[Effect of lysophosphatidic acid increase the permeability of blood-brain barrier model].
To explore if lysophosphatidic acid (LPA) can regulate the permeability of blood-brain barrier (BBB) and the possible mechanism. Astrocytes and blood microvascular endothelial cells (BMECs) of neonatal SD rat were co-cultured to establish BBB model in vitro. The BBB models were divided randomly into 3 groups: blank control group (Group C), LPA group (Group L, treated with LPA 10 micromol/L for 2 h), and Ro31-8220 plus LPA group. (Group Ro + L, pretreated with Ro31-8220, a selective protein kinase inhibitor 5 micromol/L for 2 h and then treated with LPA 10 micromol/L for 2 h). 12I-bovine serum albumin (BSA) was added into the culture fluid of the BBB models and then the permeability of the BBB models was detected by gamma-events-per-unit-time meter. The cells expressing PKC-alpha were detected by flow cytometry (FCM). Phalloidin staining and fluorescence microscopy were used to detect the expression of F-actin. The BBB-tight-junction (TJ) was observed by electron microscopy. The expression of claudin-5 was detected by Western blotting. The throughput of 125I-BSA of Group L was 364 cmp +/- 15 cmp, significantly higher than those of the Group C and Group RO + L (184 cmp +/- 10 cmp and 223 cmp 9 cmp respectively, both P < 0.01). FCM showed that the rate of PKC-alpha expressing-BMECs of Group L was 77% +/- 7%, significantly higher than those of Groups C and Ro + L (42% +/- 4% and 52% +/- 3% respectively, both P < 0.01). The claudin-5 expression of Group L was 0.035 +/- 0.004, significantly lower than those of Groups C and Ro + L (1.00 +/- 0.03 and 0. 574 +/- 0.07 respectively, both P < 0.01). Phalloidin staining showed that a zone of F-actin filaments in Group C, intercellular spaces were seen in Group L, and F-actin filaments were recombined in Group Ro + L. Transmission electron microscopy showed that there was continuous high-density BBB-TJ in Group C, the BBB-TJ of Group L was obviously opened, and the BBB-TJ of Group Ro + L was partially opened at a lower degree. LPA accommodates the BBB-TJ and the permeability of BBB via the activation of PKC-alpha channel which down-regulates the caudin-5 expression and F-actin recombination. Lysophosphatidic acid;


Evolution of Cryoglobulinemia in Direct-Acting Antiviral-Treated Asian Hepatitis C Patients With Sustained Virological Responses: A 4-Year Prospective Cohort Study.
How cryoglobulinemia evolves after sustained virological response (SVR) following direct-acting antiviral (DAA) treatment in Asian hepatitis C virus (HCV)-infected patients remains elusive. A prospective cohort study was conducted in 422 Taiwanese patients (358 completed DAA therapy and 353 experienced SVRs). Serum cryoglobulins were surveyed at baseline and every 3-6 months posttherapy. Of 422, 227 (53.8%) had cryoglobulinemia, 8 (1.89%) had cryoglobulinemic vasculitis. Of 227, 54 (23.8%), 57 (25.1%) and 116 (51.1%) had 1, 2 and 3 cryoglobulins, respectively; those with 3 cryoglobulins had the highest alanine aminotransferase, immunoglobulin G (IgG) and fibrosis-4 index. During a 4-year follow-up, among SVR patients, cryoglobulinemia rates decreased from 56.4% to 15.4%, single cryoglobulin rates increased (21.6% to 63.9%) and 3 cryoglobulin rates decreased (55.7% to 11.1%). Compared with baseline values, among SVR patients with baseline cryoglobulinemia, complement component 4 levels increased, and IgG and IgM levels decreased until 48 weeks posttherapy for those without posttherapy cryoglobulinemia. All 8 cryoglobulinemic vasculitis patients exhibited SVRs; 5 (62.5%) achieved complete clinical response 12 weeks posttherapy, of whom, 2 (40%) experienced clinical relapse 24~48 weeks posttherapy. Baseline IgM levels were associated with posttherapy cryoglobulinemia in SVR patients (cut-off values at 12, 24, 48 weeks and 4 years posttherapy: 130, 105, 118 and 168 mg/dL, respectively). Among DAA-treated SVR patients, in 4 years, cryoglobulinemia rates decreased from 56.4% to 15.4%, multiple cryoglobulin rates decreased, cryoglobulinemia signals reversed, 62.5% of cryoglobulinemic vasculitis patients achieved complete clinical response (40% had relapse), and baseline IgM levels indicated posttherapy cryoglobulinemia.


Short QT Syndrome in Current Clinical Practice.
Short QT syndrome is a rare inherited autosomal dominant cardiac channelopathy associated with malignant ventricular and atrial arrhythmias. A shortened corrected QT interval is a marker for risk of malignant arrhythmias, which are secondary to increased transmural dispersion of repolarization. The underlying gain of function mutations in the potassium channels are most common but genetic testing remains low yield. This review discusses the cellular mechanisms, genetic involvement, clinical presentation, and current recommended management of patients with short QT syndrome relevant to current clinical practice.


Splitting and flattening of helical carbon nanofibers by acid treatment.
Helical carbon nanofibers (HCNFs), such as the carbon nanocoil (CNC) and the carbon nanotwist (CNTw), were synthesized by catalytic chemical vapor deposition using a substrate. HCNFs are classified into round and angular types according to the fiber cross-sections. When four types of HCNFs (round-type CNC and CNTw, angular-type CNC and CNTw) were acidified in a 30% hydrogen peroxide solution, only the angular type CNC was found to show a drastic shape change. The shape change observed was a splitting followed by a flattening of the angular type CNCs. The CNC was split into two or three thinner flat fibers. As a function of the treatment temperature, the weight of the CNCs decreased above 80 degrees C and the CNCs were etched effectively at 140 degrees C. The longer the reaction time the lower the weight of the CNCs, and the weight loss reached a saturation point when the reaction time was greater than 45 min at 140 degrees C. The splitting and flattening of the CNC occurred during the weight loss process. To analyze the CNC structure, electron tomography of the as-grown and acid-treated CNCs was obtained using a computerized tomograph system with transmission electron microscopy (TEM). The 3D-images were constructed using the TEM images collected at different tilt angles. The 3D image reconstructions showed that the CNCs had a tubular structure and were composed of several helical fibers which act as frames.


Ciprofloxacin treatment of urinary infections results in increased resistance of urinary E. coli to ciprofloxacin and co-trimoxazole.
Between 2000 and 2006 the sum of ciprofloxacin and folic acid antagonists prescriptions to Bavarian (South-eastern Gemany) outpatients stayed constant. However, prescription numbers of ciprofloxacin increased while those of folic acid antagonists decreased suggesting an apparent shift in the treatment of urinary infections toward ciprofloxacin. During the observation period the proportion of E. coli resistant against ciprofloxacin increased from 5% to 10% while that against co-trimoxazole increased from 21% to 27%. The proportion of E. coli simultaneously exhibiting resistance to ciprofloxacin and co-trimoxazole increased from 3.9% to 8.5%. A leading influence of ciprofloxacin application for these developments is discussed.


Large adrenal leiomyoma presented as adrenal incidentaloma in an AIDS patient: A rare entity.
The literature on adrenal gland tumour in HIV-infected patients is scarce. We report a 46-year-old Malay man with HIV and Hepatitis C infection presenting with a large nonfunctioning adrenal tumour. Computed tomography showed a large right adrenal tumour with heterogeneous enhancement and central necrosis. A high index of suspicion of a malignant tumour or pheochromocytoma led us to surgical removal of the adrenal gland. In this case report, we highlight important features to look for during pre-op evaluation of a large adrenal mass. Appropriate action should be taken when there is a suspicion of a pheochromocytoma or malignancy.


Detector response function of an energy-resolved CdTe single photon counting detector.
While spectral CT using single photon counting detector has shown a number of advantages in diagnostic imaging, knowledge of the detector response function of an energy-resolved detector is needed to correct the signal bias and reconstruct the image more accurately. The objective of this paper is to study the photo counting detector response function using laboratory sources, and investigate the signal bias correction method. Our approach is to model the detector response function over the entire diagnostic energy range (20 keV <E< 140 keV) using a semi-analytical method with 12 parameters. The model includes a primary photo peak, an exponential tail, and four escape peaks. Four radioactive isotopes including Cdmium-109, Barium-133, Americium-241 and Cobalt-57 are used to generate the detector response function at six photon energies. The 12 parameters are obtained by non-linear least-square fitting with the measured detector response functions at the six energies. The correlations of the 12 parameters with energy are also investigated with the measured data. The analytical model generally describes the detector response function and is in good agreement with the measured data. The trend lines of the 12 parameters indicate higher energies tend to cause grater spectrum distortion. The spectrum distortion caused by the detector response function on spectral CT reconstruction is analyzed theoretically, and a solution to correct this spectrum distortion is also proposed. In spectral and fluorescence CT, the spectrum distortion caused by detector response function poses a problem and cannot be ignored in any quantitative analysis. The detector response function of a CdTe detector can be obtained by a semi-analytical method.


Profile and Determinants of Neurocognitive Dysfunction in a Sample of Adult Nigerians With Heart Failure.
Heart failure (HF) in Africans is peculiar because subjects are younger than whites and have lower socioeconomic and educational level in addition to the high prevalence of hypertension-related etiology and increased mortality. Whereas cognitive dysfunction have been demonstrated among whites with HF, the prevalence and pattern of cognitive dysfunction among sub-Saharan African patients with HF have not been evaluated against this background. The aim of this study is to determine the 1-year prevalence and the factors contributing to cognitive dysfunction in a cohort of Nigerian patients with HF. In this cross-sectional case-control study, cognitive performance was evaluated in 111 consecutive individuals (60 HF patients and 51 controls matched for age, gender, and level of education) using the Community Screening Interview for Dementia, Word List Learning Delayed Recall, Boston Naming Test, and Modified Token Test. Other clinical and disease-specific variables were collated and correlated with cognitive performance. The mean total Community Screening Interview for Dementia, Word List Learning Delayed Recall, Boston Naming Test, and Modified Token Test scores were significantly lower among HF patients (P = < .001). The prevalence of global cognitive dysfunction was 90.0% in HF and 5.9% among controls (odds ratio, 15.3; 95% confidence interval, 5.08-46.01). Elevated systolic blood pressure, increased comorbidity index, and wide pulse pressure were significantly associated with poorer performance on at least 1 neuropsychological test. Using a multivariate linear regression analysis, pulse pressure retained its significance (P = .029; 95% confidence interval, -0.117 to -0.007) as the most important predictor of cognitive dysfunction in the cohort of HF patients. Cognitive dysfunction is prevalent among this sample of Nigerians with HF. Regular cognitive screening is therefore advocated among this high-risk group. Controlling comorbidities as well as blood pressure may improve cognitive performance among patients with HF.


Vascular endothelial senescence: from mechanisms to pathophysiology.
Most mitotically competent mammalian cell types can react to stress by undergoing a phenotypically distinctive and permanent form of growth arrest called "cellular senescence." This response has been extensively characterized in cell culture and more recently it has been found to occur also in vivo in a number of tissues. In this review I will present the case for the occurrence of senescence in the vascular endothelium. I will also discuss the mechanisms and factors that modulate endothelial cell replicative capacity and the onset of senescence. Finally, I will examine the senescent phenotype and its possible consequences for the development and progression of vascular diseases.


A ζ-carotene desaturase gene, IbZDS, increases β-carotene and lutein contents and enhances salt tolerance in transgenic sweetpotato.
ζ-Carotene desaturase (ZDS) is one of the key enzymes in carotenoid biosynthesis pathway. However, the ZDS gene has not been applied to carotenoid improvement of plants. Its roles in tolerance to abiotic stresses have not been reported. In this study, the IbZDS gene was isolated from storage roots of sweetpotato (Ipomoea batatas (L.) Lam.) cv. Nongdafu 14. Its overexpression significantly increased β-carotene and lutein contents and enhanced salt tolerance in transgenic sweetpotato (cv. Kokei No. 14) plants. Significant up-regulation of lycopene β-cyclase (β-LCY) and β-carotene hydroxylase (β-CHY) genes and significant down-regulation of lycopene ε-cyclase (ε-LCY) and ε-carotene hydroxylase (ε-CHY) genes were found in the transgenic plants. Abscisic acid (ABA) and proline contents and superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) activities were significantly increased, whereas malonaldehyde (MDA) content was significantly decreased in the transgenic plants under salt stress. The salt stress-responsive genes encoding pyrroline-5-carboxylate reductase (P5CR), SOD, CAT, ascorbate peroxidase (APX) and POD were found to be significantly up-regulated in the transgenic plants under salt stress. This study indicates that the IbZDS gene has the potential to be applied for improving β-carotene and lutein contents and salt tolerance in sweetpotato and other plants.


Case-Fatality Ratio of Blood Culture-Confirmed Typhoid Fever in Dhaka, Bangladesh.
With impending rollout of new conjugate typhoid vaccines, better estimates of typhoid case-fatality ratio are needed for countries to set priorities for public health programs. We enrolled 1425 patients of all ages with blood culture-confirmed Salmonella Typhi from laboratory networks serving inpatients and outpatients in Dhaka, Bangladesh. Participants were asked about symptoms and complications including death experienced over a median 3-month period following blood culture diagnosis. Four fatal cases were identified (case-fatality ratio of 0.3% [95% confidence interval, .05%-.55%]). Applying this case-fatality ratio to global typhoid burden estimates would reduce deaths by 70%.


Penile cellulitis due to community-acquired methicillin-resistant Staphylococcus aureus in an HIV-positive man.
This is a study of aggressive penile cellulitis in an HIV-positive man due to community-acquired methicillin-resistant Staphylococcus aureus. Discussion focuses on the importance of recognizing this pathogen in the sexual health setting and possible causes of penile cellulitis.


Molecular architecture of the Mn2+-dependent lactonase UlaG reveals an RNase-like metallo-beta-lactamase fold and a novel quaternary structure.
The ulaG gene, located in the ula regulon, is crucial for the catabolism of l-ascorbate under anaerobic conditions and it has been proposed to encode for the putative l-ascorbate-6-P lactonase. The ulaG gene is widespread among eubacteria, including human commensal and pathogenic genera such as Escherichia, Shigella, Klebsiella and Salmonella. Here, we report the three-dimensional structures of the apoenzyme and Mn(2+) holoenzyme of UlaG from E. coli to 2.6 A resolution, determined using single-wavelength anomalous diffraction phasing and molecular replacement, respectively. The structures reveal a highly specialized metallo-beta-lactamase-like fold derived from an ancient structural template that was involved in RNA maturation and DNA repair. This fold has a novel quaternary architecture consisting of a hexameric ring formed by a trimer of UlaG dimers. A mononuclear Mn(2)(+)-binding site resides at the core of the active site, which displays micromolar affinity for Mn(2+) and a distorted trigonal bipyramidal coordination. The active site Mn(2+) ion can be replaced by Co(2+) or Zn(2+), but not by Fe(3+). We further show that the Mn(2+) or Co(2)(+)-loaded enzyme exhibits lactonase activity towards l-ascorbate 6-P, thereby providing the first direct evidence of its catalytic role in the L-ascorbate catabolic pathway. Guided by the structural homology, we show that UlaG is able to cleave phosphodiester linkages in cyclic nucleotides, suggesting that the conservation of the fold and of the key catalytic residues allows for the evolutionary acquisition of substrate specificity for novel but related substrates.


Amphiphilic nanosheet self-assembly at the water/oil interface: computer simulations.
In this paper, dissipative particle dynamics simulations are performed to study the interfacial and emulsion stabilizing properties of various systems of amphiphilic nanosheets (ANs) self-assembled at the oil/water (O/W) interface. The ANs have a dimensional symmetry structure that encompasses a triangular-plate at the center and two soft comb-like shells constructed with hydrophilic and hydrophobic polymers. As the simulation results show, the AN molecules are highly oriented in interfacial films with their triangular nanosheets parallel to the O/W interface, while their hydrophobic and hydrophilic segments attempt to immerse into the oil phase and aqueous phase, respectively. These results reveal that the rotation of ANs at oil/water interfaces is greatly restricted, meanwhile, their nanosheet (or planar) configuration facilitates their favorable orientation thereby, thus making the emulsion more stable. At higher concentrations, a wrapped-like or micelle morphology is observed. The O/W emulsions stabilized by ANs were also simulated, and it is interesting to find AN 'patches' at the O/W interface which resembles the leather patches on a football. By introducing the "amphiphilic nanosheet balance" concept, the hydrophilic-lipophilic balance (HLB) values of ANs were calculated. Due to their properties of two-dimensional symmetry, the HLB values of ANs tend to approximately 1 which reveals a stronger stability for emulsions.


Quadruplex-forming properties of FRAXA (CGG) repeats interrupted by (AGG) triplets.
The (CGG) repeats associated with X-chromosome fragility are generally believed to form quadruplexes. This notion has persisted although it had been shown that only very short (CGG)(n) sequences form quadruplexes and that this quadruplex formation occurs in conditions far from physiological. We have now studied, using CD and absorption spectroscopies, quadruplex formation of (CGG)(n) (n=4, 7, 8, or 16) and their analogs interrupted by (AGG) triplets under various solvent conditions. In healthy individuals, (AGG) triplets are interspersed throughout the (CGG) repeat regions and appear to hinder (CGG)(n) motif expansion. Here we show that (CGG) repeats do not form quadruplexes under physiological conditions in aqueous solution but, interestingly, quadruplexes are readily formed in water-ethanol solutions. The presence of (AGG) triplets markedly stabilized quadruplex formation. Quadruplexes may thus hinder rather than support (CGG)(n) motif expansion.


Sexual homicide in the USA committed by juveniles and adults, 1976-2007: Age of arrest and incidence trends over 32 years.
Reliable epidemiological data on sexual homicide are sparse, especially on trends in its incidence over time and age at arrest. Our main aims were to study age at arrest and incidence trends for sexual homicide in the USA over about three decades (1976-2007). We conducted longitudinal analyses of data from the largest USA homicide database available for the years 1976-2007. The mean age at arrest for a sexual homicide was 26.3 years (range 7-76; modal 21 years). Three quarters of these offenders were young adults aged 18-35. Age at probable first arrest for a sexual homicide rose significantly from a mean of 25 to a mean of 29 years over the study period. The last decade of the three studied accounted for just one quarter of the homicides as charged in the whole period, but the proportion of sexual homicides specifically fell with each decade, so that the first period accounted for 56% of those in the whole period, the second for 33% and the final decade for just 11%. This was reflected in a reduction in the proportion of all homicides that were sexual, from 1.4% in the first decade to 0.8% in the second and 0.4% in the third, declining by a factor of five for adults and seven for juveniles. Use of official national criminal statistics has limitations in studying the epidemiology of any particular behaviour. Nonetheless, our findings of falling sexual homicide rates and of changes in at least one important demographic of these killers indicate a need for a considered reappraisal of such crimes. Establishment of accurate epidemiology and a study of associated factors may assist in the improvement of investigative and preventive strategies.


Angioleiomyoma in the tonsil: an uncommon tumour in a rare site.
An angioleiomyoma was excised from the palatine tonsil in a 30-year-old woman who complained of a painless swelling in the region of the tonsil. The mucosa covering the lesion showed prominent dilated blood vessels, necessitating vascular laboratory investigations to exclude any possibility of an aneurysm arising from the carotid system. The mass was excised with little blood loss. This was an uncommon tumour in an unusual site and required radio-imaging and angiographic studies of the great vessels of the head and neck before any operation was attempted. To the best of our knowledge, this is the first case reported in English.


Feminizing genitoplasty: a synopsis of issues relating to genital surgery in intersex individuals.
This review of the literature relevant to genitoplasty explores multiple factors that could impact and improve long-term outcomes. In 1998, surgeons began a dialogue that fostered interactive multidisciplinary exchanges regarding necessity, timing, and risks related to genitoplasty. Prior practice had embraced a simplistic approach--make an intersexed child resemble either a typical boy or girl. But surgery was never 'perfect' because function was often sacrificed for form, the goal being to create an aesthetic appearance. Compounding the difficulties of this type of surgery were the demands of the patients and parents for clarity, sure direction, and surgery that looked cosmetically authentic and provided good function. They demanded answers that medical experts could not readily provide regarding long-term outcomes. To increase patient satisfaction, we seek such outcomes and knowledge to better our understanding for optimal patient management and care. A review of current research is provided that might have important implications impacting surgical issues. Knowledge garnered from fields other than surgery is explored for potential applications that could improve surgical outcomes. Surgical technique modifications may be part of the solution to a complex problem, but they are not the sole solution. A multidisciplinary approach is required because to this date, surgical promise is limited at best. Better understanding of the anatomy and physiology, as well as the related hormonal environment and its impact on healing, may be the key toward improvement of outcomes and heightened patient satisfaction.


Application and Development of Shape Memory Micro/Nano Patterns.
Shape memory polymers (SMPs) are a class of smart materials that change shape when stimulated by environmental stimuli. Different from the shape memory effect at the macro level, the introduction of micro-patterning technology into SMPs strengthens the exploration of the shape memory effect at the micro/nano level. The emergence of shape memory micro/nano patterns provides a new direction for the future development of smart polymers, and their applications in the fields of biomedicine/textile/micro-optics/adhesives show huge potential. In this review, the authors introduce the types of shape memory micro/nano patterns, summarize the preparation methods, then explore the imminent and potential applications in various fields. In the end, their shortcomings and future development direction are also proposed.


Platelet transport rates and binding kinetics at high shear over a thrombus.
Thrombus formation over a ruptured atherosclerotic plaque cap can occlude an artery with fatal consequences. We describe a computational model of platelet transport and binding to interpret rate-limiting steps seen in experimental thrombus formation over a collagen-coated stenosis. The model is used to compute shear rates in stenoses with growing boundaries. In the model, moving erythrocytes influence platelet transport based on shear-dependent enhanced diffusivity and a nonuniform platelet distribution. Adhesion is modeled as platelet-platelet binding kinetics. The results indicate that observed thrombus growth rates are limited by platelet transport to the wall for shear rates up to 6000 s(-1). Above 7000 s(-1), the thrombus growth rate is likely limited by binding kinetics (10(-4) m/s). Thrombus growth computed from these rate-limiting steps match the thrombus location and occlusion times for experimental conditions if a lag time for platelet activation is included. Using fitted parameters, the model is then used to predict thrombus size and shape at a higher Reynolds number flow consistent with coronary artery disease.


Multi-arm covariate adjusted response adaptive designs for ordinal outcome clinical trials.
Covariate adjusted response adaptive designs are developed with ordinal categorical responses for phase III clinical trial involving multiple treatments. Stochastic ordering principle is used to order the treatments according to effectiveness and consequently allocation functions are developed by combining the cumulative odds ratios suitably. The performance of the proposed designs is investigated through relevant exact as well as large sample measures. To investigate the performance in a real situation, a real clinical trial involving lung cancer patients is further redesigned using the proposed allocation design.


Fingerprinting the folding of a group I precursor RNA.
Evidence that folding of the Tetrahymena pre-rRNA follows a defined path and is rate-determining for splicing at physiological temperatures is presented. Structural isomers were separated by native polyacrylamide gel electrophoresis and their splicing activities were compared. GTP binding selectively shifts the active form of the pre-RNA to an electrophoretic band containing both spliced and unspliced RNA. In situ chemical modification provides evidence for base-pair rearrangements in the 5' exon and structural alterations in the intron core of partially and fully active forms. Transition to the fully active precursor requires high temperature, but the activation energy is lower than expected for opening of RNA helices. Implications for control of RNA conformation during splicing are discussed.


Driver reaction time before and after treatment for lumbar radiculopathy.
Prospective observational pilot study. OBJECTIVE.: To investigate the effect of right and left radiculopathy on driver reaction time (DRT), and the effect of selective nerve root block (SNRB) on DRT. The effect of many orthopedic procedures on DRT has already been assessed. To date the effect of radiculopathy and SNRB on DRT has not been studied. DRTs of 20 radiculopathic patients (10 right, 10 left) were measured using a custom-built car simulator. Each patient was tested pre-SNRB, immediately post-SNRB, and 2 and 6 weeks post-SNRB. As controls 20 age- and sex-matched normal subjects were tested once. Full departmental, institutional, and ethical committee approval were obtained. Mean DRT of the control group was 452 milliseconds. Mean DRT of patients with right or left radiculopathy pre-SNRB was 521 milliseconds (P < 0.045) and 535 milliseconds (P < 0.018), respectively. In the right radiculopathic group, the measurements immediately post-SNRB, 2 weeks, and 6 weeks were 656 milliseconds (P < 0.005), 589 milliseconds (P < 0.019), and 564 milliseconds (P < 0.10), respectively. The delay immediately and at 2 weeks post-SNRB translates into an increase in stopping distance of 3.8 and 1.9 m, respectively at the speed of 100 km/h. In the left radiculopathic group, the measurements immediately post-SNRB, 2 weeks, and 6 weeks were 585 milliseconds (P < 0.037), 534 milliseconds, and 530 milliseconds, respectively. The delay immediately post-SNRB translates into an increase in stopping distance of 1.4 m at the speed of 100 km/h. The study identified significant DRTs' changes both in radiculopathy and after SNRB. Right and left radiculopathic patients should be advised about the possible changes in their DRTs post-SNRB. Future research with regard to the suitability for radiculopathic patients to drive and the best time to resume driving post-SNRB is needed.


Effect of ventilatory drive on carbon dioxide sensitivity below eupnea during sleep.
We determined the effects of changing ventilatory stimuli on the hypocapnia-induced apneic and hypopneic thresholds in sleeping dogs. End-tidal carbon dioxide pressure (PET(CO2)) was gradually reduced during non-rapid eye movement sleep by increasing tidal volume with pressure support mechanical ventilation, causing a reduction in diaphragm electromyogram amplitude until apnea/periodic breathing occurred. We used the reduction in PET(CO2) below spontaneous breathing required to produce apnea (DeltaPET(CO2)) as an index of the susceptibility to apnea. DeltaPET(CO2) was -5 mm Hg in control animals and changed in proportion to background ventilatory drive, increasing with metabolic acidosis (-6.7 mm Hg) and nonhypoxic peripheral chemoreceptor stimulation (almitrine; -5.9 mm Hg) and decreasing with metabolic alkalosis (-3.7 mm Hg). Hypoxia was the exception; DeltaPET(CO2) narrowed (-4.1 mm Hg) despite the accompanying hyperventilation. Thus, hyperventilation and hypocapnia, per se, widened the DeltaPET(CO2) thereby protecting against apnea and hypopnea, whereas reduced ventilatory drive and hypoventilation narrowed the DeltaPET(CO2) and increased the susceptibility to apnea. Hypoxia sensitized the ventilatory responsiveness to CO2 below eupnea and narrowed the DeltaPET(CO2); this effect of hypoxia was not attributable to an imbalance between peripheral and central chemoreceptor stimulation, per se. We conclude that the DeltaPET(CO2) and the ventilatory sensitivity to CO2 between eupnea and the apneic threshold are changeable in the face of variations in the magnitude, direction, and/or type of ventilatory stimulus, thereby altering the susceptibility for apnea, hypopnea, and periodic breathing in sleep.


Structure and biosynthesis of human salivary mucins.
Human salivary glands secrete two types of mucins: oligomeric mucin (MG1) with molecular mass above 1 MDa and monomeric mucin (MG2) with molecular mass of 200-250 kDa. Monomers of MG1 and MG2 contain heavily O-glycosylated tandem repeats located at the central domain of the molecules. MG1 monomers are linked by disulfide bonds located at sparsely glycosylated N- and C-end. MG1 are synthesized by mucous cells and MG2 by the serous cells of human salivary glands.


The reliability of regional ecological knowledge to build local interaction networks: a test using seed-dispersal networks across land-bridge islands.
Building ecological networks is the fundamental basis of depicting how species in communities interact, but sampling complex interaction networks is extremely labour intensive. Recently, indirect ecological information has been applied to build interaction networks. Here we propose to extend the source of indirect ecological information, and applied regional ecological knowledge to build local interaction networks. Using a high-resolution dataset consisting of 22 locally observed networks with 17 572 seed-dispersal events, we test the reliability of indirectly derived local networks based on regional ecological knowledge (REK) across islands. We found that species richness strongly influenced 'local interaction rewiring' (i.e. the proportion of locally observed interactions among regionally interacting species), and all network properties were biased using REK-based networks. Notably, species richness and local interaction rewiring strongly affected estimations of REK-based network structures. However, locally observed and REK-based networks detected the same trends of how network structure correlates to island area and isolation. These results suggest that we should use REK-based networks cautiously for reflecting actual interaction patterns of local networks, but highlight that REK-based networks have great potential for comparative studies across environmental gradients. The use of indirect regional ecological information may thus advance our understanding of biogeographical patterns of species interactions.


Associations between maternal phenol and paraben urinary biomarkers and maternal hormones during pregnancy: A repeated measures study.
A number of phenols and parabens are added to consumer products for a variety of functions, and have been found at detectable levels in the majority of the U.S. Among other functions, thyroid hormones are essential in fetal neurodevelopment, and could be impacted by the endocrine disrupting effects of phenols and parabens. The present study investigated the association between ten maternal urinary phenol and paraben biomarkers (bisphenol S, triclosan, triclocarban, benzophenone-3, 2,4-dichlorophenol, 2,5-dichlorophenol, and ethyl, butyl, methyl and propyl paraben) and four plasma thyroid hormones in 439 pregnant women in a case-control sample nested within a cohort study based in Boston, MA. Urine and blood samples were collected from up to four visits during pregnancy (median weeks of gestation at each visit: Visit 1: 9.64, Visit 2: 17.9, Visit 3: 26.0, Visit 4: 35.1). Linear mixed models were constructed to take into account the repeated measures jointly, followed by multivariate linear regression models stratified by gestational age to explore potential windows of susceptibility. We observed decreased total triiodothyronine (T3) in relation to an IQR increase in benzophenone-3 (percent change [%Δ] = -2.07; 95% confidence interval [CI] = -4.16, 0.01), butyl paraben (%Δ = -2.76; 95% CI = -5.25, -0.26) and triclosan (%Δ = -2.53; 95% CI = -4.75, -0.30), and triclocarban at levels above the LOD (%Δ = -5.71; 95% CI = -10.45, -0.97). A 2.41% increase in T3 was associated with an IQR increase in methyl paraben (95% CI = 0.58, 4.24). We also detected a negative association between free thyroxine (FT4) and propyl paraben (%Δ = -3.14; 95% CI = -6.12, -0.06), and a suggestive positive association between total thyroxine (T4) and methyl paraben (%Δ = 1.19; 95% CI = -0.10, 2.47). Gestational age-specific multivariate regression analyses showed that the magnitude and direction of some of the observed associations were dependent on the timing of exposure. Certain phenols and parabens were associated with altered thyroid hormone levels during pregnancy, and the timing of exposure influenced the association between phenol and paraben, and hormone concentrations. These changes may contribute to downstream maternal and fetal health outcomes. Additional research is required to replicate the associations, and determine the potential biological mechanisms underlying the observed associations.


Biologically produced nanosilver: current state and future perspectives.
Silver nanoparticles are one of the most commercialized nanomaterials. They are widely applied as biocides for their strong antimicrobial activity, but also their conductive, optic and catalytic properties make them wanted in many applications. The chemical and physical processes which are used to synthesize silver nanoparticles generally have many disadvantages and are not eco-friendly. In this review, we will discuss biological alternatives that have been developed using microorganisms or plants to produce biogenic silver. Until now, only their antimicrobial activity has been studied more into detail. In contrast, a wide range of practical applications as biocide, biosensor, and catalyst are still unexplored. The shape, size, and functionalization of the nanoparticles is defined by the biological system used to produce the nanoparticles, hence for every application a specific biological production process needs to be chosen. On the other hand, biogenic silver needs to compete with chemically produced nanosilver on the market. Large scale production generating inexpensive nanoparticles is needed. This can only be achieved when the biological production system is chosen in function of the yield. Hence, the true challenge for biogenic silver is finding the balance between scalability, price, and applicability.


Heart failure and renal outcomes according to baseline and achieved blood pressure in patients with type 2 diabetes: results from EMPA-REG OUTCOME.
The sodium-glucose co-transporter 2 (SGLT2) inhibitor empagliflozin reduced cardiovascular death or heart failure hospitalizations in type 2 diabetes (T2D) in addition to a reduction of SBP. As heart failure patients often present with low SBP, which can challenge treatment initiation, we explored if empagliflozin's effect on SBP was independent of baseline SBP and heart failure status, and if the effect on cardiovascular and heart failure outcomes was influenced by updated mean SBP or by an early change in SBP after drug initiation. A total of 7020 patients were treated with empagliflozin 10 mg, 25 mg or placebo and followed for a median of 3.1 years. All of them had BP measurement at baseline. We evaluated changes in SBP in the context of heart failure status at baseline and according to baseline SBP categories (<120, 120--<130, 130--<140, 140--<160, ≥160 mmHg). The updated mean SBP during the trial was calculated as a time-dependent variable. We then assessed the association of baseline and updated mean SBP with three-point major adverse cardiovascular events (3P-MACE), hospitalization for heart failure, cardiovascular death, hospitalization for heart failure or cardiovascular death, all-cause death, and incident/worsening nephropathy, and whether treatment effect of empagliflozin vs. placebo on these outcomes differed if adjusted for updated mean SBP. Finally, we evaluated the impact of early decline in SBP (≥5 mmHg at week 4) on the treatment effect of empagliflozin vs. placebo on these outcomes. Analyses were performed via Cox regression adjusting for baseline risk factors including a term for treatment subgroup interaction, and by landmark analyses starting at week 4. The difference in SBP reduction at week 12 between empagliflozin and placebo was 3--5 mmHg and similar regardless of baseline SBP category or HF status at baseline. Baseline SBP and updated mean SBP categories showed no association with cardiovascular outcomes, but was associated with new/worsening nephropathy. The treatment effects of empagliflozin on all explored outcomes were independent of updated mean SBP as well of the early drop in SBP on treatment. In addition to decreasing SBP, empagliflozin reduced cardiovascular, heart failure and renal outcomes independently of updated mean SBP during the trial, and of the early SBP drop. These results suggest a BP-independent effect of empagliflozin on cardiovascular and heart failure outcomes. CLINICALTRIALS. NCT01131676.


A deep learning-based model for automatic segmentation and evaluation of corneal neovascularization using slit-lamp anterior segment images.
Corneal neovascularization (CoNV) is a common sign in anterior segment eye diseases, the level of which can indicate condition changes. Current CoNV evaluation methods are time-consuming and some of them rely on equipment which is not widely available in hospitals. Thus, a fast and efficient evaluation method is now urgently required. In this study, a deep learning (DL)-based model was developed to automatically segment and evaluate CoNV using anterior segment images from a slit-lamp microscope. A total of 80 cornea slit-lamp photographs (from 80 patients) with clinically manifested CoNV were collected from December 2021 to July 2022 at Tianjin Medical University Eye Hospital. Of these, 60 images were manually labelled by ophthalmologists using ImageJ software to train the vessel segmentation network IterNet. To evaluate the performance of this automated model, evaluation metrics including accuracy, precision, area under the receiver operating characteristic (ROC) curve (AUC), and F1 score were calculated between the manually labelled ground truth and the automatic segmentations of CoNV of 20 anterior segment images. Furthermore, the vessels pixel count was automatically calculated and compared with the manually labelled results to evaluate clinical usability of the automated segmentation network. The IterNet model achieved an AUC of 0.989, accuracy of 0.988, sensitivity of 0.879, specificity of 0.993, area under precision-recall of 0.921, and F1 score of 0.879. The Bland-Altman plot between manually labelled ground truth and automated segmentation results produced a concordance correlation coefficient of 0.989, 95% limits of agreement between 865.4 and -562.4, and the vessels pixel count's Pearson coefficient of correlation was 0.981 (P<0.01). The fully automated network model IterNet provides a time-saving and efficient method to make a quantitative evaluation of CoNV using slit-lamp anterior segment images. This method demonstrates great value and clinical application potential for patient care and future research.


The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) in Dentistry. Management of Biological Risk in Dental Practice.
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a novel coronavirus first identified in Wuhan, China, and the etiological agent of Coronavirus Disease-2019 (COVID-19). This infection spreads mainly through direct contact with Flügge micro droplets or core droplets that remain suspended as aerosol. Moreover, it has been reported that infected subjects, both with and without clinical signs of COVID-19, can transmit the virus. Since the infection typically enters through mouth, nose, and eyes, dentistry is one of the medical practices at highest risk of infection due to the frequent production of aerosol and the constant presence of saliva. The World Health Organization (WHO) has suggested that only emergency/urgent procedures should be performed during the coronavirus outbreak. Considering the virus' route of transmission, a specific protocol should be applied to reduce the risk of infection in addition to measures that prevent the spread of infection from a patient to another person or medical tools and equipment (cross-infection). This protocol should be implemented by modifying both patient management and clinical practice, introducing particular devices and organizational practices. This paper aims to discuss and suggest the most appropriate procedures in every aspect of dental practice to reduce infection risk.


A comprehensive investigation of lipid-transfer proteins from Cicer arietinum disentangles their role in plant defense against Helicoverpa armigera-infestation.
Lipid Transfer Proteins (LTPs) play a crucial role in synthesizing lipid barrier polymers and are involved in defense signaling during pest and pathogen attacks. Although LTPs are conserved with multifaceted roles in plants, these are not yet identified and characterized in Cicer arietinum. In this study, a genome-wide analysis of LTPs was executed and their physiochemical properties, biochemical function, gene structure analysis, chromosomal localization, promoter analysis, gene duplication, and evolutionary analysis were performed using in silico tools. Furthermore, tissue-specific expression analysis and gene expression analysis during pest attack was also conducted for the LTPs. A total of 48 LTPs were identified and named as CaLTPs. They were predicted to be small unstable proteins with "Glycolipid transfer protein" and "Alpha-Amylase Inhibitors, Lipid Transfer and Seed Storage" domains, that are translocated to the extracellular region. CaLTPs were predicted to possess 3-4 introns and were located on all the eight chromosomes of chickpea with half of the CaLTPs being localized on chromosomes 4, 5, and 6, and found to be closely related to LTPs of Arabidopsis thaliana and Medicago trancatula. Gene duplication and synteny analysis revealed that most of the CaLTPs have evolved due to tandem or segmental gene duplication and were subjected to purifying selection during evolution. The promoters of CaLTPs had development-related, phytohormone-responsive, and abiotic and biotic stress-related cis-acting elements. A few CaLTP transcripts exhibited differential expression in diverse tissue types, while others showed no/very low expression. Out of 20 jasmonate-regulated CaLTPs, 14 exhibited differential expression patterns during Helicoverpa armigera-infestation, indicating their role in plant defense response. This study identified and characterized CaLTPs from an important legume, C. arietinum, and indicated their involvement in plant defense against H. armigera-infestation, which can be further utilized to explore lipid signaling during plant-pest interaction and pest management.


Photoinduced and N-bromosuccinimide-mediated cyclization of 2-azido-N-phenylacetamides.
An efficient synthesis of quinoxalin-2(1H)-ones or spiro[cyclohexene-1,2'-imidazol]-4'-ones has been achieved in moderate to high yields by the visible light-induced and N-bromosuccinimide-mediated cyclization reaction of 2-azido-N-phenylacetamides at ambient temperature. Both the regioselectivity and the speed of cyclization are affected by the substituents attached to the phenyl ring. For example, quinoxalin-2-ones are produced as the main products when the substrates bear electron-withdrawing groups at the para-position of the phenyl ring; in contrast, spiro[cyclohexene-1,2'-imidazol]-4'-ones are obtained as the main products when the substrates bear electron-donating groups at the para-position.


A developmentally regulated form of insulin-like growth factor receptor beta-subunit in C2 myoblasts exhibiting altered requirements for differentiation.
Ligand-dependent autophosphorylation and immunoprecipitation have been used to distinguish insulin and insulin-like growth factor-I (IGF-I) receptor beta-subunits in the permissive and inducible subclones of the C2 myoblast cell line. Permissive myoblasts differentiate spontaneously, whereas myoblasts of the inducible subclone require exogenous IGFs to undergo terminal differentiation. Permissive myoblasts contain beta-subunits of 95 and 101 kilodalton (kDa) mol wt. The 95-kDa subunits are immunoprecipitated with antipeptide antibodies directed against tyrosine kinase (AbP2), juxtamembrane (AbP4), and carboxy-terminal (AbP5) domains of the insulin receptor and insulin receptor monoclonal antibody 29B4. The tryptic phosphopeptide map of the 95-kDa band suggests that it contains both insulin and IGF-I receptor beta-subunits. The 101-kDa subunit is immunoprecipitated by AbP2, AbP4, and AbP5, because it forms a hybrid complex with the 95-kDa protein, but it does not react directly with AbP4, AbP5, or antibody 29B4. Phosphorylation of the 101-kDa subunit is more responsive to IGF-I than to IGF-II or insulin, indicating that it is a second IGF-I receptor beta-subunit. Inducible myoblasts exhibit a single major beta-subunit of 106 kDa mol wt. Its immunoreactivity and phosphopeptide map are virtually identical to those of the 101-kDa IGF-I receptor beta-subunit from permissive cells. However, unlike the 101-kDa beta-subunit, phosphorylation of the 106-kDa protein appears to be more responsive to IGF-II than to either IGF-I or insulin. It is lost upon differentiation of myoblasts into myotubes concomittant with the appearance of 95- and 101-kDa beta-subunits. These data demonstrate 1) an alpha 2 beta 2 IGF receptor that has high sensitivity for IGF-II in inducible, but not in permissive, myoblasts; 2) the beta-subunit of this receptor exhibits different migration in sodium dodecyl sulfate-polyacrylamide gels from either of those found in permissive cells; and 3) expression of this beta-subunit is developmentally regulated. This suggests that the inducible cell beta-subunit is a component of a stage-specific alpha 2 beta 2 IGF receptor subtype that functions as an IGF-II receptor.


Morphological Study of the Anterior Surface of the Distal Radius.
The shape of the anterior surface of the distal radius is important for designing a distal radius plate for wrist fracture surgery. The aim of this study was to describe the shape of the anterior surface of the distal radius and to compare the results between female and male. We used 90 sides from three-dimensional radial models based on computer tomography images from Korean adult cadavers for this study. The anterior surface was measured in two dimensions in the coronal view, and we sectioned the anterior surface of the models to obtain intermediate and radial sections to measure the curved shape of the anterior surface in sagittal view. Several parameters were statistically different between females and males; however, there were no differences between the right and left sides for any parameters. The width of the anterior surface in the coronal view was larger in males than females, and the curved part of the anterior surface of the males was longer and more concave than that of females. In both the female and male specimens, the intermediate section was longer and more concave than the radial section. Our results are useful for anthropological studies and for designing distal radial plates.


Stable RNA interference of synaptotagmin I in PC12 cells results in differential regulation of transmitter release.
In sympathetic neurons, it is well-established that the neurotransmitters, norepinephrine (NE), neuropeptide Y (NPY), and ATP are differentially coreleased from the same neurons. In this study, we determined whether synaptotagmin (syt) I, the primary Ca(2+) sensor for regulated release, could function as the protein that differentially regulates release of these neurotransmitters. Plasmid-based RNA interference was used to specifically and stably silence expression of syt I in a model secretory cell line. Whereas stimulated release of NPY and purines was abolished, stimulated catecholamine (CA) release was only reduced by approximately 50%. Although expression levels of tyrosine hydroxylase, the rate-limiting enzyme in the dopamine synthesis pathway, was unaffected, expression of the vesicular monoamine transporter 1 was reduced by 50%. To evaluate whether NPY and CAs are found within the same vesicles and whether syt I is found localized to each of these NPY- and CA-containing vesicles, we used immunocytochemistry to determine that syt I colocalized with large dense core vesicles, with NPY, and with CAs. Furthermore, both CAs and NPY colocalized with one another and with large dense core vesicles. Electron micrographs show that large dense core vesicles are synthesized and available for release in cells that lack syt I. These results are consistent with syt I regulating differential release of transmitters.


Efficient synthesis of functionalized furans via ruthenium-catalyzed cyclization of epoxyalkyne derivatives.
Ruthenium catalyst TpRuPPh(3)(CH(3)CN)(2)Cl is found to effect the cyclization of epoxyalkynes to furans in the presence of Et(3)N. The reactions worked well for various epoxyalkynes with suitable oxygen and nitrogen functionalities with low loading of catalyst. It failed with disubstituted epoxyalkynes. The mechanism was elucidated by a deuterium labeling experiment that suggested that the mechanism involved a ruthenium-vinylidenium intermediate.


Synthesis of α-(aminoethyl)-α,β-enones via alkyne aza-Prins cyclization and their synthetic application to pyrrolidines.
We developed a synthetic method for α-(aminoethyl)-α,β-enones from aryl-substituted homopropargyl sulfonamides and aldehydes, representing the first synthesis of conjugated enones via alkyne aza-Prins cyclization. These products could be converted into pyrrolidines by a formal 5-endo-trig cyclization.


RNA-sequence analysis of gene expression from honeybees (Apis mellifera) infected with Nosema ceranae.
Honeybees (Apis mellifera) are constantly subjected to many biotic stressors including parasites. This study examined honeybees infected with Nosema ceranae (N. ceranae). N. ceranae infection increases the bees energy requirements and may contribute to their decreased survival. RNA-seq was used to investigate gene expression at days 5, 10 and 15 Post Infection (P.I) with N. ceranae. The expression levels of genes, isoforms, alternative transcription start sites (TSS) and differential promoter usage revealed a complex pattern of transcriptional and post-transcriptional gene regulation suggesting that bees use a range of tactics to cope with the stress of N. ceranae infection. N. ceranae infection may cause reduced immune function in the bees by: (i)disturbing the host amino acids metabolism (ii) down-regulating expression of antimicrobial peptides (iii) down-regulation of cuticle coatings and (iv) down-regulation of odorant binding proteins.


Violence, Exclusion and Resilience among Ivoirian Travestis.
Among sexual and gender minorities in Côte d'Ivoire, travestis are defined as individuals born anatomically male who live as women on a full- or part-time basis. Travestis encounter harsher stigmatization and violence than sexual minorities whose gender normativity allows them to avoid unwanted attention. Moreover, they have traditionally been underserved by Ivoirian sexual minority rights groups, who have worked to distance themselves from travestis, framing them as recklessly indiscreet. In this paper, we examine the extent to which travestis' isolation has lessened in the wake of the post-election violence that followed Côte d'Ivoire's 2010 presidential election. We trace how Ivoirian travestis became increasingly vulnerable following the installation of a new national army that proved more hostile to them. And we show how, as a result of anti-travesti abuses committed by the army, non-travesti sexual minority activists became increasingly aware of the plight of travestis, and took steps to include them in their programming. These activists may have also been motivated by an increasing interest in transgender issues on the part of international donors. Finally, we explore the extent to which emerging human rights and HIV/AIDS programming has resulted in newly embodied positions for travestis as they confront identifications reflecting Western trans-spectrum identities.


Oncoplastic Breast Reconstruction for Large Pediatric Breast Tumors: A Case Series.
Large breast fibroadenomas in pediatric females may cause discomfort, asymmetry, and psychological stress, and patients may elect for surgical excision. There are no criteria for reconstruction after the excision of these masses, and the research is limited in describing oncoplastic techniques in pediatric fibroadenoma excision. Nononcoplastic techniques, such as mastectomy with implant or flap reconstruction, have been used for pediatric fibroadenoma excision reconstruction. Oncoplastic techniques using Wise pattern or circumareolar incisions have shown to have efficacious outcomes. In addition, pediatric females undergoing breast surgery risk long-term complications such as continued breast asymmetry due to further breast growth, nipple and breast hypoesthesia, and future breastfeeding difficulty. This case series describes the oncoplastic techniques used for large benign mass excision and reconstruction of 3 pediatric females. A Wise pattern technique was used for all 3 patients, and 2 underwent a free-nipple graft. Oncoplastic techniques for pediatric breast mass excision provide satisfactory aesthetic outcomes with minimal surgical morbidity. Further research assessing the long-term effects of pediatric breast mass excision and reconstruction would be beneficial.


Peer pressure and risk-taking behaviors in children.
We asked 771 children in grades 5-8 about the dares or challenges they received from other children. A pilot study established categories for classification of the actions proposed ("What did they try to get you to do?"); the techniques utilized ("How did they try to get you to do that?"); and children's responses ("What did you say or do?"). Peer pressure was reported most frequently by 8th grade students. About 50 per cent of the dares encouraged problem behaviors that placed the children (or others) at risk for personal injury, or the potential development of habits hazardous to their health. With increasing age, more occurred in the school environment and fewer involved risk of personal injury. Among 7th and 8th graders, more boys were dared to perform acts of violence, and more girls were challenged to be sexually active.


In vitro biocompatibility and electrical stability of thick-film platinum/gold alloy electrodes printed on alumina.
High-density electrode arrays are a powerful tool in both clinical neuroscience and basic research. However, current manufacturing techniques require the use of specialised techniques and equipment, which are available to few labs. We have developed a high-density electrode array with customisable design, manufactured using simple printing techniques and with commercially available materials. Electrode arrays were manufactured by thick-film printing a platinum-gold alloy (Pt/Au) and an insulating dielectric on 96% alumina ceramic plates. Arrays were conditioned in serum and serum-free conditions, with and without 1 kHz, 200 µA, charge balanced stimulation for up to 21 d. Array biocompatibility was assessed using an extract assay and a PC-12 cell contact assay. Electrode impedance, charge storage capacity and charge injection capacity were before and after array conditioning. The manufactured Pt/Au electrodes have a highly porous surface and exhibit electrical properties comparable to arrays manufactured using alternative techniques. Materials used in array manufacture were found to be non-toxic to L929 fibroblasts by extract assay, and neuronal-like PC-12 cells adhered and extended neurites on the array surfaces. Arrays remained functional after long-term delivery of electrical pulses while exposed to protein-rich environments. Charge storage capacities and charge injection capacities increased following stimulation accounted for by an increase in surface index (real surface area) observed by vertical scanning interferometry. Further, we observed accumulation of proteins at the electrode sites following conditioning in the presence of serum. This study demonstrates the in vitro biocompatibility of commercially available thick-film printing materials. The printing technique is both simple and versatile, with layouts readily modified to produce customized electrode arrays. Thick-film electrode arrays are an attractive tool that may be implemented for general tissue engineering and neuroscience research.


Clinical association of autoimmune diseases with diabetes mellitus: analysis from southern India.
The adult form of polyglandular autoimmune syndrome (type 2) is associated with disorders of the thyroid, adrenal, and pancreas (type 1 diabetes mellitus). We profile the clinical association of autoimmune diseases among patients from our center in southern India: autoimmune diseases were diagnosed in 1.68% of persons with diabetes mellitus (147/15,523). Diabetes mellitus was diagnosed in 2.3% of persons with hypothyroidism (33/1435) and in 4.35% with thyrotoxicosis (15/345).


BARD1 regulates BRCA1 apoptotic function by a mechanism involving nuclear retention.
BRCA1 is involved in maintaining genomic integrity and, as a regulator of the G2/M checkpoint, contributes to DNA repair and cell survival. The overexpression of BRCA1 elicits diverse cellular responses including apoptosis due to the stimulation of specific signaling pathways. BRCA1 is normally regulated by protein turnover, but is stabilized by BARD1 which can recruit BRCA1 to the nucleus to form a ubiquitin E3 ligase complex involved in DNA repair or cell survival. Here, we identify BARD1 as a regulator of BRCA1-dependent apoptosis. Using transfected MCF-7 breast cancer cells, we found that BRCA1-induced apoptosis was independent of p53 and was stimulated by BRCA1 nuclear export. Conversely, BARD1 reduced BRCA1-dependent apoptosis by a mechanism involving nuclear sequestration. Regulation of apoptosis by BARD1 was reduced by BRCA1 cancer mutations that disrupt Ub ligase function. Transfection of BRCA1 N-terminal peptides that disrupted the cellular BRCA1-BARD1 interaction caused a loss of nuclear BRCA1 that correlated with increased apoptosis in single cell assays, but did not alter localization or expression of endogenous BARD1. Reducing BARD1 levels by siRNA caused a small increase in apoptosis. Our findings identify a novel apoptosis inhibitory function of BARD1 and suggest that nuclear retention of BRCA1-BARD1 complexes contributes to both DNA repair and cell survival.


Annonaceae Family Alkaloids as Agents Against Leishmaniasis: A Review and Molecular Docking Evaluation.
Leishmaniasis is a neglected disease that affects 15 million people worldwide. Existing treatments are associated with limitations, including high costs and toxicity. Several classes of natural substances have been reported to display leishmanicidal activity in the literature. Isoquinoline alkaloids, which are commonly found in the Annonaceae family, represent an important skeleton for the development of anti-leishmaniasis products. This study presents an overview of the potential use of Annonaceae alkaloids to treat leishmaniasis and describes a molecular docking study examining 215 isoquinoline alkaloids. All selected compounds contain a bisbenzyltetrahydroisoquinoline, suggesting the affinity of this skeleton for the target.


Census survey for a primary health care programme.
To describe the process of gathering information from a census survey as a preliminary step for supporting the working of a primary health care center. It also presents briefly the results of the survey and its broader implications on the health needs of the local population. A questionnaire was used to obtain basic information regarding the ethnicity/area of origin, number of household members and their breakdown according to gender, age and marital status. The medical students of different batches were involved in the data collection process, as part of their Survey Methodology course of Community Health Sciences (CHS) in first year. Data was obtained from 2,033 houses, having a total population of 16,118 persons. Fifty three per cent of the population was under fifteen years, 42% were between 15-49 and 5% were over 50 years of age. The overall percentage of males was 52% and females 48%. Approximately 79 percent people were Pushto speaking. Sikanderabad is a typical slum settlement, with an emigrant population being mostly of Pathan and Afghan refugees. The fertility rate in Sikanderabad is much higher than that of Karachi. This highlights the need for education and availability of family planning facilities. At the same time, due to the fact that there is a major portion of the population aged under five years, so facility for treating children must be appropriately provided. The Primary Health Care center established in Sikanderabad is based on the above information. The emphasis is on maternal and childcare, including antenatal and postnatal care; family planning and nutritional counseling.


Should social work clients have the right to effective treatment?
Currently, the codes of ethics developed for social workers by NASW and other professional associations do not suggest that clients have the right to receive effective, empirically validated treatment. In addition, the codes place no explicit emphasis on empirically validated treatments when referring to social work competence, education, research, supervision, or the profession as a whole. Does the social work client have the right to receive effective treatment when such interventions are known to be available? Should the NASW Code of Ethics include such requirements to encourage more responsible behavior on the part of social work practitioners? This article considers some of the issues involved in this debate and offers suggestions as to how codes of ethics could be modified to include clients' right to receive effective treatment and social workers' obligation to be educated about and to provide such treatment.


Well-being and the anticipation of future positive experiences: The role of income, social networks, and planning ability.
The present study aims to answer two questions: (1) are expectations of future positive experiences related to well-being in the general population?; and (2) what factors (social, psychological, economic) enable people to have expectations of future positive experiences. A community sample (N = 84) was assessed on a measure of anticipation of future positive and negative experiences, factors that might enable positive anticipation (measures of income, social networks, planning ability, and affective capacity) and measures of subjective well-being (positive and negative affect and life satisfaction). Subjective well-being was related to having more anticipated positive experiences, which was in turn related to having a large social network, having a high number of steps in plans to achieve goals, and, more marginally, to having a high household income.


Global insights into micro-macro mechanisms and environmental implications of limestone calcined clay cement (LC3) for sustainable construction applications.
Limestone calcined clay cement (LC3) has gained attention in the research paradigm, and useful data is available in scattered form, necessitates comprehensive review to provide global insight into important research questions, i.e., micro-macro response, and environmental implications, keeping in view the future research directions. In this regard, the current article provides a comprehensive insight into LC3, focusing on its micro-macro mechanisms and critically examining different aspects such as chemical composition, hydration chemistry with special attention on phase assemblage, impacts of various salts and carbonation, rheological properties, mechanical behavior, high-temperature exposure, and compatibility with different admixtures. Additionally, this article explores the sustainable and environmentally friendly applications of LC3, with an emphasis on its economic and environmental advantages highlighted by pertinent data and lifecycle assessments (LCA). Comprehensive data was gathered from a micro-macro perspective considering SCMs from different regional sources, and comparisons were drawn with Ordinary Portland Cement (OPC). Further, comparative economic and environmental aspects for different grades of LC3 and OPC were evaluated and analyzed considering energy demand, cost-effectiveness, and energy efficiency. The micro-macro characteristics of LC3 are found to be majorly dependent on its constituent, particularly clinker composition and alumina content in SCMs, which varies regionally. This review study outlines the critical research directions, i.e., enhancement of mechanical behavior and rheology, incorporation of super plasticizers and waste materials for resource conservation, and improvement of carbonation resistance for durability to make LC3 a sustainable and first-choice cement.


Cerebrospinal Fluid HIV-1 Escape in Patients With Neurocognitive Symptoms: Pooled Data From a Neuro-HIV Platform and the NAMACO Study.
Despite modern antiretroviral therapy, human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) escape into the cerebrospinal fluid (CSF) may occur. We examined the prevalence of and factors associated with CSF HIV-1 escape among people living with HIV (PLWH) in Switzerland. The Neurocognitive Assessment in the Metabolic and Aging Cohort study is an ongoing, prospective, longitudinal, multicenter study within the Swiss HIV Cohort Study. The neuro-HIV platform is a multidisciplinary, single-day outpatient consultation at Lausanne University Hospital. We pooled data from the Neurocognitive Assessment in the Metabolic and Aging Cohort study and the neuro-HIV platform participants who underwent lumbar puncture between 2011 and 2019. Both patient groups had neurocognitive symptoms. Cerebrospinal fluid HIV-1 escape was defined as the presence of quantifiable CSF HIV-1 RNA when plasma HIV-1 RNA was suppressed or CSF HIV-1 RNA greater than plasma HIV-1 RNA when the latter was detectable. Of 1166 PLWH assessed, 288 underwent lumbar puncture. Cerebrospinal fluid HIV-1 escape was observed in 25 PLWH (8.7%) of whom 19 (76%) had suppressed plasma HIV-1 RNA. Characteristics of PLWH were comparable whether they had CSF HIV-1 escape or not, including comorbidities, time since HIV diagnosis (15 vs 16 years, P = 0.9), median CD4 nadir (158.5/mm 3 vs 171/mm 3 , P = 0.6), antiretroviral CSF penetration-effectiveness score (7 vs 7 points, P = 0.8), and neurocognitive diagnosis based on Frascati criteria and radiological findings. In this large pooled sample of PLWH with neurocognitive symptoms, CSF HIV-1 escape occurred in 8.7% of PLWH. People living with HIV with CSF HIV-1 escape presented no distinctive clinical or paraclinical characteristics. We conclude that lumbar puncture is unavoidable in confirming CSF HIV-1 escape.


Multilocus sequence typing for characterization of clinical and environmental salmonella strains.
Multilocus sequence typing (MLST) based on the 16S RNA, pduF, glnA, and manB genes was developed for Salmonella, and its discriminatory ability was compared to those of pulsed-field gel electrophoresis (PFGE) and serotyping. PFGE differentiated several strains undifferentiable by serotyping, and 78 distinct PFGE types were identified among 231 Salmonella isolates grouped into 22 serotypes and 12 strains of undetermined serotype. The strains of several PFGE types were further differentiated by MLST, which suggests that the discriminatory ability of MLST for the typing of Salmonella is better than that of serotyping and/or PFGE typing. manB-based sequence typing identified two distinct genetic clusters containing 32 of 54 (59%) clinical isolates whose manB gene sequences were analyzed. The G+C contents and Splitstree analysis of the manB, glnA, and pduF genes of Salmonella indicated that the genes differ in their evolutionary origins and that recombination played a significant role in their evolution.


Ubiquitin-specific protease 8 is a novel prognostic marker in early-stage lung adenocarcinoma.
Alterations of epidermal growth factor receptor (EGFR) expression frequently occur in early-stage lung adenocarcinoma. Ubiquitin-specific protease 8 (USP8) has been reported to stabilize EGFR protein at the plasma membrane through the recycling pathway. Here, we examined the correlation between USP8 expression and the expression or mutation status of EGFR, as well as the clinicopathological features of lung adenocarcinoma and patient outcome. Expression of EGFR and USP8 in surgically resected specimens of lung adenocarcinoma (82 cases) was examined by immunohistochemistry. Overexpression of EGFR was mutually correlated with that of USP8, and was also associated with clinicopathological features including pathological subtype, lymphatic permeation, and vascular invasion. Moreover, patients who had USP8-positive tumors had a significantly poorer outcome than those who were USP8-negative, not only overall but also patients who were EGFR-negative. Although EGFR was expressed in invasive adenocarcinoma but not in adenocarcinoma in situ (AIS), USP8 was overexpressed in not only invasive adenocarcinoma but also 38.1% of AIS cases. In vitro, USP8 regulated the expression and half-life of EGFR in immortalized AIS cells, and also cell proliferation. Our findings indicate that overexpression of USP8 in lung adenocarcinoma is an early event during the course of tumor progression, and is related to EGFR expression.


Role of IL-6 in dendritic cell functions.
Dendritic cells (DCs) are efficient antigen-presenting cells that serve as a link between the innate and adaptive immune systems. These cells are broadly involved in cellular and humoral immune responses by presenting antigens to initiate T cell reactions, cytokine and chemokine secretion, T cell differentiation and expansion, B cell activation and regulation, and the mediation of immune tolerance. The functions of DCs depend on their activation status, which is defined by the stages of maturation, phenotype differentiation, and migration ability, among other factors. IL-6 is a soluble mediator mainly produced by a variety of immune cells, including DCs, that exerts pleiotropic effects on immune and inflammatory responses through interaction with specific receptors expressed on the surface of target cells. Here, we review the role of IL-6, when generated in an inflammatory context or as derived from DCs, in modulating the biologic function and activation status of DCs and emphasize the importance of searching for novel strategies to target the IL-6/IL-6 signaling pathway as a means to diminish the inflammatory activity of DCs in immune response or to prime the immunogenic activity of DCs in immunosuppressive conditions.


[Study on the effect of cluster needling of scalp acupuncture on the plasticity protein MAP-2 in rats with focal cerebral infarction].
To investigate the material base and underlying mechanism of the effect of cluster needling of scalp acupuncture on the neuronal plasticity in rats with focal cerebral infarction. The model rats with acute cerebral infarction were made by blocking the middle cerebral artery with monofilament. One hundred and thirty two Wistar rats were randomly divided into 4 groups: sham-operation group (A), model group (B), point-to-point scalp acupuncture group (C) and cluster-needling of scalp acupunture group (D). Puncturing from "Baihui (GV 20)" to "Qubin (GB 7)" was used in group C. Cluster needling of scalp acupuncture was used in group D, in which needles were inserted forward and slantingly into "Baihui (GV 20)" and its left and right sides at 4 mm. In both groups, the treatment was carried out with rapid twirling reinforcing-reducing for 1 min then retaining needle for 30 min, once a day, 6 days in one course, for treating 4 courses. There was no treatment for group A and B. The change of neurological function was evaluated with Bederson score, while the expression of microtubule-associated protein 2 (MAP-2) in the ischemic penumbra was examined with immunohistochemistry (streptavidin-peroxidase method). In comparison,with group B, the score of neurological function in group D decreased on 7th day (P<0.05), while the scors in group C and D also decreased on 14th and 28th days (both P<0.05). As compared with group C, the score of neurological function in group D obviously decreased on 28th days (P<0. 05). Comparing with group B, the expression of MAP-2 on the ischemic cortex was significantly increased in group D and C on 7th, 14th and 28th days (all P<0. 05), however, this expression in group D was higher than that in group C on 14th and 28th days (P<0. 05). Cluster needling of scalp acupuncture can improve the neurological function of rats with focal cerebral infarction, and increase the expression of MAP-2 in the ischemic penumbra.


Improving Seed Morphology and Germination Potential in Australian Native Grasses Using Seed Enhancement Technologies.
Difficult to handle seed material and poor germination commonly limit the uptake of native grasses in restoration and commercial-scale seeding efforts. Seed enhancement technologies (SETs) offer valuable solutions for improving the handling of seed material and optimising germination. This study considered eight widespread Australian native grasses; two representative of Mediterranean to temperate climates ('cool-climate' species) and six representative of arid to subtropical climates ('warm-climate' species). Through a series of experiments, this study logically selected and applied SET treatments to improve seed handling and germination for each study species. Seed handling was prioritised and addressed using flash flaming and/or acid digestion, while hydropriming was used following seed-handling treatments to enhance germination. Flash flaming and acid digestion were both applied to successfully reduce or remove bulky floret structures while maintaining or improving germination. Flaming at 110 ± 10 °C with continuous exposure for 10 min and acid digestion concentrations of 75-80% with exposure times of 1-2.5 min were generally successful. Sub-optimal concentrations of sulphuric acid often compromised germination. Hydropriming did not improve germination outcomes when applied following flaming or acid digestion. Optimising SETs for germination, emergence and establishment in different environments, and the viability and costs of application on larger seed batches are key considerations for the implementation and upscaling of SETs in the future.


In situ hybridization in HIV research.
In situ hybridization (ISH) for HIV is an arduous, demanding means of detecting viral genetic material in cells and tissues. Good ISH requires broad technical skills and devotion to controls for every step of the process as well as a critical eye when interpreting results. ISH may be used to detect HIV in three ways: by hybridizing to viral RNA, by hybridizing to proviral mRNA being produced for virion packaging, and by hybridizing to proviral DNA in the cytoplasm or integrated in the nucleus of an infected cell. Here we discuss the technical considerations involved and the problems encountered in using ISH to study the pathobiology of HIV infection.


Effects of UV radiation on the ultrastructure of human common pigmented naevi and lentigines.
In order to investigate how sunlight may affect naevi and lentigines, their melanocytes and the basement membrane, three irradiation protocols were applied directly to ten naevi and five lentigines on 2 subjects. Neither volunteer had sufficient naevi and lentigines to be able to use the three irradiation protocols on each of the subjects. Skin biopsies were fixed in glutaraldehyde followed by osmium tetroxide, thin-sectioned and examined in a Hitachi H-7000 transmission electron microscope. Following 14 consecutive single exposures of 3 MED of UVB or single exposures followed by 25 J/cm2 of UVA, 350 J/cm2 UVA with either 2040 or 2280 mJ/cm2 UVB, the basement membrane maintained its continuity. Melanocytes were not observed on the dermal side of the epidermal-dermal junction. UVA irradiation stimulated reinforcement of the basement membrane zone by collagen fibers. Centrioles found in melanocytes following irradiation suggest that these melanocytes maybe undergoing mitosis. Dermal fibroblasts were found to contain comparatively large quantities of melanin pigment. The pigment contained in these fibroblasts may in fact constitute an additional barrier against UV irradiation.


Canonical and Non-canonical Genomic Imprinting in Rodents.
Genomic imprinting is an epigenetic phenomenon that results in unequal expression of homologous maternal and paternal alleles. This process is initiated in the germline, and the parental epigenetic memories can be maintained following fertilization and induce further allele-specific transcription and chromatin modifications of single or multiple neighboring genes, known as imprinted genes. To date, more than 260 imprinted genes have been identified in the mouse genome, most of which are controlled by imprinted germline differentially methylated regions (gDMRs) that exhibit parent-of-origin specific DNA methylation, which is considered primary imprint. Recent studies provide evidence that a subset of gDMR-less, placenta-specific imprinted genes is controlled by maternal-derived histone modifications. To further understand DNA methylation-dependent (canonical) and -independent (non-canonical) imprints, this review summarizes the loci under the control of each type of imprinting in the mouse and compares them with the respective homologs in other rodents. Understanding epigenetic systems that differ among loci or species may provide new models for exploring genetic regulation and evolutionary divergence.


Evaluation of the specificity and sensitivity of two commercial enzyme-linked immunosorbent assay kits, the serum plate agglutination test, and the hemagglutination-inhibition test for antibodies formed in response to Mycoplasma gallisepticum.
Two commercial enzyme-linked immunosorbent assay (ELISA) kits, seven serum plate agglutination (SPA) antigens, and the hemagglutination-inhibition (HI) test for antibodies to Mycoplasma gallisepticum (MG) were compared for sensitivity and specificity using known MG-positive and MG-negative sera from leghorn chickens. All SPA antigens proved to be highly sensitive when testing MG-positive sera. Laboratory-prepared SPA antigens yielded fewer positive reactions when testing MG-negative sera than commercial SPA antigens. Both MG ELISA kits showed high rates of positive reactions when testing sera from birds given commercial M. synoviae bacterin, fowl coryza (Haemophilus paragallinarum) bacterin, inactivated infectious bursal disease virus vaccine, and to a lesser extent fowl cholera (Pasteurella multocida) bacterin. Immunization with Frey's medium with 12% swine serum-in-oil or Staphylococcus aureus-in-oil resulted in sera which yielded numerous positive ELISA reactions. During the first 1 to 3 weeks, antibodies induced by experimental infection with MG were better detected by the SPA test than by the ELISAs and the HI test, thus confirming the SPA test's importance in Mycoplasma diagnostic serology. The HI test can serve to confirm positive SPA results.


Recurrent synovial chondromatosis of the wrist: case report and literature review.
Synovial chondromatosis of the wrist is rare. We report the case of a 35-year-old man with synovial chondromatosis of the left wrist with an 8-year follow-up. Frequent recurrences finally resulted in total wrist arthrodesis. A review of the literature produced 24 case reports of synovial chondromatosis of the wrist with only three cases showing recurrence.


Effects of ytterbium laser surface treatment on the bonding of two resin cements to zirconia.
Monolithic zirconia crowns bonded to zirconia abutments have become more commonly used in the construction of cement-retained implant superstructures. The present study aimed to examine the effects of laser surface treatments on the bond strength of two resin cements to zirconia. Three types of surfaces were examined: untreated, alumina blasted, and ytterbium laser treated; and two types of resin cements: 4-META/MMA-TBB resin cement and composite resin cement. Half of the specimens were subjected to a thermocycling process. Subsequently, a shear bond test was carried out. In addition, surface roughness was measured for each surface type. The results showed that laser treatment increased zirconia surface roughness and that laser treatment significantly increased shear bond strength after the thermocycling of both cement types compared to no treatment. Our experimental results suggested that ytterbium laser surface treatment of zirconia increased the bond strength of resin cements.


Podocyte is the major culprit accounting for the progression of chronic renal disease.
The concept that the podocyte is the major culprit underlying development and progression of glomerular diseases leading to chronic renal failure is well established. The essential steps in this process are (1) the establishment of tuft adhesions to Bowman's capsule; (2) the formation by capillaries contained in a tuft adhesion of a filtrate that is delivered, instead into Bowman's space, towards the interstitium; and (3) the spreading of this filtrate on the outer aspect of the affected nephron leading to the degeneration of this nephron. The present review summarizes the pros and cons concerning the relevance of misdirected filtration for a nephron-to-nephron transfer of the disease at the level of the tubular interstitium. Surprisingly, the histopathology clearly shows that interstitial proliferation surrounding degenerating nephrons tends to encapsulate the degenerative process, confining it to the already affected nephron. No evidence is available that the disease, mediated by interstitial proliferation and matrix deposition, may jump to a neighboring, so far unaffected, nephron. It appears that the process that leads to the degeneration of a nephron in the context of "classic" FSGS always starts separately in the respective glomerulus by severe podocyte injury.


Incidence Trends of Inflammatory Bowel Disease in a Southern European Country: A Mirror of the Western World?
Inflammatory bowel disease (IBD) affects people from all age categories worldwide. Although the incidence of the disease is stabilizing or decreasing in most Western world countries, its prevalence is still increasing because of the rise in life expectancy and better disease management. This work intends to identify the trends related to IBD incidence nationwide, analyzing regional, sex, and age distributions. Data were provided by the Portuguese Shared Services of the Ministry of Health. This study consisted of a retrospective analysis of all first consultations coded for "Chronic enteritis/ulcerative colitis" (D94) in a primary healthcare setting, between 2017 and 2020, in Portugal. The primary outcome measure was the IBD incidence rate per 100,000 inhabitants. We also calculated the incidence rate per person-year and forecasted incidence until 2024. Between 2017 and 2019, the incidence rate of IBD in Portugal decreased from 54.9 to 48.6 per 100,000 inhabitants. The average incidence was 20 new cases of IBD per 1,000 person-year. It was predicted that, in December 2023, IBD incidence would reach 305.4 new cases (95% Prediction Interval 156.6-454.3), a similar result to the values forecasted for December 2021 (305.4, 95% Prediction Interval 197.3-413.6). The incidence of IBD slightly declined from 2017 to 2019, and it is posed to stabilize in the future. The presented data are of the utmost importance for the characterization of IBD in Southern European countries and the establishment of future health policies in the setting of compounding prevalence in the Western world.


High-dose erythropoietin in patients with progressive multiple sclerosis: A randomized, placebo-controlled, phase 2 trial.
Erythropoietin (EPO) is a part of an endogenous neuroprotective system in the brain and may address pathophysiological mechanisms in progressive multiple sclerosis (MS). To evaluate a treatment effect of EPO on progressive MS. This was a single-center, randomized, double-blind, placebo-controlled phase 2 trial, in which 52 patients with secondary or primary progressive MS were allocated to treatment with recombinant EPO (48,000 IU) or placebo, administered intravenously 17 times during 24 weeks. Patients had an Expanded Disability Status Score (EDSS) from 4 to 6.5 and clinical progression without relapses in the 2 preceding years. The primary outcome was the change in a composite measure of maximum gait distance, hand dexterity, and cognition from baseline to 24 weeks. A total of 50 patients completed the study. Venesection was performed often but no thromboembolic events occurred. We found no difference in the primary outcome between the EPO and the placebo group using the intention-to-treat principle ( p = 0.22). None of the secondary outcomes, neither clinical nor magnetic resonance imaging (MRI) measures showed any significant differences. This study provides class II evidence that treatment with high-dose EPO is not an effective treatment in patients with moderately advanced progressive MS.


Clinical effects and pharmacokinetics of different dosage schedules of adriamycin.
Adriamycin was administered to 60 adults and 21 children by 3 different dosage schedules: 22.5 mg/sq m (0.6 mg/kg) daily for 4 days, 15 mg/sq m (0.4 mg/kg) every 8 hr for a total of 6 doses, and 50 to 120 mg/sq m as a single dose every 3 to 4 weeks. Objective responses lasting more than 1 month occurred in 5 subjects with acute leukemias or lymphoma, 3 with transitional cell carcinomas, 2 with sarcomas, 2 with Ewing's sarcoma and 1 each with bronchogenic carcinoma, orchidoblastoma, and thymoma. Toxic reactions included nausea, vomiting, stomatitis, alopecia, and hematopoietic depression, but significant cardiac toxicity occurred in only 1 patient. Pharmacokinetic data, collected in 25 patients by fluorometric and chromatographic assay, suggested a biphasic plasma clearance of drug with initial and secondary half-lives of about 1.5 and 14 to 21 hr, respectively. When drug was given every 8 hr there was evidence of loss of an initial very rapid phase of distribution of adriamycin and its metabolites. Urinary excretion accounted for 3.4 to 38.1% of administered fluorescence over a 72-hr period; in the first 24 hr, between 48.2 and 100% of this urinary material was in the form of adriamycin; leter, this fraction declined. No adriamycin or its fluorescent metabolites could be extracted from the stools.


[Caring for "young" Alzheimer's patients in a home for dependent elderly people].
Alzheimer's disease can affect people under the age of 60, considered as "young" patients. In France, the disease affects 8 000 such people today. Caring for them at home is sometimes impossible and the 2008-2012 Alzheimer plan comprises a measure to reflect on requirements with regard to medico-social establishments. For the last ten years, a residential home for dependent elderly people in the north of France has regularly taken in "young" residents with Alzheimer's disease and reports, via a study, on their characteristics and their needs.


Charged-particle therapy in cancer: clinical uses and future perspectives.
Radiotherapy with high-energy charged particles has become an attractive therapeutic option for patients with several tumour types because this approach better spares healthy tissue from radiation than conventional photon therapy. The cost associated with the delivery of charged particles, however, is higher than that of even the most elaborate photon-delivery technologies. Reliable evidence of the relative cost-effectiveness of both modalities can only come from the results of randomized clinical trials. Thus, the hurdles that currently limit direct comparisons of these two approaches in clinical trials, especially those related to insurance coverage, should be removed. Herein, we review several randomized trials of charged-particle therapies that are ongoing, with results that will enable selective delivery to patients who are most likely to benefit from them. We also discuss aspects related to radiobiology, including the immune response and hypoxia, which will need to be taken into consideration in future randomized trials to fully exploit the potential of charged particles.


Therapeutic endoscopic ultrasound.
Endoscopic ultrasound (EUS) is now firmly established as one of the essential tools for diagnosis in most gastrointestinal MDTs across the UK. However, the ability to provide therapy with EUS has resulted in a significant impact on the management of the patients. These include drainage of peripancreatic collections, EUS-guided endoscopic retrograde cholangiopancreatogram, EUS-guided coeliac plexus blocks, etc. The rapid development of this area in endoscopy is a combination of newer tools and increasing expertise by endosonographers to push the boundaries of intervention with EUS. However, the indications are limited and we are at the start of the learning curve for these high-risk procedures. These therapies should, therefore, be confined to centres with a robust multidisciplinary team, including interventional endoscopists, radiologists and surgeons.


Biliary secretion and enterohepatic recycling of fenbendazole metabolites in sheep.
Fenbendazole (FBZ) was administered intraruminally at 5.0 mg/kg, containing a trace of [14C]-FBZ, to sheep fitted with a permanent bile duct cannula and the behaviour of FBZ and its metabolites examined in bile and plasma. Of the administered radiolabelled dose, 47% was secreted in bile of which 34% was accounted for as conjugated and 4% as unconjugated (free) metabolites. Hydroxylated oxfendazole (OH.OFZ) was the major biliary metabolite contributing 66%, and hydroxy-FBZ (OH.FBZ) 27%, of the total metabolites characterized. Small amounts of OFZ and hydroxy FBZ sulphone (OH.FBZ.SO2) were also present in bile. The rapid appearance of OH.OFZ in bile, even before maximum concentrations of OFZ occurred in plasma, indicated that sulphoxidation and hydroxylation was the major route of FBZ metabolism. Following intraduodenal infusion of free biliary metabolites, FBZ and its metabolites rapidly appeared in bile indicating absorption from the small intestine. When conjugated metabolites were infused they continued to appear in bile for a further 15-20 h after cessation of infusion indicating that absorption of hydroxylated metabolites occurred largely after bacterial deconjugation in the large intestine. Approximately 40% of biliary metabolites were estimated to undergo enterohepatic reabsorption but they contributed minimally to the metabolite content in plasma. It is suggested that during the process of recycling-biliary metabolites make substantial contact with parasites in the mucosa of the small and large intestine thereby contributing to the anti-helminthic activity of FBZ.


E-cigarette support for smoking cessation: Identifying the effectiveness of intervention components in an on-line randomized optimization experiment.
The aim of this study was to determine which combination(s) of five e-cigarette-orientated intervention components, delivered on-line, affect smoking cessation. An on-line (UK) balanced five-factor (2 × 2 × 2 × 2 × 2 = 32 intervention combinations) randomized factorial design guided by the multi-phase optimization strategy (MOST) was used. A total of 1214 eligible participants (61% female; 97% white) were recruited via social media. The five on-line intervention components designed to help smokers switch to exclusive e-cigarette use were: (1) tailored device selection advice; (2) tailored e-liquid nicotine strength advice; (3): tailored e-liquid flavour advice; (4) brief information on relative harms; and (5) text message (SMS) support. The primary outcome was 4-week self-reported complete abstinence at 12 weeks post-randomization. Primary analyses were intention-to-treat (loss to follow-up recorded as smoking). Logistic regressions modelled the three- and two-way interactions and main effects, explored in that order. In the adjusted model the only significant interaction was a two-way interaction, advice on flavour combined with text message support, which increased the odds of abstinence (odds ratio = 1.55, 95% confidence interval = 1.13-2.14, P = 0.007, Bayes factor = 7.25). There were no main effects of the intervention components. Text-message support with tailored advice on flavour is a promising intervention combination for smokers using an e-cigarette in a quit attempt.


Control over the cosmic radiation level during flight of space vehicles Vostok 3, Vostok 4, Vostok 5 and Vostok 6.
1. During the flights of the"Vostok"series of spaceships the radiation conditions in space were kept under operative control which comprised: a. The solar activity observation and forecasting of the solar flares followed by the appearance of proton fluxes in the near space. b. Probing the upper atmosphere with the help of balloon launchings at high altitudes. c. Direct measuring radiation level inside the "Vostok" spaceships. 2. The radiation dose received by the cosmonauts during the flights of the "Vostok" spaceships is given. Contributions of various components of cosmic radiation are considered. 3. The possibility of flights of the "Vostok" series of spaceships at high altitudes is evaluated.


Predictors of change on the smoking uptake continuum among adolescents.
Understanding how advertising and other risk and demographic factors affect adolescent susceptibility to smoking would allow for the development of more effective youth-targeted tobacco prevention and cessation programs and policies. To examine the effect of various demographic and risk factors on different stages of smoking among adolescents. A nationally representative cross-sectional survey, The Robert Wood Johnson Foundation's Survey of Tobacco Price Sensitivity, Behavior, and Attitudes Among Teenagers and Young Adults. The Robert Wood Johnson Foundation's Survey of Tobacco Price Sensitivity, Behavior, and Attitudes Among Teenagers and Young Adults included 17,287 adolescent respondents (aged, 13-19 years) in 1996. Stage of susceptibility and correlates of progression toward regular smoking. Of all never [corrected] smoking adolescents, 32% were susceptible smokers (have never smoked, but might) with younger adolescents almost 3 times more likely than older adolescents to be susceptible. Female subjects were 50% [corrected] more likely than male subjects to be susceptible. In addition to exposure to others' smoking, owning or willingness to own tobacco promotional items, having a favorite cigarette advertisement, skipping school, poor school performance, and lack of attendance in religious activities were associated with progression along the uptake continuum. Improved understanding of the tobacco use trajectories of adolescents and the risk factors associated with progression will help clinicians and tobacco control advocates create effective youth-targeted interventions and policies. Findings suggest that physicians and other health care providers should redouble their efforts to ask preadolescents and young adults about smoking or the likelihood of their smoking. Nonsmokers should also be advised about the addictive nature of tobacco products and the resulting loss of control that accompanies addiction.