Community involvement in dengue vector control: cluster randomised trial.
To assess the effectiveness of an integrated community based environmental management strategy to control Aedes aegypti, the vector of dengue, compared with a routine strategy. Design Cluster randomised trial. Setting Guantanamo, Cuba. Participants 32 circumscriptions (around 2000 inhabitants each). Interventions The circumscriptions were randomly allocated to control clusters (n=16) comprising routine Aedes control programme (entomological surveillance, source reduction, selective adulticiding, and health education) and to intervention clusters (n=16) comprising the routine Aedes control programme combined with a community based environmental management approach. The primary outcome was levels of Aedes infestation: house index (number of houses positive for at least one container with immature stages of Ae aegypti per 100 inspected houses), Breteau index (number of containers positive for immature stages of Ae aegypti per 100 inspected houses), and the pupae per inhabitant statistic (number of Ae aegypti pupae per inhabitant). All clusters were subjected to the intended intervention; all completed the study protocol up to February 2006 and all were included in the analysis. At baseline the Aedes infestation levels were comparable between intervention and control clusters: house index 0.25% v 0.20%, pupae per inhabitant 0.44 x 10(-3) v 0.29 x 10(-3). At the end of the intervention these indices were significantly lower in the intervention clusters: rate ratio for house indices 0.49 (95% confidence interval 0.27 to 0.88) and rate ratio for pupae per inhabitant 0.27 (0.09 to 0.76). A community based environmental management embedded in a routine control programme was effective at reducing levels of Aedes infestation. Trial Registration Current Controlled Trials ISRCTN88405796.


Plasmonic nanopillar arrays for large-area, high-enhancement surface-enhanced Raman scattering sensors.
Efforts to create reproducible surface-enhanced Raman scattering (SERS)-based chemical and biological sensors has been hindered by difficulties in fabricating large-area SERS-active substrates with a uniform, reproducible SERS response that still provides sufficient enhancement for easy detection. Here we report on periodic arrays of Au-capped, vertically aligned silicon nanopillars that are embedded in a Au plane upon a Si substrate. We illustrate that these arrays are ideal for use as SERS sensor templates, in that they provide large, uniform and reproducible average enhancement factors up to ∼1.2 × 10(8) over the structure surface area. We discuss the impact of the overall geometry of the structures upon the SERS response at 532, 633, and 785 nm incident laser wavelengths. Calculations of the electromagnetic field distributions and intensities within such structures were performed and both the wavelength dependence of the predicted SERS response and the field distribution within the nanopillar structure are discussed and support the experimental results we report.


Analytical approach for determining beam profiles in water phantom of symmetric and asymmetric fields of wedged, blocked, and open photon beams.
Nowadays, in most radiotherapy departments, the commercial treatment planning systems (TPS) used to calculate dose distributions needs to be verified; therefore, quick, easy-to-use, and low-cost dose distribution algorithms are desirable to test and verify the performance of the TPS. In this paper, we put forth an analytical method to calculate the phantom scatter contribution and depth dose on the central axis based on the equivalent square concept. Then, this method was generalized to calculate the profiles at any depth and for several field shapes - regular or irregular fields - under symmetry and asymmetry photon beam conditions. Varian 2100 C/D and Siemens Primus Plus linacs with 6 and 18 MV photon beam were used for irradiations. Percentage depth doses (PDDs) were measured for a large number of square fields for both energies and for 45° wedge, which were employed to obtain the profiles in any depth. To assess the accuracy of the calculated profiles, several profile measurements were carried out for some treatment fields. The calculated and measured profiles were compared by gamma-index calculation. All γ-index calculations were based on a 3% dose criterion and a 3 mm dose-to-agreement (DTA) acceptance criterion. The γ values were less than 1 at most points. However, the maximum γ observed was about 1.10 in the penumbra region in most fields and in the central area for the asymmetric fields. This analytical approach provides a generally quick and fairly accurate algorithm to calculate dose distribution for some treatment fields in conventional radiotherapy.


Randomized Phase III Study of Continuation Maintenance Bevacizumab With or Without Pemetrexed in Advanced Nonsquamous Non-Small-Cell Lung Cancer: COMPASS (WJOG5610L).
Patients with non-small-cell lung cancer (NSCLC) have been shown to benefit from maintenance therapy. COMPASS evaluated the efficacy and safety of bevacizumab with or without pemetrexed as continuation maintenance therapy after carboplatin, pemetrexed, and bevacizumab induction therapy. Patients with untreated advanced nonsquamous NSCLC without confirmed EGFR 19 deletion or L858R mutation received first-line therapy with carboplatin area under the curve 6, pemetrexed 500 mg/m2, and bevacizumab 15 mg/kg once every 3 weeks for 4 cycles. Patients without disease progression during the induction therapy were randomly assigned 1:1 for maintenance therapy with pemetrexed 500 mg/m2 plus bevacizumab 15 mg/kg or bevacizumab 15 mg/kg once every 3 weeks until disease progression or unacceptable toxicity. The primary end point was overall survival (OS) after random assignment. Between September 2010 and September 2015, 907 patients received induction therapy. Of those, 599 were randomly assigned: 298 received pemetrexed plus bevacizumab, and 301 received bevacizumab. The median OS was 23.3 v 19.6 months (hazard ratio [HR], 0.87; 95% CI, 0.73 to 1.05; 1-sided stratified log-rank P = .069). In the wild-type EGFR subset, the OS HR was 0.82 (95% CI, 0.68 to 0.99; 1-sided unstratified log-rank P = .020). The median progression-free survival (PFS) was 5.7 v 4.0 months (HR, 0.67; 95% CI, 0.57 to 0.79; 2-sided log-rank P < .001). The safety data were consistent with previous reports of treatment regimens. In terms of the primary end point of OS, no statistically significant benefit was observed; however, PFS in the total patient population and OS in patients with wild-type EGFR was prolonged with the addition of pemetrexed to bevacizumab maintenance therapy.


Effects of Vitamin D Supplementation on Cardiovascular and Glycemic Biomarkers.
Background Experimental and observational studies have suggested a link between vitamin D and cardiovascular and metabolic disease, but this has not been confirmed in randomized controlled trials. We sought to determine whether vitamin D supplementation reduces biomarkers of insulin resistance, inflammation, neurohormonal activation, and lipids. Methods and Results This was a prespecified, secondary analysis of the DAYLIGHT (Vitamin D Therapy in Individuals at High Risk of Hypertension) randomized controlled trial. We measured circulating homeostatic model assessment of insulin resistance, hs-CRP (high-sensitivity C-reactive protein), N-terminal pro-B-type natriuretic peptide, renin, aldosterone, and lipids at baseline and at 6 months in 289 individuals with low vitamin D status (25-hydroxyvitamin-D [25-OH-D] ≤25 ng/mL) receiving low-dose (400 IU/d) versus high-dose (4000 IU/d) vitamin D3 for 6 months. A meta-analysis of randomized controlled trials reporting biomarker changes after vitamin D supplementation was then performed. Levels of 25-OH-D increased in the high-dose relative to the low-dose vitamin D group (+15.5 versus +4.6 ng/mL, P<0.001). Changes in biomarkers of glycemia, inflammation, and neurohormonal activation did not differ by dose. Lipids did not differ between groups, other than triglycerides, which increased in the high-dose compared with the low-dose group (+11.3 versus -6.2 mg/dL, P<0.001). The meta-analysis showed potential modest decreases in homeostatic model assessment of insulin resistance and hs-CRP, but no changes in low-density lipoprotein, after vitamin D supplementation compared with control groups. Conclusions In the DAYLIGHT randomized controlled trial, high-dose vitamin D supplementation did not improve biomarkers of glycemia, inflammation, neurohormonal activation, or lipids. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01240512.


Relationships between personality and time-related strains.
Using data from a Dutch representative national sample of 1,249 respondents (40% women and 60% men), all engaged in paid labor, the relationships between Big Five personality traits and time-related strains (i.e., Time Pressure and Work Pressure) were examined. Hierarchical regression analyses showed that Emotional Stability was negatively and Openness to Experience was positively related to both types of time-related strains. Emotional Stability and Agreeableness were more strongly negatively associated with generalized Time Pressure than with context-specific Work Pressure. This supports the Strong versus Weak Situations Hypothesis of Mischel.


Agraphia in Korean patients with early onset Alzheimer's disease.
Agraphia in Korean patients may be different from agraphia in other patients who use alphabetical writing systems due to the "visuoconstructional script" characteristics of the Korean writing system, Hangul. Patients with early onset Alzheimer's disease (EOAD) have a severe degree of hypometabolism in the parietal area, which is known to be involved in processing visuospatial function. Thus, we explored the diverse error patterns manifested in writing single syllables in Korean patients with EOAD. A study sample of 35 patients with EOAD and 18 healthy controls (HC) performed a Hangul writing task. We analyzed the erroneous responses of the subjects according to visuoconstructional and linguistic characteristics. In addition, we evaluated the relationship between Hangul writing and the neuropsychological variables as well as the severity of dementia. When comparing the total number of erroneous responses between EOAD and HC groups, the performances of EOAD patients were significantly worse than those of HC. EOAD patients demonstrated visuoconstructional errors even in the early stages of the disease. Severity of dementia and multiple cognitive domains such as attention, language, immediate memory, and frontal executive functions significantly correlated with the performance of Hangul writing. Our findings suggest that patients with EOAD exhibit not only linguistic errors but also visuoconstructional manifestations of agraphia, which are associated with cognitive impairments in the multiple domains.


A theoretical study on the mechanistic highlights behind the Brønsted-acid dependent mer-fac isomerization of homoleptic carbenic iridium complexes for PhOLEDs.
Recently, a successful Brønsted-acid mediated geometric isomerization of the meridional homoleptic carbenic iridium(iii) complexes tris-(N-phenyl,N-methyl-benzimidazol-2-yl)iridium(iii) (1) and tris-(N-phenyl,N-benzyl-benzimidazol-2-yl)iridium(iii) (2) into their facial form has been reported. In the present work the pronounced acid-dependency of this particular isomerization procedure is revisited and additional mechanistic pathways are taken into account. Moreover, the acid-induced material decomposition is addressed. All calculations are carried out using density functional theory (DFT) while the environmental effects in solution are accounted for by the COSMO-RS model. The simulated results clearly reveal the outstanding importance of the complex interplay between acid strength, coordinating power of the corresponding base and the steric influence of the ligand system in contrast to the plain calculation of minimum energy pathways for selected complexes. Eventually, general rules to enhance the material-specific reaction yields are provided.


Is growth hormone bad for your heart? Cardiovascular impact of GH deficiency and of acromegaly.
At present, there is growing evidence implicating GH and/or IGF-I in the intricate cascade of events connected with the regulation of heart development and hypertrophy. Moreover, GH excess and/or deficiency have been shown to include in their advanced clinical manifestations almost always an impaired cardiac function, which may reduce life expectancy. This finding is related both to a primitive impairment of heart structure and function and to metabolic changes such as hyperlipidemia, increase of body fat and premature atherosclerosis. Patients with childhood or adulthood-onset GH deficiency have a reduced left ventricular mass and ejection fraction and the indexes of left ventricular systolic function remain markedly depressed during exercise. Conversely, in acromegaly the cardiac enlargement, which is disproportionate to the increase in size of other internal body organs, has been a rather uniform finding. The severity of the acromegalic cardiomyopathy was reported to be correlated better with the disease duration than with circulating GH and/or IGF-I levels. Myocardial hypertrophy with interstitial fibrosis, lymphomononuclear infiltration and areas of monocyte necrosis often results in concentric hypertrophy of both ventricles. The treatment of GH deficiency and excess improved cardiac function. Interestingly, based on the evidence that GH increases cardiac mass, recombinant GH was administered to patients with idiopathic dilated cardiomyopathy. It increased the myocardial mass and reduced the size of the left ventricular chamber, resulting in improvement of hemodynamics, myocardial energy metabolism and clinical status. These promising results open new perspectives for the use of GH in heart failure.


Acute effect of front crawl sprint resisted swimming on the propulsive forces of the hand.
The purpose of the current study was to investigate the acute effect of sprint resisted front crawl swimming on the propulsive forces of the hand. Eight female swimmers swam 25 m with maximal intensity, with and without added resistance. A bowl with a capacity of 2.2, 4 and 6 L was used as low, moderate and high added resistance, respectively. The underwater motion of the swimmer's right hand was recorded using 4 cameras (60 Hz) and the digitization was undertaken using the Ariel Performance Analysis System. Repeated-measures ANOVA revealed that the velocity of the hand, the pitch and the sweepback angles of the hand, as well as the magnitude and the relative contribution of the drag and lift forces were not significantly modified and thus the magnitude of the resultant force did not change. Moreover, the magnitude of the effective force, as well as the angle formed between the resultant force and the axis of the swimming propulsion were not significantly affected. Thus, it could be concluded that resistance added as in this study did not alter the pattern of the propulsive hand forces associated with front crawl sprinting.


Microfibril-associated glycoprotein-1 (MAGP-1) binds to the pepsin-resistant domain of the alpha3(VI) chain of type VI collagen.
The interactions of type VI collagen have been investigated, using solid phase binding assays, with two components of the fibrillin-containing microfibrils, the elastin-binding protein, MAGP-1 and its structural relative MAGP-2. Both native and pepsin-treated forms of type VI collagen specifically bound to MAGP-1 but not to MAGP-2. Pepsin type VI collagen was shown to block the binding of MAGP-1 to native type VI collagen indicating that the major MAGP-1-binding site was in the triple-helical region of the molecule. MAGP-1 was found not to bind to collagens I, III, and V. Affinity blotting of pepsin-treated type VI collagen showed that MAGP-1 binding was specific for the collagenous domain of the alpha3(VI) chain. Decorin and biglycan were found not to inhibit the interaction of pepsin-treated type VI collagen with MAGP-1, indicating that its binding site on the collagen is not close to that for the proteoglycans. Reduction and alkylation of disulfide bonds in MAGP-1 did not destroy its type VI collagen-binding properties, indicating that the binding site was likely to be in the cysteine-free, N-terminal domain of MAGP-1. Interestingly, the interaction of MAGP-1 with type VI collagen was inhibited by tropoelastin, suggesting that the binding sites for tropoelastin and type VI collagen may be in the same domain of MAGP-1. A peptide, corresponding to amino acids 29-38 of MAGP-1, was found to inhibit the interactions of MAGP-1 with type VI collagen and tropoelastin. The results suggest that the peptide may contain the binding sequences for both type VI collagen and tropoelastin, and thus that these two proteins may share the same binding site on MAGP-1. The interactions of MAGP-1 with type VI collagen and tropoelastin were both determined to be of moderately high affinity, with Kd values of 5.6 x 10(-7) M and 2.6 x 10(-7) M, respectively. The findings indicate that MAGP-1 may mediate a molecular interaction between type VI collagen microfibrils and fibrillin-containing microfibrils, structures which are often found in close proximity to each other in a wide range of extracellular matrices.


How electroencephalography serves the anesthesiologist.
Major clinical endpoints of general anesthesia, such as the alteration of consciousness, are achieved through effects of anesthetic agents on the central nervous system, and, more precisely, on the brain. Historically, clinicians and researchers have always been interested in quantifying and characterizing those effects through recordings of surface brain electrical activity, namely electroencephalography (EEG). Over decades of research, the complex signal has been dissected to extract its core substance, with significant advances in the interpretation of the information it may contain. Methodological, engineering, statistical, mathematical, and computer progress now furnishes advanced tools that not only allow quantification of the effects of anesthesia, but also shed light on some aspects of anesthetic mechanisms. In this article, we will review how advanced EEG serves the anesthesiologist in that respect, but will not review other intraoperative utilities that have no direct relationship with consciousness, such as monitoring of brain and spinal cord integrity. We will start with a reminder of anesthestic effects on raw EEG and its time and frequency domain components, as well as a summary of the EEG analysis techniques of use for the anesthesiologist. This will introduce the description of the use of EEG to assess the depth of the hypnotic and anti-nociceptive components of anesthesia, and its clinical utility. The last part will describe the use of EEG for the understanding of mechanisms of anesthesia-induced alteration of consciousness. We will see how, eventually in association with transcranial magnetic stimulation, it allows exploring functional cerebral networks during anesthesia. We will also see how EEG recordings during anesthesia, and their sophisticated analysis, may help corroborate current theories of mental content generation.


Novel multipurpose methodology for detection of mycobacteria in pulmonary and extrapulmonary specimens by smear microscopy, culture, and PCR.
A novel, robust, reproducible, and multipurpose universal sample processing (USP) methodology for highly sensitive smear microscopy, culturing on solid and liquid media, and inhibition-free PCR which is suitable for the laboratory diagnosis of both pulmonary and extrapulmonary tuberculosis (TB) has been developed. This method exploits the chaotropic properties of guanidinium hydrochloride for sample processing and involves incubating the specimen with USP solution, concentrating bacilli by centrifugation, and using the processed specimen for smear microscopy, culture, and PCR. The detection limit for acid-fast bacilli in spiked sputum by smear microscopy is approximately 300 bacilli per ml of specimen. USP solution-treated specimens are fully compatible with culturing on solid and liquid media. High-quality, PCR-amplifiable mycobacterial DNA can be isolated from all types of clinical specimens processed with USP solution. The method has been extensively validated with both pulmonary and extrapulmonary specimens. Furthermore, the USP method is also compatible with smear microscopy, culture, and PCR of mycobacteria other than tubercle bacilli. In summary, the USP method provides smear microscopy, culture, and nucleic acid amplification technologies with a single sample-processing platform and, to the best of our knowledge, is the only method of its kind described to date. It is expected to be useful for the laboratory diagnosis of TB and other mycobacterial diseases by conventional and modern methods.


Neuropsychiatric Symptoms and In Vivo Alzheimer's Biomarkers in Mild Cognitive Impairment.
Neuropsychiatric symptoms (NPS) carry an increased risk of progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). There is a need to understand how to integrate NPS into the paradigm outlined in the 2018 NIA-AA Research Framework. To evaluate a prediction model of MCI-AD progression using a collection of variables, including NPS, cognitive testing, apolipoprotein E4 status (APOE4), imaging and laboratory AD biomarkers. Of 300 elderly subjects, 219 had stable MCI and 81 MCI-AD progression over a 5-year follow-up. NPS were measured using the Neuropsychiatric Inventory (NPI). A multivariate Cox Proportional Hazards Regression Analysis assessed the effects of APOE4, baseline NPI, baseline CSF amyloid-β, phosphorylated and total tau, baseline AD-signature MRI biomarker, baseline memory and executive function on MCI-AD progression. 27% progressed to dementia (median follow-up = 43 months). NPS were found in stable MCI (62.6%) and MCI-AD converters (70.3%). The Cox model exhibited a good fit (p < 0.001), and NPS (HR = 1.033, p = 0.027), phosphorylated tau (HR = 1.011, p = 0.025), total tau (HR = 1.005, p = 0.024), AD-signature MRI biomarker (HR = 0.111, p = 0.002), executive function (HR = 0.727, p = 0.045), and memory performance (HR = 0.387, p < 0.001) were significantly associated with dementia. NPS may inform dementia risk assessment in conjunction with cognitive testing and imaging and laboratory AD biomarkers. NPS is independently associated with the risk of MCI-dementia progression, over and beyond the contributions of CSF biomarkers.


Antiferromagnetic Ordering and Paramagnetic Behavior of Ferromagnetic Cu6 and Cu18 Clusters in BaCuO2+x.
Magnetization and neutron diffraction measurements on polycrystalline BaCuO2+x revealed a combination of magnetic behaviors. The Cu(6) ring clusters and Cu(18) sphere clusters in this compound had ferromagnetic ground states with large spins 3 and 9, respectively. The Cu(6) rings ordered antiferromagnetically below the Néel temperature T(N) = 15 +/- 0.5 kelvin, whereas the Cu(18) spheres remained paramagnetic down to 2 kelvin. The ordered moment below T(N) was 0.89(5) Bohr magnetons per Cu in the Cu(6) rings, demonstrating that quantum fluctuation effects are small in these atomic clusters. The Cu(18) clusters are predicted to exhibit ferromagnetic intercluster order below about 1 kelvin.


Efficacy and safety of topiramate in migraine prophylaxis: an open controlled randomized study comparing Sincronil and topamax formulations.
Topiramate is a small molecule widely used for the treatment of epilepsy, migraine, bipolar disorders and alcoholism, and its availability as a generic formulation could significantly reduce the National Health Service expenditure. A generic formulation, available in Italy under the trademark Sincronil, recently showed superimposable blood levels, after oral administration to healthy volunteers, with the reference formulation. In the present study we report the results of an open label, parallel group, randomized, controlled study performed to evaluate the efficacy, tolerability and impact on disability of two different formulations of topiramate (Sincronil and Topamax) in patients with migraine without aura. Sixty patients aged between 18 and 65 years, suffering from migraine without aura with an attack frequency of 3-15 attacks/month were enrolled and received, after a titration phase lasting 20 days, randomly either Sincronil or Topamax at the dose of 25 mg twice daily for 3 months. Fifteen out of the 30 patients who were administered Sincronil reported an improvement in the clinical condition, with a decrease in the frequency of attacks at the 3rd month of treatment higher than 50% with respect to the run-in period, 9 reported their clinical condition as being substantially unchanged and 6 reported that they had suspended the treatment within the first 4 weeks of therapy due to side effects. Among the 24 patients who continued treatment up to the 3rd month, the frequency of attacks during the 3rd month of treatment was significantly decreased from 7 ± 3.6 to 3.7 ± 3.7 (P<0.0001), migraine severity was reduced from 2.5 ± 0.5 to 1.7 ± 0.7 (P<0.0005) and the MIDAS score was reduced from 14.3 ± 4.9 to 8.6 ± 5.5 (P<0.0001). Sixteen out of the 30 patients who were administered Topamax reported an improvement in the clinical condition with a reduction in the attack frequency at the 3rd month of treatment higher than 50% with respect to the run-in period, 10 reported a substantially unchanged clinical condition and 4 stopped the treatment within the first weeks due to side effects. Among the 26 patients who continued treatment up to the 3rd month, headache frequency during the 3rd month of treatment was significantly reduced, from 7.3 ± 2.6 to 3.5 ± 2.7 (P<0.0001), migraine severity decreased from 2.4 ± 0.6 to 1.6 ± 0.8 (P<0.0005) and the MIDAS score from 14.1 ± 4.2 to 6.8 ± 4.8 (P<0.0001). In conclusion, in this study Topamax (reference product) and Sincronil (generic formulation) have proven therapeutically equivalent and both products were well tolerated.


An evaluation of the gingival biotype and the width of keratinized gingiva in the mandibular anterior region of individuals with different dental malocclusion groups and levels of crowding.
To evaluate the relationship of gingival thickness (GT) and the width of keratinized gingiva (WKG) with different malocclusion groups and the level of crowding. A total of 187 periodontally healthy subjects (121 females and 66 males) who presented at the Faculty of Dentistry in Yüzüncü Yıl University for orthodontic treatment were enrolled in the study. The individuals involved in the study were divided into three groups; Angle Class I malocclusion, Angle Class II malocclusion, and Angle Class III malocclusion. Each group was classified as mild, moderate, or severe according to the level of crowding. WKG was determined as the distance between the mucogingival junction and the free gingival margin. GT was determined by the transgingival probing technique. Factorial variance analysis and the Duncan multiple comparison test were employed to identify the extent to which a difference was apparent between the groups according to these parameters. It was determined that teeth in the mandibular anterior region display the thin gingival biotype. WKG and GT were observed as being higher at the mandibular incisor teeth in the severe crowding group and at the mandibular canine teeth in the mild crowding group. The GT of the mandibular right central and lateral incisors was found to be thinner in the Angle Class III group. Within the limits of this study, the results demonstrate that, there is no significant relationship of WKG and the mean GT in the mandibular anterior region according to the Angle classification.


Chronic nonbacterial osteomyelitis in children: a retrospective multicenter study.
To determine the clinical presentation, current treatment and outcome of children with nonbacterial inflammatory bone disease. Retrospective multicenter study of patients entered into the Swiss Pediatric Rheumatology Working Group registry with a diagnosis of chronic nonbacterial osteomyelitis (CNO) and synovitis acne pustulosis hyperostosis osteitis (SAPHO) syndrome. The charts were reviewed for informations about disease presentation, treatment, course and outcome. Forty-one children (31 girls and 10 boys) from 6 pediatric hospitals in Switzerland diagnosed between 1995 and 2010 were included in the study. The diagnosis was multifocal CNO (n = 33), unifocal CNO (n = 4) and SAPHO syndrome (n = 4). Mean age at onset of CNO was 9.5 years (range 1.4-15.6) and mean follow-up time was 52 months (range 6-156 months). Most patients (n = 27) had a chronic persistent disease course (>6 months), 8 patients had a course with one or more relapses and 6 patients had only one episode of CNO. Forty nine percent had received at least one course of antibiotics. In 57% treatment with nonsteroidal anti-inflammatory drugs (NSAID) was sufficient to control the disease. Twelve out of 16 children with NSAID failure subsequently received corticosteroids, methotrexate, TNF α inhibitors, bisphosphonates or a combination of these drugs. In a multicenter cohort of 41 children 22% started with unifocal lesion with a significant diagnostic delay. A higher proportion presented with chronic persistent disease than with a recurrent form. An osteomyelitis in the pelvic region is significantly associated with other features of juvenile spondylarthritis.


Effect of disulfiram in experimentally induced vitamin E deficiency myopathy in lambs.
Vitamin E deficiency myopathy (white muscle disease) was induced in 14 suckling lambs (2 experiments; 7 lambs/experiment) by addition of cod liver oil to the diet. Disulfiram, an antioxidant, was administered orally once each day to 8 of the 14 lambs at 2 different doses. Serum creatine kinase (CK) activity was measured weekly for 5 weeks. Increased CK activity was evident in some lambs beginning at week 3. By week 4, serum CK was abnormally increased in 5 of the 6 nontreated lambs (ie, disulfiram not given) and in 4 of the 8 treated lambs. The combined disulfiram groups had significantly lower serum CK values during the study (P less than 0.05). Serum alpha-tocopherol, measured on samples from week 5 for lambs of experiment 1, was significantly higher in treated lambs (P less than 0.01). Microscopic examination of the vastus lateralis muscle indicated that the most severe lesions, consistent with nutritional myopathy, were seen in nontreated lambs. Therefore, disulfiram may have an antioxidant effect in lambs with vitamin E deficiency.


A deletion common to two independently derived waxy mutations of maize.
A mutation at the maize waxy locus, wx1240, was isolated following treatment of pollen with EMS and self-pollinating ears on M1 plants. This allele was cloned and found to contain a 30-bp deletion within the gene and additional lesions upstream of the transcription start site. Using fine structure genetic mapping, we determined that the deletion is responsible for the mutant phenotype. In addition, the position of wx1240 on the genetic map coincided with the previously determined positions of two other waxy mutations, the spontaneous wx-C, which is reference allele, and the putative ethyl methanesulfonate (EMS)-induced wx-BL2. Molecular analysis of these alleles revealed that both contain the same deletion as wx1240, and that the wx-BL2 allele is similar to wx-C and possibly resulted from wx-C contamination. The deleted sequence responsible for these mutations is flanked by a short, 4-bp, direct repeat. Similar structures are favored sites for spontaneous deletions in other organisms. The data suggests that EMS is capable of inducing structural alterations in plant genes in addition to the point mutations normally ascribed to EMS-induced mutations.


Effectiveness of antibiotic prophylaxis in cholecystectomy: a prospective population-based study of 1171 cholecystectomies.
The aim of this study was to assess the benefit from antibiotic prophylaxis (AP) during cholecystectomy in a population-based cohort study. All cholecystectomies performed in Uppsala County, 2003-2005, were registered prospectively according to a standardized protocol. High-risk procedures (HP) were defined as operations for acute cholecystitis and procedures including exploration of the common bile duct. Infections requiring surgical or percutaneous drainage and non-surgical infections that prolonged hospital stay were defined as major infectious complications (IC). Altogether 1171 patients underwent cholecystectomy. AP was given to 130 of 867 (15%) of the patients undergoing low-risk procedures (LP) and 205 of 304 (67%) of those undergoing H-R P. Major IC were seen in 6 of 205 (3%) of the patients undergoing H-R P with AP and 1 of 99 of the patients undergoing H-R P without AP. No major IC was seen after L-R P. Minor IC were seen after 5 of 205 (2%) HP with AP, 1 of 99 (1%) HP without AP, 0 of 130 (0%) LP with AP, and 2 of 737 (0.3%) LP without AP. In univariate logistic analysis, the overall risk for IC was found to be higher with AP (p < 0.05), but the increase did not remain significant if adjusting for age, gender, ASA class, H-R P/L-R P and surgical approach or limiting the analysis to major IC. There is no benefit from AP in uncomplicated procedures. The effectiveness of antibiotic prophylaxis in complicated cholecystectomy must be evaluated in randomized controlled trials.


Conformations and membrane-driven self-organization of rodlike fd virus particles on freestanding lipid membranes.
Membrane-mediated interactions and aggregation of colloidal particles adsorbed to responsive elastic membranes are challenging problems relevant for understanding the microscopic organization and dynamics of biological membranes. We experimentally study the behavior of rodlike semiflexible fd virus particles electrostatically adsorbed to freestanding cationic lipid membranes and find that their behavior can be controlled by tuning the membrane charge and ionic strength of the surrounding medium. Three distinct interaction regimes of rodlike virus particles with responsive elastic membranes can be observed. (i) A weakly charged freestanding cationic lipid bilayer in a low ionic strength medium represents a gentle quasi-2D substrate preserving the integrity, structure, and mechanical properties of the membrane-bound semiflexible fd virus, which under these conditions is characterized by a monomer length of 884 ± 4 nm and a persistence length of 2.5 ± 0.2 μm, in perfect agreement with its properties in bulk media. (ii) An increase in the membrane charge leads to the membrane-driven collapse of fd virus particles on freestanding lipid bilayers and lipid nanotubes into compact globules. (iii) When the membrane charge is low, and the mutual electrostatic repulsion of membrane-bound virus particles is screened to a considerable degree, membrane-driven self-organization of membrane-bound fd virus particles into long linear tip-to-tip aggregates showing dynamic self-assembly/disassembly and quasi-semiflexible behavior takes place. These observations are in perfect agreement with the results of recent theoretical and simulation studies predicting that membrane-mediated interactions can control the behavior of colloidal particles adsorbed on responsive elastic membranes.


Monoamine oxidase inhibition dramatically prolongs the duration of nicotine withdrawal-induced place aversion.
Long-lasting effects of withdrawal from nicotine are hypothesized to contribute to relapse and persistence of tobacco habits, and significant evidence supports a role of monoamine oxidase inhibitors (MAOI) contained in cigarette smoke as potent modulators of the rewarding effects of tobacco. With quantification of somatic signs of withdrawal and the place aversion conditioning paradigm, we assessed the effects of MAOI pretreatment on both somatic and aversive motivational components of mecamylamine-induced nicotine withdrawal in rats rendered dependent on nicotine by the subcutaneous implantation of osmotic minipumps (vehicle or nicotine tartrate 9 mg/kg/day). In nicotine-infused rats, mecamylamine induced a place aversion that lasted 6 weeks. When nicotine-infused rats were also treated with a MAOI, mecamylamine-induced conditioned place aversion persisted for at least 8 months of abstinence. The MAOI treatment slightly decreased ratings of somatic signs induced by mecamylamine administration but had no effect on the threshold or the magnitude of mecamylamine-induced conditioned place aversion. These results show that MAOI pretreatment induces a long-lasting conditioned placed aversion associated with nicotine withdrawal, possibly through a potentiation of learning and memory process, and provides some indications on protracted abstinence that might be useful for delineating the neurobiological substrate of relapse.


Intrinsic Pink-Noise Multidecadal Global Climate Dynamics Mode.
Understanding multidecadal variability is an essential goal of climate dynamics. For example, the recent phenomenon referred to as the "global warming hiatus" may reflect a coupling to an intrinsic, preindustrial, multidecadal variability process. Here, using a multifractal time-series method, we demonstrate that 42 data sets of 79 proxies with global coverage exhibit pink-noise characteristics on multidecadal timescales. To quantify the persistence of this behavior, we examine high-resolution ice core and speleothem data to find pink noise in both pre- and postindustrial periods. We examine the spatial structure with an empirical orthogonal function analysis of the monthly averaged surface temperature from 1901 to 2012. The first mode clearly shows the distribution of ocean heat flux sinks located in the eastern Pacific and the Southern Ocean and has pink-noise characteristics on a multidecadal timescale. We hypothesize that this pink-noise multidecadal spatial mode may resonate with externally driven greenhouse gas forcing, driving large-scale climate processes.


Examining Depression as a Risk Factor for Cardiovascular Disease in People with HIV: A Systematic Review.
People with human immunodeficiency virus (HIV) have an increased risk of cardiovascular disease (CVD) not fully accounted for by traditional or HIV-specific risk factors. Successful management of HIV does not eliminate this excess risk. Thus, there is a need to identify novel risk factors for CVD among people with HIV (PWH). Our objective was to systematically review the literature on one such candidate CVD risk factor in PWH-depression. A systematic literature search of PubMed, PsycINFO, EMBASE, Web of Science, and CINAHL was performed to identify published English-language studies examining associations of depression with clinical CVD, subclinical CVD, and biological mechanisms (immune activation, systemic inflammation, altered coagulation) among PWH between the earliest date and June 22, 2021. Thirty-five articles were included. For clinical CVD (k = 8), findings suggests that depression is consistently associated with an increased risk of incident CVD. For subclinical CVD (k = 5), one longitudinal analysis reported a positive association, and four cross-sectional analyses reported null associations. For immune activation (k = 13), systemic inflammation (k = 17), and altered coagulation (k = 5), findings were mixed, and there was considerable heterogeneity in sample characteristics and methodological quality across studies. Depression may be an independent risk factor for CVD among PWH. Additional research is needed to confirm depression's association with clinical CVD and to determine whether depression is consistently and meaningfully associated with subclinical CVD and biological mechanisms of CVD in HIV. We propose a research agenda for this emerging area.


Retinoid suppression of transglutaminase activity and envelope competence in cultured human epidermal carcinoma cells. Hydrocortisone is a potent antagonist or retinyl acetate but not retinoic acid.
Growth of SCC-13 squamous carcinoma cultures in the presence of retinoids considerably reduced the expression of two differentiation markers, the cellular capability to form cross-linked envelopes, and the enzyme transglutaminase required for cross-linking. A limited survey of retinoids showed that all-trans retinoic acid, 13-cis retinoic acid, and arotinoid Ro 13-6298 were highly effective in the absence of hydrocortisone and were only slightly antagonized by its presence in the medium. In contrast, retinyl acetate, retinol, and retinol bound to its plasma binding protein were quite active in the absence of hydrocortisone but were essentially inactive in its presence. Dexamethasone was also highly effective in antagonizing the suppressive action of retinyl acetate on envelope formation, while the corticosteroid antagonists cortexolone and progesterone were inactive. These results suggest that there are separate pathways, which are differentially regulated by hydrocortisone, for either the metabolism or action of retinol and retinoic acid in SCC-13 cells.


Analysis of neuroendocrine markers, HER2 and CEA before and after chemotherapy in patients with stage IIIA non-small cell lung cancer: a Cancer and Leukemia Group B study.
Several studies have suggested that biochemical or molecular markers examined in non-small cell lung cancer carry prognostic or treatment response information. Non-small cell lung cancer patients whose tumors have neuroendocrine (NE) features may be more responsive to chemotherapy. In addition, increased expression of HER2 (c-erbB-2), a membrane-bound receptor with tyrosine kinase activity, has been associated with shortened survival. The Cancer and Leukemia Group B (CALGB) performed a study of patients with stage IIIA (N2 nodes positive) non-small cell lung cancer in which patients received initial chemotherapy followed by surgery, then post-operative therapy consisting of sequential chemotherapy and radiation therapy. Since all patients underwent mediastinoscopy, this provided an opportunity to compare pre- and post-chemotherapy tumor specimens to test the hypothesis that these proteins would predict treatment response. In particular, we hypothesized that the post-chemotherapy specimens would be enriched for NE marker negative cells because of the increased sensitivity of NE positive cells to chemotherapy. We performed immunohistochemical analysis for a panel of NE markers [neuron-specific enolase (NSE), Leu-7, chromogranin A (ChrA), synaptophysin (Syn)], HER2 and CEA to determine if there was an effect of therapy on the percentage of cells expressing these markers. Secondary endpoints were a correlation with chemotherapy response and survival. Slides were scored for intensity (0-4) and percentage of cells positive (0-4). Of 61 eligible patients, there were 38 with both pre- and post-chemotherapy specimens. When both intensity of staining and percentage of positive cells were considered, post-chemotherapy specimens had a higher percentage of positive NE markers compared with pre-chemotherapy. In addition, there was no correlation between NE marker, HER2 or CEA expression (prior to or post treatment) and response to chemotherapy or survival. These data do not support the hypothesis that NE positive tumor cells are preferentially killed by chemotherapy in patients with stage IIIA non-small cell lung cancer.


Variations in reason for intention not to vaccinate across time, region, and by race/ethnicity, NIS-Teen (2008-2016).
Human papillomavirus (HPV) vaccination is expected to reduce HPV-related disease and cancer in the US. However, many parents are hesitant to obtain the vaccine for their children. The purpose of this study is to examine how the reasons for refusing the HPV vaccine vary across regions of the US, across time, and by race/ethnicity. This study used data on 13-17 year old adolescents collected by the National Immunization Survey - Teen (NIS-Teen) annually between 2008 and 2016. We evaluated the frequencies of parents who did not intend to vaccinate their children in the next year among unvaccinated children. Among these non-intenders, we evaluated how reasons for HPV vaccine hesitancy changed across time, by region of the US, and race/ethnicity. The proportion of non-intenders among unvaccinated decreased from 72% in 2010 to 58% in 2016. The most frequent reason for vaccine hesitancy was that parents felt HPV vaccination was not necessary (22.4%), followed by lack of provider recommendation (16.2%), and lack of knowledge (15.6%). Lack of provider recommendation increased in frequency as a reason for HPV vaccine hesitancy until 2012, then decreased in frequency through 2016. Cost was one reason that was elevated in all regions compared to the Northeast. Black non-intenders were less likely to report safety, costs, or their children's fear as reasons for not intending to vaccinate their children compared to white non-intenders. Hispanic non-intenders were more likely to report lack of knowledge and that the vaccine is not a school requirement as reasons not to vaccinate their children compared to white non-intenders. National advocacy for improving provider recommendation for HPV vaccination likely contributed to a sharp decline in HPV vaccine hesitancy due to lack of provider recommendation. Results indicate the need for multifaceted interventions to increase HPV vaccination.


Diaphragmatic activity during REM sleep in the adult cat.
Diaphragmatic electromyograms from five adult cats were studied to determine whether diaphragmatic activity, like central respiratory activity, increases in rapid-eye-movement (REM) sleep. Breaths with inspiratory durations between 250 and 2,000 ms were analyzed. 1) There was a greater slope of the moving time average of diaphragmatic activity in REM than in non-REM (NREM) sleep. These greater slopes occurred whether the route of breathing was through the upper airways or through an endotracheal tube and may have resulted from early recruitment of motor units. 2) Mean diaphragmatic activity was also greater, but other variables (peak activity, the area under the curve of diaphragmatic activity, mean intratracheal pressures, inspiratory airflow rates, and tidal volumes) were not greater in REM than in NREM sleep. 3) Diaphragmatic activity was similar in REM sleep and active wakefulness. 4) Across states, slope of the moving time average varied with the duration of inspiration: greater slopes were associated with shorter breaths. These results are consistent with an increase in central respiratory drive in REM sleep that increases the rate of rise of diaphragmatic activity.


Analysis of interleukin-4 and interleukin-10 and their association with the lymphocytic infiltrate in the small intestine of patients with coeliac disease.
Concentrations of pro-inflammatory cytokines are raised in the small intestine of patients with coeliac disease after ingestion of gluten but there are equivalent data on interleukin-4 (IL-4) and interleukin-10 (IL-10) producing cells. These cytokines are known to exert important regulatory effects on pro-inflammatory cytokine production from lymphocytes and macrophages. To investigate whether there is a primary deficiency of IL-4 and IL-10 producing cells and their site of production in the small intestine of patients with coeliac disease in relation to the changes in inflammatory cell infiltrate. Jejunal biopsy specimens from patients with coeliac disease (11 untreated, 10 treated) and nine disease controls were studied. Immunohistochemical staining of sections for IL-4 and IL-10 cytokines and the cell phenotypic markers CD3 (T lymphocytes) and CD45 (total inflammatory cell infiltrate) was carried out using monoclonal antibodies. Expression of IL-4 and IL-10 messenger RNA was detected by in situ hybridisation with oligonucleotide probe cocktails for each cytokine. IL-4 and IL-10 mRNA and protein were detected in the lamina propria of treated and untreated coeliac patients and disease controls but not in the epithelium. A significant increase in the number of CD45 (p < 0.005) and CD3 (p < 0.05) positive cells was found in the lamina propria of patients with untreated coeliac disease compared with treated coeliac patients and disease controls but there were no differences in IL-4 or IL-10 between these groups with either method. There is no primary deficiency of IL-4 and IL-10 producing cells in the small intestine of patients with coeliac disease. Detectable concentrations of IL-4 and IL-10 were found in control patients which suggests that these cytokines are involved in normal mucosal immunoregulation. The increased number of T lymphocytes but not IL-4 or IL-10 producing cells in the lamina propria of patients with untreated than in those with treated disease suggests not only that the lamina propria is the major mucosal compartment for cytokine production but that newly recruited mucosal T lymphocytes are directed to a predominant Th1 and not a Th2 cytokine response in coeliac patients on a diet containing gluten.


Models of academic nurse-managed centers.
It is unclear as to what degree these models form developmental stages. It is clear that each model has its strengths and areas of concern. Community needs, faculty expertise and interests, educational focus of the school of nursing, and the university's mission and goals are major determinants in identifying which model is most appropriate for any given school of nursing. Much can be learned from the experiences of other schools, which will be helpful for those already involved in the NMC movement of those faculty and schools of nursing considering developing such a school of nursing-managed health care service.


Synthesis of bimetallic complexes bridged by 2,6-bis(benzimidazol-2-yl) pyridine derivatives and their catalytic properties in transfer hydrogenation.
A series of binuclear rhodium(i) and iridium(i) complexes with 2,6-bis(benzimidazol-2-yl) pyridine (bzimpy) derivatives were synthesized and characterized by elemental analysis and spectroscopic methods. The molecular and crystal structures of complex 3d were determined by the single crystal X-ray diffraction technique. Their monometallic analogues were prepared to compare the catalytic properties of the bimetallic complexes. To determine the catalyst properties that result in a cooperative, bimetallic enhancement of the reaction rate, the systematic variation of the intermetallic distance and the ligand donor properties of the bimetallic complexes were explored based on the transfer hydrogenation reactions of ketones.


Genetic basis of myelodysplastic syndromes.
During the past decade, substantial progress has been made in the field of the genetics of myelodysplastic syndromes (MDS). These comprise a group of chronic myeloid neoplasms with abnormal cell morphology and progression to acute myeloid leukemia (AML), where revolutionary sequencing technologies have played a major role. Through extensive sequencing of a large number of MDS genomes, a comprehensive registry of driver mutations involved in the pathogenesis of MDS has been revealed, along with their impacts on clinical phenotype and prognosis. The most frequently affected molecules are involved in DNA methylations, chromatin modification, RNA splicing, transcription, signal transduction, cohesin regulation, and DNA repair. These mutations show strong positive and negative correlations with each other, suggesting the presence of functional interactions between mutations, which dictate disease progression. Because these mutations are associated with disease phenotype, drug response, and clinical outcomes, it is essential to be familiar with MDS genetics not only for better understanding of MDS pathogenesis but also for management of patients.


[IMPACT OF OPISTHORCHIS INVASION ON THE COURSE OF A SKIN PROCESS IN PATIENTS WITH ROSACEA].
The authors give the data-and results of their investigations of 47 patents with rosacea concurrent with chronic opisthorchiasis (Group 1) and 40 patients with rosacea without opisthorhiasis (Group 2): It is found that the severer clinical manifestations of rosacea are, the lower the quality of life is in patients. The patients with rosacea concurrent with chronic opisthorchiasis were found to have severe clinical forms. Rosacea diagnostic rating scores was 1.1-fold higher than in the patients without helminthiasis, suggesting a severer course. Quality-of-life dissatisfaction in patients with rosacea concurrent with chronic opisthorchiasis was significantly higher than in those with rosacea only.


Phaeobacter leonis sp. nov., an alphaproteobacterium from Mediterranean Sea sediments.
A novel Gram-stain-negative, strictly aerobic, heterotrophic bacterium, designated 306(T), was isolated from near-surface (109 cm below the sea floor) sediments of the Gulf of Lions, in the Mediterranean Sea. Strain 306(T) grew at temperatures between 4 and 32 °C (optimum 17-22 °C), from pH 6.5 to 9.0 (optimum 8.0-9.0) and between 0.5 and 6.0% (w/v) NaCl (optimum 2.0%). Its DNA G+C content was 58.8 mol%. On the basis of 16S rRNA gene sequence similarity, the novel isolate belongs to the class Alphaproteobacteria and is related to the genus Phaeobacter. It shares 98.7% 16S rRNA sequence identity with Phaeobacter arcticus, its closest phylogenetic relative. It contained Q-10 as the only respiratory quinone, C(18:1)ω7c and C(16:0) as major fatty acids (>5%) and phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, diphosphatidylglycerol, two unidentified lipids and an aminolipid as polar lipids. The chemotaxonomic data are consistent with the affiliation of strain 306(T) to the genus Phaeobacter. Results of physiological experiments, biochemical tests and DNA-DNA hybridizations (with P. arcticus) indicate that strain 306(T) is genetically and phenotypically distinct from the five species of the genus Phaeobacter with validly published names. Strain 306(T) therefore represents a novel species, for which the name Phaeobacter leonis sp. nov. is proposed. The type strain is 306(T) ( =DSM 25627(T) =CIP 110369(T) =UBOCC 3187(T)).


Inability of mice to generate cytotoxic T lymphocytes to vesicular stomatitis virus restricted to H-2Kk or H-2Dk.
H-2k mice are unable to generate cytotoxic T lymphocytes (CTL) to vesicular stomatitis virus (VSV). This apparent unresponsiveness is found for both major serotypes of VSV, VSV-Indiana and VSV-New Jersey. CTL unresponsiveness occurs despite the ability of H-2k mice to generate a humoral immune response against VSV that is comparable to that found in responder (H-2b and H-2a) strains. All H-2k mice regardless of background genes, including various Ig allotypes, were found to be nonresponders. H-2k-linked unresponsiveness mapped to both H-2Kk and H-2Dk and occurred despite the presence of responder alleles in (responder x nonresponder)F1 mice. The unresponsiveness cannot be attributed to an inability of VSV-infected H-2k target cells to express viral surface antigens of H-2 molecules. Further, unresponsiveness cannot be overcome by using secondary stimulation in vivo or in vitro. H-2k-linked unresponsiveness does not appear to be due to suppression, and no complementation has been found in various (nonresponder x nonresponder)F1 mice. Thus unresponsiveness to VSV in association with H-2Kk or H-2Dk appears to represent an extensive defect of immune responsiveness that probably occurs because VSV is not a natural mouse pathogen.


Membrane lipid order of human red blood cells is altered by physiological levels of hydrostatic pressure.
The effect of hydrostatic pressure at levels applied in diving or hyperbaric treatment (thus considered "physiological") on the order of lipid domains in human red blood cell (RBC) membrane was studied. Membrane order was determined by measuring 1) the fluorescence anisotropy (FAn) of lipid probes, 2) the resonance energy transfer from tryptophan to lipid probes, and 3) spectral shifts in Laurdan fluorescence emission. It was found that the application of mild pressure (< 15 atm) 1) increased, selectively, the FAn of lipid probes that monitor the membrane lipid core, 2) increased the tryptophan FAn, 3) increased the resonance energy transfer from tryptophan to lipid probes residing in the lipid core, and 4) induced changes in the Laurdan fluorescence spectrum, which corresponded to reduced membrane hydration. It is proposed that the application of pressure of several atmospheres increases the phase order of membrane lipid domains, particularly in the proximity of proteins. Because the membrane lipid order ("fluidity") of RBCs plays an important role in their cellular and rheological functions, the pressure-induced alterations of the RBC membrane might be pertinent to microcirculatory disorders observed in humans subjected to elevated pressure.


Biocompatible Nanostructured Silver-Incorporated Implant Surfaces Show Effective Antibacterial, Osteogenic, and Anti-Inflammatory Effects in vitro and in Rat Model.
Titanium (Ti) and its alloys are widely utilized in endosseous implants. However, their clinical efficacy is marred by complications arising from bacterial infections owing to their inadequate antibacterial properties. Consequently, enhancing the antibacterial attributes of implant surfaces stands as a pivotal objective in the realm of implantable materials research. In this study, we employed sequential anodization and plasma immersion ion implantation (PIII) technology to fabricate a silver-embedded sparsely titania nanotube array (SNT) on the near-β titanium alloy Ti-5Zr-3Sn-5Mo-15Nb (TLM) implants. The surface characteristics, antimicrobial properties, biocompatibility, and osteogenic activity of the silver-nanomodified SNT implant (SNT Ag) surface, alongside peri-implant inflammatory responses, were meticulously assessed through a combination of in vitro and in vivo analyses. Compared with polished TLM and SNT, the silver-embedded SNT (SNT Ag) surface retained the basic shape of nanotubes and stably released Ag+ at the ppm level for a long time, which demonstrated an effective inhibition and bactericidal activity against Staphylococcus aureus (SA) while maintaining ideal cytocompatibility. Additionally, the subtle modifications in nanotubular topography induced by silver implantation endowed SNT Ag with enhanced osteogenic activity and mitigated inflammatory capsulation in soft tissue peri-implants in a rat model. Incorporating a silver-embedded SNT array onto the implant surface demonstrated robust antibacterial properties, impeccable cytocompatibility, exceptional osteogenic activity, and the potential to prevent inflammatory encapsulation around the implant site. The Silver-PIII modification strategy emerges as a highly promising approach for surface applications in endosseous implants and trans-gingival implant abutments.


Renal contribution to thermolability in rats: role of renal nerves.
Body temperature is closely regulated via the integration of a number of mechanisms, the study of which has been greatly assisted by the exploitation of comparative physiology. Previous studies have demonstrated that chronic renal failure patients have significantly lower body temperatures than healthy subjects when artifacts from circadian changes were taken into consideration. We hypothesize that the blunting of renal sensory neurons after kidney partial ablation may contribute to the lack of suppression of sympathetic efferent outflow towards BAT, modifying the glucose metabolism signaling pathway, UCP 1 expression and liver mitocondrial respiratory chain activity. To evaluate the influence of renal mass reduction, renal denervation and chronic deafferentation by capsaicin on thermoregulation, glucose metabolism, UCP1 expression and liver mitocondrial respiration, was used respectively, the blocking of heat dissipation by thermoneutral body water immersion, the oxygen consumption by Clark-type electrode, and western blot method. The study confirmed that, following 5/6 nephrectomy, the basal core temperature of rats was significantly lower than that of control animals when maintained in a thermoneutral body water immersion recipient, as compared to controls. Additionally, we demonstrated that exposure of bilateral renal denervated or of renal chronic capsaicin-treated rats to a similar experimental protocol results in a fast and high rise in rectal temperature response, and this is associated with a significant increase in the basal serine phosphorylation and protein levels of Akt and protein levels of UCP1. This was observed despite unchanged liver mitochondria respiratory control and ADP/O ratios in 5/6 Nx, as well as DNx, when compared to control mitochondria. Speculatively, it may be suggested that one of the renal sensory nerve signal defects associated with decreased kidney energy generation, induced by kidney ablation, may result in an inability to control the body temperature.


Allergic reaction to Hulka clips.
Hulka clip sterilization has become a popular method of tubal occlusion. A case is presented in which the gold covering the Hulka clip resulted in an allergic reaction, evidenced by sterile abscess formation and resulting in exploratory laparotomy for removal of the Hulka clips, sterile abscess, and resultant adhesions. To the authors' knowledge, no previous case has been presented of this type of gold allergy. It would appear that careful screening for gold allergy should be undertaken before tubal sterilization with Hulka clips.


Less drinking, yet more problems: understanding African American drinking and related problems.
Researchers have found that, compared to European Americans, African Americans report later initiation of drinking, lower rates of use, and lower levels of use across almost all age groups. Nevertheless, African Americans also have higher levels of alcohol problems than European Americans. After reviewing current data regarding these trends, we provide a theory to understand this apparent paradox as well as to understand variability in risk among African Americans. Certain factors appear to operate as both protective factors against heavy use and risk factors for negative consequences from use. For example, African American culture is characterized by norms against heavy alcohol use or intoxication, which protects against heavy use but also provides within-group social disapproval when use does occur. African Americans are more likely to encounter legal problems from drinking than European Americans, even at the same levels of consumption, perhaps thus resulting in reduced consumption but more problems from consumption. There appears to be one particular group of African Americans, low-income African American men, who are at the highest risk for alcoholism and related problems. We theorize that this effect is due to the complex interaction of residential discrimination, racism, age of drinking, and lack of available standard life reinforcers (e.g., stable employment and financial stability). Further empirical research will be needed to test our theories and otherwise move this important field forward. A focus on within-group variation in drinking patterns and problems is necessary. We suggest several new avenues of inquiry.


Kocuria kristinae: an emerging pathogen in medical practice.
Introduction. Kocuria kristinae is becoming a growing public health challenge, especially for its ability to cause infections in immunocompromised patients. This bacterium is a Gram+coccus, catalase+, coagulase, and it is a common inhabitant of skin and oral mucosa.Aim. To investigate the spectrum of infections caused by K. K ristinae.Methodology. Between January-March 2018, we carried out a systematic search in PubMed utilizing the key search term 'Kocuria kristinae'. The selection criteria for studies were studies reporting cases of human infections due to K. kristinae, case-control and cohort studies and studies published in English or Spanish.Results. The literature search yielded 48 publications: after title, abstract and full-text analysis, 20 papers were consistent with the selection criteria. These studies were carried out in the period 2001-2017 in the USA, Japan, Taiwan, Hong Kong, Ukraine, Egypt, Bahrain, Serbia, India, Italy, Spain, Turkey and Mexico. K. kristinae was involved in 17 cases of central venous catheter-related bacteremia, four infective endocarditis, three acute peritonitis, one abdominal abscess, umbilical sepsis, acute cholecystitis and urinary tract infection. Additionally, K. kristinae was found in 40 % of carious cavities, although it is not clear whether they are directly involved in the development of caries. Antibiotic susceptibility testing has sometimes revealed multi-drug resistance.Conclusions. The clinical spectrum of K. kristinae infections has recently widened. The increasing spread of this underestimated bacterium and its resistance to antibiotics represent a new challenge for public health, which requires specific actions to limit it.


Risk factors for visceral leishmaniasis in India: further evidence on the role of domestic animals.
Studies investigating risk factors for visceral leishmaniasis (VL) on the Indian Subcontinent have shown contradictory results related to the role of domestic animals. In some studies having animals in or around the house was a risk factor, in others it was protective. We investigated the specific hypothesis that keeping domestic animals inside the house at night is a risk factor for VL. Individually matched case-control study. All patients with VL diagnosed in the study area in Bihar, India between March 1st, 2007 and December 1st, 2008 were eligible. For each case, we selected two random controls, with no history of previous VL; matched on sex, age group and neighbourhood. Patients and controls were subjected to a structured interview on the main exposure of interest and potential confounders; a conditional logistic regression model was used to analyse the data. We enrolled 141 patients and 282 controls. We found no significant associations between VL and keeping domestic animals inside the house (OR of 0.88 for bovines and 1.00 for 'any animal') or ownership of domestic animals (OR of 0.97 for bovines and 1.02 for 'any animal'). VL was associated with housing conditions. Living in a thatched house (OR 2.60, 95% CI 1.50-4.48) or in a house with damp floors (OR 2.60, 95% CI 1.25-5.41) were risk factors, independently from socio economic status. Keeping animals inside the house is not a risk factor for VL in Bihar, India. Improving housing conditions for the poor has the potential to reduce VL incidence.


Design and synthesis of DNA four-helix bundles.
The field of DNA nanotechnology has evolved significantly in the past decade. Researchers have succeeded in synthesizing tile-based structures and using them to form periodic lattices in one, two and three dimensions. Origami-based structures have also been used to create nanoscale structures in two and three dimensions. Design and construction of DNA bundles with fixed circumference has added a new dimension to the field. Here we report the design and synthesis of a DNA four-helix bundle. It was found to be extremely rigid and stable. When several such bundles were assembled using appropriate sticky-ends, they formed micrometre-long filaments. However, when creation of two-dimensional sheet-like arrays of the four-helix bundles was attempted, nanoscale rings were observed instead. The exact reason behind the nanoring formation is yet to be ascertained, but it provides an exciting prospect for making programmable circular nanostructures using DNA.


The delayed use of positive end-expiratory pressure (PEEP) during respiratory resuscitation following near drowning with fresh or salt water.
Investigations on the delayed use of positive end-expiratory pressure (PEEP) following a standardized form of near drowning with 12.5 ml/kg body weight of either fresh or salt water were carried out on 14 anaesthetized and ventilated young pigs. After a 3-min period of apnoea the animals were ventilated with 100% oxygen and with either the same or an increased tidal volume, and a PEEP of 5 cmH2O delayed to 20 min, over a period of 2 h. In both fresh and salt water, initial values of PaO2 and AaDo2 were regained by the end of the period of observation when a delayed PEEP was applied. The intrapulmonary right to left shunt, which increased to 40% of the cardiac output, fell by a half within 10 min of beginning PEEP ventilation, initial values being regained after 120 min. During the period of apnoea the arterial partial pressure of carbon dioxide almost doubled, and, when the tidal volume remained unaltered, was still some 20-30% above initial values at the end of 2 h, despite the use of PEEP. Normal PaCO2 levels were achieved on increasing the tidal volume by a factor of 1.4. The larger tidal volume had no influence on either the degree of shunt or the PaO2. The effective compliance, which was considerably reduced after near drowning, increased again with the use of delayed PEEP ventilation. On beginning respiratory resuscitation there was an initial tachycardia and, despite a fall in stroke volume, an increase in mean arterial pressure and cardiac output because of the previous hypoxia. Only minimal cardiocirculatory changes, and no change in oxygen availability, occurred secondary to the use of PEEP.


A study on the post-radiotherapy changes of temporomandibular joint in nasopharyngeal carcinoma patients.
Radiation-induced trismus, which is resulted from damage of the temporomandibular joint (TMJ), is one of the common late complications in nasopharyngeal carcinoma (NPC) patients after radical radiotherapy. This study investigated the radiation induced TMJ changes using ultrasonography in post-radiotherapy (post-RT) NPC patients. 114 NPC patients, who had completed radiotherapy for more than 4 years, were assessed with the maximum incisal distance (MID) and ultrasonography examination of TMJ from which the maximum disc thickness of the joint disc, the condyle irregularity (CI), joint vascularity (JV) and relative muscle echogenicity were assessed. The same assessments were conducted on 100 age-matched normal subjects. The results were compared among the patients with and without trismus, and the control group. The mean doses to the TMJ were estimated using the treatment planning system and their correlation with the magnitude of MID was also investigated by the Pearson correlation test. 39 out of the 114 patients (34.2%) presented with trismus. The average mean TMJ for all patients was 41.4 Gy, in which patients with trismus was significantly higher than patients without trismus (p = 0.017). The mean MID of patient group was significantly lower than control group (p < 0.001). The mean maximum disc thickness of the patient group was significantly smaller than the control group, whereas the mean CI and JV were significantly higher in patient group. For relative muscle echogenicity, a higher percentage of the control group showed hyperechoic pterygoid muscle than the patient group. The mean total dose to the TMJs for the patient group was 41.4 Gy and there was a mild negative correlation between the mean TMJ dose and the MID (r = -350). The TMJ in post-RT NPC patients showed reduction of disc thickness, increase of CI and JV. Patients with trismus demonstrated thinner disc thickness and higher JV than those without trismus. Advances in knowledge: Our study was the first cross-sectional comparative study involving over 100 patients and normal subjects that used ultrasound to assess the radiation-induced morphological changes of TMJ. Post-RT TMJ changes characterized by the reduction of disc thickness, increase of CI and JV were detected in the NPC patients. The parameters used in this study were able to detect the morphological differences between the patient group and control group, and therefore can be effectively used to monitor the TMJ condition of post-RT NPC patients.


Comparison of platelet storage in PL146 and PL732 plastic packs: preliminary in vitro studies.
This paper is a preliminary report of in vitro studies comparing platelet storage in the new polyolefin PL732 packs with the present polyvinyl PL146 packs. The parameters used to assess platelet viability in these studies were the recovery from the hypotonic stress test (HST) and the pH. The effect of the mass of concentrate was assessed by preparing 20 g, 35 g and 50 g packs. The method of agitation was tested comparing a vertical rotator with a flat-bed, rocking agitator. In all the subgroups the PL732 packs fared better than the PL146 packs in terms of HST recovery and pH. The 35 g and 50 g packs were statistically inseparable but the 20 g packs were significantly worse both in PL732 and PL146. The vertical rotator augmented the beneficial effects of the PL732 plastic especially in terms of pH. The 35 g and 50 g packs in PL732 on a vertical rotator gave results after 5 days storage at 22 degrees C which were vastly superior (p less than or equal to 0.001) to the 35 g and 50 g packs in PL146 after only three days storage. Thus it would appear that the use of PL732 packs might enable the storage life of platelet concentrates to be increased to five days. Further in vivo studies are to be undertaken to ensure these in vitro improvements benefit the patient.


Alu elements support independent origin of prosimian, platyrrhine, and catarrhine Mhc-DRB genes.
The primate major histocompatibility complex (Mhc) genes fall into two classes and each of the classes into several families. Of the class II families, the DRB family has a long and complex evolutionary history marked by gene turnover, rearrangement, and molecular convergence. Because the history is not easily decipherable from sequences alone, Alu element insertions were used as cladistic markers to support the surmised phylogenetic relationships among the DRB genes. Intron 1 segments of 24 DRB genes from five platyrrhine species and five DRB genes from three prosimian species were amplified by PCR and cloned, and the amplification products were sequenced or PCR-typed for Alu repeats. Three Alu elements were identified in the platyrrhine and four in the prosimian DRB genes. One of the platyrrhine elements (Alu50J) is also found in the Catarrhini, whereas the other two (Alu62Sc, Alu63Sc) are restricted to the New World monkeys. Similarly, the four prosimian elements are found only in this taxon. This distribution of Alu elements is consistent with the phylogeny of the DRB genes as determined from their intron 1 sequences in an earlier and the present study. It contradicts the exon 2-based phylogeny and thus corroborates the conclusion that the evolution of DRB exon 2 sequences is, to some extent, shaped by molecular convergence. Taken together, the data indicate that each of the assemblages of DRB genes in prosimians, platyrrhines, and catarrhines is derived from a separate ancestral gene.


Joint cognition and the role of human agency in random number choices.
Joint cognition refers to the mental systems that support group performance when carrying out a shared, or jointly owned task. We focused here on understanding the social configurations that underpin key phenomena in joint cognition, in particular, whether individual cognition in task-sharing environments is mostly shaped by social factors or not. To this end, we investigated, first and mainly, whether human presence is necessary for the creation of joint performance; second and separately, whether prior experience of task sharing has an adaptive influence on subsequent individual choices; and third and additionally, whether individual differences in a social trait mediate joint performance. We describe an experiment in which participants combined with another human or a computer as they attempted to generate a paired sequence that was as random as possible. First, we found little difference in joint performance with regard to whether a human or a computer was the co-participant, except for immediate repetitive response. Second, we found evidence for choice adaptation, but only under the lower time pressure. Third, we replicated previous research in which no systematic link was established between social desirability and joint performance. We conclude that joint cognition phenomena may be rooted primarily in turn-taking configurations rather than in social dynamics per se.


Treatment of Kaposi's sarcoma.
The classic form of Kaposi's sarcoma (KS) is a rare multifocal neoplasm, as described by Kaposi in 1872. One hundred nine years after Kaposi's first description of the disease, the interest in all aspects of this disease escalated because of the emergence of human immunodeficiency virus (HIV), which is frequently accompanied by KS. This prompted zealous research, as reflected by numerous reports. Despite recent important discoveries, we are still far from understanding the pathogenesis of the disease and the mechanism of action of its various treatment modalities. As of today, treatment consists of most of the old modalities, some old ones in an updated improved version, and some new and experimental therapies. Our purpose is to focus on recent or novel data and to mention available treatments and their advantages, disadvantages, and side effects. We will also speculate on future directions.


Preparticipation injury complaint is a risk factor for injury: a prospective study of the Moscow 2013 IAAF Championships.
To determine the health status of athletes before the start of an international athletics championship and to determine whether preparticipation risk factors predicted in-championship injuries. At the beginning of the 2013 International Association of Athletics Federations (IAAF) World Championships, all registered athletes (n=1784) were invited to complete a preparticipation health questionnaire (PHQ) on health status during the month preceding the championships. New injuries that occurred at the championships were prospectively recorded. The PHQ was completed by 698 (39%) athletes; 204 (29.2%) reported an injury complaint during the month before the championships. The most common mode of onset of preparticipation injury complaints was gradual (43.6%). Forty-nine athletes in the study reported at least one injury during the championships. Athletes who reported a preparticipation injury complaint were at twofold increased risk for an in-championship injury (OR=2.09; 95% CI 1.16 to 3.77); p=0.014). Those who reported a preparticipation gradual-onset injury complaint were at an almost fourfold increased risk for an in-championship time-loss injury (OR=3.92; 95% CI 1.69 to 9.08); p=0.001). Importantly, the preparticipation injury complaint severity score was associated with the risk of sustaining an in-championship injury (OR=1.14; 95% CI 1.06 to 1.22); p=0.001). About one-third of the athletes participating in the study reported an injury complaint during the month before the championships, which represented a risk factor for sustaining an injury during the championship. This study emphasises the importance of the PHQ as a screening tool to identify athletes at risk of injuries before international championships.


Ara h 6 complements Ara h 2 as an important marker for IgE reactivity to peanut.
The similarities of two major peanut allergens, Ara h 2 and Ara h 6, in molecular size, amino acid sequence, and structure have made it difficult to obtain natural Ara h 6 free of Ara h 2. The objectives of this study were to purify natural Ara h 6 that is essentially free of Ara h 2 and to compare its IgE reactivity and potency in histamine release assays to Ara h 2. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the highly purified allergen (<0.01% Ara h 2) revealed a single 14.5 kD band, and the identity of Ara h 6 was confirmed by liquid chromatography-tandem mass spectrometry. Ara h 6 showed a higher seroprevalence in chimeric IgE enzyme-linked immunosorbent assay (n = 54) but a weaker biological activity in basophil histamine release assays than Ara h 2. Purified Ara h 6 will be useful for diagnostic IgE antibody assays as well as molecular and cellular studies to investigate the immunological mechanisms of peanut allergy.


Hypertensive urgencies and emergencies. Prevalence and clinical presentation.
The prevalence and clinical picture of hypertensive urgencies and emergencies in an emergency department are poorly known. The aim of the present study was to evaluate the prevalence of hypertensive crises (urgencies and emergencies) in an emergency department during 12 months of observation and the frequency of end-organ damage with related clinical pictures during the first 24 hours after presentation. Hypertensive crises (76% urgencies, 24% emergencies) represented more than one fourth of all medical urgencies-emergencies. The most frequent signs of presentation were headache (22%), epistaxis (17%), faintness, and psychomotor agitation (10%) in hypertensive urgencies and chest pain (27%), dyspnea (22%), and neurological deficit (21%) in hypertensive emergencies. Types of end-organ damage associated with hypertensive emergencies included cerebral infarction (24%), acute pulmonary edema (23%), and hypertensive encephalopathy (16%) as well as cerebral hemorrhage, which accounted for only 4.5%. Age (67 +/- 16 versus 60 +/- 14 years [mean +/- SD], P < .001) and diastolic blood pressure (130 +/- 15 versus 126 +/- 10 mm Hg, P < .002) were higher in hypertensive emergencies than urgencies. Hypertension that was unknown at presentation was present in 8% of hypertensive emergencies and 28% of hypertensive urgencies. In conclusion hypertensive urgencies and emergencies are common events in the emergency department and differ in their clinical patterns of presentation. Cerebral infarction and acute pulmonary edema are the most frequent types of end-organ damage in hypertensive emergencies.


Noncovalent assembly. A rational strategy for the realization of chain-growth supramolecular polymerization.
Over the past decade, major progress in supramolecular polymerization has had a substantial effect on the design of functional soft materials. However, despite recent advances, most studies are still based on a preconceived notion that supramolecular polymerization follows a step-growth mechanism, which precludes control over chain length, sequence, and stereochemical structure. Here we report the realization of chain-growth polymerization by designing metastable monomers with a shape-promoted intramolecular hydrogen-bonding network. The monomers are conformationally restricted from spontaneous polymerization at ambient temperatures but begin to polymerize with characteristics typical of a living mechanism upon mixing with tailored initiators. The chain growth occurs stereoselectively and therefore enables optical resolution of a racemic monomer.


Safety, tolerability, and pharmacodynamics of an anti-interleukin-1α/β dual variable domain immunoglobulin in patients with osteoarthritis of the knee: a randomized phase 1 study.
To investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ABT-981, a human dual variable domain immunoglobulin simultaneously targeting interleukin (IL)-1α and IL-1β, in patients with knee osteoarthritis (OA). This was a randomized, double-blind, placebo-controlled, single-center study of multiple subcutaneous (SC) injections of ABT-981 in patients with mild-to-moderate OA of the knee (NCT01668511). Three cohorts received ABT-981 (0.3, 1, or 3 mg/kg) or placebo every other week for a total of four SC injections, and one cohort received ABT-981 (3 mg/kg) or placebo every 4 weeks for a total of three SC injections. Assessment of safety and tolerability were the primary objectives. A panel of serum and urine biomarkers of inflammation and joint degradation were evaluated. A total of 36 patients were randomized (ABT-981, n = 28; placebo, n = 8); 31 (86%) completed the study. Adverse event (AE) rates were comparable between ABT-981 and placebo (54% vs 63%). The most common AE reported with ABT-981 vs placebo was injection site erythema (14% vs 0%). ABT-981 significantly reduced absolute neutrophil count and serum concentrations of IL-1α/IL-1β, high-sensitivity C-reactive protein, and matrix metalloproteinase (MMP)-derived type 1 collagen. Serum concentrations of MMP-derived type 3 collagen and MMP-degraded C-reactive protein demonstrated decreasing trends with ABT-981. Antidrug antibodies were found in 37% of patients but were not associated with the incidence or severity of AEs. ABT-981 was generally well tolerated in patients with knee OA and engaged relevant tissue targets, eliciting an anti-inflammatory response. Consequently, ABT-981 may provide clinical benefit to patients with inflammation-driven OA.


Spatial distribution, movements, and geographic range of Steller sea lions (Eumetopias jubatus) in Alaska.
The two stocks of Steller sea lions (Eumetopias jubatus) in Alaska include an endangered western stock, recently recovering in parts of its range following decades of decline, and an eastern stock which was removed from the U.S. Endangered Species List in 2013 following increasing numbers since the 1970s. Information on overlapping distributions of eastern and western sea lions is needed for management considerations. We analyzed >30,000 sightings collected from 2000-2014 of 2,385 sea lions that were branded as pups at 10 Alaskan rookeries to examine mesoscale (mostly <500km) spatial distribution, geographic range, and geographic population structure based on natal rookery, sex, and age during breeding and non-breeding seasons. Analyses of summary movement measures (e.g., natal rookery, sex, and age-class differences in spatial distribution and geographic range) indicate wide variation in rookery-specific movement patterns. Correlations between movement measures and population dynamics suggested movement patterns could be a function of density dependence. Animals from larger rookeries, and rookeries with slower population growth and lower survival, had wider dispersion than animals from smaller rookeries, or rookeries with high growth and survival. Sea lions from the largest rookery, Forrester Island, where survival and population trends are lowest, were the most widely distributed. Analysis of geographic population structure indicated that animals born in the eastern Aleutian Islands had the most distinct movements and had little overlap with other western sea lions. Northern Southeast Alaska, within the eastern stock, is the area of greatest overlap between stocks, and is important to western animals, especially those born in Prince William Sound. Detailed knowledge of distribution and movements of western sea lions is useful for defining recovery and population trend analysis regions that better reflect dispersion and population structure and provides valuable information to managers as critical habitat is re-evaluated and the location of the stock boundary reconsidered.


Baseline survey of sexually transmitted infections in a cohort of female bar workers in Mbeya Region, Tanzania.
To determine baseline prevalence of sexually transmitted infections (STI) and other reproductive tract infections (RTI) and their association with HIV as well as sociodemographic and behavioural characteristics in a newly recruited cohort of female bar workers in Mbeya Region, Tanzania. 600 female bar workers were recruited from 17 different communities during September to November 2000 and underwent gynaecological examination, laboratory testing for HIV/STI, and interviews using structured questionnaires. HIV-1 seroprevalence was 68%. Prevalences of STI/RTI were high titre syphilis (TPPA/RPR >/=1/8), 9%; herpes simplex virus 2 antibodies, 87%; chlamydia, 12%; gonorrhoea, 22%; trichomoniasis, 24%; and bacterial vaginosis, 40%. HIV infection was associated with TPPA and HSV-2 seropositivity, bacterial vaginosis and clinically diagnosed genital ulcers, blisters, and warts. Reported high risk sexual behaviour during the past year (having multiple casual partners) was associated with prevalent STI. Female bar workers in Mbeya are at high risk of STI and HIV infection. Targeted STI/HIV prevention interventions for these women and their sexual partners need to be reinforced. Methods should be sought to improve healthcare seeking and to provide easily accessible and affordable STI care services.


α-Fetoprotein promoter-driven Cre/LoxP-switched RNA interference for hepatocellular carcinoma tissue-specific target therapy.
RNA interference (RNAi) has recently emerged as a potential treatment modality for hepatocellular carcinoma (HCC) therapy, but the lack of cellular targets and sustained efficacy limits its application. The purpose of this study is to develop an HCC tissue-specific RNAi system and investigate its possibility for HCC treatment. Two different HCC-specific RNAi systems in which therapeutic miRNA or shRNA against target gene (Beclin 1) was directly or indirectly driven by alpha-fetoprotein promoter (AFP-miRNA and AFP-Cre/LoxP-shRNA) were constructed. Human HCC cell lines (HepG2, Hep3B and HCCLM3) and non-HCC cell lines (L-02, Hela and SW1116) were infected with the systems. The effectiveness and tissue-specificity of the systems were examined by Q-PCR and western blot analysis. The efficacy of the systems was further tested in mouse model of HCC by intravenous or intratumoral administration. The feasibility of the system for HCC treatment was evaluated by applying the system as adjuvant therapy to enhance sorafenib treatment. An AFP-Cre/LoxP-shRNA system targeting Atg5 gene (AFP-Cre/LoxP-shRNA-Atg5) was constructed and its efficacy in sensitizing HCC cells (MHCC97L/PLC) to sorafenib treatment was examined by apoptosis assay in vitro and tumorigenesis assay in vivo. The AFP-miRNA system could silence target gene (Beclin 1) but required a high titer which was lethal to target cells. The AFP-Cre/LoxP-shRNA system could efficiently knockdown target gene while maintain high HCC specificity. Intratumoral injection of the AFP-Cre/LoxP-shRNA system could efficiently silence target gene (Beclin 1) in vivo while intravenous administration could not. The AFP-Cre/LoxP-shRNA system target Atg5 gene could significantly sensitize MHCC97L/PLC cells to sorafenib-induced apoptosis in vitro and tumor growth suppression in vivo. An efficient HCC tissue-specific RNAi system (AFP-Cre/LoxP-shRNA) was successfully established. The system provides a usable tool for HCC-specific RNAi therapy, which may serve as a new treatment modality for HCC.


Magnets applied to acupuncture points as therapy - a literature review.
To summarise the acu-magnet therapy literature and determine if the evidence justifies further investigation of acu-magnet therapy for specific clinical indications. Using various search strategies, a professional librarian searched six electronic databases (PubMed, AMED, ScienceDirect College Edition, China Academic Journals, Acubriefs, and the in-house Journal Article Index maintained by the Oregon College of Oriental Medicine Library). English and Chinese language human studies with all study designs and for all clinical indications were included. Excluded were experimental and animal studies, electroacupuncture and transcranial magnetic stimulation. Data were extracted on clinical indication, study design, number, age and gender of subjects, magnetic devices used, acu-magnet dosing regimens (acu-point site of magnet application and frequency and duration of treatment), control devices and control groups, outcomes, and adverse events. Three hundred and eight citations were retrieved and 50 studies met our inclusion criteria. We were able to obtain and translate (when necessary) 42 studies. The language of 31 studies was English and 11 studies were in Chinese. The 42 studies reported on 32 different clinical conditions in 6453 patients from 19862007. A variety of magnetic devices, dosing regimens and control devices were used. Thirty seven of 42 studies (88%) reported therapeutic benefit. The only adverse events reported were exacerbation of hot flushes and skin irritation from adhesives. Based on this literature review we believe further investigation of acu-magnet therapy is warranted particularly for the management of diabetes and insomnia. The overall poor quality of the controlled trials precludes any evidence based treatment recommendations at this time.


Stingray placental analogues: structure of trophonemata in Rhinoptera bonasus.
The cownose ray, Rhinoptera bonasus, displays a non-placental form of viviparity since direct maternal-embryonic connections are lacking. Early stage embryos depend on yolk reserves for growth to 215 mm disc width; growth to term, 405 mm disc width, is effected by ingestion of uterine histotrophe. During late gestation, the maternal uterine epithelium possesses 2-3 cm long spatulate, villiform appendages, termed trophonemata. These secrete histotrophe, which is a viscous, nutrient fluid. Scanning electron microscopy of the trophonematal surface reveals branching ridges, each of which is supplied by a capillary. The secretory unit is composed of 8-10 cells joined by extensive junctional complexes. Characteristically, secretory cells have a rough endoplasmic reticulum whose irregular cisternae are grossly distended and filled with low density flocculent material. Uncoated vesicles are given off by an extensive juxtanuclear Golgi complex. Coated vesicles are also present, but are not directly associated with the Golgi complex. Electron dense granules, larger lysosome-like vesicles, and multivesicular bodies are in the vicinity of the Golgi.


Mapping and conservation of the group-specific component gene in mouse.
The group-specific component (GC), also known as the vitamin D-binding protein, transports vitamin D and its metabolites in plasma to target tissues throughout the body. The GC gene shares an evolutionary origin with genes encoding albumin (ALB) and alpha-fetoprotein (AFP). All three genes are descendants of an evolutionary ancestor that arose from an intragenic triplication. As a result, each gene is composed of three homologous domains. The study described here characterizes and compares mouse GC to the corresponding nucleotide and amino acid sequences of GC from human and rat. The deduced amino acid sequence of mouse GC was 78% identical to human and 91% identical to rat GC. The results suggest that, unlike the corresponding sequences in the ALB and AFP genes, chromosomal sequences encoding the first domain and the leader sequence of the GC gene have specifically been conserved throughout vertebrate evolution. Protection of domain I during evolution may correlate with an important functional aspect of its sequence. The mouse GC gene was mapped to chromosome 5, where the ALB and AFP genes are also located, demonstrating conservation of the three genes in vertebrate species.


Observing, performing, and understanding actions: revisiting the role of cortical motor areas in processing of action words.
Language content and action/perception have been shown to activate common brain areas in previous neuroimaging studies. However, it is unclear whether overlapping cortical activation reflects a common neural source or adjacent, but distinct, sources. We address this issue by using multivoxel pattern analysis on fMRI data. Specifically, participants were instructed to engage in five tasks: (1) execute hand actions (AE), (2) observe hand actions (AO), (3) observe nonbiological motion (MO), (4) read action verbs, and (5) read nonaction verbs. A classifier was trained to distinguish between data collected from neural motor areas during (1) AE versus MO and (2) AO versus MO. These two algorithms were then used to test for a distinction between data collected during the reading of action versus nonaction verbs. The results show that the algorithm trained to distinguish between AE and MO distinguishes between word categories using signal recorded from the left parietal cortex and pre-SMA, but not from ventrolateral premotor cortex. In contrast, the algorithm trained to distinguish between AO and MO discriminates between word categories using the activity pattern in the left premotor and left parietal cortex. This shows that the sensitivity of premotor areas to language content is more similar to the process of observing others acting than to acting oneself. Furthermore, those parts of the brain that show comparable neural pattern for action execution and action word comprehension are high-level integrative motor areas rather than low-level motor areas.