over the right hemisphere. Results demonstrate that, in contrast to much of the prior literature, the N170 can be selective to words over the right hemisphere. This discrepancy is explained in terms of variability in trial-to-trial peak latency for responses to words over the right hemisphere.


[Emergencies in oncology].
Emergencies in oncologic patients are common and diverse. Almost every cancer patient will develop at least one emergency situation at the beginning or in the further course of his disease. The cancer itself or cancer treatment typically give rise to otherwise rare emergency development. In this review detailed descriptions of spatial cord compression syndrome, superior vena cava obstruction as well as hypercalcemia are given. Finally problems due to cerebral metastases, pulmonary embolism, hyperviscosity and hyperuricemia are briefly summarized.


Can We Measure Immigrants' Legal Status? Lessons from Two U.S. Surveys.
This research note examines response and allocation rates for legal status questions asked in publicly available U.S. surveys to address worries that the legal status of immigrants cannot be reliably measured. Contrary to such notions, we find that immigrants' response rates to questions about legal status are typically not higher than response rates to other immigration-related questions, such as country of birth and year of immigration. Further exploration of two particular surveys - the Los Angeles Family and Neighborhood Survey (LAFANS) and the Survey of Income and Program Participation (SIPP) - reveals that these data sources produce profiles of the unauthorized immigrant population that compare favorably to independently estimated profiles. We also find in the case of the SIPP that the introduction of legal status questions does not appear to have an appreciable "chilling effect" on the subsequent survey participation of unauthorized immigrant respondents. Based on the results, we conclude that future data collection efforts should include questions about legal status in order to (a) improve models of immigrant incorporation and (b) better position assimilation research to inform policy discussions.


Assessing Compatibility of Isaria fumosorosea and Buprofezin for Mitigation of Aleurodicus rugioperculatus (Hemiptera: Aleyrodidae): An Invasive Pest in the Florida Landscape.
Rugose spiraling whitefly (RSW), Aleurodicus rugioperculatus Martin (Hemiptera: Aleyrodidae) is a new invasive whitefly pest in the Florida landscape, known to feed on a wide range of plants including palms, woody ornamentals, shrubs, and fruits. With the objective to find an alternative to neonicotinoid insecticides, and develop an ecofriendly management program for RSW, in the current study we evaluated the efficacy of a biopesticide containing the entomopathogenic fungi, Isaria fumosorosea Wize (Hypocreales: Clavicipitaceae), and an insect growth regulator buprofezin applied alone and in combination under laboratory and field conditions. Before assessing the two products, their compatibility was studied at six different concentrations of buprofezin. No significant inhibitive effect of buprofezin was observed on I. fumosorosea spore germination, and the average linear growth of the colony measured 14 d postinoculation. Under laboratory conditions, I. fumosorosea treatments (alone or mixed with buprofezin) provided higher RSW mortality than buprofezin alone. However, in both outdoor cage studies, the efficacy of buprofezin treatments (alone or mixed with I. fumosorosea) was higher than I. fumosorosea alone. A significant reduction in RSW population was reported for more than 5 wk in buprofezin alone and more than 7 wk in the combination treatments. In fall of 2014 and summer of 2015, the mean whitefly mortality observed during the 10-wk assessment period was 52.4 and 42.1% for I. fumosorosea, 79.6 and 79.0% for buprofezin, and 87.6 and 84.3% in mixed treatments, respectively. Results suggest that buprofezin can offer an effective alternate in the battle against invasive whiteflies such as RSW in Florida ecosystems, either as a stand-alone strategy or in an integrated approach.


Tumor necrosis factor- α, adiponectin and their ratio in gestational diabetes mellitus.
It has been suggested that inflammation might be implicated in the gestational diabetes mellitus (GDM) complications, including insulin resistance. The aims of the current study were to explore maternal circulating values of TNF-α, adiponectin and the adiponectin/TNF-α ratio in women with GDM compared with normal pregnancy and their relationships with metabolic syndrome biomarkers. Forty women with GDM and 40 normal pregnant women were included in the study. Commercially available enzyme-linked immunosorbent assay methods were used to measure serum levels of TNF-α and total adiponectin. Women with GDM had higher values of TNF-α (225.08±27.35 vs 115.68±12.64 pg/ml, p<0.001) and lower values of adiponectin (4.50±0.38 vs 6.37±0.59 µg/ml, p=0.003) and the adiponectin/TNF-α ratio (4.31±0.05 vs 4.80±0.07, P<0.001) than normal pregnant women. The adiponectin/TNF-α ratio showed negative correlations with insulin resistance (r=-0.68, p<0.001) and triglyceride (r=-0.39, p=0.014) and a positive correlation with insulin sensitivity (r=0.69, p<0.001). Multiple linear regression analysis showed that values of the adiponectin /TNF-α ratio were independently associated with insulin resistance. Binary logistic regression analysis showed that GDM was negatively associated with adiponectin /TNF-α ratio. In summary, the adiponectin/TNF-α ratio decreased significantly in GDM compared with normal pregnancy. The ratio might be an informative biomarker for assessment of pregnant women at high risk of insulin resistance and dyslipidemia and for diagnosis and therapeutic monitoring aims in GDM.


A Smart Molecule for Selective Sensing of Nitric Oxide: Conversion of NO to HSNO; Relevance of Biological HSNO Formation.
A smart molecule, QT490, containing thiosemicarbazide moiety acts as a highly selective turn-on in vitro NO sensor through the unprecedented NO-induced transformation of thiosemicarbazide moiety to 1,3,4-oxadiazole heterocycle with the concomitant release of HSNO, thereby eliminating any interference from various endogenous biomolecules including dehydroascorbic acid, ascorbic acid, etc. The kinetic studies of the reactions between QT490 and NO provide a mechanistic insight into formation of HSNO/RSNO from the reaction between H2S/RSH and NO in the biological system. This novel probe is non-cytotoxic, cell permeable, water-soluble, and appropriate for intracellular cytoplasmic NO sensing with the possibilities of in vivo applications.


[The incidence of congenital angiocardiopathies].
Among 229,846 children born alive between 1971 and 1980 in the districts Erfurt and Suhl--this figure coincide with the total number of live births a year in the GDR--1638 patients with structural congenital heart disease were identified. The study is based on an analysis of cardiac patients of this districts and autopsy protocols of all deceased children of the 10-year period. Additional attempt has been made to assess the proportion of cases in adults undergoing cardiac catheterisation with congenital heart disease, undetected in childhood. In our study we found malformations of the heart in 7.13 of 1,000 live births. There is agreement with the results of foreign studies. It is evident, however, that the result requires correction to 8-10/1,000. Our study of the incidence of congenital heart disease in children born between 1971 and 1980 concludes that over the 10-year period the overall incidence has remained constant.


New insights into the mechanisms of gastric cancer multidrug resistance and future perspectives.
Gastric cancer is still the second leading cause of cancer death worldwide. Chemotherapy is one of the major treatment options for advanced gastric cancer. The efficacy of chemotherapy for gastric cancer is poor due to insensitivity and the development of multidrug resistance (MDR). Gastric cancer MDR involves a large number of molecules and complex mechanisms. Classical drug-resistant molecules, such as P-glycoprotein/ABCB1 and MRP1/ABCC1, have been found to play important roles in mediating MDR in some gastric cancers. In recent years, new molecules and mechanisms have been found to be associated with the development of gastric cancer MDR and might provide new targets for tackling gastric cancer MDR. Combined use of molecularly targeted therapy with chemotherapy may offer improved outcomes for gastric cancer patients and might provide new threads of hope for gastric cancer treatment.


Minimal access cranial suspension lift: a modified S-lift.
There is a strong trend at hand toward less dramatic facial rejuvenation surgery. Most of the authors' patients want a cosmetic improvement but not at the cost of prolonged disfigurement or a high risk of complications. In 1999, a very simple but effective rhytidectomy technique, termed an S-lift, was described in the literature and was adopted by the authors. Its basic principle is the suspension of sagging facial features by a strong, permanent purse-string suture. The procedure is performed with the patient under local anesthesia. Significant modifications were applied to the incision, to the purse-string suture anchoring site, and to the direction and shape of the skin excision. The authors named the modified procedure the minimal access cranial suspension lift to specifically describe the concept of the technique. Through an inverted L-shaped preauricular incision with extension below the sideburn, a limited skin undermining is performed. Two strong, permanent purse-string sutures are woven into the superficial musculoaponeurotic system tissues in a vertical U and an oblique O shape, initiating from a strong anchorage in the deep temporal fascia at the level of the helical crus. Tying these sutures produces a very powerful vertical correction of descended facial features that acts mainly on the jowls and the upper neck. The procedure can be extended by continuing the dissection over the malar fat pad, placing a third vertical purse-string suture with strong action on the nasolabial groove, and vertically repositioning the midfacial volumes. During 20 months, pleasing results and a very low complication rate were obtained in 88 consecutive patients with a mean age of 551/2 years. In this article, the authors provide a detailed description of the anesthetic and surgical technique, a demonstration of the results in different patient age categories, and a discussion comparing the minimal access cranial suspension lift with other types of facial rejuvenation procedures.


Vaccinia virus l1 protein is required for cell entry and membrane fusion.
Genetic and biochemical studies have provided evidence for an entry/fusion complex (EFC) comprised of at least eight viral proteins (A16, A21, A28, G3, G9, H2, J5, and L5) that together with an associated protein (F9) participates in entry of vaccinia virus (VACV) into cells. The genes encoding these proteins are conserved in all poxviruses, are expressed late in infection, and are components of the mature virion membrane but are not required for viral morphogenesis. In addition, all but one component has intramolecular disulfides that are formed by the poxvirus cytoplasmic redox system. The L1 protein has each of the characteristics enumerated above except that it has been reported to be essential for virus assembly. To further investigate the role of L1, we constructed a recombinant VACV (vL1Ri) that inducibly expresses L1. In the absence of inducer, L1 synthesis was repressed and vL1Ri was unable to form plaques or produce infectious progeny. Unexpectedly, assembly and morphogenesis appeared normal and the noninfectious virus particles were indistinguishable from wild-type VACV as determined by transmission electron microscopy and analysis of the component polypeptides. Notably, the L1-deficient virions were able to attach to cells but the cores failed to penetrate into the cytoplasm. In addition, cells infected with vL1Ri in the absence of inducer did not form syncytia following brief low-pH treatment even though extracellular virus was produced. Coimmunoprecipitation experiments demonstrated that L1 interacted with the EFC and indirectly with F9, suggesting that L1 is an additional component of the viral entry apparatus.


Oral misoprostol does not protect the kidneys from diclofenac induced toxicity: data from an unilateral ureteral obstructive rat model.
Ureteral obstruction leads to permanent changes in the structure of the kidney by several mechanisms. In this study, it was hypothesized that there would be a protective effect of misoprostol against diclofenac in rats with unilateral ureteral obstruction (UUO). Twenty-two female rats were randomized into 5 groups of 4 and 2 rats for the control group. The right ureter was sutured. The rats were grouped as control, contrast agent, contrast agent +N-acetylcysteine (NAC), diclofenac and diclofenac + misoprostol groups.Radiographic contrast agent was given iv on the 3rd day and other agents were administered orally for 1 week. The rats were sacrified after 1 week and histopathological and biochemical oxidative stress markers were evaluated. The contrast agent and NAC group had lower rates of hemorrhage, inflammation, obstructive dilatation and fatty degeneration compared to the contrast agent only group (p < 0.05). No differences were seen in the normal kidneys. Between all the groups, there was no difference for tubule epithelium damage (p > 0.05). The contrast agent and NAC group had higher rates of antioxidant SH level compared to the contrast agent only group (p < 0.05) and lower rates of oxidative end product carbonyl groups (p < 0.05). For normal kidneys no difference was seen. No statistical difference was seen in MDA levels (p > 0.05). Statistically no difference was seen between the diclofenac group and the diclofenac and misoprostol group neither pathologically nor chemically (p > 0.05). These results showed that NAC is protective against radiographic contrast agent toxicity when given before and after administration in obstructed kidneys as in previous data. Misoprostol was not observed to have any protective effect against diclofenac in obstructed kidneys.


Some new views of the cell surface.
In recent years, it has become possible to investigate the cell surface of normal and tumor cells in new ways, and a number of lines of evidence obtained by various investigators have provided important new views of the surface of mammalian cells. Recent work has, for example, revealed the structure of the histocompatibility antigens, which appear to be ubiquitous on mammalian cells of different types. The dependency on these antigens of lymphocyte interactions with viruses suggests a new hypothesis: histocompatibility molecules may serve as cell surface adaptors for the recognition of foreign antigens such as viruses by T cell receptors. Contrary to older notions, the molecules that make up the cell surface, including the histocompatibility antigens, are not fixed but move freely in the cell membrane, which is a bilayer of lipid. It has been shown in several laboratories that cross-linking of cell surface proteins or "receptors" such as antibodies leads to clustering of these mobile receptor molecules into patches which are subsequently collected as a cap at one pole of the cell. The interactions among different cells and signaling from the surface of each cell to the interior depend upon the structure and physico-chemical interactions of such receptors and on their linkage to structures underlying the cell membrane. Work in our laboratory has produced consistent evidence that the motion and distribution of cell surface molecules are under control of an intracellular system consisting of a network of special proteins. We have found, for example, that mitogenic lectins such as concanavalin A bind to the carbohydrate portions of surface receptors and cross-link them. This binding to some receptors leads to inhibition of motion of all other receptors on the cell surface, suggesting that the original cross-linkage affects a general network responsible for anchoring cell surface receptors. Explorations of the nature of this network suggest that it consists in part of assemblies below the surface membrane containing microfilaments and microtubules.


Family Structure Experiences and Child Socioemotional Development During the First Nine Years of Life: Examining Heterogeneity by Family Structure at Birth.
A vast amount of literature has documented negative associations between family instability and child development, with the largest associations being in the socioemotional (behavioral) domain. Yet, prior work has paid limited attention to differentiating the role of the number, types, and sequencing of family transitions that children experience, as well as to understanding potential heterogeneity in these associations by family structure at birth. We use data from the Fragile Families and Child Wellbeing Study and hierarchical linear models to examine associations of family structure states and transitions with children's socioemotional development during the first nine years of life. We pay close attention to the type and number of family structure transitions experienced and examine whether associations differ depending on family structure at birth. For children born to cohabiting or noncoresident parents, we find little evidence that subsequent family structure experiences are associated with socioemotional development. For children born to married parents, we find associations between family instability and poorer socioemotional development. However, this largely reflects the influence of parental breakup; we find little evidence that socioemotional trajectories differ for children with various family structure experiences subsequent to their parents' breakup.


Heterologous Gene Regulation in Clostridia: Rationally Designed Gene Regulation for Industrial and Medical Applications.
Several species from the Clostridium genus show promise as industrial solvent producers and cancer therapeutic delivery vehicles. Previous development of shuttle plasmids and genome editing tools has aided the study of these species and enabled their exploitation in industrial and medical applications. Nevertheless, the precise control of gene expression is still hindered by the limited range of characterized promoters. To address this, libraries of promoters (native and synthetic), 5' UTRs, and alternative start codons were constructed. These constructs were tested in Escherichia coli K-12, Clostridium sporogenes NCIMB 10696, and Clostridium butyricum DSM 10702, using β-glucuronidase (gusA) as a gene reporter. Promoter activity was corroborated using a second gene reporter, nitroreductase (nmeNTR) from Neisseria meningitides. A strong correlation was observed between the two reporters. In C. sporogenes and C. butyricum, respectively, changes in GusA activity between the weakest and strongest expressing levels were 129-fold and 78-fold. Similar results were obtained with the nmeNTR. Using the GusA reporter, translation initiation from six alternative (non-AUG) start codons was measured in E. coli, C. sporogenes, and C. butyricum. Clearly, species-specific differences between clostridia and E. coli in translation initiation were observed, and the performance of the start codons was influenced by the upstream 5' UTR sequence. These results highlight a new opportunity for gene control in recombinant clostridia. To demonstrate the value of these results, expression of the sacB gene from Bacillus subtilis was optimized for use as a novel negative selection marker in C. butyricum. In summary, these results indicate improvements in the understanding of heterologous gene regulation in Clostridium species and E. coli cloning strains. This new knowledge can be utilized for rationally designed gene regulation in Clostridium-mediated industrial and medical applications, as well as fundamental research into the biology of Clostridium species.


Reexamining epilepsy-associated stigma: validation of the Stigma Scale of Epilepsy in Zambia.
Epilepsy-associated stigma is an important patient-centered outcome, yet quantification remains challenging. Jacoby's 3-item Stigma Scale is commonly used to assess felt stigma among people with epilepsy (PWE) yet has ceiling effects. The Stigma Scale of Epilepsy (SSE) is a 24-item instrument that measures felt stigma among PWE and stigmatizing attitudes among others. If cross-culturally valid, the SSE may elucidate stigma determinants and provide an outcome measure for interventions. We assessed the properties of the SSE in 102 Zambian PWE using exploratory and confirmatory item response theories and compared the latent traits assessed by the SSE to those assessed by Jacoby's Stigma Scale. Differential item functioning based on forced disclosure of epilepsy was examined. The SSE yielded two latent traits--the first reflected difficulties faced by PWE; the second reflected emotions associated with epilepsy. Jacoby's Stigma Scale was associated only with the first latent trait. Forced disclosure was associated with "worry" and "pity" that were associated with the second latent trait. In Zambian PWE, the SSE captured two latent traits. One trait represents feelings associated with epilepsy, which is theorized as a substantial yet unmeasured part of stigma. The SSE performs well across cultures and may more comprehensively assess felt stigma than other instruments. Further validation is required to determine whether the SSE adequately assesses stigmatizing attitudes among people without epilepsy.


Stabilization With Prescribed Instant for High-Order Integrator Systems.
This article develops a new controller design approach to stabilize system states onto the equilibrium at an arbitrarily selected time instant irrespective of the initial system states and parameters. By the stabilization approach, the actual convergence time (not the bound of actual convergence time) is independent of the initial value of system states. This feature differentiates our proposed prescribed-instant stability from conventional fixed, predefined, and prescribed time stability. In this work, we propose the controller design method for the prescribed-instant stability of n -order integrator systems. The proposed control is bounded and can gradually go to zero at an arbitrarily selected time instant, at which the system states reach zero simultaneously. This special stability of the controlled system is analyzed by reduction to absurdity. In simulations, an example of comparison with frequently used prescribed-time control is presented to show the difference. Moreover, the proposed stabilization method is validated by a magnetic suspension system with matched disturbances.


[Further aspects of combination antibiotic therapy. Critical review and personal case studies].
A brief account of the aims sought by multiple antibiotic management is followed by an assessment of the antagonism and synergism displayed by associations of two bactericidal antibiotics, two bacteriostatic antibiotics, and one bactericidal and one bacteriostatic antibiotic. Instances of synergism between bactericides (particularly penicillins and aminosides) are mentioned. Stress is laid on recent studies on the mechanism of action of antibacterial drugs showing unmistakeable synergism between trimethoprim and sulphamethoxazol and between chloramphenicol and tetracycline. The antagonism between bactericides and bacteriostatics noted by Jawetz et Al. has not been confirmed clinically in a number of reported series. The main indications for combined antiobiotic therapy are reviewed: endocarditis, purulent meningitis, staphylococcia, brucellosis, salmonellosis, shigellosis, other Gram-negative infections and fever in the course of blood diseases. References is made to personal experience in the management of 35 cases of bacterial endocarditis, 15 cases of purulent meningitis and various forms of serious Gram-negative infection. Leaving aside exceptional cases, the clinical effects of antibiotic associations are uncertain and influenced by too many variables. The technique is still of importance, however, despite the introduction of many new antibiotics. It must not be thought of as a handy method for indiscriminate use, however; its indications (which are summarised) are quite clear.


The dl1520 virus is found preferentially in tumor tissue after direct intratumoral injection in oral carcinoma.
dl1520 (also known as Onyx-015) is an E1B-deleted adenovirus designed to selectively lyse p53-deficient cancer cells. Clinical trials involving patients with recurrent squamous cell carcinoma of the head and neck have shown clinical efficacy, but no direct evidence as to the tumor or p53 selectivity of the virus was demonstrated. We wanted to determine whether dl1520 is selective for survival and replication within tumor tissue after direct injection and whether this is determined by p53 status of the tissues. We also wanted to ascertain whether the virus has any macroscopic effect on normal tissue. An open-label Phase II trial was devised in which a fixed dose of the virus was administered to 15 patients via a direct intertumoral injection before surgery for untreated oral squamous cell carcinoma. The agent was also delivered into an area of adjacent normal buccal mucosa. Specimens of the excised tumor and of biopsies of the injected normal tissue were assessed for viral presence and p53 status. We demonstrated that the virus replicates selectively in tumor as opposed to normal tissue after this direct injection. It was not possible to determine whether this selectivity was p53 related. It was found that dl1520 triggers an early rise in apoptosis levels in injected normal tissues. No adverse effects of viral injection were noted. This is the first report of injection of dl1520 into previously untreated squamous cell cancer. The data support the concept that dl1520 is replication deficient in normal, compared with cancerous, tissues and has potential as a selective anticancer agent against tumor tissues.


Comparison of three different methods for radiolabelling human activated T lymphocytes.
One approach in the treatment of ovarian cancer patients involves the infusion of autologous T lymphocytes coupled with a bispecific monoclonal antibody MOv18/anti-CD3 (biMAb OC/TR), which recognizes a 38-kDa glycoprotein expressed on ovarian carcinomas and the CD3 T cell receptor. However, little is known about the in vivo biodistribution of injected activated lymphocytes, information that could be obtained by scintigraphic imaging of radiolabelled T cells in order to visualize the migratory pattern. We compared the efficiency, stability and toxicity of technetium-99m hexamethylpropylene amine oxime (HMPAO), indium-111 oxine and fluorine-18 2-fluoro-2-deoxy-d-glucose (FDG) in radiolabelling activated lymphocytes targeted with biMAb OC/TR. The mean labelling efficiencies of 111In-oxine and 18F-FDG using 2.5x10(8) lymphocytes (68% and 64%, respectively) were more than twice that of 99mTc-HMPAO (31%). Retention of the radionuclide in the cell was highest in the case of 111In-oxine labelling (less than 25% of the initial cell-bound activity released after 240 min, as compared with 44% of the 99mTc label in the same period and 45% of 18F radionuclide released after 150 min). None of the three radiolabelling reagents induced any significant alteration in cell viability or immunophenotype. However, both 111In-oxine and 18F-FDG induced a loss of cytotoxic activity of lymphocytes against the ovarian carcinoma cell line IGROV1, and all three radiolabelling reagents caused a significant reduction in the proliferative ability of labelled lymphocytes compared to controls, with cell death occurring after 8-9 days. Radiolabelling with the more stable 111In-oxine reagent using a higher number of lymphocytes (1.4x10(9)) but the same total activity (around 55.5 MBq) resulted in improved labelled T cell viability and proliferative ability, although the mean labelling efficiency decreased (35.8%). Together the data suggest that 111In-oxine at low activity per cell is the most appropriate reagent for radiolabelling activated retargeted T lymphocytes useful for in vivo biodistribution studies.


Some pharmacological effects of an ethanolic extract of Trema guineensis on the central nervous system in rodents.
The present study investigates some neuropharmacological effects of an ethanolic extract of the leaves of Trema guineensis (Ulmaceae), a medicinal plant of central Africa. Intraperitoneal administration of the extract induced hypothermia. In addition, the extract significantly shortened the latency to sleep and prolonged the duration of sleeping time induced by sodium pentobarbital in mice. Moreover, T. guineensis significantly delayed the onset of clonic seizures induced by pentylenetetrazole in mice. In contrast, T. guineensis did not affect convulsions induced by maximal electroshock and picrotoxin in mice nor status epilepticus produced by pilocarpine and kainic acid in rats.


Tiadinil, a plant activator of systemic acquired resistance, boosts the production of herbivore-induced plant volatiles that attract the predatory mite Neoseiulus womersleyi in the tea plant Camellia sinensis.
Plants respond with various defense mechanisms to pathogenic or herbivorous attack. Some chemicals called plant activators that induce the plant defense response against pathogens have been commercially used to protect plants. Here we studied the effects of tiadinil (TDL) on defense mechanisms against herbivores. TDL suppresses pathogenic fungi on tea leaves by inducing defense mechanisms. We used one of the major trophic systems in tea consisting of the herbivorous mite, Tetranychus kanzawai, and the predatory mite, Neoseiulus womersleyi. TDL enhanced the production of herbivore-induced plant volatiles that attract predatory mites. The predatory mites preferred the T. kanzawai-induced volatiles from TDL-treated plants to those produced by untreated plants. These results suggest that TDL activates the plant defense response via an indirect process mediated by plant volatiles that attract natural enemies of the herbivores. In contrast, the oviposition rate, adult maturation rate, and sex ratio of T. kanzawai were not affected by TDL treatment. These results suggest that TDL did not activate any direct defense against the herbivorous mite.


Narrative Messages and the Use of Emotional Appeals on Endometriosis Screening Intention: The Mediating Role of Positive Affect.
Endometriosis affects around 10% of women globally, yet the awareness and screening rates for this condition are relatively low. Utilizing an online survey-based experiment with a sample of 18-30-year-old young women (N = 326), this study aimed to investigate the efficacy of narrative messages vs. non-narrative messages for promoting endometriosis screening intention, as well as to evaluate the effectiveness of hope appeal vs. fear appeal in narrative messages. The study also examined the potential mediating mechanisms through self-efficacy and positive affect responses that may help elucidate the effect of emotional appeals on behavioral intentions, while taking into account an individual's readiness to change. Findings indicated that narrative and non-narrative messages did not produce significantly different screening intentions. Compared to the use of fear appeal, the hope appeal in narrative messages predicted a higher level of positive affect responses, which was associated with increased endometriosis screening intentions. Individual difference in readiness to engage in endometriosis screening was not found to be a significant moderator. These results have implications for future research utilizing hope appeals in narrative health messaging. The observed significant mediational pathway through positive affect advances understanding of positive discrete emotions as facilitators to health-related cognition and behavior changes.


Isolation of ioxynil degraders from soil-enrichment cultures.
A soil enrichment technique was used to isolate microorganisms which could degrade ioxynil (3,5-diiodo-4-hydroxybenzonitrile). Many isolates obtained were able to degrade ioxynil to various products. However, only a fungal isolate (Fusarium solani) and a Gram-negative bacterium (Klebsiella ozaenae) released 14CO2 from ring-labeled ioxynil. No appreciable degradation was detected in pure cultures without the addition of exogenous nutrients. Results indicated that the degradation of ioxynil to CO2 proceeded more slowly in pure culture. Ioxynil was degraded in pure culture at a faster rate by F. solani than by K. ozaenae. Analyses of radioactivity distribution in the cultures indicated that a sizable fraction of radioactivity was in the form of polar products. Several degradation products were detected in the ethyl acetate extracts by thin-layer chromatography and subsequent radioautography. Screening of pure cultures of ioxynil degraders revealed that most isolates degraded ioxynil to the same products which were extractable with ethyl acetate.


Production of oil palm (Elaeis guineensis) fronds lignin-derived non-toxic aldehyde for eco-friendly wood adhesive.
Lignocellulosic materials can significantly contribute to the development of eco-friendly wood adhesives. In this work, glyoxal-phenolic resins for plywood were prepared using organosolv lignin, which was isolated from black liquor recovered from organosolv pulping of oil palm fronds (OPF) and considered to be an alternative to phenol. Glyoxal, which is a dialdehyde obtained from several natural resources, was used as substitute for formaldehyde. The structure of organosolv lignin and the resins were characterized by FTIR and NMR, and for thermal stability by TGA and DSC. The resins were further studied for their viscosity, pH, solids content and gel times. The resins performance as wood adhesive was further established from mechanical test in terms of tensile strength and modulus of elasticity (MOE) to obtain the optimum ratios of organosolv lignin, which replaces phenol in organosolv lignin phenol glyoxal (OLPG) resins. The adhesive composition having 50% (w/w) of phenol substituted by organosolv lignin, termed as 50% OLPG showed highest adhesive strength compared to phenol formaldehyde (PF) commercial adhesive.


The influence of cortical end-plate on broadband ultrasound attenuation measurements at the human calcaneus using scanning confocal ultrasound.
Quantitative ultrasound (QUS) assessment, including broadband ultrasound attenuation (BUA), is an efficient technique for assessing bone quality in various statuses, e.g., osteoporosis. While assessing trabecular bone loss is essential to bone quality, the existence of cortical bone can substantially reduce the accuracy of BUA measurement. In this study, we developed an approach to quantify the influence of the cortical end-plate in the QUS on 18 cadaver calcanei using both analytical and experimental analyses. A simplified cortical-trabecular-cortical sandwich model has been developed for simulation of wave propagations. Results show that the cortical end-plate has a significant effect on BUA (yielding 8.5 +/- 3.6 dB/MHz in cortical bone alone), approximately 15% of the BUA value over the whole bone BUA measurement (54.1 +/- 20.1 dB/MHz). The phenomenon has been predicted by the developed analytical model with a high correlation (r2 = 0.63, p < 0.0001). The data have suggested that the mechanism of the BUA attributed to the cortical end-plate is primarily due to the ultrasonic wave transmission and reflection within the cortical layers. Therefore, the influence of the cortical end-plate in BUA can be quantified and incorporated into the QUS assessment for bone quality, which may provide insight into BUA measurement for accurate diagnosis of bone diseases.


Time-resolved infrared absorption studies of the solvent-dependent vibrational relaxation dynamics of chlorine dioxide.
We report a series of time-resolved infrared absorption studies on chlorine dioxide (OClO) dissolved in H2O, D2O, and acetonitrile. Following the photoexcitation at 401 nm, the evolution in optical density for frequencies corresponding to asymmetric stretch of OClO is measured with a time resolution of 120+/-50 fs. The experimentally determined optical-density evolution is compared with theoretical models of OClO vibrational relaxation derived from collisional models as well as classical molecular-dynamics (MD) studies. The vibrational relaxation rates in D2O are reduced by a factor of 3 relative to H2O consistent with the predictions of MD. This difference reflects modification of the frequency-dependent solvent-solute coupling accompanying isotopic substitution of the solvent. Also, the geminate-recombination quantum yield for the primary photofragments resulting in the reformation of ground-state OClO is reduced in D2O relative to H2O. It is proposed that this reduction reflects enhancement of the dissociation rate accompanying vibrational excitation along the asymmetric-stretch coordinate. In contrast to H2O and D2O, the vibrational-relaxation dynamics in acetonitrile are not well described by the theoretical models. Reproduction of the optical-density evolution in acetonitrile requires significant modification of the frequency-dependent solvent-solute coupling derived from MD. It is proposed that this modification reflects vibrational-energy transfer from the asymmetric stretch of OClO to the methyl rock of acetonitrile. In total, the results presented here provide a detailed description of the solvent-dependent geminate-recombination and vibrational-relaxation dynamics of OClO in solution.


A linguist's view of the Bellman-Goldberg thesis.
From a linguistic perspective, the Bellman-Goldberg thesis of a necessary relationship between the abilities of organisms to move and communicate is very interesting. Since several concepts and terms are represented in both the thesis and contemporary linguistic literature, these items are discussed in further detail. Questions of the implicit assumptions of the homology of the motor and linguistic systems are also raised here. Finally, there are requests for further clarification on issues of evolution in this test of the strength of the thesis.


Hyperintense acute reperfusion marker associated with hemorrhagic transformation in the WAKE-UP trial.
Hyperintense acute reperfusion marker (HARM) is an indicator of early disruption of the blood-brain-barrier. Our aim was to investigate the incidence of HARM in patients with a diffusion weighted imaging (DWI) - fluid attenuated inversion recovery (FLAIR) mismatch and determine the association between this marker and hemorrhagic complications as well as clinical outcome. We included patients from the Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke (WAKE-UP) trial who underwent baseline perfusion weighted imaging (PWI). HARM was defined as a hyperintense signal in the cerebrospinal fluid space on FLAIR imaging at 24 h after baseline imaging. We compared baseline characteristics in patients with and without HARM and investigated the association between HARM and any hemorrhagic transformation (HT) and parenchymal hematoma (PH) in a multivariate logistic regression. We also explored HARM as an independent predictor of poor outcome, defined as a modified Rankin Scale of 3-6 at 90 days. HARM was present in 14 of 223 (6%) patients with a DWI-FLAIR mismatch and baseline characteristics were similar in patients with vs without HARM. HARM showed an independent relationship with any HT (OR 6.67; 95%CI 1.72-26.58) and any PH (OR 6.92; 95%CI 1.34-29.49). The rate of HARM was similar in patients with good and poor outcome (5%, p = 0.90). In the WAKE-UP trial, the incidence of HARM was only 6% at 24 h. An association was present between HARM and hemorrhagic complications, but no relationship with functional outcome was observed.


Effect of manidipine hydrochloride, a calcium antagonist, on isoproterenol-induced left ventricular hypertrophy.
We examined the effect of a calcium antagonist, manidipine hydrochloride, on cardiac hypertrophy and the expression of the atrial natriuretic peptide (ANP), transforming growth factor beta 1 (TGF-beta 1), and extracellular matrix protein genes in rats with isoproterenol-induced cardiac hypertrophy. Rats were continuously infused with saline or isoproterenol (0.5 mg/kg per day) for 7 days using an osmotic minipump. Treatment with manidipine hydrochloride (once a day at 3 mg/kg) began 1 day before minipump implantation and continued until the end of the experiments (each group; n = 6). After treatment, left ventricular weight was measured and mRNA was extracted and analyzed by Northern blot hybridization. Isoproterenol increased left ventricular weight (2.40 +/- 0.04 g/kg; p < 0.01) without increasing blood pressure. ANP, collagen type I and type III, and fibronectin mRNAs were increased 1.5-(p < 0.01), 1.9- (p < 0.01), 2.7- (p < 0.01), and 3.2-fold (p < 0.01), respectively, by isoproterenol infusion. However, TGF-beta 1, collagen type IV, and laminin B1 and B2 mRNA levels were unchanged by isoproterenol. Manidipine hydrochloride prevented isoproterenol-induced left ventricular hypertrophy (2.26 +/- 0.02 g/kg; p < 0.01) and expression of mRNA of ANP (0.9-fold of the control value; p < 0.01), collagen types I (1.1-fold; p < 0.01) and type III (1.6-fold; p < 0.01), and fibronectin (1.1-fold; p < 0.01). Thus, manidipine hydrochloride prevented cardiac hypertrophy and changes in the expression of genes for ANP and interstitial components of extracellular matrix induced by isoproterenol.


A retrospective comparison of weight, lipid, and glucose changes between risperidone- and olanzapine-treated inpatients: metabolic outcomes after 1 year.
Metabolic side effects have been increasingly noted during therapy with novel antipsychotics, but there is a dearth of comprehensive comparative data in this area. The goal of this retrospective study was to examine the changes in weight parameters, fasting glucose, and fasting lipids in long-term inpatients treated with either risperidone or olanzapine. A retrospective study was performed by reviewing charts of patients at Oregon State Hospital, Salem, who were treated during July and August 1999, comparing metabolic outcomes during the first year of therapy with either risperidone or olanzapine. Data were analyzed also by age, sex, and concurrent use of lithium or valproate. Included for analysis were patients at least 18 years old with baseline weights obtained within 3 weeks of drug initiation, and baseline fasting triglycerides, cholesterol, and glucose obtained within 3 months prior to drug initiation and at 1 year of treatment (+/- 4 weeks). The patients meeting these criteria in each drug cohort (risperidone, N = 47; olanzapine, N = 47) included 1 patient with diagnosed diabetes mellitus prior to onset of treatment. Among those patients under 60 years old, olanzapine patients (N = 37) experienced significantly greater increases at 1 year in all metabolic parameters than the risperidone group (N = 39), except for weight variables: triglycerides +104.8 mg/dL (olanzapine) versus +31.7 mg/dL (risperidone) (p = .037); cholesterol +30.7 mg/dL (olanzapine) versus +7.2 mg/dL (risperidone) (p = .004); glucose +10.8 mg/dL (olanzapine) versus +0.74 mg/dL (risperidone) (p = .030). Patients under 60 years of age with concurrent use of lithium or valproate were associated with greater weight gain in both drug groups, but this difference was statistically significant only for the olanzapine cohort. Neither weight change nor use of lithium or valproate was associated with increases in glucose or lipids among those under 60 years old for either drug. Olanzapine therapy is associated with significantly greater increases in fasting glucose and lipid levels for nongeriatric adult patients than risperidone, and the increases are not correlated with changes in weight parameters. Appropriate monitoring of fasting glucose and serum lipid levels should be considered during extended treatment with atypical antipsychotics.


Rivastigmine for Alzheimer's disease.
Alzheimer's disease is the most common form of neurodegenerative dementia and poses considerable health challenges to both patients and their families. Rivastigmine is a powerful slow-reversible, noncompetitive carbamate cholinesterase inhibitor that is approved for the treatment of mild-to-moderate Alzheimer's disease. Randomized, double-blind, placebo-controlled trials of up to 6 months duration have shown beneficial effects of rivastigmine compared with placebo in measures of cognition and global functioning. Less rigorous but growing data suggest that the beneficial effects may endure for up to 5 years, extend to more advanced stages of Alzheimer's disease and may occur in noncognitive domains, such as activities of daily living and the behavioral symptoms of Alzheimer's disease. Evidence from controlled studies also supports the use of rivastigmine for cognitive and behavioral symptoms in Alzheimer's disease associated with vascular risk factors, dementia with Lewy bodies and Parkinson's disease dementia. Early and continued treatment of Alzheimer's disease with rivastigmine maximizes the observed beneficial effects. The most prominent adverse effect of rivastigmine is centrally mediated cholinergic gastrointestinal events, which can be minimized by slower dose-escalation intervals and administration with a full meal. Therapeutic dosing is 6-12 mg/day given twice daily, with higher doses having the potential for greater benefits.


Optimally tolerated dose of lapatinib in combination with docetaxel plus trastuzumab in first-line treatment of HER2-positive metastatic breast cancer.
This phase IB, open-label, dose-escalation study evaluated the safety, tolerability, and optimally tolerated regimen (OTR) of lapatinib in combination with docetaxel and trastuzumab in patients with previously untreated stage IV metastatic breast cancer (MBC) tumors overexpressing human epidermal growth factor receptor 2 (HER2). Evaluated dose regimens included lapatinib (500-1500 mg/day), docetaxel (triweekly; 60-100 mg/m²), and trastuzumab (weekly; 2 mg/kg fixed dose); prophylactic granulocyte colony-stimulating factor was included with regimens with ≥750 mg/day lapatinib. End points included OTR and safety/tolerability (primary), overall response rate (ORR), and pharmacokinetics (secondary). None of the patients (N = 53) experienced dose-limiting toxic effects (DLTs) at the highest dose level; thus, the OTR of lapatinib with 100 mg/m(2) docetaxel was not determined. Common adverse events included diarrhea, nausea, alopecia, fatigue, and rash; grade 3/4 (≥2 patients) were neutropenia, diarrhea, leukopenia, peripheral neuropathy, and rash. Seven patients had DLTs (cycle 1). In 45 patients with measurable disease confirmed by bone scan, investigator-assessed ORR was 31%; without bone scan, confirmation was 64%; 8 patients without measurable disease were evaluated as stable. Lapatinib/docetaxel plasma concentrations were positively associated with complete response. Lapatinib/docetaxel/trastuzumab is a feasible and well-tolerated treatment of untreated HER2-positive stage IV MBC. Two lapatinib/docetaxel OTR doses were recommended (1250 mg/75 mg/m²; 1000 mg/100 mg/m²). NCT00251433.


Evaluating the comparative efficiency of medical centers in Taiwan: a dynamic data envelopment analysis application.
People in Taiwan enjoy comprehensive National Health Insurance coverage. However, under the global budget constraint, hospitals encounter enormous challenges. This study was designed to examine Taiwan medical centers' efficiency and factors that influence it. We obtained data from open sources of government routine publications and hospitals disclosed by law to the National Health Insurance Administration, Ministry of Health and Welfare, Taiwan. The dynamic data envelopment analysis (DDEA) model was adopted to estimate all medical centers' efficiencies during 2015-2018. Beta regression models were used to model the efficiency level obtained from the DDEA model. We applied an input-oriented approach under both the constant returns-to-scale (CRS) and variable returns-to-scale (VRS) assumptions to estimate efficiency. The findings indicated that 68.4% (13 of 19) of medical centers were inefficient according to scale efficiency. The mean efficiency scores of all medical centers during 2015-2018 under the CRS, VRS, and Scale were 0.85, 0.930, and 0.95,respectively. Regression results showed that an increase in the population less than 14 years of age, assets, nurse-patient ratio and bed occupancy rate could increase medical centers' efficiency. The rate of emergency return within 3-day and patient self-pay revenues were associated significantly with reduced hospital efficiency (p < 0.05). The result also showed that the foundation owns medical center has the highest efficiency than other ownership hospitals. The study results provide information for hospital managers to consider ways they could adjust available resources to achieve high efficiency.


EGFL7 participates in regulating biological behavior of growth hormone-secreting pituitary adenomas via Notch2/DLL3 signaling pathway.
Growth hormone-secreting pituitary adenoma accounts for about 20% of the third most common intracranial neoplasm-pituitary adenomas-which makes up 15% of all intracranial tumors. The growth hormone-secreting pituitary adenoma invasion is a key risk factor associated with the operation results and highly correlated with the clinical prognosis. The epidermal growth factor-like domain multiple 7 protein, a unique 29 kDa secreted angiogenic factor, can result in pathologic angiogenesis and enhance the tumor migration and invasion. In this study, for the first time we found that epidermal growth factor-like domain multiple 7 protein expression was markedly higher in invasive growth hormone-secreting pituitary adenoma than non-invasive growth hormone-secreting pituitary adenoma. The tumor volume, histologic subtypes, invasiveness and recurrence of growth hormone-secreting pituitary adenoma were significantly associated with epidermal growth factor-like domain multiple 7 protein expression. Furthermore, we discovered that the histological classification methods of growth hormone-secreting pituitary adenoma according to electron microscopic examination and biological marker classification methods according to epidermal growth factor-like domain multiple 7 protein expression are more valuable in clinical application than the traditional classification methods based on Knosp and Hardy-Wilson grades. In summary, our results indicated epidermal growth factor-like domain multiple 7 protein participates in growth hormone-secreting pituitary adenoma proliferation and invasion regulation via Notch2/DLL3 signaling pathway. These findings raised the possibility that epidermal growth factor-like domain multiple 7 protein might serve as a useful biomarker to assess growth hormone-secreting pituitary adenoma invasion and prognosis or a potential therapeutic target for growth hormone-secreting pituitary adenoma treatment.