cAMP-response element-binding protein mediates tumor necrosis factor-alpha-induced vascular smooth muscle cell migration.
Migration of vascular smooth muscle cells (VSMCs) contributes to formation of vascular stenotic lesions such as atherosclerosis and restenosis after angioplasty. Previous studies have demonstrated that tumor necrosis factor-alpha (TNF-alpha) is a potent migration factor for VSMCs. cAMP-response element-binding protein (CREB) is the stimulus-induced transcription factor and activates transcription of target genes such as c-fos and interleukin-6. We examined whether CREB is involved in TNF-alpha-induced VSMC migration. TNF-alpha induced CREB phosphorylation with a peak at 15 minutes of stimulation. Pharmacological inhibition of p38 mitogen-activated protein kinase (p38-MAPK) inhibited TNF-alpha-induced CREB phosphorylation. Adenovirus-mediated overexpression of dominant-negative form of CREB suppressed TNF-alpha-induced CREB phosphorylation and c-fos mRNA expression. VSMC migration was evaluated using a Boyden chamber. Overexpression of dominant-negative form of CREB suppressed VSMC migration as well as Rac1 expression induced by TNF-alpha. Overexpression of dominant-negative Rac1 also inhibited TNF-alpha-induced VSMC migration. Our results suggest that p38-MAPK/CREB/Rac1 pathway plays a critical role in TNF-alpha-induced VSMC migration and may be a novel therapeutic target for vascular stenotic lesion. Migration of vascular smooth muscle cells (VSMCs) contributes to formation of vascular stenotic lesions. TNF-alpha, a potent migration factor for VSMCs, activated CREB through p38 mitogen-activated protein kinase (p38-MAPK). CREB inhibition suppressed TNF-alpha-induced VSMC migration and Rac1 expression. These results suggest p38-MAPK/CREB/Rac1 pathway mediates TNF-alpha-induced VSMC migration.


A prospective naturalistic study of antidepressant-induced jitteriness/anxiety syndrome.
Patients often develop neuropsychiatric symptoms such as anxiety and agitation after they have started taking an antidepressant, and this is thought to be associated with a potentially increased risk of suicide. However, the incidence of antidepressant-induced jitteriness/anxiety syndrome has not been fully investigated, and little has been reported on its predictors. The aim of this study was to survey the incidence of antidepressant-induced jitteriness/anxiety syndrome and clarify its predictors in a natural clinical setting. Between January 2009 and July 2012, we prospectively surveyed 301 patients who had not taken any antidepressants for 1 month before presentation, and who were prescribed antidepressants for 1 month after their initial visit. Patients were classified as developing antidepressant-induced jitteriness/anxiety syndrome if they experienced any symptoms of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, or mania during the first month. Among the 301 patients, 21 (7.0%) developed antidepressant-induced jitteriness/anxiety syndrome. Major depressive disorder and a diagnosis of mood disorder in first-degree relatives of patients were significantly associated with induction of antidepressant-induced jitteriness/anxiety syndrome (odds ratio 10.2, P=0.001; odds ratio 4.65, P=0.02; respectively). However, there was no such relationship for sex, age, class of antidepressant, combined use of benzodiazepines, or diagnosis of anxiety disorder. The findings of this study suggest that major depressive disorder and a diagnosis of mood disorder in first-degree relatives may be clinical predictors of antidepressant-induced jitteriness/anxiety syndrome.


Enhancement of U4/U6 small nuclear ribonucleoprotein particle association in Cajal bodies predicted by mathematical modeling.
Spliceosomal small nuclear ribonucleoprotein particles (snRNPs) undergo specific assembly steps in Cajal bodies (CBs), nonmembrane-bound compartments within cell nuclei. An example is the U4/U6 di-snRNP, assembled from U4 and U6 monomers. These snRNPs can also assemble in the nucleoplasm when cells lack CBs. Here, we address the hypothesis that snRNP concentration in CBs facilitates assembly, by comparing the predicted rates of U4 and U6 snRNP association in nuclei with and without CBs. This was accomplished by a random walk-and-capture simulation applied to a three-dimensional model of the HeLa cell nucleus, derived from measurements of living cells. Results of the simulations indicated that snRNP capture is optimal when nuclei contain three to four CBs. Interestingly, this is the observed number of CBs in most cells. Microinjection experiments showed that U4 snRNA targeting to CBs was U6 snRNP independent and that snRNA concentration in CBs is approximately 20-fold higher than in nucleoplasm. Finally, combination of the simulation with calculated association rates predicted that the presence of CBs enhances U4 and U6 snRNP association by up to 11-fold, largely owing to this concentration difference. This provides a chemical foundation for the proposal that these and other cellular compartments promote molecular interactions, by increasing the local concentration of individual components.


A physical concept of soil-water equilibria for nonionic organic compounds.
Soil-water equilibrium data suggest that the transfer of nonionic chemicals from water to soil may be described in terms of a hypothesis of solute partitioning in the soil organic matter. This concept allows estimation of soil-water distribution coefficients either from solvent-water partition coefficients or aqueous solubilities.


Synthetic Triterpenoid RTA dh404 (CDDO-dhTFEA) Ameliorates Acute Pancreatitis.
Nuclear factor-erythroid-2-related factor (Nrf2) is a ubiquitous transcriptional factor that regulates expression of cellular antioxidant and detoxifying molecules. This study was undertaken to test the hypothesis that administration of the Nrf2 activator (dh404) may attenuate acute pancreatitis. Rats were treated with dh404 (1 mg/kg) 24 hours before induction of pancreatitis and for 3 days thereafter. Pancreatitis was induced with L-arginine (600 mg/100 g) or cerulein (40 μg/kg). Pancreases were processed for histology and malondialdehyde, whereas serum was analyzed for amylase. Islet extracted human pancreatic tissue from organ donors were used for in vitro studies. The tissues were incubated with dh404 at 0, 250, and 500 nM for 30 minutes, 60 minutes, 12 hours, and 24 hours. Nuclear factor-erythroid-2-related factor nuclear translocation and expression of Nrf2's target genes and inflammatory mediators were determined. The dh404-treated rat pancreases demonstrated significantly less infiltration of inflammatory cells, destruction of acinar architecture, perilobar edema, and necrosis. Serum amylase and pancreatic malondialdehyde in the dh404-treated rats were significantly lower. dh404-treated human pancreatic tissue showed a significantly higher expression of antioxidant enzymes, lower expression of inflammatory mediators, and greater viability against oxidative stress. Administration of dh404 attenuates acute pancreatitis by lowering oxidative stress and reducing proinflammatory mediators.


Magnetic color-flavor locking phase in high-density QCD.
We investigate the effects of an external magnetic field in the gap structure of a color superconductor with three massless quark flavors. Using an effective theory with four-fermion interactions, inspired by one-gluon exchange, we show that the long-range component B of the external magnetic field that penetrates the color-flavor locked phase modifies its gap structure, producing a new phase of lower symmetry. A main outcome of our study is that the B field tends to strengthen the gaps formed by Q-charged and Q-neutral quarks that coupled among themselves through tree-level vertices. These gaps are enhanced by the field-dependent density of states of the Q-charged quarks on the Fermi surface. Our considerations are relevant for the study of highly magnetized compact stars.


Design principles of a low voltage cardiac defibrillator based on the effect of feedback resonant drift.
We explore the possibility of exploiting the phenomenon of the resonant drift of autowave vortices in the design of low-voltage cardiac defibrillators. The problem of reflection of resonantly drifting vortices by inexcitable boundaries is overcome by using feedback. Numerical studies show that the voltage needed for defibrillation by this method may be substantially less (by an order of magnitude) than that used in conventional single-shock defibrillation.


An ANOVA approach for statistical comparisons of brain networks.
The study of brain networks has developed extensively over the last couple of decades. By contrast, techniques for the statistical analysis of these networks are less developed. In this paper, we focus on the statistical comparison of brain networks in a nonparametric framework and discuss the associated detection and identification problems. We tested network differences between groups with an analysis of variance (ANOVA) test we developed specifically for networks. We also propose and analyse the behaviour of a new statistical procedure designed to identify different subnetworks. As an example, we show the application of this tool in resting-state fMRI data obtained from the Human Connectome Project. We identify, among other variables, that the amount of sleep the days before the scan is a relevant variable that must be controlled. Finally, we discuss the potential bias in neuroimaging findings that is generated by some behavioural and brain structure variables. Our method can also be applied to other kind of networks such as protein interaction networks, gene networks or social networks.


Ratiometric detection of Cu2+ in water and drinks using Tb(III)-functionalized UiO-66-type metal-organic frameworks.
As an important trace element in the human body, the concentration of Cu2+ has an important impact on the environment and human health, and its quantitative determination is of great significance in the fields of environmental protection and food safety. Here, a ratiometric fluorescent probe based on Tb(III)-functionalized UiO-66-type MOFs has been synthesized via a facile post-synthetic modification method by employing mixed linkers containing terephthalic acid and 2,6-pyridinedicarboxylic acid for Cu2+ detection. The blue fluorescence intensity at 440 nm from the ligands of MOFs does not change much with increasing Cu2+ concentrations and can be used as a reference signal, while the green fluorescence of Tb3+ can be rapidly and selectively quenched, causing fluorescence intensity at 547 nm to decrease. The probe can be used as a ratiometric sensor for Cu2+ detection with a good linear response and low detection limit. The use of the probe for the determination of Cu2+ in real water samples and drinks shows good practicality. This method for Cu2+ detection is simple, specific and visualized to meet the needs of environmental monitoring and food analysis and provides a new strategy for the construction of new copper ion fluorescent sensors to analyze complex samples.


Biomimetic Human Lung Alveolar Interstitium Chip with Extended Longevity.
Determining the mechanistic causes of lung diseases, developing new treatments thereof, and assessing toxicity whether from chemical exposures or engineered nanomaterials would benefit significantly from a preclinical human lung alveolar interstitium model of physiological relevance. The existing preclinical models have limitations because they fail to replicate the key anatomical and physiological characteristics of human alveoli. Thus, a human lung alveolar interstitium chip was developed to imitate key alveolar microenvironmental factors including an electrospun nanofibrous membrane as the analogue of the basement membrane for co-culture of epithelial cells with fibroblasts embedded in 3D collagenous gels, physiologically relevant interstitial matrix stiffness, interstitial fluid flow, and 3D breathing-like mechanical stretch. The biomimetic chip substantially improved the epithelial barrier function compared to transwell models. Moreover, the chip having a gel made of a collagen I-fibrin blend as the interstitial matrix sustained the interstitium integrity and further enhanced the epithelial barrier, resulting in a longevity that extended beyond eight weeks. The assessment of multiwalled carbon nanotube toxicity on the chip was in line with the animal study.


Electrorheological response and orientational bistability of a homogeneously aligned nematic capillary.
We consider a homogeneously aligned nematic liquid crystal confined in the region between two rotating coaxial cylinders. We study the nematic's director and velocity profiles induced by the imposed Couette flow and an applied radial electric field. We present calculations for the specific flow-aligning nematic liquid crystal 4(')-n-pentyl-4-cyanobiphenyl and numerically solve a hydrodynamic model assuming hard anchoring and nonslip boundary conditions. We calculate a phase diagram in the parameter space showing a region where there exist multiple equilibrium solutions for the nematic's configuration and a region where there exists only one stationary solution. We also study the rheology of the system by calculating the apparent viscosity and the first normal stress difference. We find that the competition between the Couette flow and the electric field gives rise to an interesting non-Newtonian response which switches its behavior from shear thickening to shear thinning by exceeding a critical field.


Extended-range grazing-incidence spectrometer for high-resolution extreme ultraviolet measurements on an electron beam ion trap.
A high-resolution grazing-incidence grating spectrometer has been implemented on the Livermore electron beam ion traps for performing very high-resolution measurements in the soft x-ray and extreme ultraviolet region spanning from below 10 Å to above 300 Å. The instrument operates without an entrance slit and focuses the light emitted by highly charged ions located in the roughly 50 μm wide electron beam onto a cryogenically cooled back-illuminated charge-coupled device detector. The measured line widths are below 0.025 Å above 100 Å, and the resolving power appears to be limited by the source size and Doppler broadening of the trapped ions. Comparisons with spectra obtained with existing grating spectrometers show an order of magnitude improvement in spectral resolution.


Schistosoma haematobium infection and morbidity risk factors for pre-school age children in western Angola: A knowledge, attitudes and practices survey.
Urogenital schistosomiasis is one of the most prevalent parasitic diseases in sub-Saharan Africa. It is a poverty-related disease conditioned by behavioural practices. Our objective is to evaluate the awareness, mindset and habits about urogenital schistosomiasis in the community of Cubal (Angola), as well as its association with infection and urinary tract morbidity in pre-school age children. A cross-sectional study of knowledge, attitudes and practices at home was conducted between February and May 2022 with 250 participants. Overall, 93.6% of those surveyed had some prior knowledge about schistosomiasis and, among all the symptoms associated with this disease, blood in the urine was the best known (54.4%). Nevertheless, 57.6% obtained a medium knowledge score. Regarding attitude, the majority of respondents had a high attitude score (79.2%) with 96.0% willing to participate in mass drug administration campaigns. Laundry in the river was the most common risk practice (61.2%) and 55.2% out of the total were classified with a low practice score. Low knowledge about symptoms and transmission by caregivers was the outstanding risk factor for infection in pre-school age children (OR = 16.93, 95%CI: 3.93-72.82), and lack of knowledge that avoiding entering the river prevents schistosomiasis was the main risk factor for morbidity in PSAC (OR = 8.14, 95%CI: 1.14-58.25).


Persistence and shedding of senecavirus A in naturally infected boars.
Senecavirus A (SVA) infection in pigs causes vesicular disease and results in a short viremia and transient shedding of the virus, mainly in oral fluids and feces. Here we describe the consistent prolonged shedding of SVA in the semen of 2 boars, and persistence of SVA within the tonsils and testes of 3 adult boars. Two SVA-infected boars that were identified on a Minnesota sow farm in 2017 shed SVA RNA in semen for >3 mo after an outbreak of vesicular disease had occurred on the farm. SVA was isolated from 1 semen sample collected 9 d after clinical disease began on the farm. The third SVA-infected boar was identified on an Indiana sow farm in 2020. All boars had SVA RNA detected in the testes and tonsils by RT-rtPCR, with lower Ct values obtained for the testes than from the tonsils. All boars had multifocal lymphocytic orchitis with segmental degeneration and atrophy of the germinal epithelium within the seminiferous tubules. One boar also had areas of seminiferous tubule collapse and interstitial fibrosis within the testes. In all boars, in situ hybridization demonstrated the presence of SVA mRNA within cells located basally in the seminiferous tubules of the testes, and within the basal surface epithelial cells, crypt epithelial cells, and subepithelial and parafollicular lymphocytes and histiocytes of the tonsil.


Prevalence, Pattern, and Severity of Molar Incisor Hypomineralization in 8-12-year-old Schoolchildren of Moradabad City.
Recently, molar incisor hypomineralization (MIH) has become more evident and one of the most common reasons for loss of teeth in children after dental caries. Being a country with a diverse ethnic population, the prevalence of MIH in different regions of India may differ. Hence, the present study was undertaken to determine the prevalence, pattern, and severity of MIH in 8-12-year-old Schoolchildren in Moradabad city. This study was conducted in various schools of Moradabad city to target a sample of 2,300 children aged between 8 and 12 years. The examination was done in their respective schools by a calibrated examiner in natural daylight using European Academy of Pediatric Dentistry diagnostic criteria for MIH 2015. The results, thus obtained, were statistically analyzed using Pearson's Chi-square test. A prevalence of 3.96% (91/2300) for MIH was reported without any gender predilection. Molar hypomineralization showed a prevalence of 1.3% (29/2300) whereas the prevalence for hypomineralization of second primary molars was 1.4% (22/1620). The most common type of defect was type 2 and most of the affected teeth were of grade I. Mandibular molars were more commonly affected compared to the maxillary molars. A prevalence of 3.96% (91/2300) was observed for MIH. Frequent dental screening camps should be organized in schools at the community level for the enhancement of early diagnosis of MIH and designing appropriate management strategies. Khan A, Garg N, Mayall SS, et al. Prevalence, Pattern, and Severity of Molar Incisor Hypomineralization in 8-12-year-old Schoolchildren of Moradabad City. Int J Clin Pediatr Dent 2022;15(2):168-174.


Examining changes in African American mothers' racial socialization patterns during adolescence: Racial discrimination as a predictor.
Racial socialization is a culturally relevant parenting strategy known to combat the detrimental consequences of racial discrimination for African American youth. Three limitations hinder our developmental understanding of the racial socialization process. Few studies have accounted for the combination of messages that primary caregivers convey, examined how these messages change over time, or investigated how caregivers and adolescents experiences with racial discrimination predict change in the combination of messages conveyed. Given that African American mothers are often the primary socializers in families, the current study used data from a community sample of 497 African American adolescents (52% Female; Time 1 Mage = 15.69; Time 2 Mage = 18.74) and their mothers (Time 1 Mage = 40.43; Time 2 Mage = 43.39) to identify patterns in mothers' racial socialization messages, identify how mothers' racial socialization patterns change from middle to late adolescence, and investigate whether mother- and adolescent-reported racial discrimination contribute to changes in mothers' racial socialization patterns. Latent profile analysis and latent transition analysis were used to examine these questions. Findings revealed three racial socialization patterns: balanced socializers who mistrust, cultural socialization and preparation for bias emphasizers, and low racial socializers. Most mothers were in the low racial socializers group, and most provided similar messages in middle and late adolescence. Mothers' reports of their own racial discrimination influenced the racial socialization messages mothers delivered; however, adolescent-reported racial discrimination did not. These results have implications for community-based interventions designed to help families manage racial discrimination. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Dietary vitamin E and pulmonary biochemical responses of rats to cigarette smoking.
The effect of dietary vitamin E on cellular susceptibility to cigarette smoking was studied in rats. Young male rats maintained on a basal vitamin E-deficient diet with or without 100 ppm vitamin E supplementation for 4 or 5 weeks were exposed to either sham or cigarette smoke for up to 7 days. Higher animal mortality rate was observed in the animals fed the vitamin E-deficient diet than in the supplemented group when they were subjected to acute levels of cigarette smoking. Relative to the respective sham groups, a greater alteration of biochemical parameters, such as reduced glutathione (GSH) and related enzymes, was found in the lungs of smoked rats fed the deficient diet than in the supplemented group. Animal lungs exhibited a greater biochemical response to whole smoke than the gaseous phase of smoke. The results suggest that the nutritional status of vitamin E may influence the cellular susceptibility of rats to cigarette smoking.


[Long-term prognosis of idiopathic chronic adult hydrocephalus: I. The University Hospital Marqués de Valdecilla diagnostic and therapeutic protocol].
Despite the existence of published guidelines for more than a decade, there is still a substantial variation in the management of idiopathic normal pressure hydrocephalus due to its diagnostic and therapeutic complexity. The diagnostic and therapeutic protocol for the management of idiopathic normal pressure hydrocephalus in use at the Department of Neurosurgery of the University Hospital Marqués de Valdecilla is presented. The diagnostic process includes neuropsychological testing, phase contrast cine MRI, urodynamic evaluation, continuous intracranial pressure monitoring, cerebrospinal fluid hydrodynamics by means of lumbar infusion testing, and intra-abdominal pressure measurement. A patient is considered a surgical candidate if any of the following criteria is met: mean intracranial pressure >15mmHg, or B-waves present in >10% of overnight recording; pressure-volume index <15ml, or resistance to cerebrospinal fluid outflow (ROUT) >4.5mmHg/ml/min in bolus infusion test; ROUT >12mmHg/ml/min, intracranial pressure >22mmHg, or high amplitude B-waves in the steady-state of the continuous rate infusion test; or a clinical response to high-volume cerebrospinal fluid withdrawal. The implementation of a diagnostic and therapeutic protocol for idiopathic normal pressure hydrocephalus management could improve various aspects of patient care. It could reduce variability in clinical practice, optimise the use of health resources, and help in identifying scientific uncertainty areas, in order to direct research efforts in a more appropriate way.


Incidence of postoperative pancreatic fistula and hyperamylasemia after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
The purpose of this study was to analyze the postoperative pancreatic morbidity of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal surface malignancies (PSM). Two hundred and sixty five patients (87M/178F) with PSM underwent 270 consecutive procedures. The mean age was 52 years (range: 22-79 years). CRS was performed using peritonectomy procedures. HIPEC through the closed abdomen technique was conducted using cisplatin (CDDP 25 mg/m2/L of perfusate)+mitomycin C (MMC 3.3 mg/m2/L of perfusate) or CDDP (43 mg/L of perfusate)+doxorubicin (Dx 15.25 mg/L of perfusate), at 42.5 degrees C. Diagnosis and classification of postoperative pancreatic fistula (POPF) were performed according to the international study group on pancreatic fistula criteria. Serum amylase alterations were graded according to the National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) v3. POPF was observed in 13 (4.8%) cases. Three cases were classified as major (grade C). Two cases presented postoperative pancreatitis. G3-4 alteration of amylase was observed in 12.3% of the cases. Performing splenectomy and CDDP dosage for HIPEC >240 mg were proven to be independent risk factors for both G3-4 hyperamylasemia and POPF. CRS+HIPEC presented an acceptable rate of pancreatic morbidity which did not contribute to the mortality related to the procedure. Most of the POPF were mild and/or easily controlled by conservative measures. Although not specific a normal amylasemia could be a useful marker of pancreatic integrity after CRS+HIPEC.


Modified end-to-side double-layer open pancreaticogastrostomy after Whipple procedure: surgical tips for a safe anastomosis.
Pancreatic fistula (PF) remains the Achilles' heel of pancreaticoduodenectomy (PD). Pancreaticogastrostomy (PG) appears to be associated with a lower risk of postoperative leak according to recent evidence. We started to fashion PG, especially in soft pancreas, modifying the original technique described by Bassi. At our institution, 105 PD procedures were carried out from January 2011 to December 2016; pancreatic-enteric continuity was restored by PG in 35 cases. Superior mesenteric/portal vein resection/reconstruction was necessary in three patients. A total of 34/35 patients underwent PG with an open anterior gastrostomy approach. Briefly, our double-layer PG anastomosis (illustrated by a video) starts with a posterior row of interrupted absorbable 4/0 monofilament sutures including the gastric serosa and the pancreatic capsule. It is essential to mobilize the left pancreas for 4-5 cm and to shape the posterior gastrostomy shorter than the pancreatic stump. After a wide anterior auxiliary gastrostomy the pancreas is invaginated into the stomach and an interrupted row of sutures between the posterior gastric wall (full-thickness) and the body of the pancreatic stump is fashioned. The anterior gastrostomy is closed with an absorbable running suture. Finally, a further layer of sutures is applied over the posterior suture line between the gastric serosa and the pancreatic capsule. The 90-day postoperative mortality was nihil. No biliary leakage was detected and the overall PF rate was 11.4% (4/35) according to the ISGPF study group. Only one patient suffered a grade B PF (in this case, PG was carried out only through a posterior gastrostomy), whereas three patients had a minor (grade A) PF. Our modified PG proved to be safe and easy to perform, while it carried excellent outcomes even in the setting of soft pancreas. Despite the limited number of cases, such modified PG appears promising, particularly for pancreatic remnants at higher risk of PF.


Efflux transporter variants as predictors of drug toxicity in lung cancer patients: systematic review and meta-analysis.
Chemotherapeutic drugs are underutilized in lung cancer management due in part to serious adverse drug reactions (ADRs). With studies revealing an association between interindividual patient ADR variation and efflux transporter variants, we carried out a meta-analysis and systemic review, in order to highlight current knowledge regarding the strength of association between efflux transporter SNPs variants and chemotherapeutic-drug induced ADRs. Papers were sourced from MEDLINE, Cochrane Library, CINHL, EMBASE, Web of Knowledge, Scopus. The Cochrane Collaboration Risk of Bias Tool v13 was used to evaluate six types of bias domains for each of the publications reviewed. Twenty-five publications comprising three randomised control trials, two retrospective case-controls and 20 clinical observation studies, totalling 3578 patients, were deemed eligible for review. Of the known efflux drug transporters, we report findings on the ABC members ABCB1, ABCC1, ABCC2, ABCG2, ABCA1, ABCC4 and ABCC5. Meta-analysis showed an decreased risk of irinotecan-induced neutropenia in patients expressing ABCB1 2677G>T/G (odds ratio [OR]: 0.24; 95% CI: 0.1-0.59; p = 0.002) but increased risk for ABCC2 3972T>T (OR: 1.67; 95% CI: 1.01-2.74; p = 0.04). ABCG2 34G>A was associated with a threefold increased risk of irinotecan-induced diarrhea (95% CI: 1.00-6.24; p = 0.05). The majority of studies have identified a role for variants in effluxdrug transporters in contributing to lung cancer treatment-associated ADRs. However, for implementation of use of these transporter genetic variants as prognostic markers for ADR risk, future studies must incorporate larger patient numbers.


Retrospective Injury Epidemiology and Risk Factors for Injury in CrossFit.
The objective of the study is to examine injury epidemiology and risk factors for injury in CrossFit athletes. A survey was administered to athletes at four owner-operated facilities in South Florida. Respondents reported number, location of injury, and training exposure from the preceding six months and answered questions regarding potential risk factors for injury. Fifty out of 191 athletes sustained 62 injuries during CrossFit participation in the preceding six months. The most frequently injured locations were the shoulder, knee, and lower back. Injury incidence was 2.3/1000 athlete training hours. Competitors were more likely to be injured (40% v 19%, p = 0.002) and had greater weekly athlete training hours (7.3 ± 7.0 v 4.9 ± 2.9, p < 0.001) than non-competitors. Athletes who reported injury also reported significantly higher values for the following risk factors: years of participation (2.7 ± 1.8 v 1.8 ± 1.5, p = 0.001), weekly athlete training hours (7.3 ± 3.8 v 4.9 ± 2.1, p = 0.020), weekly athlete-exposures (6.4 ± 3.8 v 4.7 ± 2.1, p = 0.003), height (1.72 ± 0.09 m v 1.68 ± 0.01 m, p = 0.011), and body mass (78.24 ± 16.86 kg v 72.91 ± 14.77 kg, p = 0.037). Injury rates during CrossFit and location of injuries were similar to those previously reported. Injury incidence was similar to related sports, including gymnastics and powerlifting. While being a competitor was related to injury, increased exposure and length of participation in CrossFit likely underlied this association. Specifically, increased exposure to training in the form of greater weekly athlete training hours and weekly participations may contribute to injury. Increased height and body mass were also related to injury which is likely reflective of increased load utilized during training. Further research is warranted to determine if biomechanical factors associated with greater height and ability to lift greater loads are modifiable factors that can be adapted to reduce the increase risk of injury during CrossFit.


Physician Assistants in Ophthalmology: A National Survey.
To evaluate the scope of practice and training of current physician assistants (PAs) in ophthalmology and gauge their interest in further training and involvement in ophthalmology. Cross-sectional survey study. An anonymous survey on vision and ocular care in the PA profession was administered to PAs in ophthalmology within the American Academy of Physician Assistants member database. All survey questions were optional. A total response rate of 47/94 (50.0%) was obtained. Respondents reported an average of 9.8 years (SD = 9.0) of experience as a PA in ophthalmology. Over half of the respondents (59.5%) did not have previous experience in vision and ocular health before becoming a PA. Most respondents (79.5%) reported that they are able to provide their primary clinical responsibilities for ophthalmic care independently. In addition to providing clinical ophthalmic care, many of the respondents have duties that involve consenting patients for ophthalmic surgery and procedures (62.5%) and assisting in ophthalmic surgery and minor procedures (65.0%). Only a minority of respondents independently perform procedures, such as intravitreal injections (23.1%) and minor lid procedures (38.5%). Most respondents reported interest in additional training in providing vision and ocular care (69.0%), in continuing their career as a PA in ophthalmology (87.5%), and in joining a specialty organization for PAs in ophthalmology (88.1%). The PAs participating in this survey provide a range of clinical and some procedural ophthalmic care. The development of formal PA postgraduate training programs in ophthalmology may expand the pool of PAs qualified to practice ophthalmology.


New Antibiotics in Development Target Highly Resistant Gram-Negative Organisms.
Upcoming antibacterial agents in the pipeline appear promising, but it is difficult to predict their long-term durability. This article focuses on investigational agents that target resistant gram-negative organisms commonly found in the health care setting.


The physiological roles of ICAM-1 and ICAM-2 in neutrophil migration into tissues.
Neutrophil extravasation from the blood into tissues is initiated by tethering and rolling of neutrophils on endothelial cells, followed by neutrophil integrin activation and shear resistant arrest, crawling, diapedesis and breaching the endothelial basement membrane harbouring pericytes. Endothelial intercellular cell adhesion molecule (ICAM)-1 and ICAM-2, in conjunction with ICAM-1 on pericytes, critically contribute to each step. In addition, epithelial ICAM-1 is involved in neutrophil migration to peri-epithelial sites. The most recent findings on the role of ICAM-1 and ICAM-2 for neutrophil migration into tissues will be reviewed here. Signalling via endothelial ICAM-1 and ICAM-2 contributes to stiffness of the endothelial cells at sites of chronic inflammation and junctional maturation, respectively. Endothelial ICAM-2 contributes to neutrophil crawling and initiation of paracellular diapedesis, which then proceeds independent of ICAM-2. Substantial transcellular neutrophil diapedesis across the blood-brain barrier is strictly dependent on endothelial ICAM-1 and ICAM-2. Endothelial ICAM-1 or ICAM-2 is involved in neutrophil-mediated plasma leakage. ICAM-1 on pericytes assists the final step of neutrophil extravasation. Epithelial ICAM-1 rather indirectly promotes neutrophil migration to peri-epithelial sites. ICAM-1 and ICAM-2 are involved in each step of neutrophil extravasation, and have redundant but also distinct functions. Analysis of the role of endothelial ICAM-1 requires simultaneous consideration of ICAM-2.


Pivotal role of the protein corona in the cell uptake of fluorinated nanoparticles with increased sensitivity for 19F-MR imaging.
In vivo cell tracking by non-invasive imaging technologies is needed to accelerate the clinical translation of innovative cell-based therapies. In this regard, 19F-MRI has recently gained increased attention for unbiased localization of labeled cells over time. To push forward the use of 19F-MRI for cell tracking, the development of highly performant 19F-probes is required. PLGA-based NPs containing PERFECTA, a multibranched superfluorinated molecule with an optimal MRI profile thanks to its 36 magnetically equivalent fluorine atoms, are promising 19F-MRI probes. In this work we demonstrate the importance of the surface functionalization of these NPs in relation to their interaction with the biological environment, stressing the pivotal role of the formation of the protein corona (PC) in their cellular labelling efficacy. In particular, our studies showed that the formation of PC NPs strongly promotes the cellular internalization of these NPs in microglia cells. We advocate that the formation of PC NPs in the culture medium can be a key element to be used for the optimization of cell labelling with a considerable increase of the detection sensitivity by 19F-MRI.


Abu-Sahl al-Masihi (died circa 1010 AD): The Persian physician in the early medieval era.
In the early medieval era, in the time which is called the Islamic Golden Age, medicine flourished through the practice of Persian physicians (9th to 12th century AD). Abu-Sahl al-Masihi (died circa 1010 AD) was one of the physicians in that period who had great influence on the progress of medicine by his own writings as well as his influence on great scholars like Biruni and Avicenna as their teacher. He was a polymath and had many writings in various fields of science, in particular medical sciences. Some of his manuscripts in medicine were Al-Mia fil-Tibb (Book of the Hundred), Kitab al-Teb al-Koli (The General Medicine), Ezhar al-Hekmat Allah Ta'ala fi Khalgh al-Ensan (God's Mystery on the Creation of Man), Resalat al-Adwiya (Treatise of Drugs), Osool Elm Nabz (the Principles of Pulse), and Resala f ī Taḥqiq Amral-Waba' (On the determination of the matter of infectious diseases). As a sign of his impact in Persian medicine, many later physicians (until 19th century) referred to and cited his works in their manuscripts several times.


[Delayed results of Wiltse's operation in the management of spondylolisthesis].
Wiltse's spondylodesis was performed in 111 patients in the Department of Orthopaedics, National Institute for Rhelvmatology and Physiotherapy between 1978-1982. 58 of them were reexamined by the authorsclinically and radiologically more than 5 years after the operation. In 47 of the 58 patients good or adequate clinical results were found whereas in 43 cases the development of bone bridge could be observed. Attention is called to the good operative indication and the exact operative technique.


G-quadruplex DNA: A Longer Story.
G-quadruplexes (G4s) are distinctive four-stranded DNA or RNA structures found within cells that are thought to play functional roles in gene regulation and transcription, translation, recombination, and DNA damage/repair. While G4 structures can be uni-, bi-, or tetramolecular with respect to strands, folded unimolecular conformations are most significant in vivo. Unimolecular G4 can potentially form in sequences with runs of guanines interspersed with what will become loops in the folded structure: 5'GxLyGxLyGxLyGx, where x is typically 2-4 and y is highly variable. Such sequences are highly conserved and specifically located in genomes. In the folded structure, guanines from each run combine to form planar tetrads with four hydrogen-bonded guanine bases; these tetrads stack on one another to produce four strand segments aligned in specific parallel or antiparallel orientations, connected by the loop sequences. Three types of loops (lateral, diagonal, or "propeller") have been identified. The stacked tetrads form a central cavity that features strong coordination sites for monovalent cations that stabilize the G4 structure, with potassium or sodium preferred. A single monomeric G4 typically forms from a sequence containing roughly 20-30 nucleotides. Such short sequences have been the primary focus of X-ray crystallographic or NMR studies that have produced high-resolution structures of a variety of monomeric G4 conformations. These structures are often used as the basis for drug design efforts to modulate G4 function.We believe that the focus on monomeric G4 structures formed by such short sequences is perhaps myopic. Such short sequences for structural studies are often arbitrarily selected and removed from their native genomic sequence context, and then are often changed from their native sequences by base substitutions or deletions intended to optimize the formation of a homogeneous G4 conformation. We believe instead that G-quadruplexes prefer company and that in a longer natural sequence context multiple adjacent G4 units can form to combine into more complex multimeric G4 structures with richer topographies than simple monomeric forms. Bioinformatic searches of the human genome show that longer sequences with the potential for forming multiple G4 units are common. Telomeric DNA, for example, has a single-stranded overhang of hundreds of nucleotides with the requisite repetitive sequence with the potential for formation of multiple G4s. Numerous extended promoter sequences have similar potentials for multimeric G4 formation. X-ray crystallography and NMR methods are challenged by these longer sequences (>30 nt), so other tools are needed to explore the possible multimeric G4 landscape. We have implemented an integrated structural biology approach to address this challenge. This approach integrates experimental biophysical results with atomic-level molecular modeling and molecular dynamics simulations that provide quantitatively testable model structures. In every long sequence we have studied so far, we found that multimeric G4 structures readily form, with a surprising diversity of structures dependent on the exact native sequence used. In some cases, stable hairpin duplexes form along with G4 units to provide an even richer landscape. This Account provides an overview of our approach and recent progress and provides a new perspective on the G-quadruplex folding landscape.


Condensate density of interacting bosons: A functional renormalization group approach.
We calculate the temperature-dependent condensate density rho0(T) of interacting bosons in three dimensions using the functional renormalization group (FRG). From the numerical solution of suitably truncated FRG flow equations for the irreducible vertices we obtain rho0(T) for arbitrary temperatures. We carefully extrapolate our numerical results to the critical point and determine the order parameter exponent beta approximately 0.32 in reasonable agreement with the expected value 0.345 associated with the XY -universality class. We also calculate the condensate density in two dimensions at zero temperature using a truncation of the FRG flow equations based on the derivative expansion including cubic and quartic terms in the expansion of the effective potential in powers of the density. As compared with the widely used quadratic approximation for the effective potential, the coupling constants associated with the cubic and quartic terms lead to small corrections of the condensate density.


Ultrastructure of spermiogenesis and spermatozoa in Marchalina hellenica (Gennadius) (Hemiptera: Sternorrhyncha, Marchalinidae).
The spermiogenesis, the sperm structure and the sperm motility of Marchalina hellenica (Gennadius) were examined. In the early spermiogenesis a centriolar apparatus was identified, but this structure is not involved in the production of the sperm flagellum. As in other Coccoidea, the flagellar axoneme originates by the activity of the thickened tip of the numerous microtubules surrounding the nuclear anterior region close to the periphery of the cell. This region pushes against a narrow cytoplasmic layer, giving rise to a papilla. In this region a novel structure, consisting of a regular network of thin filaments, arranged orthogonally to the bundle of microtubules, is visible. The sperm flagellum consists of a series of about 260 microtubules, regularly arranged in rings around the axial nucleus. This latter extends in the middle part of the sperm length. As usual in scale insects, sperm form a bundle, which in M. hellenica is composed of 64 sperm cells, surrounded by somatic cyst cells. The sperm bundle has an helicoidal array, with a cap of dense material at its apex, lending the anterior and the posterior region of the sperm bundle with a different structural organization. This difference is responsible of the different speed gradient observed in the helical wave propagating along the sperm bundle.


For Better or Worse: Friendship Choices and Peer Victimization Among Ethnically Diverse Youth in the First Year of Middle School.
As children approach early adolescence, the risk of peer victimization often increases. Many children experience some form of peer victimization during this time, but children who experience chronic victimization may be particularly vulnerable to adjustment difficulties. Thus, identifying risk and protective factors associated with chronic victimization continues to be an important area of research. This study examined the effect of change in the victimization of friends on change in children's own victimization, taking into account the ethnic group representation of children in their classes. Over 3000 6th grade students (52 % female; M = 11.33 years) were drawn from 19 middle schools varying in ethnic composition. Friendships were distinguished by type-reciprocal, desired, and undesired-and a novel methodology for measuring ethnic group representation at the individual level was employed. Multilevel modeling indicated that change in friends' victimization from fall to spring of 6th grade had a differential impact on children's own victimization by friendship type and that the benefits and consequences of change in friends' victimization were especially pronounced for children in the numerical ethnic majority. The findings underscore the role of friendship choices in peer victimization, even if those choices are not reciprocated, and highlight the unique social risks associated with being in the numerical ethnic majority.


Changing Practice in Gastrointestinal Endoscopy: Reducing Distractions for Patient Safety.
Failure in communication during the process of delivering healthcare can have dangerous repercussions. Specifically, failure in interdisciplinary team communication contributes to lapses in patient care. Distractions in procedural areas disrupt team communication. Application of a structured communication algorithm creates agreed-upon cues that promote team communication and facilitate clinical decision making. Frequent disruptions before, during, and after gastro-intestinal endoscopy procedures place veterans at risk for an error. A hierarchical culture promotes intimidation and reduces the likelihood that staff will speak up for patient safety. An endoscopy procedure area implemented a "sterile cockpit" methodology to reduce the number of distractions during procedures. Data collected from a self-reported safety awareness were measured by two different questionnaires and collected through observation of actual practice. Improved awareness of distraction and the impact on patient safety was reported, with a reduction from 24 observed interruptions to zero in 9 months. After reducing distractions in the procedural area, there is a perception of improved nursing quality of care. Additional support is required to consistently remove electronic distractions during a procedure.


[Retrograde balloon catheter dilatation of urethral stenosis--experience in benign prostatic hypertrophy and postoperative urethral stricture].
Retrograde transurethral balloon dilatation of urethral stenosis was performed in five patients: four patients with benign prostatic hypertrophy and one with urethral stricture following open prostatectomy. Significant resolution of symptoms of dysuria was seen in four patients throughout the follow-up period of 12 to 18 months. A balloon diameter of 25 mm was considered to be necessary for prostatic hypertrophy. The unsatisfactory result in one patient with prostatic hypertrophy was believed to be caused by incomplete dilation due to a small balloon diameter. Mild transient hematuria was seen in all cases. Only one patient with postoperative urethral stricture complained of pain during balloon inflation, while other patients with prostatic hypertrophy did not complain of any apparent pain. We conclude that this technique is a safe and effective method of treatment for prostatic hypertrophy and other urethral strictures.


Impact of Long Term Plasticity on Information Transmission Over Neuronal Networks.
The realization of bio-compatible nanomachines would pave the way for developing novel diagnosis and treatment techniques for the dysfunctions of intra-body nanonetworks and revolutionize the traditional healthcare methodologies making them less invasive and more efficient. The network of these nanomachines is aimed to be used for treating neuronal diseases such as developing an implant that bridges over the injured spinal cord to regain its normal functionality. Thus, nanoscale communication paradigms are needed to be investigated to facilitate communication between nanomachines. Communication among neurons is one of the most promising nanoscale communication paradigm, which necessitates the thorough communication theoretical analysis of information transmission among neurons. The information flow in neuro-spike communication channel is regulated by the ability of neurons to change synaptic strengths over time, i.e. synaptic plasticity. Thus, the performance evaluation of the nervous nanonetwork is incomplete without considering the influence of synaptic plasticity. In this paper, we focus on information transmission among hippocampal pyramidal neurons and provide a comprehensive channel model for MISO neuro-spike communication, which includes axonal transmission, vesicle release process, synaptic communication and spike generation. In this channel, the spike timing dependent plasticity (STDP) model is used to cover both synaptic depressiofan and potentiation depending on the temporal correlation between spikes generated by input and output neurons. Since synaptic strength changes depending on different physiological factors such as spiking rate of presynaptic neurons, number of correlated presynaptic neurons and the correlation factor among them, we simulate this model with correlated inputs and analyze the evolution of synaptic weights over time. Moreover, we calculate average mutual information between input and output of the channel and find the impact of plasticity and correlation among inputs on the information transmission. The simulation results reveal the impact of different physiological factors related to either presynaptic or postsynaptic neurons on the performance of MISO neuro-spike communication. Moreover, they provide guidelines for selecting the system parameters in a bio-inspired neuronal network according to the requirements of different applications.


Variation in δ15 N and δ13 C values of forages for Arctic caribou: effects of location, phenology and simulated digestion.
The use of stable isotopes for dietary estimates of wildlife assumes that there are consistent differences in isotopic ratios among diet items, and that the differences in these ratios between the diet item and the animal tissues (i.e., fractionation) are predictable. However, variation in isotopic ratios and fractionation of δ13 C and δ15 N values among locations, seasons, and forages are poorly described for arctic herbivores especially migratory species such as caribou (Rangifer tarandus). We measured the δ13 C and δ15 N values of seven species of forage growing along a 200-km transect through the range of the Central Arctic caribou herd on the North Slope of Alaska over 2 years. We compared forages available at the beginning (May; n = 175) and the end (n = 157) of the growing season (September). Purified enzymes were used to measure N digestibility and to assess isotopic fractionation in response to nutrient digestibility during simulated digestion. Values for δ13 C declined by 1.38 ‰ with increasing latitude across the transect, and increased by 0.44 ‰ from the beginning to the end of the season. The range of values for δ15 N was greater than that for δ13 C (13.29 vs 5.60 ‰). Differences in values for δ13 C between graminoids (Eriophorum and Carex spp.) and shrubs (Betula and Salix spp.) were small but δ15 N values distinguished graminoids (1.87 ± 1.02 ‰) from shrubs (-2.87 ± 2.93 ‰) consistently across season and latitude. However, undigested residues of forages were enriched in 15 N when the digestibility of N was less than 0.67. Although δ15 N values can distinguish plant groups in the diet of arctic herbivores, variation in the digestibility of dietary items may need to be considered in applying fractionation values for 15 N to caribou and other herbivores that select highly digestible items (e.g. forbs) as well as heavily defended plants (e.g. woody browse). Published in 2017. This article is a U.S. Government work and is in the public domain in the USA.


Clonal dynamics of nasal Staphylococcus aureus and Staphylococcus pseudintermedius in dog-owning household members. Detection of MSSA ST(398).
The objective of this study was to investigate the dynamics of nasal carriage by Staphylococcus aureus (SA) and Staphylococcus pseudintermedius (SP) among healthy dog-owning household members involved in 7 previous index cases of suspected anthropozoonotic (n = 4) and zoonotic (n = 3) interspecies transmission [4 direct cases, identical SA (n = 3) or SP (n = 1) in owner and dog; three indirect, SP in owner (n = 2) or SA in dog (n = 1)]. Co-carriage with methicillin-resistant coagulase-negative staphylococci (MRCoNS) was also evaluated. Sixteen owners and 10 dogs were sampled once every three months for one year. In total, 50 SA and 31 SP were analysed by MLST, and SA also by spa typing. All isolates were subjected to ApaI/SmaI-PFGE and antimicrobial resistance and virulence profiles were determined. All index owners were persistent SA carriers in all direct-anthropozoonotic transmission cases, while only one dog was persistent SA carrier. Owner and dog exhibited a persistent SP carriage status in the direct-zoonotic transmission case. SP was maintained in the index human over time in one indirect-zoonotic transmission case. Only one SP was methicillin-resistant. SA belonged to genetic backgrounds of MRSA pandemic clones: CC45, CC121, CC30, CC5 and CC398. Three individuals carried a MSSA t1451-ST398 clone with the erm(T)-cadD/cadX resistance genes. SA or SP were persistently detected in the nasal cavity of 7 (43.8%) and 2 (12.5%) owners, and in one and 2 dogs, respectively. SA was recovered as the single species in 10 owners and in one dog; SP in 3 owners and 4 dogs; and both bacterial species in one owner and 4 dogs. Co-carriage of SA or SP with MRCoNS isolates was common (30.7%). This is the first study on the dynamics of nasal carriage of SA and SP in healthy pet-owning household members. Dog-contact may play a role in the staphylococcal species distribution of in-contact individuals.


Renal denervation attenuates hypertension and renal dysfunction in a model of cardiovascular and renal disease, which is associated with reduced NADPH and xanthine oxidase activity.
Oxidative stress is considered a central pathophysiological event in cardiovascular disease, including hypertension. Early age reduction in renal mass is associated with hypertension and oxidative stress in later life, which is aggravated by increased salt intake. The aim of the present study was to examine if renal sympathetic denervation can exert blood pressure lowering effects in uninephrectomized (UNX) rats (3-week old) fed with high salt (HS, 4%; w/w) diet for 4 weeks. Moreover, we investigated if renal denervation is associated with changes in NADPH and xanthine oxidase-derived reactive oxygen species. Rats with UNX + HS had reduced renal function, elevated systolic and diastolic arterial pressures, which was accompanied by increased heart weight, and cardiac superoxide production compared to sham operated Controls. UNX + HS was also associated with higher expression and activity of NADPH and xanthine oxidase in the kidney. Renal denervation in rats with UNX + HS attenuated the development of hypertension and cardiac hypertrophy, but also improved glomerular filtration rate and reduced proteinuria. Mechanistically, renal denervation was associated with lower expression and activity of both NADPH oxidase and xanthine oxidase in the kidney, but also reduced superoxide production in the heart. In conclusion, our study shows for the first time that renal denervation has anti-hypertensive, cardio- and reno-protective effects in the UNX + HS model, which can be associated with decreased NADPH oxidase- and xanthine oxidase-derived reactive oxygen species (i.e., superoxide and hydrogen peroxide) in the kidney.


Clinical efficacy of ticagrelor in patients undergoing emergency intervention for acute myocardial infarction and its impact on platelet aggregation rate.
This study aims to investigate the clinical efficacy of ticagrelor in patients who underwent emergency percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI), and its impact on platelet aggregation rate. A total of 257 AMI patients who underwent emergency PCI in our hospital were included in the present study. These patients were randomly divided into two groups: ticagrelor group (n = 129), patients took 180 mg of ticagrelor (qd) before the intervention, and subsequently took 90 mg of ticagrelor (bid) for maintenance; clopidogrel group (n = 128), patients took 300 mg of clopidogrel (qd) before PCI, and subsequently took 75 mg of clopidogrel (qd) for maintenance. Patients in both groups took 100 mg of aspirin. The major adverse cardiovascular events (MACE) within one year, changes in LVEF and LVEDD, platelet aggregation rate and drug safety before PCI and at one week and 30 days after PCI were observed in these two groups. The differences in baseline data between these two groups were not statistically significant. Within one year after the intervention, in the ticagrelor group, the total incidence of MACE was lower (P < 0.05), LVEF and LVEDD was improved (P < 0.05), and the decrease in platelet aggregation rate after the intervention was more significant (P < 0.05). Furthermore, the incidence of bleeding events was higher in the ticagrelor group than in the clopidogrel group (P < 0.05). Compared with clopidogrel, ticagrelor decreases the incidence of adverse cardiovascular events in AMI patients who underwent emergency PCI, does better in improving the fluctuation level of LVEF and LVEDD, and strongly inhibits platelet aggregation. Some patients encountered adverse drug events, but drug withdrawal or medication change did not occur.


Functional characterization of peripheral blood neutrophils in patients with primary hypothyroidism.
The clinical observations of increased risk of bacterial infection in patients with severe hypothyroidism motivated investigations of the biological function of neutrophils in peripheral blood of 30 women with primary hypothyroidism. The following functions of neutrophils were examined: phagocytosis, adherence to fibers, as well as spontaneous migration of leukocytes. The total number of leukocytes and neutrophils was also determined. The results were compared with those in a control group formed by 20 healthy women. The data show that in patients with primary hypothyroidism, the adherence of neutrophils was increased (63 +/- 8% in patients and 53 +/- 11% in control subjects) and spontaneous migration decreased (45 +/- 20 cm2 in patients and 65 +/- 30 cm2 in the control group). However, there were no significant deviations of phagocytic activity of neutrophils in hypothyroid individuals as compared to euthyroid controls.


In SCID-hu mice, passive transfer of a humanized antibody prevents infection and atrophic change of medulla in human thymic implant due to intravenous inoculation of primary HIV-1 isolate.
Using SCID-hu mice, it was tested whether humanized mAb Rmu5.5 could prevent infection by HIV-1 i.v. inoculation. The Ab that recognizes the IHIGPGRAFYT motif in the principal neutralizing determinant (PND) of HIV(MN), as well as the original mouse mAb mu5.5, neutralized HIV(MN) with high activity. Seven primary field isolates from Japanese hemophiliacs seropositive for HIV-1 clade B were compared for their reactivities to Rmu5.5. Rmu5.5 was effective, particularly against the viruses that matched amino acid sequences of the PND region of HIV-1, and it completely neutralized primary isolates. Moreover, the passive transfer of the Ab elicited protection against challenge by the primary isolates in SCID-hu or hu-PBL-SCID mice after i.v. inoculation with the virus by both quantitative PCR and PBMC-based virus isolation in vitro. Further, inoculation with the Ab also prevented the atrophic change in the medulla of the thymic transplant that was induced by i.v. inoculation of the virus. Thus, the humanized neutralizing Ab Rmu5.5 appears to protect SCID-hu mice from infection by primary field isolates.


Color and physiochemical attributes of pointed gourd (Trichosanthes dioica Roxb.) influenced by modified atmosphere packaging and postharvest treatment during storage.
The efficiency of modified atmosphere packaging (MAP) in combination with postharvest treatment on the shelf-life, physiochemical attributes, color, and nutrition of pointed gourd was studied after storing in refrigerated (low temperature, LT) and ambient (room temperature, RT) conditions. Fresh pointed gourd fruits were dipped in NaOCl solution (0.01% w/v) and potassium metabisulphite (KMS) (0.05% w/v), blanched (100°C for 4 min), and then packed in perforated and non-perforated polythene and polypropylene packets of each type and brown paper bags as MAP before storing at LT and RT. Physiochemical attributes, color, and nutrition were measured until the marketable level of acceptance (up to shelf-life) after storage and compared with the untreated and unpacked samples (control). The results showed profound differences among the treatment variables in all the studied dependent parameters regarding the LT and RT storage conditions. Among the treatments, perforated and non-perforated polyethylene (NPE) and polypropylene (NPP) packaging performed well to retain a considerable amount of ascorbic acid, β-carotene, and greenish color (lower L*, high h*) in pointed gourd treated with NaOCl (0.01%) and KMS (0.05%) after storing at LT and RT. Furthermore, the principal component analysis suggested that five major quality attributes (L*, C*, h*, shelf-life, and ascorbic acid) were influenced remarkably in terms of non-perforated polyethylene packaging in combination with KMS treatment both in LT and RT storage conditions. However, perforated polythene and polypropylene in combination with NaOCl responded well in RT but only for the shortest storage life. Thus, a non-perforated polythene package with KMS treatment would be the best solution for retaining market quality acceptance with green color up to the extended shelf-life of 23 and 10 days, respectively, in the refrigerator (LT) and in ambient (RT) storage conditions.


The processing of two-digit numbers in bilinguals.
We explored possible between-language influences when bilinguals processed two-digit numbers. Spanish/English bilinguals and German/English bilinguals performed a number comparison task with Arabic digits and verbal numbers in their first language (L1) and second language (L2) while the unit-decade compatibility was manipulated. The two bilingual groups showed regular compatibility effect with Arabic digits. In L1, Spanish/English bilinguals showed reverse compatibility effect, while German/English bilinguals showed regular compatibility effect. However, both groups of bilinguals presented reverse compatibility effect in English (L2), which suggested that the bilinguals' L1 did not determine the processing of number words in their L2. The results indicated that bilinguals processed two-digit number words selectively in their L1 and L2 and that they did not transcode L2 numbers into Arabic format.


Encapsulated islet transplantation: strategies and clinical trials.
Encapsulation of tissue has been an area of intense research with a myriad number of therapeutic applications as diverse as cancer, tissue regeneration, and diabetes. In the case of diabetes, transplantation of pancreatic islets of Langerhans containing insulin-producing beta cells has shown promise toward a cure. However, anti-rejection therapy that is needed to sustain the transplanted tissue has numerous adverse effects, and the islets might still be damaged by immune processes. Furthermore, the profound scarcity of healthy human donor organs restricts the availability of islets for transplant. Islet encapsulation allows the protection of this tissue without the use of toxic medications, while also expanding the donor pool to include animal sources. Before the widespread application of this therapy, there are still issues that need to be resolved. There are many materials that can be used, differing shapes and sizes of capsules, and varied sources of islets to name a few variables that need to be considered. In this review, the current options for capsule generation, past animal and human studies, and future directions in this area of research are discussed.


Radiation impedance of an array of circular capacitive micromachined ultrasonic transducers.
The radiation impedance of a capacitive micromachined ultrasonic transducer (cMUT) with a circular membrane is calculated analytically using its velocity profile for the frequencies up to its parallel resonance frequency for both the immersion and the airborne applications. The results are verified by finite element simulations. The work is extended to calculate the radiation impedance of an array of cMUT cells positioned in a hexagonal pattern. A higher radiation resistance improves the bandwidth as well as the efficiency of the cMUT. The radiation resistance is determined to be a strong function of the cell spacing. It is shown that a center-to-center cell spacing of 1.25 wavelengths maximizes the radiation resistance, if the membranes are not too thin. It is also found that excitation of nonsymmetric modes may reduce the radiation resistance in immersion applications.


Immunologic reaction and genetic factors in biliary atresia.
The characteristic histopathological features seen in the livers of patients with biliary atresia (BA) are very similar to those of primary biliary cirrhosis, which is an autoimmune disease. To clarify whether BA liver possess an immunological response similar to that in primary biliary cirrhosis, we studied HLA-DR expression in liver tissue of BA patients, using a HLA-DR staining method, and determined the frequency of HLA types in BA patients and their families. HLA-DR was expressed by the bile duct epithelium in 11 of 16 liver specimens obtained from 13 BA patients. By contrast, HLA-DR was not expressed in liver specimens from 6 patients with congenital biliary dilatation. Among the HLA types seen in BA patients and their families, HLA-A33, -B44 and -DR6 were frequently expressed in blood. These results suggest that certain immunological factors and disease-susceptible genes might be involved in the etiology of BA.


The effects of visual barriers on exiting behavior in a dementia care unit.
Exiting due to wandering was a problem for caregivers in this dementia care unit. Previous attempts to control exiting by wanderers proved ineffective. We manipulated the view and light through a window using visual barriers: window blind, cloth barrier, and a combination of the two. The closed blind reduced exiting by 44%. The cloth barrier was the most effective solution, reducing exiting by 96%. The combination of the blind and cloth barrier reduced exiting 88%. These findings support those of Namazi, Rosner, and Calkins (1989).


Expression of activated rat neu oncogene is sufficient to induce experimental metastasis in 3T3 cells.
Amplification or overexpression of the human neu oncogene has been shown to correlate with the number of lymph node metastases in breast cancer patients, suggesting that expression of the neu oncogene may be associated with increased metastatic potential. However, there has been no systematic study on the role of the neu oncogene in metastasis to support this correlation. In our study, mouse embryo fibroblast 3T3 cells transformed by the mutation-activated rat neu oncogene exhibited metastatic properties both in vitro and in vivo, while parental 3T3 cells did not. Monoclonal antibodies capable of inducing down-regulation of the neu-encoded p185 protein reduced the metastatic potential induced by neu. These data provide strong experimental evidence that neu oncogene expression is sufficient for the induction of metastasis in the 3T3 cell system and supply a molecular basis supporting the correlations found in clinical observation. The results also suggest that neu-specific monoclonal antibodies may have preventative or therapeutic potential for neu-induced metastasis.


[Polarimetric determination of alpha-amylase activity (author's transl)].
In the study of the relatively slow amylase-catalysed hydrolysis of oligosaccharides, it is assumed that the subsequent mutarotation has essentially no effect on the kinetics of the total reaction. Relatively large sampled and long measurement times (slow rate of change in angle of rotation) are necessary for the polarimetric determination of alpha-amylase activity. For these reasons, only urine and duodenal juice are suitable as sample sources. Owing to the absence of coupled reactions and auxilliary enzymes, the polarimetrically determined kinetics are generally more representative of the true kinetics of the amylase reaction, than those obtained with fully enzymic methods; in addition, single determinations by the polarimetric method are less subject to interference by sample components. With measurement times in the order of minutes, the polarimetric method shows excellent linearity, very good proportionality between analytical response and quantity of enzyme, and good precision in series (CV = 1.3%). Comparison of the polarimetric with a chromogenic and a fully enzymic method showed an acceptable correlation (r for each method was about 0.98). T, the polarimetric method shows excellent linearity, very good proportionality between analytical response and quantity of enzyme, and good precision in series (CV = 1.3%). Comparison of the polarimetric with a chromogenic and a fully enzymic method showed an acceptable correlation (r for each method was about 0.98). T, the polarimetric method shows excellent linearity, very good proportionality between analytical response and quantity of enzyme, and good precision in series (CV = 1.3%). Comparison of the polarimetric with a chromogenic and a fully enzymic method showed an acceptable correlation (r for each method was about 0.98). The advantages and disadvantages of the polarimeatric method, with consideration of possible interfering factors, are discussed.


A team approach to bladder retraining: a pilot study.
Research has shown that bladder retraining can reverse or reduce symptoms of urge or stress/urge incontinence. An analysis of the A+ Links bladder-retraining program showed improved urinary symptoms and improved quality of life. There were statistically significant reductions in nocturia and episodes of urinary incontinence. There was also a significant increase in the mean amount of urine voided in milliliters. This pilot study appeared to validate and provide evidence that a bladder retraining program is a valuable strategy to reduce the impact of this most debilitating problem.


Interconnectedness in nursing: a concept analysis.
Interconnectedness will be clarified and defined by providing a description and context and take an important step toward increasing use in nursing literature and research. The literature is limited by focusing on relationships between people, but connection can be physical as with physics or spiritual by reflecting a higher power or purpose. Thorough examination will increase understanding of interconnectedness in nursing. Chinn and Kramer's method for creating conceptual meaning includes definitions, visual images, popular/classical literature, music, poetry, and professional research across many disciplines. Interconnectedness reflects that people and the universe are connected in a powerful way. Its essential meaning reflects that regardless of the worldly barriers of politics, religion, or culture, people can share in a universal reciprocity of love and responsibility. Nursing maintains the values of compassion, responsibility, holism, and to greater meaning in experiences, and interconnectedness will likely have increased significance in nursing.


Early diagnosis of Addison's disease; pigmentation as sole symptom.
A diagnosis of primary adrenocortical insufficiency was made in a shapely, suntanned girl whose sole complaint was increasing pigmentation. Plasma cortisol was low in spite of markedly elevated levels of ACTH. Plasma cortisol, urinary 17-oxogenic steroids and urinary aldosterone did not respond to three days of ACTH stimulation. Addison's disease can be diagnosed and treated before development of anorexia, weight loss, weakness and other classical symptoms.


Autoimmune encephalitis associated with voltage-gated potassium channels-complex and leucine-rich glioma-inactivated 1 antibodies - a national cohort study.
The aim of this study was to describe clinical and paraclinical characteristics of all Danish patients who tested positive for anti-voltage-gated potassium channels (VGKC)-complex, anti-leucine-rich glioma-inactivated 1 (LGI1) and anti-contactin-associated protein-2 antibodies in the serum/cerebrospinal fluid between 2009 and 2013 with follow-up interviews in 2015 and 2016. We evaluated antibody status, symptoms leading to testing, course of disease, suspected diagnosis and time of admission as well as diagnosis and treatment. All magnetic resonance imaging, electroencephalography and 18 F-fluorodeoxyglucose positron emission tomography scans were re-evaluated by experts in the field. A total of 28/192 patients tested positive for VGKC-complex antibodies by radioimmunoassay and indirect immunofluorescence; 17 had antibodies to LGI1 and 6/7 of the available cerebrospinal fluids from these patients were seropositive. These 17 patients all had a clinical phenotype appropriate to LGI1 antibodies. The remaining 11 were LGI1 negative (n = 4) or not tested (n = 7). Of these, two had a phenotype consistent with limbic encephalitis. The remaining phenotypes were Guillain-Barré syndrome, Creutzfeldt-Jakob disease, neuromyotonia and anti-N-methyl-D-aspartate receptor encephalitis. Magnetic resonance imaging abnormalities were demonstrated in 69% of the LGI1-positive patients. Two patients with normal magnetic resonance imaging demonstrated temporal lobe hypermetabolism using 18 F-fluorodeoxyglucose positron emission tomography. Abnormal electroencephalography recordings were found in 86% of the patients. Upon follow-up (median 3.2 years), the median modified Rankin Scale score of anti-LGI1-positive patients was 2 and only two patients reported seizures in the past year. Patients diagnosed with anti-LGI1 autoimmune encephalitis increased significantly from 2009 to 2014, probably due to increased awareness. In contrast to seropositive anti-VGKC-complex patients, all anti-LGI1-positive patients presented with a classical limbic encephalitis. The majority of patients recovered well.


[Prevalence of metacercariae of Clonorchis sinensis in wild freshwater fishes from Nenjiang River around Qiqihaer City].
From May to November 2013, a total of 1175 wild freshwater fishes were collected from the rivers of Chuoer, Yalu, Wuyuer, Alun, and Yin in Nenjiang River basin Qiqihaer City, and examined for metacercariae by direct compression method. The metacercariae were collected by artificial digestion method. Forty Kunming mice were infected with 30-40 metacercariae of Clonorchis sinensis. The mice were sacrificed 36 days after infection, and the adult worms were collected from bile duct, and observed under microscope. The results showed that a total of 1 175 fishes, belonging to nine species were taken from the Nenjiang basin of Qiqihaer region. The infection rate of Clonorchis sinensis metacercariae was 51.2% (602/1 175). All the species were infected besides Silurus asotus, and the highest prevalence (82.7%, 91/149) was found in Longnose gudgeon and the lowest (7.1%, 6/84) in Perccottus glenii. Among the rivers, the highest prevalence of metacercariae was in Wuyuer River. (65.7%, 218/332), and the lowest was in Alun River and Yin River (24.1%, 67/278) (P<0.05). Each part of the body in the Carassius auratus and Pseudorasbora parva were susceptible for metacercariae. The main infection site in Longnose gudgeon was the fish scales, and C. sinensis metacercaria was first discovered in the brain tissue of Phoxinus lagowskii. The experimental results showed that the adult worms of C. sinensis were found in the hepatic bile duct of the mice, with an infection rate of 85.0% (34/40). The suckers, digestive system and reproductive system of C. sinensis were visible clearly.


[A casuistic contribution to therapy with gestagen in metastasizing corpus carcinoma (author's transl)].
Casuistic contribution of a sucessfully with Gestagen treated stage IV corpus carcinoma which previously had been operated and undergone radiotherapy. Ten years after the primary treatment the patient presented herself asymptomatic and clinically free of a tumor. The possible mechanism of the effect of the Gestagen-therapy is discussed as well as the indication for the administration of Gestagen in a corpus carcinoma.


Is pegylated interferon superior to interferon, with ribavarin, in chronic hepatitis C genotypes 2/3?
Over the past decade, significant improvements have been made in the treatment of chronic hepatitis C (CHC), especially with the introduction of combined therapy using both interferon and ribavarin. The optimal dose and duration of treatment is still a matter of debate and, importantly, the efficacy of this combined treatment varies with the viral genotype responsible for infection. In general, patients infected with viral genotypes 2 or 3 more readily achieve a sustained viral response than those infected with viral genotype 1. The introduction of a pegylated version of interferon in the past decade has produced better clinical outcomes in patients infected with viral genotype 1. However, the published literature shows no improvement in clinical outcomes in patients infected with viral genotypes 2 or 3 when they are treated with pegylated interferon as opposed to non-pegylated interferon, both given in combination with ribavarin. This is significant because the cost of a 24-wk treatment with pegylated interferon in less-developed countries is between six and 30 times greater than that of treatment with interferon. Thus, clinicians need to carefully consider the cost-versus-benefit of using pegylated interferon to treat CHC, particularly when there is no evidence for clinically measurable benefits in patients with genotypes 2 and 3 infections.


Gene cloning of porcine adiponectin gene from adipose tissue and construction of its eukaryotic expression vector.
To clone adiponectin (ADPN) gene from Shaziling porcine adipocyte and construct its eukaryotic expression vector, total RNA was extracted from subcutaneous fatty tissue. One pair of specific primers was designed by Primer 5.0 software according to the sequence of ADPN gene of porcine available in GenBank. The ADPN gene was amplified by PCR from cDNA and cloned into pMD18-T vector to construct recombinant clonal vector pMD-ADPN, sequenced and analysed. A recombinant expression plasmid pPICZaA-ADPN was constructed by subcloning the cloned ADPN gene into the linearized pPICZaA vector. Then, the plasmid pPICZaA-ADPN was expressed in Pichia pastoris (GS115) by electrotransformation. Western blot and Bradford analysis were used to determine the target protein induced by methanol. Results showed that the genome size of ADPN was 732 bp and encoded 244 amino acid, the nucleotide sequence of ADPN shared 100% identity with that of porcine available in GenBank. Western blot and Bradford analysis showed that the recombinant ADPN was expressed in GS115 correctly and has certain immune activity. The expression level of ADPN was 28.5 μg/ml. In conclusion, the recombinant ADPN could express in eukaryotic expression vector pPICZaA-ADPN constructed in this study effectively.


A hermeneutic phenomenological study of community nurses' CPD.
Continuing professional development (CPD) is a mandatory aspect of nurse registration. In the NHS, more demanding professional roles compel nurses to develop and update their knowledge and skills through CPD. Even though CPD is an essential component of nurse education, research investigating community practitioners' views, experiences and perceptions of the link between reflection and CPD is limited. This phenomenological study explored community health practitioners' experiences of CPD and perceptions of the link between CPD and reflection. Ten community practitioners who specialized in district or school nursing and health visiting were interviewed using an in-depth approach. Data was analysed using thematic networks as a tool (Attride-Stirling, 2001). Findings revealed that community practitioners viewed CPD positively, perceived the benefits as both professional and personal development. Development needs were identified through reflective practice and appraisal. Even though significant barriers were apparent, the organization provided opportunities to access formal and self-directed learning events. There is a need for organizations to invest in CPD of the workforce, consider cheaper alternatives for meeting CPD needs and for further research to assess the impact of CPD on clinical practice.


Metabolic efficiency during arm and leg exercise at the same relative intensities.
This study was conducted to compare gross efficiency (GE), net efficiency (NE), work efficiency (WE), and delta efficiency (DE) between arm crank and cycle exercise at the same relative intensities. Eight college-aged males underwent two experimental trials presented in a randomized counterbalanced order. During each trial subjects performed three intermittent 7-min exercise bouts separated by 10-min rest intervals on an arm or semirecumbent leg ergometer. The power outputs for the three bouts of arm crank or cycle exercise corresponded to 50, 60, and 70% of the mode-specific VO2peak. GE, NE, and WE were determined as the ratio of Kcal.min-1 equivalent of power output to Kcal.min-1 of total energy expended, energy expended above rest and energy expended above unloaded exercise, respectively. DE was determined as the ratio of the increment of Kcal.min-1 of power output above the previous lower intensity to the increment of kcal.min-1 of total energy expended above the previous lower intensity. GE and NE did not differ between arm crank and cycle exercises. However, WE was lower (P < 0.05) during arm crank than cycle exercise at 50, 60, and 70% VO2peak. DE was also lower (P < 0.05) during arm crank than cycle exercise at delta 50-60 and at delta 60-70% VO2peak. It is concluded metabolic efficiency as determined by work and delta efficiency indices was lower during arm crank compared with cycle exercise at the same relative intensities. These findings add to the understanding of the difference in metabolic efficiency between upper and lower body exercise.


High-performance liquid chromatography of some basic drugs on a n-octadecylphosphonic acid modified magnesia-zirconia stationary phase.
The high-performance liquid chromatographic behavior of some basic drugs was studied on a n-octadecylphosphonic acid modified magnesia-zirconia (C18PZM) stationary phase. The effect of mobile phase variables such as methanol content, ionic strength, and pH on their chromatographic behavior was investigated. The retention mechanism of basic drugs on the stationary phase was elucidated. The results indicate that both hydrophobic and cation-exchange interactions contribute to solute retention under most chromatographic conditions. The inherent Brönsted-acid sites and also the adsorbed Lewis base anionic buffer constituents on accessible ZM surface Lewis acid sites play a role in the retention of ionized solutes by cation-exchange interaction. However, especially at high mobile phase pH, the retention of basic drugs depends mainly on hydrophobic interactions between solutes and support. Separations of the basic drugs on the C18PZM phase by a predominantly reversed-phase retention mode were very promising. The mixed-mode retention feature on this phase, as a result of the adsorbed Lewis base anionic buffer constituents acting as sites for cation-exchange, could also be very useful, e.g. for enhancing the chromatographic selectivity of such analytes. The C18PZM seems to be an excellent alternative to silica-based reversed-phase stationary phase for the separation of strongly basic solutes.


Different hepatitis C virus (HCV) RNA load profiles following seroconversion among injecting drug users without correlation with HCV genotype and serum alanine aminotransferase levels.
Hepatitis C virus (HCV) infection often persists in association with chronic hepatitis. Different factors have been proposed to determine the clinical outcome of HCV infection. The aim of this study was to examine three different factors of HCV infection among injecting drug users. Nineteen untreated HCV seroconverters were tested longitudinally for the presence of HCV RNA by reverse transcriptase (RT) PCR, and results were quantified by the branched-DNA (bDNA) assay. HCV genotypes were determined with the first sample taken after HCV seroconversion. To assess the natural course of infection, serum alanine aminotransferase (ALT) levels were measured at three stages in every individual. The concordance between bDNA and RT-PCR was 98.9%. Three distinct patterns were found, according to the HCV RNA load after seroconversion during a mean follow-up period of 5 years (range, 1 to 8 years). HCV genotype 1a was predominant (52.6%). There was a significant increase in serum ALT levels (mean 55.5 U/liter) in the early phase of HCV infection, compared with basal serum ALT levels before HCV seroconversion and at the end of the follow-up period. Three distinct HCV RNA load profiles were found, without apparent relationship to genotype and serum ALT levels in the first 5 years of HCV infection.


Molecular mechanisms of tumour invasion: regulation by calcium signals.
Intracellular calcium (Ca2+ ) signals are key regulators of multiple cellular functions, both healthy and physiopathological. It is therefore unsurprising that several cancers present a strong Ca2+ homeostasis deregulation. Among the various hallmarks of cancer disease, a particular role is played by metastasis, which has a critical impact on cancer patients' outcome. Importantly, Ca2+ signalling has been reported to control multiple aspects of the adaptive metastatic cancer cell behaviour, including epithelial-mesenchymal transition, cell migration, local invasion and induction of angiogenesis (see Abstract Figure). In this context Ca2+ signalling is considered to be a substantial intracellular tool that regulates the dynamicity and complexity of the metastatic cascade. In the present study we review the spatial and temporal organization of Ca2+ fluxes, as well as the molecular mechanisms involved in metastasis, analysing the key steps which regulate initial tumour spread.


Spontaneous Core Rotation in Ferrofluid Pipe Flow.
Ferrofluid flow along a tube of radius R in a constant axial magnetic field is revisited. Our analytical solution and numerical simulations predict a transition from an initially axial flow to a steady swirling one. The swirl dynamo arises above some critical pressure drop and magnetic field strength. The new flow pattern consists of two phases of different symmetry: The flow in the core resembles Poiseuille flow in a rotating tube of the radius r_{*}<R, where each fluid element moves along a screw path, and the annular layer of the thickness R-r_{*}, where the flow remains purely axial. These phases are separated by a thin domain wall. The swirl appearance is accompanied with a sharp increase in the flow rate that might serve for the detection of the swirling instability.


Evolution of Massachusetts physician attitudes, knowledge, and experience regarding the use of antiretrovirals for HIV prevention.
The Center for the AIDS Programme of Research in South Africa (CAPRISA) 004 and Pre-exposure Prophylaxis Initiative (iPrEx) studies demonstrated that topical or oral chemoprophylaxis could decrease HIV transmission. Yet to have an appreciable public health impact, physicians will need to be educated about these new HIV prevention modalities. Massachusetts physicians were recruited via e-mail to complete an online survey of their knowledge and use of HIV prevention interventions. Data were collected before (July-December, 2010) (n=178) and after (December, 2010-April, 2011) (n=115) the release of iPrEx data. Over the two time intervals, knowledge of oral PrEP significantly increased (79% to 92%, p<0.01), whereas knowledge about topical microbicides was already high (89% pre-iPrEx). Post-iPrEx, specialists were more knowledgeable about oral PrEP (p<0.01) and topical microbicides (p<0.001) than generalists. The majority of the respondents would prefer to prescribe topical microbicides (75%) than oral PrEP (25%; p<0.001), primarily because they perceived fewer side effects (95%). Respondents indicated that PrEP should be available if it were a highly effective, daily pill; however, ongoing concerns included: potential drug resistance (93%), decreased funds for other forms of HIV prevention (88%), medication side effects (83%), and limited data regarding PrEP's clinical efficacy (75%). Participants indicated that formal CDC guidelines would have the greatest impact on their willingness to prescribe PrEP (96%). Among Massachusetts physicians sampled, chemoprophylaxis knowledge was high, but current experience was limited. Although topical gel was preferred, responses suggest a willingness to adapt practices pending additional efficacy data and further guidance from normative bodies. Educational programs aimed at incorporating antiretroviral chemoprophylaxis into physicians' HIV prevention practices are warranted.


Combinatorial influence of environmental parameters on transcription factor activity.
Cells receive a wide variety of environmental signals, which are often processed combinatorially to generate specific genetic responses. Changes in transcript levels, as observed across different environmental conditions, can, to a large extent, be attributed to changes in the activity of transcription factors (TFs). However, in unraveling these transcription regulation networks, the actual environmental signals are often not incorporated into the model, simply because they have not been measured. The unquantified heterogeneity of the environmental parameters across microarray experiments frustrates regulatory network inference. We propose an inference algorithm that models the influence of environmental parameters on gene expression. The approach is based on a yeast microarray compendium of chemostat steady-state experiments. Chemostat cultivation enables the accurate control and measurement of many of the key cultivation parameters, such as nutrient concentrations, growth rate and temperature. The observed transcript levels are explained by inferring the activity of TFs in response to combinations of cultivation parameters. The interplay between activated enhancers and repressors that bind a gene promoter determine the possible up- or downregulation of the gene. The model is translated into a linear integer optimization problem. The resulting regulatory network identifies the combinatorial effects of environmental parameters on TF activity and gene expression. The Matlab code is available from the authors upon request. Supplementary data are available at Bioinformatics online.


BMJ response to Dr. Gupta.
We sent a questionnaire survey to a random sample of 125 correspondents to the BMJ who had previously sent a letter which had been rejected. The objective was to evaluate the policy of sending on some unpublished letters to the authors of the articles to which they referred. There were 94 replies, a response rate of 75%. The key finding was that although most respondents agreed with the policy, a third thought it unconstructive. A quarter of the respondents said that the BMJ policy would discourage them from sending a letter to the journal for publication. This survey has led to a change of policy at the BMJ. Letters which are not published are not now sent on to the authors of the original articles.


Metal-catalyzed oxidation of extracellular matrix proteins disrupts integrin-mediated adhesion of mesangial cells.
We undertook the present study to determine whether oxidation of extracellular matrix could alter RGD (arginine-glycine-aspartic acid)-integrin interaction in mesangial cells. Mesangial cells demonstrated significantly less adhesion to matrix oxidized using a metal-catalyzed oxidation system and lost their typical spindle-shaped morphology. N-tert-butyl-alpha-phenylnitrone reversed in part both oxidation and impaired adhesion to matrix. Mesangial cells adhered to plates coated with GRGDSP but demonstrated impaired adhesion to oxidized GRGDSP. Oxidation of this peptide was demonstrated using immunoblot analysis with an antibody to dinitrophenylhydrazine bound to carbonyl groups on oxidized amino acid residues. This represents the first report demonstrating that oxidative modification of extracellular matrix impairs integrin-mediated adhesion and suggests that the mechanism may be oxidative modification of one or more amino acids in the RGD sequence. These data suggest a new mechanism by which cell-matrix interaction may be altered in disease states characterized by enhanced oxidative stress.


Cognitive Implications of Correlated Structural Network Changes in Schizophrenia.
Schizophrenia is a brain disorder characterized by diffuse, diverse, and wide-spread changes in gray matter volume (GM) and white matter structure (fractional anisotropy, FA), as well as cognitive impairments that greatly impact an individual's quality of life. While the relationship of each of these image modalities and their links to schizophrenia status and cognitive impairment has been investigated separately, a multimodal fusion via parallel independent component analysis (pICA) affords the opportunity to explore the relationships between the changes in GM and FA, and the implications these network changes have on cognitive performance. Images from 73 subjects with schizophrenia (SZ) and 82 healthy controls (HC) were drawn from an existing dataset. We investigated 12 components from each feature (FA and GM). Loading coefficients from the images were used to identify pairs of features that were significantly correlated and showed significant group differences between HC and SZ. MANCOVA analysis uncovered the relationships the identified spatial maps had with age, gender, and a global cognitive performance score. Three component pairs showed significant group differences (HC > SZ) in both gray and white matter measurements. Two of the component pairs identified networks of gray matter that drove significant relationships with cognition (HC > SZ) after accounting for age and gender. The gray and white matter structural networks identified in these three component pairs pull broadly from many regions, including the right and left thalamus, lateral occipital cortex, multiple regions of the middle temporal gyrus, precuneus cortex, postcentral gyrus, cingulate gyrus/cingulum, lingual gyrus, and brain stem. The results of this multimodal analysis adds to our understanding of how the relationship between GM, FA, and cognition differs between HC and SZ by highlighting the correlated intermodal covariance of these structural networks and their differential relationships with cognitive performance. Previous unimodal research has found similar areas of GM and FA differences between these groups, and the cognitive deficits associated with SZ have been well documented. This study allowed us to evaluate the intercorrelated covariance of these structural networks and how these networks are involved the differences in cognitive performance between HC and SZ.


Thromboelastographic evaluation in dogs with Asian pit viper (Gloydius) envenomation.
The objective of this study was to investigate the thromboelastography (TEG) variables and platelet count after Asian pit viper (Gloydius) envenomation in dogs compared with healthy control dogs. Ten dogs with snake envenomation and twenty healthy dogs were included. There was a significant decrease in G (P=0.017), maximum amplitude (MA) (P=0.012), angle value (P=0.041), platelet count (P<0.001, as well as an increase in K value (P=0.034) and R value (P=0.007) in dogs with snake envenomation. The results of this study revealed that dogs with Asian pit viper (Gloydius) envenomation showed a hypocoagulable state compared with healthy dogs. Our findings may support the use of TEG for diagnosing and monitoring coagulopathy after Asian pit viper (Gloydius) envenomation in dogs.


Capital interplays and social inequalities in health.
We explore the ramifications of applying Pierre Bourdieu's theory of capitals to epidemiological research on socioeconomic health inequalities. Capitals are resources used by individuals and groups to maintain and enhance their positions in the social order. The notion of capital interplay refers to the interconnectedness of multiple forms of capital in the production of good health. We provide definitions of economic, cultural and social capitals and describe a variety of causally distal processes-namely, capital acquisition, multiplier and transmission interplays-from which new hypotheses can be developed to guide future study of socioeconomic health inequalities in modern societies.