Protective effect of a novel antifungal peptide derived from human chromogranin a on the immunity of mice infected with Candida krusei.
Invasive fungal infections threat the life of immunocompromised patients. Chromogranin A N-46 (CGA-N46), corresponding to the 31st to 76th amino acids of the N-terminus of human chromogranin A, is an antifungal peptide. In order to elucidate the antifungal effects of CGA-N46 in vivo, we studied its effects on cell-mediated immunity in Candida krusei-infected mice. The results showed that the treatment with CGA-N46 increased the average body weight and decreased the mortality of the immunocompromised mice model infected with Candida krusei. The spleen and thymus indices of treated mice has markedly increased compared with that of the control group (P<0.05), and the immune cell levels in peripheral blood also increased significantly (P<0.05). The immuno-modulatory effect of CGA-N46 (60 mg/kg/day) was found to be comparable to that of terbinafine. Additionally, CGA-N46 could alleviate or eliminate histopathological symptoms in the liver, spleen, kidney, and lung tissues. In conclusion, the present study suggests that CGA-N46 may offer a new strategy for antifungal therapeutic option. This study is an essential step in elucidating the effect of CGA-N46 in vivo.


Epidemiology and secular trends of malignant lymphoma in Japan: Analysis of 9426 cases according to the World Health Organization classification.
This study provides an overview of the epidemiology and secular trends of malignant lymphoma in Japan. Using data from clinics and hospitals throughout Japan, we analyzed 9426 cases of malignant lymphoma diagnosed in 2007-2014. We show that the proportion of follicular lymphoma and methotrexate-associated lymphoproliferative disorder increased during this time, as did the onset age for follicular lymphoma and diffuse large B-cell lymphoma. Significant increases in onset age for follicular lymphoma and diffuse large B-cell lymphoma were observed in both men and women (all P values <0.0001 except for P = 0.0448 for the latter disease in women). Further studies are required to determine the reasons for the higher proportion of and onset age for these lymphomas. Additionally, we believe that continued observation of these trends is necessary.


Internal Chain of Correlation of Sagittal Cervical Alignment in Asymptomatic Subjects.
Cross-sectional observational study in a prospective cohort. To analyze the cervical alignment characteristics and their chain of correlation in a sample of asymptomatic individuals. Asymptomatic adults who had full spinal radiographs performed. Cervical radiographic parameters were measured, including upper cervical curvature (McGregor line-C2), lower cervical curvature (C2-C7), McGregor slope, and sagittal vertical axis from C2-C7 (CSVA) and T1-slope (T1S). Subjects were stratified by age into 3 groups (18-39 years, 40-59 years, and >60 years), and radiographic parameters were compared across age groups and based on sex. 102 asymptomatic subjects (mean age, 50 years) were included. The T1S significantly increased with age, accompanied by an increase in C2-C7 lordosis. The cervical sagittal alignment, represented by CSVA, did not significantly differ based on age. There was a close correlation among the cervical sagittal parameters, such that the CSVA may be predicted based on the T1S and C2-C7 lordosis. Comparisons of the normative values identified in the present study with those reported in previous studies demonstrate variability in what constitutes normal in different populations. This analysis of cervical alignment in a sample of asymptomatic volunteers revealed that with increasing age there is an observed increase in the sagittal inclination of the base of the cervical spine (T1S) that is accompanied by an increase in cervical lordosis as a means of maintaining cervical sagittal alignment (CSVA). The variability in what constitutes normal values for cervical parameters suggests that further study is warranted using standardized methodologies across diverse populations.


Use of IMEX SK-circular external fixator hybrid constructs for fracture stabilization in dogs and cats.
Complex long-bone fractures with short juxta-articular fracture segments can be difficult to manage. Recently, IMEX Veterinary, Inc., began producing titanium hybrid rods that can be secured to ring components of the IMEX circular external skeletal fixation system to create SK-circular hybrids. In this case series, SK-circular hybrids were used to stabilize long-bone fractures (two femoral, one humeral, and three tibial fractures) with short distal bone segments in three dogs and three cats with body weights ranging from 1.9 to 15 kg (mean, 6.7 kg; median, 5.4 kg). Although three cases required surgical revision, animals ambulated well and all fractures obtained union. Time to radiographic union ranged from 62 to 137 days (mean, 90 days; median, 84 days). The functional outcome was considered excellent in all six cases.


Shedding some light on laser pointer eye injuries.
Laser use has become common in the home and workplace. We present a review of laser eye injuries and guidance for the emergency medicine physician on evaluation of laser eye injury-related complaints. A review of the literature on the potential for injury, concerning signs and symptoms, evaluation, and referral recommendations is discussed. The scientific literature finds that laser eye injuries are uncommon from use of nonindustrial lasers. Furthermore, an eye injury from a regulated Class 2 or Class 3A by a transient sweep across the line of vision does not result in injury, but injury can occur with a direct intentional prolonged exposure. Patient's history of the length and type of laser exposure is important. A significant direct eye exposure to a laser, persistent after images, and decreased visual acuity should initiate urgent referral to an ophthalmologist for further ophthalmologic testing. Brief laser exposure or indirect exposures with complaints of headaches or blurry vision require other diagnostic explanations.


[Detection of Chlamydia trachomatis in routine clinical practice: increased sensitivity of cell culture in comparison with the microimmunofluorescence test].
Recently, direct immunofluorescence staining has been reported as a new tool for detection of Chlamydia trachomatis. This assay is based on monoclonal antibodies directed against a protein present in all serological variations of Chlamydia known to date. In order to evaluate whether immunofluorescence staining could substitute for the time-consuming, expensive tissue culture technique, urethral and cervical swabs of 131 patients treated for sterility were examined for infection with Chlamydia by both methods. The tissue culture technique, based on cultivation of Chlamydia in mammalian cells, was regarded as 100% sensitive and specific. Employing this method, we demonstrated infection with Chlamydia in 20 patients (15.3%). Colonization of both, cervix and urethra was found in 11.5%, whereas solitary colonization of cervix and urethra was found in 2.3 and 1.5% respectively. However, the immunofluorescence assay applied ("Micro-Trak", Syva Company) showed positive results in only 6 out of 20 cases as determined by tissue culture, thus yielding a sensitivity of 30%. Out of 111 patients with negative results in the tissue culture, 108 were detected by immunofluorescence staining, amounting to a specificity of 97.3%. With special regard to the low sensitivity of the direct immunofluorescence assay, our results indicate a superior, yet unequalled role of the tissue culture technique for detection of Chlamydia trachomatis.


Functional and structural remodeling of the myocardial microvasculature in early experimental hypertension.
Advanced hypertension (HT), associated with left ventricular hypertrophy (LVH), impairs myocardial microvascular function and structure and leads to increased myocardial hypoxia and growth factor activation. However, the effect of HT on microvascular architecture and its relation to microvascular function, before the development of LVH (early HT), remains unclear. By way of method, pigs were studied after 12 wk of renovascular HT (n = 7) or control (n = 7) animals. Myocardial microvascular function (blood volume and blood flow at baseline and in response to adenosine) was assessed by using electron beam computed tomography (CT). Microvascular architecture was subsequently studied ex vivo using micro-CT, and microvessels (diameter, <500 microm) were counted in situ in three-dimensional images (40-microm on-a-side cubic voxels). Myocardial expression of vascular endothelial growth factor, basic fibroblast growth factor, and hypoxia-inducible factor-1alpha were also measured. By way of results, left ventricular muscle mass was similar between the groups. The blood volume response to intravenous adenosine was attenuated in HT animals compared with normal animals (+7.4 +/- 17.0 vs. +46.2 +/- 12.3% compared with baseline, P = 0.48 and P = 0.01, respectively). Microvascular spatial density in HT animals was significantly elevated compared with normal animals (246 +/- 26 vs. 125 +/- 20 vessels/cm2, P < 0.05) and correlated inversely with the blood volume response to adenosine. Growth factors expression was increased in HT animals compared with control animals. In conclusion, early HT elicits changes in myocardial microvascular architecture, which are associated with microvascular dysfunction and precede changes in muscle mass. These observations underscore the direct and early effects of HT on the myocardial vasculature.


Enantioselective Synthesis of Functionalized 4-Aryl Hydrocoumarins and 4-Aryl Hydroquinolin-2-ones via Intramolecular Vinylogous Rauhut-Currier Reaction of para-Quinone Methides.
A novel strategy for the asymmetric construction of functionalized 4-aryl-3,4-dihydrocoumarins and 4-aryl-3,4-dihydroquinolin-2-ones via an intramolecular vinylogous Rauhut-Currier reaction of para-quinone methides (p-QMs) under the bifunctional catalysis of chiral amine-phosphine is described. This intramolecular mode for the catalytic enantioselective 1,6-conjugate addition of p-QMs has been explored for the first time, delivering two types of synthetically important heterocycles in high yields and enantioselectivites.


Reactions of Plasmodium falciparum Ferredoxin:NADP+ Oxidoreductase with Redox Cycling Xenobiotics: A Mechanistic Study.
Ferredoxin:NADP+ oxidoreductase from Plasmodium falciparum (PfFNR) catalyzes the NADPH-dependent reduction of ferredoxin (PfFd), which provides redox equivalents for the biosynthesis of isoprenoids and fatty acids in the apicoplast. Like other flavin-dependent electrontransferases, PfFNR is a potential source of free radicals of quinones and other redox cycling compounds. We report here a kinetic study of the reduction of quinones, nitroaromatic compounds and aromatic N-oxides by PfFNR. We show that all these groups of compounds are reduced in a single-electron pathway, their reactivity increasing with the increase in their single-electron reduction midpoint potential (E17). The reactivity of nitroaromatics is lower than that of quinones and aromatic N-oxides, which is in line with the differences in their electron self-exchange rate constants. Quinone reduction proceeds via a ping-pong mechanism. During the reoxidation of reduced FAD by quinones, the oxidation of FADH. to FAD is the possible rate-limiting step. The calculated electron transfer distances in the reaction of PfFNR with various electron acceptors are similar to those of Anabaena FNR, thus demonstrating their similar "intrinsic" reactivity. Ferredoxin stimulated quinone- and nitro-reductase reactions of PfFNR, evidently providing an additional reduction pathway via reduced PfFd. Based on the available data, PfFNR and possibly PfFd may play a central role in the reductive activation of quinones, nitroaromatics and aromatic N-oxides in P. falciparum, contributing to their antiplasmodial action.


Histone H3 lysine 36 methylation antagonizes silencing in Saccharomyces cerevisiae independently of the Rpd3S histone deacetylase complex.
In yeast, methylation of histone H3 on lysine 36 (H3-K36) is catalyzed by the NSD1 leukemia oncoprotein homolog Set2. The histone deacetylase complex Rpd3S is recruited to chromatin via binding of the chromodomain protein Eaf3 to methylated H3-K36 to prevent erroneous transcription initiation. Here we identify a distinct function for H3-K36 methylation. We used random mutagenesis of histones H3 and H4 followed by a reporter-based screen to identify residues necessary to prevent the ectopic spread of silencing from the silent mating-type locus HMRa into flanking euchromatin. Mutations in H3-K36 or deletion of SET2 caused ectopic silencing of a heterochromatin-adjacent reporter. Transcriptional profiling revealed that telomere-proximal genes are enriched for those that display decreased expression in a set2Delta strain. Deletion of SIR4 rescued the expression defect of 26 of 37 telomere-proximal genes with reduced expression in set2Delta cells, implying that H3-K36 methylation prevents the spread of telomeric silencing. Indeed, Sir3 spreads from heterochromatin into neighboring euchromatin in set2Delta cells. Furthermore, genetic experiments demonstrated that cells lacking the Rpd3S-specific subunits Eaf3 or Rco1 did not display the anti-silencing phenotype of mutations in SET2 or H3-K36. Thus, antagonism of silencing is independent of the only known effector of this conserved histone modification.


The stability of oxymetazoline hydrochloride in aqueous solution.
The kinetics of the hydrolysis reaction of oxymetazoline hydrochloride in aqueous solution at three temperatures (343 K, 353 K, 363 K), over the pH-range 0.5-12.5 and ionic strength 0.5 has been investigated. The changes of concentration of oxymetazoline hydrochloride were followed by the HPLC method with UV detection. In the pH range from 0.45 to 12.50, the hydrolysis of oxymetazoline consists of hydrolysis of oxymetazoline molecules catalyzed by hydrogen ions, spontaneous hydrolysis of the dissociated and undissociated oxymetazoline molecules. A minimal rate of the hydrolysis oxymetazoline was observed to occur in the pH range from 2.0 to 5.0. Thermodynamic parameters of the reaction: energy, entropy and enthalpy of activation and the frequency factor for the specific rate constants were determined.


Construction and analysis of dysregulated lncRNA-associated ceRNA network identified novel lncRNA biomarkers for early diagnosis of human pancreatic cancer.
It is increasing evidence that ceRNA activity of long non-coding RNAs (lncRNAs) played critical roles in both normal physiology and tumorigenesis. However, functional roles and regulatory mechanisms of lncRNAs as ceRNAs in pancreatic ductal adenocarcinoma (PDAC), and their potential implications for early diagnosis remain unclear. In this study, we performed a genome-wide analysis to investigate potential lncRNA-mediated ceRNA interplay based on "ceRNA hypothesis". A dysregulated lncRNA-associated ceRNA network (DLCN) was constructed by utilizing sample-matched miRNA, lncRNA and mRNA expression profiles in PDAC and normal samples in combination with miRNA regulatory network. The results of network analysis uncovered seven novel lncRNAs as functional ceRNAs whose aberrant expression will result in the extensive variation in tumorigenic or tumor-suppressive gene expression through DLCN at the post-transcriptional level contributing to PDAC. Therefore, we developed a 7-lncRNA signature (termed LncRisk-7) based on the expression data of seven lncRNAs and SVM algorithm as a novel diagnostic tool to improve early diagnosis of PDAC. The LncRisk-7 achieved high performance in distinguishing PDAC patients from nonmalignant pancreas samples in the discovery cohort and was further confirmed in another two independent validation cohorts. Functional analysis demonstrated that seven lncRNA biomarkers act as ceRNAs involving the regulation of cell death, cell adhesion and cell cycle. This study will help to improve our understanding of the lncRNA-mediated ceRNA regulatory mechanisms in the pathogenesis of PDAC and provide novel lncRNAs as candidate diagnostic biomarkers or potential therapeutic targets.


Enhancement of epigastric skin flap survival by adenovirus-mediated VEGF gene therapy.
A novel approach to treat ischemic tissues by using gene therapy has recently been introduced on the basis of the angiogenic potential of certain growth factors. The authors investigated the effect of adenovirus-mediated gene therapy with vascular endothelial growth factor (VEGF) delivered into the subdermal space to treat compromised skin flaps. For this purpose, the epigastric skin flap model in rats, based solely on the right inferior epigastric vessels, was used. Thirty male Sprague-Dawley rats were divided into five groups of six rats each. Viral transfection with 108 plaque-forming units was performed 2 days before the epigastric flap elevation. Rats received subdermal injections of adenovirus encoding VEGF (Ad-VEGF) or green fluorescent protein (Ad-GFP) as treatment control. Another set of animals (n = 6) received no injections and were designated as control. To determine whether site of injection had an impact on flap viability, injections were given into the predicted local ischemic area (Ad-VEGF local, n = 6; Ad-GFP local, n = 6) and into the midline of the flap (Ad-VEGF midline, n = 6; Ad-GFP midline, n = 6). A flap measuring 8 x 8 cm was outlined on the abdominal skin extending from the xiphoid process proximally and the pubic region distally, to the anterior axillary lines bilaterally. Then, the epigastric flap was elevated as an island on the right inferior epigastric vessels and sutured back to its bed. Flap viability was evaluated at 7 and 14 days after the first operation. The epigastric flaps were scanned to the computer and areas of hypoxic and/or necrotic zones relative to total flap surface area were measured and expressed as percentages by using Image Pro Plus software. Specimens were taken for histologic evaluation at day 14 before the animals were killed. Combined area of necrotic and hypoxic zones as well as necrotic zone were decreased to 9.7 +/- 1.4 percent and 1.4 +/- 0.9 percent in Ad-VEGF local, and 11.8 +/- 1.9 percent and 3.5 +/- 1.64 percent in Ad-VEGF midline compared with the control and Ad-GFP treatment groups (control, 23 +/- 3.6 percent and 20.1 +/- 3.3 percent; Ad-GFP local, 24.8 +/- 4.8 percent and 16.2 +/- 5.9 percent; and Ad-GFP midline, 23.4 +/- 6.9 percent and 19.5 +/- 7.7 percent; p < 0.05). Histologic evaluation by light microscopy failed to demonstrate any quantitative difference in vascularity of skin flaps between the treatment groups. In this study, the authors demonstrated that adenovirus-mediated gene therapy using VEGF enhanced epigastric skin flap survival, as confirmed by the significant reduction in combined area of necrotic and hypoxic zones of the flap. Compared with the control, both local and midline subdermal injections of Ad-VEGF showed improvement in overall flap survival by 57.9 and 48.7 percent, respectively. The results of this study raise the possibility of using adenovirus-mediated therapeutic angiogenesis for safer flap surgery in high-risk patients.


Acute acalculous cholecystitis in patients with systemic lupus erythematosus: A unique form of disease flare.
Objective We aimed to investigate the clinical features of acute acalculous cholecystitis (AAC) in patients with systemic lupus erythematosus (SLE). Methods SLE patients with AAC hospitalized in the Peking Union Medical College Hospital (PUMCH) from January 2001 to September 2015 were retrospectively analyzed. Their medical records were systematically reviewed. The diagnosis of AAC was based on clinical manifestations and confirmed by radiologic findings including a distended gallbladder with thickened wall, pericholecystic fluid and absence of gallstones. Results Among the 8411 hospitalized SLE patients in PUMCH, 13 (0.15%) were identified to have SLE-AAC. Eleven (84.6%) of them were female, with a mean age of 30.1 ± 8.6 years. AAC was the initial manifestation of SLE in four (30.8%) cases. Eleven (84.6%) patients complained of fever and abdominal pain, four (30.8%) had positive Murphy's sign and six (46.2%) had elevated liver enzymes. The median SLE Disease Activity Index was 8.0 (range 0-20.0) at the time of AAC. Other affected organs in SLE-AAC included kidney (11, 84.6%) and hematologic system (11, 84.6%), followed by mucocutaneous (seven, 53.8%), musculoskeletal (seven, 53.8%) and neuropsychiatric (two, 15.4%) systems. All patients received treatment of glucocorticoids and immunosuppressants but none underwent surgical intervention. During a median follow-up of 28 months (range, 2-320 months), 12 cases (92.4%) responded to treatment with no relapse and one patient (7.6%) died of septic shock. Conclusion Our study suggests that AAC is a relatively uncommon and underestimated gastrointestinal involvement of SLE that is often associated with active disease. For patients with AAC in SLE, treatment with aggressive glucocorticoids could result in a good prognosis.


Chemokine CCL2 and its receptor CCR2 in the dorsal root ganglion contribute to oxaliplatin-induced mechanical hypersensitivity.
Activation of innate immune mechanisms within the dorsal root ganglion and spinal dorsal horn has been shown to play a key role in the development of neuropathic pain including paclitaxel-related chemotherapy-induced peripheral neuropathy (CIPN). Here, we tested whether similar mechanisms are generalizable to oxaliplatin-induced CIPN. After a single intraperitoneal injection of 3 mg/kg oxaliplatin, mechanical withdrawal threshold and the expression of C-C chemokine ligand 2 (CCL2) and its receptor, CCR2, in the dorsal root ganglion were measured by behavioral testing and immunohistochemical staining, respectively. Mechanical responsiveness increased from the first day after oxaliplatin injection and persisted until day 15, the last day of this experiment. Immunohistochemical showed that the expression of CCL2/CCR2 started to increase by 4 hours after oxaliplatin treatment, was significantly increased at day 4, and then both signals became normalized by day 15. Cotreatment with intrathecal anti-CCL2 antibodies prevented the development of oxaliplatin-induced mechanical hyperresponsiveness, and transiently reversed established hyperalgesia when given 1 week after chemotherapy. This is the first study to demonstrate CCL2/CCR2 signaling in a model of oxaliplatin-related CIPN; and it further shows that blocking of this signal can attenuate the development of oxaliplatin-induced mechanical hyperalgesia. Activation of innate immune mechanisms may therefore be a generalized basis for CIPN irrespective of the specific class of agent.


Spectrum and outcome of clinical diseases in adults living with AIDS at the Ogun State University Teaching Hospital.
To evaluate the changing frequency of HIV/AIDS amongst medical admissions as well as the spectrum and outcome of clinical diseases among these patients. Retrospective study. Tertiary hospital in Nigeria. Two hundred and six People Living With AIDS (PLWA) admitted at the medical wards during the period 1992 to 2002. Treatment was symptomatic in all patients and where appropriate, specific treatment was administered for indicator diseases. Highly Active Anti-retroviral Therapy (HAART) was not used. Mortality within six months of diagnosis. PLWA constituted 4.2% of all medical admissions. The frequency increased from 0% in 1992 to 7.6% in 2001, and dropped to 5% by the year 2002. Seventy patients (34%) died within six months of diagnosis. This study has demonstrated an increasing frequency of HIV/AIDS amongst our medical in-patients from none in 1992 to 7.6% in 2001, and thereafter, a decline in 2002. We suspect that this decline could be a reflection of the health education on HIV, its increasing awareness and the widespread utilisation of effective control measures. Furthermore, the administration of highly active anti retroviral therapy (HAART) to a segment of PLWA in Sagamu by the community medicine department could be contributory. A community based study would be needed to assess the efficacy or otherwise of these current control measures. The advent of saliva and urine tests for HIV detection would ease specimen collection and increase compliance and participation at the community level.


EVOLUTION OF PARASITISM AMONG CLOSELY RELATED SPECIES: PHYLOGENETIC RELATIONSHIPS AND THE ORIGIN OF INQUILINISM IN GALL WASPS (HYMENOPTERA, CYNIPIDAE).
A new term, agastoparasitism, is proposed for parasitism among closely related species. Cynipid inquilines are typical agastoparasites. They cannot induce galls; instead their larvae live inside the galls formed by other cynipids. As in many other groups of agastoparasites, there are two competing hypotheses for the evolutionary origin of cynipid inquilines: either they arose from one of their cynipid hosts, and later radiated to exploit other gall-inducing cynipids (monophyletic origin), or they arose repeatedly, each inquiline from its host (polyphyletic origin). These hypotheses for the origin of cynipid inquilines were tested by a phylogenetic analysis of representative species of cynipid gall inducers and inquilines based on adult morphological characters. The analysis supported the monophyly of the inquilines and indicated an origin from gall inducers related to the genus Diastrophus, one of the current host groups. To examine whether the result of the analysis was influenced by convergent similarities among inquilines because of their similar mode of life, all putative apomorphies shared by some or all of the inquilines but not occurring in any of the gall inducers were removed. Despite this, the phylogenetic conclusions essentially remained the same, that is, the support for inquiline monophyly was not caused by convergent evolution. Based on these results, adaptive aspects of the evolutionary origin and maintenance of cynipid inquilinism are discussed, as well as general patterns in the evolution of agastoparasitism.


Structure and function of histone methylation-binding proteins in plants.
Post-translational modifications of histones play important roles in modulating many essential biological processes in both animals and plants. These covalent modifications, including methylation, acetylation, phosphorylation, ubiquitination, SUMOylation and so on, are laid out and erased by histone-modifying enzymes and read out by effector proteins. Recent studies have revealed that a number of developmental processes in plants are under the control of histone post-translational modifications, such as floral transition, seed germination, organogenesis and morphogenesis. Therefore, it is critical to identify those protein domains, which could specifically recognize these post-translational modifications to modulate chromatin structure and regulate gene expression. In the present review, we discuss the recent progress in understanding the structure and function of the histone methylation readers in plants, by focusing on Arabidopsis thaliana proteins.


Evaluation of methods for normalizing muscle strength in elite and young athletes.
The following equation has been most often used in order to present recorded muscle strength (F) normalised for various measures of body size (such as body mass m) Fnor = F x m(-b). Since previous studies have provided inconsistent results, the purpose of the present one was to assess the value of the exponential parameter b (b-value) that (a) provides both the normalised strength independent of body mass and (b) demonstrates the highest possible correlation between the normalised strength and standard tests of movement performance. Thirteen groups of male and female athletes of both different age and different sport specialisation were tested for maximal isometric force of various leg muscle groups, as well as for vertical and standing long jump. The data obtained on most of the experimental groups suggested that the b-value close to the theoretically predicted b=0.67, but also different from b=0 and b=1, should be used for calculation of the normalised strength independent of body mass. Although the strength normalised using b=0.67 and b=1 demonstrated higher correlation with jumping performance than the non-normalised strength (i.e., b=0), the data also suggested that b>1 could provide the highest prediction of movement performance. Muscle strength should be calculated as force per kg(2/3) rather than as absolute force or force calculated per kg of body mass in order to assess strength independent of body size in routine testing of muscle function. However, different and probably task specific normalisation methods could be required in order to predict performance of various movement tasks by assessed muscle strength.


Determining factors that predict technique survival on peritoneal dialysis: application of regression and artificial neural network methods.
Peritoneal dialysis (PD) rates continue to decline worldwide in spite of the increasing number of patients with end-stage renal disease. PD technique failure has been cited as one of the reasons for this decline. The purpose of this study was to compare the factors that predict technique survival using artificial neural network (ANN) and logistic and Cox regression methods. We used high-quality, prospectively collected data from the United Kingdom Renal Registry and created both ANN and regression models to predict technique survival. Incident PD patients in the UK from 1999 to 2004 were included in the analysis. Technique failure was defined as a change in modality to hemodialysis for a period >30 days. Removal of dialysis center code had a significant effect on the fit and/or predictive performance of all three types of models. In contrast, the effect of demographic data, comorbidity, physical examination and laboratory data varied according to the type of model. PD center significantly impacts PD technique survival. Other putative predictive factors had marginal and/or variable effects. The presence of comorbid conditions and a high body mass index is not consistently associated with increased PD technique failure.


NH2-terminal stabilization of small heat shock protein structure: a comparison of two NH2-terminal deletion mutants of alphaA-crystallin.
To assess the role of the NH2-terminal in alphaA-crystallin folding and chaperone-like activity. Two NH2-terminal deletion mutants of alphaA-crystallin were generated by standard mutagenesis methods, one with and one without a leader sequence in place of the first 50 residues. Aggregate size of each before and after thermal stress was assessed by FPLC, and chaperone-like activity was assessed using DTT-induced insulin denaturation. Both mutants assemble primarily into tetramers, and both exhibit similar levels of chaperone-like activity, but are less protective than recombinant alphaA-crystallin. After a cycle of heat stress to 70 degrees C, tetramers of the mutant without the leader sequence dissociate into dimers and monomers and show severely reduced chaperone-like activity. In contrast, the mutant with the leader sequence retains its tetrameric form and its chaperone-like activity. The NH2-terminal region is an important determinant of alpha-crystallin aggregate size, but is not required for folding of the alpha-crystallin domain, since the aggregate size and chaperone-like activity of the two mutants at room temperature are essentially the same. The leader sequence appears to increase the thermal stability of the alpha-crystallin domain and/or to contribute to the reformation of the active form after cooling, suggesting that the native NH2-terminal also plays a role in alpha-crystallin's resistance to environmental stress.


The Relationship Between Child Sexual Abuse and Alexithymic Symptoms in a Population of Recovering Adult Substance Abusers.
Recovering substance abusers with a history of childhood sexual abuse (n = 69) or no history of childhood sexual abuse (n = 68) completed the Toronto Alexithymia Scale (TAS) and a background survey assessing demographic data and (In the case of sexually abused respondents) parameters of the childhood abuse experienced. The sexually abused group scored significantly higher than the non-abused group on the TAS. Within the abused group, measured alexithymic symptomatology was found to be related positively to the duration of the abuse. Alexithymia was significantly higher when the sexual abuse first occurred after the victim had reached the age of 12, when a perpetrator of the sexual abuse was a father or stepfather, and when the abuse involved oral, vaginal, and/or anal penetration. Results were interpreted as indicating that the development of alexithymic symptoms may represent another defense victims may employ to insulate themselves from painful affect, along with dissociative symptoms and substance abuse, which have been shown previously to characterize adult survivors of child sexual abuse.


Highly Sensitive, Breathable, and Flexible Pressure Sensor Based on Electrospun Membrane with Assistance of AgNW/TPU as Composite Dielectric Layer.
Pressure sensors have been widely used in electronic wearable devices and medical devices to detect tiny physical movements and mechanical deformation. However, it remains a challenge to fabricate desirable, comfortable wearing, and highly sensitive as well as fast responsive sensors to capture human body physiological signs. Here, a new capacitive flexible pressure sensor that is likely to solve this problem was constructed using thermoplastic polyurethane elastomer rubber (TPU) electrospinning nanofiber membranes as a stretchable substrate with the incorporation of silver nanowires (AgNWs) to build a composite dielectric layer. In addition, carbon nanotubes (CNTs) were painted on the TPU membranes as flexible electrodes by screen printing to maintain the flexibility and breathability of the sensors. The flexible pressure sensor could detect tiny body signs; fairly small physical presses and mechanical deformation based on the variation in capacitance due to the synergistic effects of microstructure and easily altered composite permittivity of AgNW/TPU composite dielectric layers. The resultant sensors exhibited high sensitivity (7.24 kPa-1 within the range of 9.0 × 10-3 ~ 0.98 kPa), low detection limit (9.24 Pa), and remarkable breathability as well as fast responsiveness (<55 ms). Moreover, both continuously pressing/releasing cycle over 1000 s and bending over 1000 times did not impair the sensitivity, stability, and durability of this flexible pressure sensor. This proposed strategy combining the elastomer nanofiber membrane and AgNW dopant demonstrates a cost-effective and scalable fabrication of capacitive pressure sensors as a promising application in electronic skins and wearable devices.


The hip joint: structure, stability, and stress; a review.
A review of the structure of the hip joint as related to its stability is presented. The forces exerted at the hip and along the proximal end of the femur are discussed in relation to the anatomical position of bone and to normal stresses incurred during standing and gait. Clinical considerations of selected hip abnormalities include a review of changes in normal mechanical forces found in coxa valga, coxa vava, arthritis, and fracture.


[Estimation of age-related features of acoustic density and biometric relations of lens based on combined ultrasound scanning].
Results of combined ultrasound scanning for estimation of acoustic lens density and biometric relations of lens and other eye structures are presented. A group of 124 patients (189 eyes) was studied; they were subdivided depending on age and length of anteroposterior axis of the eye. Examination algorithm was developed that allows selective estimation of acoustic density of different lens zones and biometric measurements including volumetric. Age-related increase of acoustic density of different lens zones was revealed that indirectly shows method efficiency. Biometric studies showed almost concurring volumetric lens measurements in "normal" and "short" eyes in spite of significantly thicker central zone of the latter. Significantly lower correlation between anterior chamber volume and width of its angle was revealed in "short" eyes and "normal" and "long" eyes (correlation coefficients 0.37, 0.68 and 0.63 respectively).


Fabricating large-scale three-dimensional constructs with living cells by processing with syringe needles.
Three-dimensional (3D) cell constructs composed only of cells and cell-secreted extracellular matrix have been attractive biomaterials for tissue engineering technology; however, controlling construct morphology and eliminating dead cells after fabrication remain a challenge. It has been hypothesized that moderate stress could shape constructs and eliminate dead cells. The purpose of this study was to establish an easily available technology for shaping 3D cell constructs and eliminating dead cells postfabrication. To achieve these objectives, spherical cell constructs composed of L-929 fibroblasts were processed using different sized syringe needles. Our results revealed that large-scale rod-shaped cell constructs could be fabricated, and that their diameters could be controlled according to the size of the syringe needle. Additionally, cell viability assays showed that >94% of cells in the rod-shaped constructs were viable, suggesting that dead cells, which have low adhesion force, were dispersed when compressive stress was applied during passage through the needle. The technology described in this study will be promising for future tissue engineering, especially for fabricating elongated tissues such as nerves and blood vessels. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 904-909, 2019.


Optimizing suction blister epidermal graft technique in the surgical treatment of vitiligo.
Surgical management of vitiligo is considered an excellent terapeutic option for recalcitrant cases, provided the disease is stable and there is absence of Koebner phenomenom. Among surgical modalities, Suction Blister Epidermal Graft is a low cost and effective option (65 to 100% repigmentation can be achieved in up to 80% of patients). We describe how it can be optimized by using an alternative suction equipment, by customization of graft format and by application of an anesthetic technique that substantially reduces procedure time.


Design and biomechanical evaluation of a cementable endosteal blade implant.
A cementable endosteal blade implant has been developed and evaluated. Inherent in the design are the following factors: minimization of stress concentrators, ease of implantation, and high resistance to loosening. Other potential advantages of this design as compared with conventional endosteal blade implants include reduced hazards of postoperative infection and reduced likelihood of metallic corrosion. Six conventional endosteal implants and six cementable implants were installed in steer mandibles using standard dental surgical techniques and Simplex-brand methyl methacrylate bone cement. They were loaded in uniaxial compresstion at a loading rate of 0.0122 in./min. the stiffness (S), deformation at 900-lb load (D900), proportional limil (PL), and load at 0.04 in. deformation (L0.04) were calculated for each test. The cementable design showed a twofold increase in stiffness, only 17% of the deformation at 900lb, more than twice the proportional limit, and at least twice the load at 0.04 in. deformation when compared with similar values for the conventional endosteal implants. This study reveals that, in addition to being unstable in bone, conventional endosteal implants are also unstable when used with acrylic bone cement. The new design should eliminate most of the problems associated with endosteal blade implantation.


Synchronization in small-world networks.
In this paper we consider complete synchronization in small-world networks of identical Rössler oscillators. By applying a simple but effective dynamical optimization coupling scheme, we realize complete synchronization in networks with undelayed or delayed couplings, as well as ensuring that all oscillators have uniform intensities during the transition to synchronization. Further, we obtain the coupling matrix with much better synchronizability in a certain range of the probability p for adding long-range connections. Direct numerical simulations fully verify the efficiency of our mechanism.


Informing state policymakers: opportunities for social workers.
Colleagues, legislative staff, interest groups, administrative agencies, universities and think tanks, the media, and constituents are some of the more commonly recognized sources of information for state legislators. Results of a survey of 507 legislators in 12 U.S. states reveal that ethnic associations, grassroots organizations, the Internet, local branches of national or state organizations, and conferences are also sources of information for state legislators. The relative importance of the various sources is linked to characteristics of the legislators and the districts they represent. This suggests the need for targeted information dissemination strategies to influence state-level public policy.


Enhancing management of cancer pain: contribution of the internal working model.
The purpose of this article is to organize the current knowledge regarding patient-related factors that can have an impact on cancer pain management by using the construct of the internal working model: a theoretical framework for integrating current knowledge and interpreting and predicting factors related to the management of cancer pain. These factors include patients' beliefs and misconceptions about cancer pain and pain treatment, meanings that patients ascribe to their pain, their expectations about pain relief, and communication between patients and clinicians about pain control. The construct of the internal working model predicts and explains factors related to pain control and provides implications for practice. It has potential utility in enhancing the quality of cancer pain management.


Band Gaps and Transmission Characteristics Analysis on a Two-Dimensional Multiple-Scatter Phononic Crystal Structure.
In this paper, a novel wrap-around multi-scattering phononic crystal (PC) structure is proposed. Band gaps (BGs) and transmission characteristics of the present structure are calculated using finite element method (FEM). Through the calculations of single-scattering prototype, three complete BGs which are exhibited at low frequency and the fourth wide BG at high frequency are discovered. The transmission features and resonant spectra represented by frequency response function (FRF) shows that apparent resonance directly cause the four specific BGs. By keeping the total area of scatterers unchanged, 2 × 2, 3 × 3 and 4 × 4 scatterers are designed to obtain the change rule of BGs. Furthermore, the size ratio of 2 × 2 scatterers, the number of connection beams are investigated to obtain the regular pattern of acoustic energy transmission and attenuation. The present investigation of multiple-scatter PC structure will provide a solid support on the future design of acoustical functional materials.


The prognosis of trabeculectomy in primary angle-closure glaucoma patients.
To evaluate whether the level of thrombospondin-1 (TSP-1) in aqueous humor can predict the prognosis of trabeculectomy in patients with primary angle-closure glaucoma (PACG). This case-control study involved 26 patients with PACG who experienced a failed trabeculectomy (case group) and 78 age- and sex-matched patients with PACG who underwent successful trabeculectomy (control group). Aqueous humor was collected at the time of trabeculectomy and tested for TSP-1 and TGF-β2 levels with an enzyme-linked immunosorbent assay method. Logistic regression modeling was used to assess the risk factors for failed trabeculectomy. The mean TSP-1 aqueous concentrations were significantly higher in the case group (20.67±9.79 ng/mL) than the control group (5.17±2.29 ng/mL) (P<0.001). The transforming growth factor-β2 (TGF-β2) aqueous concentrations were significantly different between the case and control group, at 3633.25 and 1090.24 pg/mL, respectively (P<0.001). Logistic regression analysis revealed TSP-1 level as an independent risk factor for a failed trabeculectomy (OR=3.540; 95%CI=1.092-11.482). The aqueous humor TSP-1 and TGF-β2 levels are higher in PACG eyes with failed trabeculectomy than with successful trabeculectomy at one year. The aqueous humor TSP-1 level is an independent risk factor associated with failed trabeculectomy.


The critical role and potential target of the autotaxin/lysophosphatidate axis in pancreatic cancer.
Autotaxin, an ecto-lysophospholipase D encoded by the human ENNP2 gene, is expressed in multiple tissues, and participates in numerous critical physiologic and pathologic processes including inflammation, pain, obesity, embryo development, and cancer via the generation of the bioactive lipid lysophosphatidate. Overwhelming evidences indicate that the autotaxin/lysophosphatidate signaling axis serves key roles in the numerous processes central to tumorigenesis and progression, including proliferation, survival, migration, invasion, metastasis, cancer stem cell, tumor microenvironment, and treatment resistance by interacting with a series of at least six G-protein-coupled receptors (LPAR1-6). This review provides an overview of the autotaxin/lysophosphatidate axis and collates current knowledge regarding its specific role in pancreatic cancer. With a deeper understanding of the critical role of the autotaxin/lysophosphatidate axis in pancreatic cancer, targeting autotaxin or lysophosphatidate receptor may be a potential and promising strategy for cancer therapy.


Mutations in src homology regions 2 and 3 of activated chicken c-src that result in preferential transformation of mouse or chicken cells.
src homology regions 2 and 3 (SH2 and SH3) of proteins encoded by src and closely related genes are conserved domains believed to modulate the protein-tyrosine kinase activity of this class of proteins, perhaps through interactions with other proteins. To explore the possibility of using src mutants as probes for such interactions, we have compared mouse NIH 3T3 cells with chicken embryo fibroblasts as host cells for 24 previously described substitution and deletion mutants with lesions in the SH2- and SH3-encoding regions of a transformation-competent allele of chicken c-src. Although several of these mutants are equally competent or equally defective for transformation of the two cell types, four mutants (three of which map within SH3) preferentially transform NIH 3T3 cells, and seven mutants (all of which map within SH2) preferentially transform chicken cells. Some of the SH2 mutants least able to transform mouse cells exhibit augmented transforming activity in chicken cells. In general, the in vitro protein-tyrosine kinase activities of the mutants correlated with transforming activities. Thus, in many cases, the catalytic activity of a mutant protein depended upon the host cell in which the protein was made. Such host-dependent mutants may be especially useful reagents for biochemical and genetic studies of the src gene family.


Acute pancreatitis as initial manifestation of adult Henoch-Schönlein purpura: report of a case and review of literature.
Abdominal pain observed in Henoch-Schönlein purpura (HSP) is usually attributed to edema and hemorrhage in the small bowel wall, secondary to a small-vessel vasculitis. Pancreatitis secondary to HSP is extremely rare. Here we report a 53-year-old man presented with acute pancreatitis that developed into characteristic rashes seen during HSP at the second day of the clinical onset, together with arthritis and glomerulonephritis. HSP is a rare and benign cause of acute pancreatitis. This complication can occur as an initial manifestation of HSP. Elevated serum amylase level can be considered as the early diagnostic tool for HSP pancreatitis. The patients with HSP who have abdominal pain as their chief complaint should be evaluated for pancreatitis, by routine serum amylase and abdominal computed tomography scan, to plan the specific treatment and avoid unnecessary surgery.


[Adhesive technology and preparations for composites in the anterior sector].
The authors analyzec the possibility of introducing modifications in the traditional cavity designs for Class 3, 4 and 5 restorations using present adhesive techniques for bonding reinforced composite resins to tooth tissues. The concepts followed by classic authors are reviewed, compared to the characteristics recommended for new preparations and bases for their use are considered. It is concluded that it is possible to use more conservative and smaller preparations.


In vitro and in vivo antioxidant potentials of Alchornea floribunda leaf extract, fractions and isolated bioactive compounds.
Alchornea floribunda leaves are widely used in ethnomedicine for the management of immuno-inflammatory disorders. We investigated the in vivo and in vitro antioxidant activity of the leaf extract, fractions and isolated compounds of A. floribunda. The ethyl acetate fraction of the methanol leaf extract was subjected to several chromatographic separations to isolate compounds 1-4. The structures of the isolated compounds were elucidated by a combination of 1D and 2D NMR and mass spectrometry. Oxidative stress was induced with carbon tetrachloride (CCl4). Further analysis on the isolated phenolic compounds were done using 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and hydrogen peroxide scavenging activity tests. The ethyl acetate fraction at 200 mg/kg produced significant (p<0.05) elevations of catalase enzyme activity and a significant (p<0.05) reduction in serum malondialdehyde. The chemical investigation of the ethyl acetate fraction led to the isolation of three flavans, (-) cathechin (1), (-) epicathechin (2), (+) epicathechin (3) and a flavanone, 2R, 3R dihydroquercitin (4). In hydrogen peroxide scavenging assay, (-) epicathechin exhibited an EC50 value of 8 μg/ml, similar to the standard ascorbic acid (EC50 = 8 μg/ml). (-) epicathechin showed scavenging of DPPH radical with EC50 value of 19 μg/ml while in the FRAP assay, it had EC50 value of 46 μg/ml which was lower than that of the standard, ascobic acid (EC50 = 66 μg/ml). The medicinal uses of A. floribunda may be due to the antioxidant activities of its phenolic compounds.


Male-specific association of the APC rs383830 T allele with the risk of coronary heart disease.
APC is a tumor suppressor gene that is involved in the processes of cell migration and adhesion, transcriptional activation, and apoptosis. The goal of this study was to evaluate the contribution of the APC rs383830 polymorphism to coronary heart disease (CHD) in Han Chinese. A total of 783 patients with CHD and 737 controls were tested in the current association study. Although our study did not identify an association between the APC rs383830 polymorphism and CHD, a breakdown analysis by gender indicated there was a significant contribution of the rs383830 T allele to the risk of CHD in males (P = 0.046, odds ratio = 1.267, 95% confidence interval = 1.004-1.598). In conclusion, our study suggested a male-specific association of the APC rs383830 polymorphism with CHD.


Correlation of breast cancer susceptibility loci with patient characteristics, metastasis-free survival, and mRNA expression of the nearest genes.
To understand the biology of low-risk breast cancer alleles, and to investigate whether these loci also contribute to disease progression that was once established, we examined the association of SNPs tagging the low-risk breast cancer loci in or near FGFR2, LSP1, MAP3K1, H19, TOX3, POU5F1P1, MYC, and 2q35, with clinical, pathological characteristics, prognosis, and mRNA expression of the nearest genes. Tumor DNA samples of 2,480 breast cancer patients were available. Out of this cohort, 1,290 patients with lymph-node negative disease who did not receive adjuvant systemic therapy, the SNP status was associated with metastasis-free survival (MFS). In 1,401 patients, the mRNA expression levels of FGFR2, LSP1, MAP3K1, H19, TOX3, POU5F1P1, and MYC were determined and correlated with SNP genotypes. The SNP rs2981582 in FGFR2 was significantly associated with positive ER and PgR status (P < 0.001 and P = 0.003, respectively). No other significant associations with patient or tumor characteristics were observed. Only rs2107425 near H19 was significantly associated with shorter MFS in uni- and multi-variate analysis (HR: 1.53, CI: 1.12-2.08, P = 0.006 and HR: 1.59, CI: 1.16-2.20, P = 0.004, respectively), with the more aggressive minor allele displaying a recessive trait. The minor allele of SNP rs3803662 located near the TOX3 gene was associated with lower mRNA expression of this gene. In conclusion, except for the association of rs13283662 with TOX3 gene expression indicating a tumor suppressor role of TOX3, our findings suggest that breast cancer low-risk loci generally do not affect expression of the nearest gene in breast tumor tissue. Also the prognosis of patients is largely not affected by low-risk breast cancer loci except for the SNP near H19. How, this SNP affects prognosis warrants further study as it does not operate through altering H19 mRNA expression.


Nucleation Kinetics and Structure Evolution of Quasi-Two-Dimensional ZnO at the Air-Water Interface: An In Situ Time-Resolved Grazing Incidence X-ray Scattering Study.
The design and synthesis of high-quality two-dimensional (2D) materials with desired morphology are essential for property control. One critical challenge that impedes the understanding and control of 2D crystal nucleation and growth is the inability of direct observation of the nanocrystal evolution process with high enough time resolution. Here, we demonstrated an in situ X-ray scattering approach that directly reveals 2D wurtzite ZnO nanosheet growth at the air-water interface. The time-resolved grazing incidence X-ray diffraction (GID) and grazing incidence X-ray off-specular scattering (GIXOS) results uncovered a lateral to vertical growth kinetics switch phenomenon in the ZnO nanosheet growth. This switch represents the 2D to three-dimensional (3D) crystal structure evolution, which governs the size and thickness of nanosheets, respectively. This phenomenon can guide 2D nanocrystal synthesis with rationally controlled size and thickness. Our work opens a new pathway toward the understanding of 2D nanomaterial growth kinetics based on time-resolved liquid surface grazing incidence X-ray techniques.


Protective effect of sucrose on the membrane properties of Lactobacillus casei Zhang subjected to freeze-drying.
The purpose of this research was to investigate the influence of sucrose at 2.0, 4.0, and 8.0% as a protectant during freeze-drying on the viability and membrane properties of Lactobacillus casei Zhang. Membrane properties were determined using zeta potential, hydrophobicity, fluidity, and integrity before and after freeze-drying. Exposing L. casei Zhang to sucrose protected it from drastic changes in cell surface electrophoretic mobility and hydrophobicity in contrast with the untreated condition, and the effect was dose related. Sucrose caused an increase in membrane fluidity compared with the control sample. Moreover, 2.0% sucrose decreased the general polarization values less than 4.0 or 8.0% sucrose, while 4.0% sucrose and 8.0% sucrose had no significant difference in decreasing general polarization values (P < 0.05). L. casei Zhang freeze-dried in the presence of 2.0% sucrose retained up to 23.7% membrane integrity, whereas cells freeze-dried with 4.0 and 8.0% sucrose had 32.4 and 37.6% membrane integrity compared with that of L. casei Zhang before freeze-drying. Correspondingly, the number of survivors of L. casei Zhang, determined by the plate count method, decreased from 8.02 to 0.63 log CFU/ml after freeze-drying in the absence of sucrose. However, in the presence of 2.0, 4.0, and 8.0% sucrose, the numbers of survivors were 2.01, 2.87, and 3.20 log CFU/ml after freeze-drying, respectively. The present work suggested that sucrose was an effective membrane protectant at 2.0, 4.0, or 8.0% on the surface zeta potential, hydrophobicity, fluidity, and integrity of L. casei Zhang.


Optimal collection technique and devices for a quality pap smear.
Collection technique is critical in the performance of the Papanicolaou (Pap) smear as an important screening tool for cervical cancer. While superior devices have been established, less effective devices continue to be used for both conventional and liquid-based Pap smears. Our aim is to determine the performance of collection devices currently used in obtaining conventional Pap smears and whether sequence of collection is important for higher quality results. This prospective, blinded, cohort study used 2 cytology labs to analyze Pap smears done within a 1-year period. Study participants were 128 clinicians who practice in Dane County, Wis, who send their Pap smears to either of the 2 study cytology labs. Participants included advance practice nurses, family physicians, and obstetrician/gynecologists. Logistic regression was utilized for analysis. In conventional Pap smears, sequence of collection did not affect any quality indicators. The Cervex-brush (broom) was associated with absent endocervical cells (Odds Ratio = 3.12, P < .001), limited or unsatisfactory results (OR = 1.68, P < .01), and obscuring inflammation (OR = 2.01, P < .01). Of those clinicians who had high levels of absent endocervical cells on their Pap smears (defined as > 3/30 Pap smears), 47% used the broom alone. The Cytobrush optimized quality indicators, and the combination of the Cytobrush for the endocervix and spatula for the ectocervix was superior. Presence of infectious agents also contributed to the absence of endocervical cells (OR = 3.09, P < .001). The combination of the Cytobrush (endocervix) and spatula (ectocervix) is superior for a quality Pap smear. The sequence of collection was not important in conventional Pap smears. The broom alone performs poorly. Presence of infection decreases quality.


Optically transparent polymer devices for in situ assessment of cell electroporation.
In order to study cell electroporation in situ, polymer devices have been fabricated from poly-dimethyl siloxane with transparent indium tin oxide parallel plate electrodes in horizontal geometry. This geometry with cells located on a single focal plane at the interface of the bottom electrode allows a longer observation time in both transmitted bright-field and reflected fluorescence microscopy modes. Using propidium iodide (PI) as a marker dye, the number of electroporated cells in a typical culture volume of 10-100 μl was quantified in situ as a function of applied voltage from 10 to 90 V in a series of ~2-ms pulses across 0.5-mm electrode spacing. The electric field at the interface and device current was calculated using a model that takes into account bulk screening of the transient pulse. The voltage dependence of the number of electroporated cells could be explained using a stochastic model for the electroporation kinetics, and the free energy for pore formation was found to be 45.6 ± 0.5 kT at room temperature. With this device, the optimum electroporation conditions can be quickly determined by monitoring the uptake of PI marker dye in situ under the application of millisecond voltage pulses. The electroporation efficiency was also quantified using an ex situ fluorescence-assisted cell sorter, and the morphology of cultured cells was evaluated after the pulsing experiment. Importantly, the efficacy of the developed device was tested independently using two cell lines (C2C12 mouse myoblast cells and yeast cells) as well as in three different electroporation buffers (phosphate buffer saline, electroporation buffer and 10% glycerol).


Demographic trends in social work over a quarter-century in an increasingly female profession.
This article depicts the changing demographic portrait of social work education in the United States from 1974 through 2000 and considers the demographic shifts in the profession of social work. During this period, BSW and joint MSW-BSW programs increased from 150 to 404, MSW programs increased from 79 to 139, and social work doctoral programs increased from 29 to 67. BSW graduates increased by 24 percent to almost 12,000, MSW graduates grew by almost 90 percent to over 15,000, and doctoral graduates increased by 44 percent to only 229. From 1974 to 2000, people of color represented increasing proportions of social work graduates to almost 30 percent of BSW graduates, 26 percent of MSW graduates, and 19 percent of social work PhD graduates. By 2000, the proportion of women earning social work degrees had grown to 88 percent at the BSW, 85 percent at the MSW, and 73 percent at the PhD levels, and women accounted for almost two-thirds of social work faculty. The most dynamic trends within the composition of the profession are the substantial increases in the proportion of women faculty, and among MSW graduates, a decrease in the proportion of men from 43 percent in 1960 to 15 percent in 2000. Findings suggest that issues of racial, ethnic, and gender representation in particular merit discussion within the profession.


Diagnosis and treatment of polycystic ovarian syndrome and insulin resistance.
PCOS is a complex syndrome that includes clinical and biochemical evidence of hyperandrogenism and hyperinsulinism. Adolescents with PCOS are affected by the diagnosis with both short-term and long-term consequences. Adolescents with PCOS report lower self-esteem and quality of life, based on standard assessments, when compared with age matched peers. These young women also are concerned about future fertility, which may affect psychological well being and health behaviors. In addition, patients with PCOS are at an increased risk for development of insulin resistance, type 2 diabetes, metabolic syndrome, and cardiovascular disease. Therefore, this identified at-risk group requires rigorous evaluation, treatment and long-term counseling and management by healthcare providers.


Advanced nursing skill certification in critical care.
Advances in critical care therapies demand that registered nurses maintain skills consistent with the ability to provide safe patient care. Advanced nursing function (ANF) certification is one way to achieve this goal. The purpose of this article is to describe the annual certification process that occurs in one general systems critical care unit within a large urban acute care setting. Two hundred registered nurses are certified annually in cardioversion/defibrillation, pacemakers, intraspinal analgesia, pulmonary artery catheters and intracranial pressure monitoring. Involving both conceptual and psychomotor skill assessments, ANF certification not only challenges educators to possess and maintain current knowledge about ANF procedures, but also readily identifies areas of strength and weakness for the nurse regarding knowledge and practice development about a particular procedure. The critical care education committee recognized the need for advanced nursing knowledge in order to provide quality, safe patients care and to meet the needs of patients with complex care requirements. ANF certification has proved to be an efficient, cost-effective method to educate many nurses in a relatively short period of time. Most importantly, ANF certification assists to maintain an optimum standard of care within the critical care unit and, at the same time, lends itself well to the development of other advanced critical care procedures in the future.


Sandpiles subjected to sinusoidal drive.
This paper considers a sandpile model subjected to a sinusoidal external drive with the period T. We develop a theoretical model for the Green's function in a large T limit, which predicts that the avalanches are anisotropic and elongated in the oscillation direction. We track the problem numerically and show that the system additionally shows a regime where the avalanches are elongated in the perpendicular direction with respect to the oscillations. We find a crossover between these two regimes. The power spectrum of avalanche size and the grains wasted from the parallel and perpendicular directions are studied. These functions show power-law behavior in terms of the frequency with exponents, which run with T.


Bayesian calibration of simulation models for supporting management of the elimination of the macroparasitic disease, Lymphatic Filariasis.
Mathematical models of parasite transmission can help integrate a large body of information into a consistent framework, which can then be used for gaining mechanistic insights and making predictions. However, uncertainty, spatial variability and complexity, can hamper the use of such models for decision making in parasite management programs. We have adapted a Bayesian melding framework for calibrating simulation models to address the need for robust modelling tools that can effectively support management of lymphatic filariasis (LF) elimination in diverse endemic settings. We applied this methodology to LF infection and vector biting data from sites across the major LF endemic regions in order to quantify model parameters, and generate reliable predictions of infection dynamics along with credible intervals for modelled output variables. We used the locally calibrated models to estimate breakpoint values for various indicators of parasite transmission, and simulate timelines to parasite extinction as a function of local variations in infection dynamics and breakpoints, and effects of various currently applied and proposed LF intervention strategies. We demonstrate that as a result of parameter constraining by local data, breakpoint values for all the major indicators of LF transmission varied significantly between the sites investigated. Intervention simulations using the fitted models showed that as a result of heterogeneity in local transmission and extinction dynamics, timelines to parasite elimination in response to the current Mass Drug Administration (MDA) and various proposed MDA with vector control strategies also varied significantly between the study sites. Including vector control, however, markedly reduced the duration of interventions required to achieve elimination as well as decreased the risk of recrudescence following stopping of MDA. We have demonstrated how a Bayesian data-model assimilation framework can enhance the use of transmission models for supporting reliable decision making in the management of LF elimination. Extending this framework for delivering predictions in settings either lacking or with only sparse data to inform the modelling process, however, will require development of procedures to estimate and use spatio-temporal variations in model parameters and inputs directly, and forms the next stage of the work reported here.


Apoptosis Induced by Tanshinone IIA and Cryptotanshinone Is Mediated by Distinct JAK/STAT3/5 and SHP1/2 Signaling in Chronic Myeloid Leukemia K562 Cells.
Though tanshinone IIA and cryptotanshinone possess a variety of biological effects such as anti-inflammatory, antioxidative, antimetabolic, and anticancer effects, the precise molecular targets or pathways responsible for anticancer activities of tanshinone IIA and cryptotanshinone in chronic myeloid leukemia (CML) still remain unclear. In the present study, we investigated the effect of tanshinone IIA and cryptotanshinone on the Janus activated kinase (JAK)/signal transducer and activator of transcription (STAT) signaling during apoptotic process. We found that both tanshinone IIA and cryptotanshinone induced apoptosis by activation of caspase-9/3 and Sub-G1 accumulation in K562 cells. However, they have the distinct JAK/STAT pathway, in which tanshinone IIA inhibits JAK2/STAT5 signaling, whereas cryptotanshinone targets the JAK2/STAT3. In addition, tanshinone IIA enhanced the expression of both SHP-1 and -2, while cryptotanshinone regulated the expression of only SHP-1. Both tanshinone IIA and cryptotanshinone attenuated the expression of bcl-xL, survivin, and cyclin D1. Furthermore, tanshinone IIA augmented synergy with imatinib, a CML chemotherapeutic drug, better than cryptotanshinone in K562 cells. Overall, our findings suggest that the anticancer activity of tanshinone IIA and cryptotanshinone is mediated by the distinct the JAK/STAT3/5 and SHP1/2 signaling, and tanshinone IIA has the potential for combination therapy with imatinib in K562 CML cells.


A Mycobacterium leprae-specific gene encoding an immunologically recognized 45 kDa protein.
By screening a Mycobacterium leprae lambda gt11 expression library with a serum from an Ethiopian lepromatous leprosy (LL) patient a clone was isolated (LL4) belonging to hybridization group III of a panel of previously isolated M. leprae clones. Members of this hybridization group encode a serologically recognized 45 kDa protein. The complete DNA sequences of the partially overlapping clones LL4 and L1 (hybridization group III) are presented and these revealed the presence of an open reading frame (ORF) predicting a protein with a molecular size of 42,448 Da. Southern hybridizations on total genomic DNA of M. leprae, Mycobacterium tuberculosis and eight atypical mycobacteria showed that the LL4 DNA fragment is specific for M. leprae DNA even under low-stringency conditions. The M. leprae specificity of LL4 DNA was further confirmed by the polymerase chain reaction using four different sets of primers. Western blotting analyses showed that the M. leprae 45 kDa protein is frequently recognized by antibodies from leprosy patients and that this recognition is specific since no antibodies could be detected in sera of tuberculosis patients. T-cell proliferation assays also demonstrated T-cell recognition by leprosy patients and healthy contacts of the M. leprae 45 kDa protein. The specificity of the LL4 DNA region and the 45 kDa antigen that is encoded by hybridization group III could provide unique tools for the development of M. leprae-specific immunological and DNA reagents.


Associations of semen quality with pyrethroids in semen and urine samples of men with oligozoospermia: A cross-sectional study in Samsun, Turkey.
Pyrethroids (PYRs) may act as endocrine disrupters and lead to infertility. The aim of the study was to analyze the levels of anti-androgenic PYRs (cypermethrin, deltamethrin, and permethrin) and 3-phenoxy benzoic acid (3-PBA), a general metabolite of PYRs, in both semen and urine samples of men with oligozoospermia. The PYRs and 3-PBA metabolite levels in the semen and urine samples of the men were analyzed through GC-MS. The results indicated that the levels of PYRs in the semen samples of the infertile group were significantly higher than those of the fertile group. It was determined that cypermethrin exposure was associated with changes in sperm count and total sperm motility, while permethrin, deltamethrin, and 3-PBA levels were associated with changes in sperm morphology. It was determined that there was a significant negative correlation between semen deltamethrin levels and sperm morphology and sperm count. In addition, exposure of these patients to deltamethrin (range; 1.53-8.02 µg/l) and having farmer parents were determined to increase the risk of infertility. In conclusion, the findings of this study showed that exposure to environmental PYRs may adversely affect semen quality, especially in terms of sperm morphology, in men with oligozoospermia.


Organ-on-a-chip technology for nanoparticle research.
The last two decades have witnessed explosive growth in the field of nanoengineering and nanomedicine. In particular, engineered nanoparticles have garnered great attention due to their potential to enable new capabilities such as controlled and targeted drug delivery for treatment of various diseases. With rapid progress in nanoparticle research, increasing efforts are being made to develop new technologies for in vitro modeling and analysis of the efficacy and safety of nanotherapeutics in human physiological systems. Organ-on-a-chip technology represents the most recent advance in this effort that provides a promising approach to address the limitations of conventional preclinical models. In this paper, we present a concise review of recent studies demonstrating how this emerging technology can be applied to in vitro studies of nanoparticles. The specific focus of this review is to examine the use of organ-on-a-chip models for toxicity and efficacy assessment of nanoparticles used in therapeutic applications. We also discuss challenges and future opportunities for implementing organ-on-a-chip technology for nanoparticle research.


Synthesis and Biological Evaluation of 3-cyano-4H-chromene Derivatives Bearing Carbamate Functionality.
2-Aminochromene derivatives display important pharmacological properties, including mainly antibiotic and anticancer activities. The study aims to synthesize new chromene derivatives via a new approach using Grignard reagents, for the evaluation of their antibiotic and antifungal properties. A series of novel 3-cyano-4-aminochromene derivatives bearing alkyl substituents at the 4-position was prepared for biological evaluation. These compounds were obtained by the addition of various Grignard reagents into Nethoxycarbonyl- 3-cyanoiminocoumarines in moderate to good yields (72-96%). The reaction is completely regioselective. The new chromene derivatives were screened for their in vitro antimicrobial activities against a panel of six bacterial and three fungal strains using agar dilution method. The antibacterial activity of the chromene derivatives was more pronounced on Gram-positive bacteria than on Gram-negative bacteria with a significant activity observed against Staphylococcus aureus. An interesting antifungal activity against Fusarium sp. and Fusarium oxysporum was also noticed.


Haplotype Heritability Mapping Method Uncovers Missing Heritability of Complex Traits.
We propose a novel approach to analyze genomic data that incorporates haplotype information for detecting rare variants within a regional heritability mapping framework. The performance of our approach was tested in a simulation study based on human genotypes. The phenotypes were simulated by generating regional variance using either SNP(s) or haplotype(s). Regional genomic relationship matrices, constructed with either a SNP-based or a haplotype-based estimator, were employed to estimate the regional variance. The results from the study show that haplotype heritability mapping captures the regional effect, with its relative performance decreasing with increasing analysis window size. The SNP-based regional mapping approach often misses the effect of causal haplotype(s); however, it has a greater power to detect simulated SNP-based-variants. Heritability estimates suggest that the haplotype heritability mapping estimates the simulated regional heritability accurately for all phenotypes and analysis windows. However, the SNP-based analysis overestimates the regional heritability and performs less well than our haplotype-based approach for the simulated rare haplotype-based-variant. We conclude that haplotype heritability mapping is a useful tool to capture the effect of rare variants, and explain a proportion of the missing heritability.


Long-term donor-site morbidity after thumb reconstruction with twisted-toe technique.
Traumatic thumb loss is a serious injury affecting patient´s ability to work and participate in activities of daily life. The main goal for a plastic surgeon is to restore hand grip, often by microsurgical methods. However, patients should be informed of all effects associated with tissue harvesting. The aim of the study was to assess the impact on donor foot and gait cycle in patients who have undergone thumb reconstruction using twisted-toe technique modified by Kempný. Twelve patients participated in the study: all suffered a thumb loss between the years 2003 and 2011 and the twisted-toe technique for thumb reconstruction was utilized. The changes in foot pressure distribution and lower extremity joint loading were evaluated. The differences in total maximal plantar pressure, pressure time integral, contact area, and maximum force between the affected and non-affected foot were statistically significant (P 0.1). No significant differences of temporal gait parameters between the affected and non-affected extremity were observed; however, statistically significant differences in kinetics parameters, frontal ankle and knee moments were detected. Donor limb functionality and anatomical disability were assessed using pedobarography systems and 3D-gait analysis. The recorded differences in plantar pressure distribution (increased pressure in I., IV. and V. metatarsal areas) and overload of the medial compartment of the knee joint were the most significant findings. Therefore, wearing individually adapted shoe insoles as prevention of osteoarthrosis might be beneficial for patients after thumb reconstruction by a twisted-toe technique.


[Exploration on the 24 hour intraocular pressure fluctuation in glaucoma patients].
Intraocular pressure is the most important and most easily controlled clinical parameters of glaucoma. It has a fluctuation and circadian rhythm. The 24 hours intraocular pressure measurement can better reflect the changes of intraocular pressure. It is clear that peak IOP is an independent risk factor for the progression of glaucoma, but the effect of IOP on glaucoma progression is worth exploring. This article focuses on whether IOP fluctuation is an independent risk factor for glaucoma progression, how to obtain the 24-hour intraocular pressure curve, the future direction of 24-hour intraocular pressure monitoring and other issues in order to cause clinical concern. (Chin J Ophthalmol, 2017, 53: 85-88).


Initiation of Opioid Prescription and Risk of Suicidal Behavior Among Youth and Young Adults.
Opioids are involved in an increasing proportion of suicide deaths. This study examined the association between opioid analgesic prescription initiation and suicidal behavior among young people. We analyzed Swedish population-register data on 1 895 984 individuals ages 9 to 29 years without prior recorded opioid prescriptions. We identified prescriptions dispensed from January 2007 onward and diagnosed self-injurious behavior and death by suicide through December 2013. We first compared initiators with demographically matched noninitiators. To account for confounding, we applied an active comparator design, which examined suicidal behavior among opioid initiators relative to prescription nonsteroidal antiinflammatory drug (NSAID) initiators while inverse-probability-of-treatment weighting with individual and familial covariates. Among the cohort, 201 433 individuals initiated opioid prescription. Relative to demographically matched noninitiators, initiators (N = 180 808) had more than doubled risk of incident suicidal behavior (hazard ratio = 2.64; 95% confidence interval [CI], 2.47-2.81). However, in the active comparator design, opioid initiators (N = 86 635) had only 19% relatively greater risk of suicidal behavior compared with NSAID initiators (N = 255 096; hazard ratio = 1.19; 95% CI,: 1.11-1.28), corresponding to a weighted 5-year cumulative incidence of 2.2% (95% CI, 2.1-2.4) for opioid and 1.9% (95% CI, 1.9-2.0) for NSAID initiators. Most sensitivity analyses produced comparable results. Opioid initiation may make only a small contribution to the elevated risk of suicidal behavior among young people receiving pharmacologic pain management. In weighing benefits and harms of opioid initiation, our results suggest that increased risk of suicidal behavior may not be a major concern.


Evaluating the potential roles of the Gray and Extension loci in the coat coloration of Thoroughbred racing horses.
Horses have substantial variation in coat color, and the genetic loci responsible for the coat color variations have been well investigated. It has been believed that some color variations should follow a single-locus Mendelian law. Examples include the Gray locus that causes the gray phenotype and the Extension locus that specifies the chestnut phenotype. We reevaluated the roles of the Gray and Extension loci by using a large number of mating records of Thoroughbred racing horses. We showed that the data indeed fits the Mendelian law extremely well for the two loci. Furthermore, we demonstrated that the Extension and Agouti loci might have an additional role in determining the degree of melanin that should distinguish bay, dark bay, and brown.


Food Insecurity in Urban and Rural Areas in Central Brazil: Transition from Locally Produced Foods to Processed Items.
Aiming to investigate the effect of diet and food consumption with regard to health, environment, and economy in light of nutrition ecology, we studied the dimensions of nutrition and food security in urban and rural settings in the region of Chapada dos Veadeiros, Central Brazil. We tracked diet and food consumption through carbon and nitrogen stable isotope ratios in fingernails of these inhabitants together with food intake data as a proxy for their diet patterns. We estimated household food insecurity by using the Brazilian Food Insecurity Scale. Nutrition and food insecurity was observed in both urban and rural areas, but was accentuated in rural settings. The diet pattern had high δ(13)C values in fingernails and low δ(15)N. Both urban and rural areas have diets with low diversity and relying on low-quality processed food staples at the same time that nutrition and food insecurity is quite high in the region.


Classification of PTEN missense VUS through exascale simulations.
Phosphatase and tensin homolog (PTEN), a tumor suppressor with dual phosphatase properties, is a key factor in PI3K/AKT signaling pathway. Pathogenic germline variation in PTEN can abrogate its ability to dephosphorylate, causing high cancer risk. Lack of functional evidence lets numerous PTEN variants be classified as variants of uncertain significance (VUS). Utilizing Molecular Dynamics (MD) simulations, we performed a thorough evaluation for 147 PTEN missense VUS, sorting them into 66 deleterious and 81 tolerated variants. Utilizing replica exchange molecular dynamic (REMD) simulations, we further assessed the variants situated in the catalytic core of PTEN's phosphatase domain and uncovered conformational alterations influencing the structural stability of the phosphatase domain. There was a high degree of agreement between our results and the variants classified by Variant Abundance by Massively Parallel Sequencing, saturation mutagenesis, multiplexed functional data and experimental assays. Our extensive analysis of PTEN missense VUS should benefit their clinical applications in PTEN-related cancer. Classification of PTEN variants affecting its lipid phosphatase activity is important for understanding the roles of PTEN variation in the pathogenesis of hereditary and sporadic malignancies. Of the 3000 variants identified in PTEN, 1296 (43%) were assigned as VUS. Here, we applied MD and REMD simulations to investigate the effects of PTEN missense VUS on the structural integrity of the PTEN phosphatase domain consisting the WPD, P and TI active sites. We classified a total of 147 missense VUS into 66 deleterious and 81 tolerated variants by referring to the control group comprising 54 pathogenic and 12 benign variants. The classification was largely in concordance with these classified by experimental approaches.


Antimicrobial Susceptibility Testing of Mycobacterium bovis Isolates from Michigan White-Tailed Deer during the 2009 Hunting Season.
Michigan has had an ongoing outbreak of endemic Mycobacterium bovis which has been recognized within and sustained by its free-ranging white-tailed deer population since 1994. Worldwide, organisms within the Mycobacterium tuberculosis complex have exhibited the ability to develop resistance to antimicrobial agents, resulting in both the multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of human tuberculosis. Michigan's Bovine Tuberculosis Working Group has conducted active antimicrobial susceptibility testing on wildlife isolates of the endemic M. bovis organism at five-year intervals to detect any emerging drug resistance patterns. The results of 33 white-tailed deer origin isolates collected from the 2009 hunting season are reported here. There continues to be no evidence of any drug resistance except for pyrazinamide resistance. These results are likely due to the lack of antibacterial treatment applied to either wildlife or domestic animals which would provide selection pressure for the development of drug resistance.


Triazine-Based Covalent DNA-Encoded Libraries for Discovery of Covalent Inhibitors of Target Proteins.
Since ibrutinib was approved by the FDA as an effective monotherapy for chronic lymphocytic leukemia (CLL) and multilymphoma, more and more FDA-approved covalent drugs are coming back into the market. On this occasion, the resurgence of interest in covalent drugs calls for more hit discovery techniques. However, the limited numbers of covalent libraries prevent the development of this area. Herein, we report the design of covalent DNA-encoded library (DEL) and its selection method for the discovery of covalent inhibitors for target proteins. These triazine-based covalent DELs yielded potent compounds after covalent selection against target proteins, including Bruton's Tyrosine Kinase (BTK), Janus kinase 3 (JAK3), and peptidyl-prolyl cis/trans isomerase NIMA-interacting-1 (Pin1).


Effect of DL-ethionine on the intestinal absorption and transport of palmitic acid-1-14C and tripalmitin-14C. Role of intramucosal factors in the uptake of luminal lipids.
The effect of DL-ethionine on the uptake and transport of lipid by the rat small intestine was investigated. A cottonseed oil emulsion containing (14)C-labeled tripalmitin or palmitic acid was administered intragastrically to rats pretreated with DL-ethionine, DL-ethionine plus methionine, or saline, and the rats were sacrificed 2, 4, and 6 hr later. Lipids from the plasma, the stomach, the colon, the luminal contents of the small intestine, and the wall of the small intestine were extracted, fractionated, and their radioactivity assayed. Ethionine markedly inhibited the uptake of lipids by the small intestine. This inhibition was not related to impairment of intraluminal lipolysis since analagous inhibitions were observed when palmitic acid or predigested triglyceride (TG), obtained through a jejunal fistula from normal animals, was administered instead of tripalmitin. Ethionine also inhibited the transport of lipid from the wall of the small intestine. A significant fraction of the administered lipid remained in the wall of the small intestine, and only a small fraction was transported to the blood stream. Although most of the wall radioactivity was in the form of TG, significant proportions were also found in the free fatty acid (FFA) and partial glyceride fractions, indicating a marked inhibition of mucosal reesterification to TG. The degree of inhibition of mucosal reesterification and the degree of inhibition of transport of wall lipids were directly related to the degree of inhibition of uptake of luminal radioactivity. This relationship suggests that the rate of reesterification, the level of mucosal FFA, and the rate of transport of intramucosal TG may be of importance in determining the extent of uptake of intraluminal lipid by the mucosal cells. Since a significant fraction of the wall radioactivity was in the form of TG, the decreased transport of wall lipids was attributed to an impairment of chylomicron completion due to inhibition of either the synthesis of chylomicron apoprotein or the association of preformed TG with the protein moiety of chylomicrons. Experiments with labeled amino acids support the first possibility.


Enhanced dielectric polarization and electro-responsive characteristic of graphene oxide-wrapped titania microspheres.
Electric field-induced particle polarization is essential to the electro-responsive electrorheological (ER) effect of particle suspensions. In this work, we use graphene oxide (GO) as a soft and polar coating shell to prepare GO-wrapped titania dielectric microspheres for use as the dispersal phase of an ER suspension. Under a DC electric field, the ER characteristic of GO-wrapped titania microspheres dispersed in silicone oil is investigated by rheological tests, and then compared with that of a suspension of bare titania microspheres. The results show that the suspension of GO-wrapped titania microspheres possesses an enhanced ER characteristic. Its field-induced shear yield stress and storage modulus are much higher than those of the suspension of bare titania microspheres. The soft and polar GO shell is regarded as the origin of the ER enhancement. Dielectric analysis indicates that wrapping GO can enhance the interfacial polarization and thus improve the ER characteristics of titania microspheres. Wrapping GO onto the surface of titania microspheres can also reduce the particle sedimentation velocity of the suspension.


Posterior quadrant disconnection for refractory epilepsy: A case series.
To analyze the surgical outcome and safety of posterior quadrant disconnection in medically refractory epilepsy arising from the posterior head region from a level IV tertiary care center over a period of three years. Seven consecutive patients who underwent posterior quadrant disconnection for refractory epilepsy were analyzed. We analyzed the data of seven (n = 7) consecutive posterior quadrant epilepsy patients who underwent posterior quadrant disconnection with a mean age of 8.5 years over the last three years of which 4 were male and 3 females. All patients underwent extensive pre-surgical evaluation including detailed history, examination, prolonged video EEG recordings, neuropsychological testing, MRI brain, DTI, PET scan (n = 6), fMRI (n = 4), WADA test (n = 1) and invasive recording (n = 1), Of seven patients four had left sided pathology and three had right sided pathology. All patients except one underwent pure disconnection and one underwent partial resection. Posterior quadrant disconnection is effective surgical procedure for medically refractory epilepsy arising from the posterior quadrant in carefully selected patients without morbidity or functional disability across various age groups especially in children. In our series, all seven patient had good seizure outcome and none had functional disabilities.


Seroprevalence of anti-Borrelia antibodies among patients with confirmed sarcoidosis in a region of Japan where Lyme borreliosis is endemic.
Sarcoidosis is a multisystemic granulomatous disease of unknown etiology, while Lyme borreliosis is a multisystemic disorder caused by Borrelia burgdorferi. The purpose of this study is to evaluate the relationship between sarcoidosis and Lyme borreliosis in a region of Japan where Lyme borreliosis is endemic. We determined the seroprevalence of anti-Borrelia burgdorferi antibodies as well as antibodies three Japanese Borrelia strains by enzyme-linked immunosorbent assay and dotblot assay using purified Borrelia-specific proteins in 46 patients with confirmed sarcoidosis and 150 controls (50 disease controls and 100 healthy controls) in Hokkaido, the affected region. Fifteen patients with sarcoidosis (32.6%) tested positive for Borrelia spirochete in both assays, compared with two disease controls (4.0%) and two healthy controls (2.0%). The seroprevalence of anti-Borrelia antibodies in patients with sarcoidosis was much higher in the affected region than in the region in our previous study were Lyme borreliosis is non-endemic. In a region where Lyme borreliosis is endemic, Borrelia infection may be partially associated with sarcoidosis.


Augmented gastric inhibitory polypeptide and insulin responses to a meal after an increase in carbohydrate (sucrose) intake.
The gastric inhibitory polypeptide (GIP) response to certain stimuli may be exaggerated in patients with obesity and noninsulin-dependent diabetes mellitus. To explore the effects of increased caloric intake and dietary composition on GIP secretion, 20 normal lean volunteers underwent a 4-week ambulatory study. A baseline week (usual diet) was followed by 3 weeks in which the usual diet was supplemented with 45 g fat (diet A), 100 g carbohydrate in the form of sucrose (diet B), or 50 g protein (diet C) for 1 week each. Almost equal numbers of subjects followed sequence ABC, BCA, or CAB in this cross-over study. At the end of the baseline week and each study week, serum glucose, insulin, and GIP were measured in response to a 500-cal liquid test meal. Daily intake of carbohydrate, protein, or fat, as monitored by food records, increased significantly (P less than 0.01) during the appropriate dietary periods, whereas body weight changed slightly, but not significantly, during the 3 study periods. No changes occurred in the total integrated serum glucose concentrations, whereas integrated insulin concentrations changed significantly (P less than 0.05), being 32.5 +/- 3.1 (+/- SEM), 37.2 +/- 4.0, and 30.3 +/- 3.1 microU/ml min-1 during periods A, B, and C, respectively. Insulin secretion was greatest during period B, the carbohydrate week, when insulin concentrations 15-60 min after the test meal were significantly greater (P less than 0.05 to P less than 0.01) than after the baseline period. Total integrated incremental serum GIP concentrations were also significantly different (P less than 0.01) during the 3 study periods, being 1.93 +/- 0.13, 2.53 +/- 0.24, and 1.90 +/- 0.11 ng/ml min-1 during A, B, and C, respectively. Serum GIP was highest during period B (carbohydrate), when average concentrations were significantly higher (P less than 0.01) 15-60 min after the meal compared to those during the baseline study. Similar changes did not occur with the other diets. Thus, GIP and insulin secretion were substantially altered by an acute increase in sucrose intake. The exaggerated GIP response to a meal in some patients with obesity may possibly be the result of adaptation of intestinal GIP cells to diet, particularly one rich in sucrose.


RUNX3 site-specific hypermethylation predicts papillary thyroid cancer recurrence.
Papillary thyroid cancer (PTC) is the most common epithelial thyroid tumor, accounting for more than 80% of all thyroid cancers. Although PTC shows an indolent character and excellent prognosis, patients with aggressive characteristics are more likely to have a disease recurrence and die in the end. The aim of this study was to analyze BRAF(V600E) mutation and methylation levels of CpG sites in the promoters of CDH1, DAPK, RARβ and RUNX3 genes in a cohort of PTCs, and investigate their association with tumor recurrence. In this study, we used pyrosequencing method to individually quantified methylation levels at multiple CpG sites within each gene promoter, and detect BRAF(V600E) mutation in 120 PTCs and 23 goiter tissues as normal control. Moreover, appropriate cut-off values for each CpG site were set up to predict disease recurrence. Our data showed that overall average methylation levels of CDH1 and RUNX3 genes were significantly higher in PTCs than that in control subjects. Conversely, overall average methylation levels of DAPK promoter were significantly lower in PTCs than that in control subjects. Moreover, BRAF(V600E) mutation and overall average methylation levels of all these genes were not significant difference between recurrent and non-recurrent cases. However, we found that hypermethylation of RUNX3 at CpG sites -1397, -1406, -1415 and -1417 significantly increased the risk of of disease recurrence by using appropriate site-specific cut-off values. Collectively, our findings suggest RUNX3 site-specific hypermethylation may offer value in predicting or monitoring postoperative recurrence of PTC patients.


Dosimetrically triggered adaptive radiotherapy for head and neck cancer: Considerations for the implementation of clinical protocols.
Defining dosimetric rules to automatically detect patients requiring adaptive radiotherapy (ART) is not straightforward, and most centres perform ad-hoc ART with no specific protocol. This study aims to propose and analyse different steps to design a protocol for dosimetrically triggered ART of head and neck (H&N) cancer. As a proof-of-concept, the designed protocol was applied to patients treated in TomoTherapy units, using their available software for daily MVCT image and dose accumulation. An initial protocol was designed by a multidisciplinary team, with a set of flagging criteria based only on dose-volume metrics, including two action levels: (1) surveillance (orange flag), and (2) immediate verification (red flag). This protocol was adapted to the clinical needs following an iterative process. First, the protocol was applied to 38 H&N patients with daily imaging. Automatic software generated the daily contours, recomputed the daily dose and flagged the dosimetric differences with respect to the planning dose. Second, these results were compared, by a sensitivity/specificity test, to the answers of a physician. Third, the physician, supported by the multidisciplinary team, performed a self-analysis of the provided answers and translated them into mathematical rules in order to upgrade the protocol. The upgraded protocol was applied to different definitions of the target volume (i.e. deformed CTV + 0, 2 and 4 mm), in order to quantify how the number of flags decreases when reducing the CTV-to-PTV margin. The sensitivity of the initial protocol was very low, specifically for the orange flags. The best values were 0.84 for red and 0.15 for orange flags. After the review and upgrade process, the sensitivity of the upgraded protocol increased to 0.96 for red and 0.84 for orange flags. The number of patients flagged per week with the final (upgraded) protocol decreased in median by 26% and 18% for red and orange flags, respectively, when reducing the CTV-to-PTV margin from 4 to 2 mm. This resulted in only one patient flagged at the last fraction for both red and orange flags. Our results demonstrate the value of iterative protocol design with retrospective data, and shows the feasibility of automatically-triggered ART using simple dosimetric rules to mimic the physician's decisions. Using a proper target volume definition is important and influences the flagging rate, particularly when decreasing the CTV-to-PTV margin.