Caffeine ameliorates high energy diet-induced hepatic steatosis: sirtuin 3 acts as a bridge in the lipid metabolism pathway.
The beneficial effect of caffeine-containing food on non-alcoholic fatty liver disease (NAFLD) has been widely reported. The aim of this study was to explore the effect of caffeine on hepatic steatosis. C57BL/6 mice were randomly assigned to a normal diet or a high energy diet (HED). Caffeine was given to HED mice by oral gavage. Body weights, lipids in the liver and liver damage were measured. Meanwhile, cAMP, SIRT3 or AMPK inhibitors were treated respectively before incubation with caffeine in oleate-treated HepG2 cells. SIRT3 was further silenced by siRNA to confirm the results. Caffeine significantly decreased the mass of fat tissues, lipids, ALT and AST levels in the liver of HED-treated mice. Caffeine increased the transformation of ADP to ATP and activated the cAMP/CREB/SIRT3/AMPK/ACC pathway in the liver. Nile red staining demonstrated that suppression of cAMP, SIRT3 or AMPK in oleate-treated HepG2 cells counteracted the effect of caffeine. Moreover, knocking down SIRT3 could down-regulate AMPK and ACC phosphorylation by caffeine. These results demonstrate that caffeine could improve HED-induced hepatic steatosis by promoting lipid metabolism via the cAMP/CREB/SIRT3/AMPK/ACC pathway. SIRT3 functioned as a molecular bridge connecting caffeine and lipid metabolism.


Corneal hysteresis and visual field asymmetry in open angle glaucoma.
To investigate the association between corneal biomechanical parameters and asymmetric primary open angle glaucoma (POAG) using the Ocular Response Analyzer (ORA). In a prospective cross-sectional study, ORA parameters were measured in 117 POAG patients with asymmetric visual fields (VF). The asymmetry in VF was defined as a five point difference between the eyes using the Advanced Glaucoma Intervention Study (AGIS) scoring system. Subjects with previous intraocular or refractive surgery, ocular comorbidities and diabetes were excluded. In worse eyes, mean AGIS scores were significantly higher (8.1 ± 4.3 vs. 1.0 ± 1.6; P < 0.001) and mean corneal hysteresis (CH) was significantly lower (8.2 ± 1.9 vs. 8.9 ± 1.9 mm Hg; P < 0.001). Median ORA-corrected intraocular pressure was higher in the worse eyes (IOP(cc), 17.4 mm Hg vs. 16.9 mm Hg; P < 0.001). Worse eyes had a slightly lower mean corneal resistance factor (P = 0.04) and more myopic mean spherical equivalent (P = 0.02). No difference was seen in the central corneal thickness (CCT; P = 0.63) and Goldmann applanation tonometry (GAT; P = 0.32). On multivariate analysis, only CH retained an association with the worse eye (odds ratio, 25.9; 95% confidence interval, 10.1-66.5). ROC curves showed that only CH and IOP(cc) had a discriminative ability for the eye with worse VF (AUC, 0.82 and 0.70, respectively). Asymmetric POAG was associated with asymmetry in ORA parameters but not in CCT and GAT. Lower CH was associated with worse eyes independently of its effect on IOP measurement and had the best discriminability for the eye with the worse VF.


Implementation of a Clinical Decision Support System for Children With Minor Blunt Head Trauma Who Are at Nonnegligible Risk for Traumatic Brain Injuries.
To determine the effect of providing risk estimates of clinically important traumatic brain injuries and management recommendations on emergency department (ED) outcomes for children with isolated intermediate Pediatric Emergency Care Applied Research Network clinically important traumatic brain injury risk factors. This was a secondary analysis of a nonrandomized clinical trial with concurrent controls, conducted at 5 pediatric and 8 general EDs between November 2011 and June 2014, enrolling patients younger than 18 years who had minor blunt head trauma. After a baseline period, intervention sites received electronic clinical decision support providing patient-level clinically important traumatic brain injury risk estimates and management recommendations. The following primary outcomes in patients with one intermediate Pediatric Emergency Care Applied Research Network risk factor were compared before and after clinical decision support: proportion of ED computed tomography (CT) scans, adjusted for age, time trend, and site; and prevalence of clinically important traumatic brain injuries. The risk of clinically important traumatic brain injuries was known for 3,859 children with isolated findings (1,711 at intervention sites before clinical decision support, 1,702 at intervention sites after clinical decision support, and 446 at control sites). In this group, pooled CT proportion decreased from 24.2% to 21.6% after clinical decision support (odds ratio 0.86; 95% confidence interval 0.73 to 1.01). Decreases in CT use were noted across intervention EDs, but not in controls. The pooled adjusted odds ratio for CT use after clinical decision support was 0.73 (95% confidence interval 0.60 to 0.88). Among the entire cohort, clinically important traumatic brain injury was diagnosed at the index ED visit for 37 of 37 (100%) patients before clinical decision support and 32 of 33 patients (97.0%) after clinical decision support. Providing specific risks of clinically important traumatic brain injury through electronic clinical decision support was associated with a modest and safe decrease in ED CT use for children at nonnegligible risk of clinically important traumatic brain injuries.


An increase in essential amino acid availability upregulates amino acid transporter expression in human skeletal muscle.
Essential amino acids (EAA) stimulate skeletal muscle mammalian target of rapamycin complex 1 (mTORC1) signaling and protein synthesis. It has recently been reported that an increase in amino acid (AA) transporter expression during anabolic conditions is rapamycin-sensitive. The purpose of this study was to determine whether an increase in EAA availability increases AA transporter expression in human skeletal muscle. Muscle biopsies were obtained from the vastus lateralis of seven young adult subjects (3 male, 4 female) before and 1-3 h after EAA ingestion (10 g). Blood and muscle samples were analyzed for leucine kinetics using stable isotopic techniques. Quantitative RT-PCR, and immunoblotting were used to determine the mRNA and protein expression, respectively, of AA transporters and members of the general AA control pathway [general control nonrepressed (GCN2), activating transcription factor (ATF4), and eukaryotic initiation factor (eIF2) alpha-subunit (Ser(52))]. EAA ingestion increased blood leucine concentration, delivery of leucine to muscle, transport of leucine from blood into muscle, intracellular muscle leucine concentration, ribosomal protein S6 (Ser(240/244)) phosphorylation, and muscle protein synthesis. This was followed with increased L-type AA transporter (LAT1), CD98, sodium-coupled neutral AA transporter (SNAT2), and proton-coupled amino acid transporter (PAT1) mRNA expression at 1 h (P < 0.05) and modest increases in LAT1 protein expression (3 h post-EAA) and SNAT2 protein expression (2 and 3 h post-EAA, P < 0.05). Although there were no changes in GCN2 expression and eIF2 alpha phosphorylation, ATF4 protein expression reached significance by 2 h post-EAA (P < 0.05). We conclude that an increase in EAA availability upregulates human skeletal muscle AA transporter expression, perhaps in an mTORC1-dependent manner, which may be an adaptive response necessary for improved AA intracellular delivery.


Explaining Asian Americans' academic advantage over whites.
The superior academic achievement of Asian Americans is a well-documented phenomenon that lacks a widely accepted explanation. Asian Americans' advantage in this respect has been attributed to three groups of factors: (i) socio-demographic characteristics, (ii) cognitive ability, and (iii) academic effort as measured by characteristics such as attentiveness and work ethic. We combine data from two nationally representative cohort longitudinal surveys to compare Asian-American and white students in their educational trajectories from kindergarten through high school. We find that the Asian-American educational advantage is attributable mainly to Asian students exerting greater academic effort and not to advantages in tested cognitive abilities or socio-demographics. We test explanations for the Asian-white gap in academic effort and find that the gap can be further attributed to (i) cultural differences in beliefs regarding the connection between effort and achievement and (ii) immigration status. Finally, we highlight the potential psychological and social costs associated with Asian-American achievement success.


Discovery of a low-mass brown dwarf companion of the young nearby star G 196-3
A substellar-mass object in orbit at about 300 astronomical units from the young low-mass star G 196-3 was detected by direct imaging. Optical and infrared photometry and low- and intermediate-resolution spectroscopy of the faint companion, hereafter referred to as G 196-3B, confirm its cool atmosphere and allow its mass to be estimated at 25-10+15 Jupiter masses. The separation between the objects and their mass ratio suggest the fragmentation of a collapsing cloud as the most likely origin for G 196-3B, but alternatively it could have originated from a protoplanetary disc that has been dissipated. Whatever the formation process was, the young age of the primary star (about 100 million years) demonstrates that substellar companions can form on short time scales.


The use of chimeric A2K(b) tetramers to monitor HLA A2 immune responses in HLA A2 transgenic mice.
HLA A2 (A2) transgenic mice are currently being used to compare different vaccination protocols. However, the monitoring of A2 restricted CTL in A2 transgenic mice have been hampered by poor staining efficiency of mouse CTL by A2 tetramers. We demonstrate here that chimeric A2 tetramers containing mouse H-2K(b) (K(b)) alpha3 domain (A2K(b) tetramers) can be used as staining reagents to monitor A2 restricted CTL responses in A2 transgenic mice. The increased ability of A2K(b) tetramers to stain mouse A2 restricted CTL, as compared with A2 tetramers, correlated with their higher binding affinity for mouse A2 restricted CTL. The use of these novel staining reagents will allow efficient comparison of vaccination strategies and rapid identification of novel CTL epitopes in A2 transgenic mice.


Labor patterns in women with previous cesareans.
Little information exists to help determine the presence or significance of labor abnormalities in women attempting vaginal birth after previous cesarean. A case-control study was performed to obtain information on patterns of labor progress and the incidence of dysfunctional labor in patients having a trial of labor after previous cesarean delivery. Sixty-eight such women were matched to nulliparous and multiparous controls. Labor-curve characteristics for the group of women with previous cesarean differed significantly from those of both the nulliparas and multiparas. When stratified by history of previous vaginal birth, however, those with no previous vaginal birth were indistinguishable from nulliparous controls and those with a previous vaginal birth were indistinguishable from multiparous controls. Parity-specific criteria for the diagnosis of dysfunctional labor were thus indicated. Labor disorders were present most frequently in the previous-cesarean group with no previous vaginal birth (41.9%). This incidence did not differ significantly from that in the control nulliparas (27.1%) (P = .15), but did differ from that in the multiparas (15.8%) (P less than .01). Previous-cesarean patients with a previous vaginal birth had a frequency of labor disorders (14.3%) not significantly different from that of multiparous controls. We conclude that trial of labor in women with a previous cesarean should be evaluated by standard criteria for nulliparas if there has been no previous vaginal birth, and by criteria for multiparous women if there has been any previous infant born vaginally.


Eustachian valve endocarditis: Rare case reports and review of literature.
Eustachian valve endocarditis (EVE) is a distinctly rare and underdiagnosed entity. We report 2 new cases caused by vancomycin resistant Staphylococcus aureus and Staphylococcus hominis diagnosed on transesophageal echocardiography (TEE). Although, 63% of Eustachian valve endocarditis is caused by Staphylococcus aureus, we report the first case of vancomycin resistant Staphylococcus aureus and first case related to implantable venous access systems. EVE is now seen more commonly in elderly population with diverse microbial cultures and antibiotic sensitivities. TTE is the first modality for investigation of EVE, however a negative TTE does not preclude the diagnosis, as only 88% of cases were diagnosed on TEE.


The hypothiocyanite radical OSCN and its isomers.
A biologically relevant reactive sulfur species (RSS), the hypothiocyanite radical OSCN, is generated in the gas phase through flash vacuum pyrolysis (FVP) of trifluoromethyl sulfinyl cyanide CF3S(O)CN at ca. 1000 K. Upon UV light irradiation (365 nm), OSCN rearranges to novel isomers OSNC and SOCN, and further visible light irradiation (400 ± 20 nm) leads to reverse isomerization. The identification of OSCN, OSNC, and SOCN in cryogenic matrices (Ar and N2, 2.8 K) with IR spectroscopy is supported by quantum chemical calculations up to the CCSD(T)-F12/VTZ-F12 level. The potential energy surface for the interconversion of OSCN isomers and their bonding properties are computationally explored by using the CCSD(T)-F12/VTZ-F12 and EDA-NOCV methods, respectively.


Manually Steerable Catheter With Improved Agility.
A prototype steerable catheter was designed for endovascular procedures. This technical pilot study reports the initial experience using the catheter for cannulation of visceral arteries. The 7F catheter was manually steerable with operator control handle for bending and rotation of the tip. The maximum bending angle was approximately 90° and full 360° rotation of the tip was supported. The study involved 1 pig with 4 designated target arteries: the left and right renal arteries, the superior mesenteric artery, and the celiac trunk. Fluoroscopy with 3-dimensional (3D) overlay showing the ostia from preoperative computed tomography angiography was used for image guidance. The cannulation was considered successful if the guidewire was placed well inside the target artery. In addition to evaluating cannulation success, procedure time and associated radiation doses were recorded. The procedure was performed twice with 2 different operators. Both operators successfully reached all 4 target arteries, demonstrating the feasibility of the steerable catheter for endovascular cannulation of visceral arteries. No contrast medium was used, and median radiation dose was 4.5 mGy per cannulation. An average of approximately 2 minutes was used per cannulation. This study motivates further testing in a more comprehensive study to evaluate reproducibility in several animals and with inclusion of more operators. Further development by integrating the new catheter tool in a navigation system is also an interesting next step, combining fine control of catheter tip movements and 3D image guidance without ionizing radiation.


Neuropsychiatric Effects of HIV Antiviral Medications.
The development of antiretroviral therapy (ART) has dramatically increased the lifespan of HIV patients but treatment is complicated by numerous adverse effects and toxicities. ART complications include neuropsychiatric, metabolic, gastrointestinal, cardiac, and numerous other toxicities, and clinicians often have to choose one toxicity over another to offer the best medication regimen for a patient. Some antiviral drugs cause significant neuropsychiatric complications, including depression, cognitive impairment, and sleep disturbance. Even in careful studies, it may be difficult to determine which effects are related to the virus, the immune system, or the treatment. Of the six currently marketed classes of antiviral drugs, the nucleoside reverse transcriptase inhibitors and the non-nucleoside reverse transcriptase inhibitors have been most commonly associated with neuropsychiatric complications. Within these classes, certain drugs are more likely to cause difficulty than others. We review the contention regarding the central nervous system (CNS) complications of efavirenz, as well as debate about the role of CNS penetration in drug effectiveness and toxicity. A thorough working knowledge of the neuropsychiatric consequences of ART allows clinicians to tailor treatment more successfully to individual patients as well as to identify ART more quickly as the source of a problem or symptom.


Contraction-induced muscle damage is unaffected by vitamin E supplementation.
Vitamin E supplementation may confer a protective effect against eccentrically biased exercise-induced muscle damage through stabilization of the cell membrane and possibly via inhibition of free radical formation. Evidence supporting a protective role of vitamin E after contraction-induced muscle injury in humans is, however, inconsistent. The present study sought to determine the effect of vitamin E supplementation on indices of exercise-induced muscle damage and the postexercise inflammatory response after performance of repeated eccentric muscle contractions. Young healthy men performed a bout of 240 maximal isokinetic eccentric muscle contractions (0.52 rad.s-1) after being supplemented for 30 d with either vitamin E (N = 9; 1200 IU.d-1) or placebo (N = 7; safflower oil). Measurements of torque (isometric and concentric) decreased (P < 0.05) below preexercise values immediately post- and at 48 h post-exercise. Biopsies taken 24 h postexercise showed a significant increase in the amount of extensive Z-band disruption (P < 0.01); however, neither the torque deficit nor the extent of Z-band disruption were affected by vitamin E. Exercise resulted in increased macrophage cell infiltration (P = 0.05) into muscle, which was also unaffected by vitamin E. Serum CK also increased as a result of the exercise (P < 0.05) with no effect of vitamin E. We conclude that vitamin E supplementation (30 d at 1200 IU.d-1), which resulted in a 2.8-fold higher serum vitamin E concentration (P < 0.01), had no affect on indices of contraction-induced muscle damage nor inflammation (macrophage infiltration) as a result of eccentrically biased muscle contractions.


A phase I study of OncoVEXGM-CSF, a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor.
To conduct a phase I clinical trial with a second-generation oncolytic herpes simplex virus (HSV) expressing granulocyte macrophage colony-stimulating factor (Onco VEXGM-CSF) to determine the safety profile of the virus, look for evidence of biological activity, and identify a dosing schedule for later studies. The virus was administered by intratumoral injection in patients with cutaneous or s.c. deposits of breast, head and neck and gastrointestinal cancers, and malignant melanoma who had failed prior therapy. Thirteen patients were in a single-dose group, where doses of 10(6), 10(7), and 10(8) plaque-forming units (pfu)/mL were tested, and 17 patients were in a multidose group testing a number of dose regimens. The virus was generally well tolerated with local inflammation, erythema, and febrile responses being the main side effects. The local reaction to injection was dose limiting in HSV-seronegative patients at 10(7) pfu/mL. The multidosing phase thus tested seroconverting HSV-seronegative patients with 10(6) pfu/mL followed by multiple higher doses (up to 10(8) pfu/mL), which was well tolerated by all patients. Biological activity (virus replication, local reactions, granulocyte macrophage colony-stimulating factor expression, and HSV antigen-associated tumor necrosis), was observed. The duration of local reactions and virus replication suggested that dosing every 2 to 3 weeks was appropriate. Nineteen of 26 patient posttreatment biopsies contained residual tumor of which 14 showed tumor necrosis, which in some cases was extensive, or apoptosis. In all cases, areas of necrosis also strongly stained for HSV. The overall responses to treatment were that three patients had stable disease, six patients had tumors flattened (injected and/or uninjected lesions), and four patients showed inflammation of uninjected as well as the injected tumor, which, in nearly all cases, became inflamed. Onco VEXGM-CSF is well tolerated and can be safely administered using the multidosing protocol described. Evidence of an antitumor effect was seen.


A comparative propensity score-matched analysis of perioperative outcomes of intracorporeal vs extracorporeal urinary diversion after robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium.
To compare the perioperative outcomes of intracorporeal (ICUD) vs extracorporeal urinary diversion (ECUD) after robot-assisted radical cystectomy (RARC). We retrospectively reviewed the prospectively maintained International Robotic Cystectomy Consortium (IRCC) database. A total of 972 patients from 28 institutions who underwent RARC were included. Propensity score matching was used to match patients based on age, gender, body mass index (BMI), American Society of Anesthesiologists Score (ASA) score, Charlson Comorbidity Index (CCI) score, prior radiation and abdominal surgery, receipt of neoadjuvant chemotherapy, and clinical staging. Matched cohorts were compared. Multivariate stepwise logistic and linear regression models were fit to evaluate variables associated with receiving ICUD, operating time, 90-day high-grade complications (Clavien-Dindo Classification Grade ≥III), and 90-day readmissions after RARC. Utilisation of ICUD increased from 0% in 2005 to 95% in 2018. The ICUD patients had more overall complications (66% vs 58%, P = 0.01) and readmissions (27% vs 17%, P = 0.01), but not high-grade complications (21% vs 24%, P = 0.22). A more recent RC era and ileal conduit diversion were associated with receiving an ICUD. Higher BMI, ASA score ≥3, and receiving a neobladder were associated with longer operating times. Shorter operating time was associated with male gender, older age, ICUD, and centres with a larger annual average RC volume. Longer intensive care unit stay was associated with 90-day high-grade complications. Higher CCI score, prior radiation therapy, neoadjuvant chemotherapy, and ICUD were associated with a higher risk of 90-day readmissions. Utilisation of ICUD has increased over the past decade. ICUD was associated with more overall complications and readmissions compared to ECUD, but not high-grade complications.


Computer-synthesis of an interference color chart of human tear lipid layer, by a colorimetric approach.
To synthesize an interference color chart for the specific tear lipid layer interference camera, DR-1, for the conversion of the tear film lipid layer thickness into color graphic information--that is, for the quantification of the tear interference image--by a colorimetric approach. Because the color of the tear lipid layer interference image is visualized by a white light source interference phenomena, to produce gamma-corrected red, green, and blue (RGB) values of a specific interference color at a certain tear lipid film thickness, XYZ tristimulus values of the Commission Internationale de l'Eclairage (CIE) were obtained. XYZ tristimulus values were calculated from the light source spectrum of the DR-1 camera, the color-matching function of CIE, and the reflectance of the tear interference image in wavelengths ranging from 380 to 780 nm. These calculated interference colors were synthesized ranging from 0 nm to 1000 nm of lipid film thickness to produce a color chart. The applicability of the new color chart in the analysis of the lipid layer thickness was tested on a healthy control subject with normal tear function and a patient with dry eye who had aqueous tear deficiency and meibomian gland obstruction. The specific tear interference color chart for the DR-1 camera was obtained with RGB and XYZ tristimulus values. The interference chart ranged from 0 to approximately the 5th interference order. The interference colors from clinical DR-1 images could be converted to lipid thickness data by using the color chart system. A new tear interference color chart was developed in this study, which may be of benefit in converting tear interference color information to data describing the thickness of the tear film lipid layer.


The Direct 3D Printing of Functional PEEK/Hydroxyapatite Composites via a Fused Filament Fabrication Approach.
The manufacture of polyetheretherketone/hydroxyapatite (PEEK/HA) composites is seen as a viable approach to help enhance direct bone apposition in orthopaedic implants. A range of methods have been used to produce composites, including Selective Laser Sintering and injection moulding. Such techniques have drawbacks and lack flexibility to manufacture complex, custom-designed implants. 3D printing gets around many of the restraints and provides new opportunities for innovative solutions that are structurally suited to meet the needs of the patient. This work reports the direct 3D printing of extruded PEEK/HA composite filaments via a Fused Filament Fabrication (FFF) approach. In this work samples are 3D printed by a custom modified commercial printer Ultimaker 2+ (UM2+). SEM-EDX and µCT analyses show that HA particles are evenly distributed throughout the bulk and across the surface of the native 3D printed samples, with XRD highlighting up to 50% crystallinity and crystalline domains clearly observed in SEM and HR-TEM analyses. This highlights the favourable temperature conditions during 3D printing. The yield stress and ultimate tensile strength obtained for all the samples are comparable to human femoral cortical bone. The results show how FFF 3D printing of PEEK/HA composites up to 30 wt% HA can be achieved.


Osteopathic manipulative treatment in the management of biliary dyskinesia.
Biliary dyskinesia is a functional gastrointestinal disorder of the gallbladder and sphincter of Oddi. Diagnosis is made on the basis of symptoms of biliary colic in the absence of cholelithiasis and gallbladder inflammation. Palpatory findings of tissue texture changes at midthoracic levels (T6-T9) may correspond to visceral dysfunction related to the biliary system. Osteopathic manipulative treatment (OMT) of the T6-T9 segments can remove the feedback related to the somatic component, thereby affecting nociceptive facilitation at the spinal level and allowing the body to restore autonomic balance. Few reports in the current literature provide examples of treatment for patients with biliary dyskinesia using OMT. The author describes the case of a 51-year-old woman who presented with symptoms consistent with biliary dyskinesia. Her biliary colic completely resolved after OMT. Osteopathic evaluation and OMT should be considered a safe and effective option for conservative management of biliary dyskinesia.


Crystallization Kinetics and Morphology Control of Formamidinium-Cesium Mixed-Cation Lead Mixed-Halide Perovskite via Tunability of the Colloidal Precursor Solution.
The meteoric rise of the field of perovskite solar cells has been fueled by the ease with which a wide range of high-quality materials can be fabricated via simple solution processing methods. However, to date, little effort has been devoted to understanding the precursor solutions, and the role of additives such as hydrohalic acids upon film crystallization and final optoelectronic quality. Here, a direct link between the colloids concentration present in the [HC(NH2 )2 ]0.83 Cs0.17 Pb(Br0.2 I0.8 )3 precursor solution and the nucleation and growth stages of the thin film formation is established. Using dynamic light scattering analysis, the dissolution of colloids over a time span triggered by the addition of hydrohalic acids is monitored. These colloids appear to provide nucleation sites for the perovskite crystallization, which critically impacts morphology, crystal quality, and optoelectronic properties. Via 2D X-ray diffraction, highly ordered and textured crystals for films prepared from solutions with lower colloidal concentrations are observed. This increase in material quality allows for a reduction in microstrain along with a twofold increase in charge-carrier mobilities leading to values exceeding 20 cm2 V-1 s-1 . Using a solution with an optimized colloidal concentration, devices that reach current-voltage measured power conversion efficiency of 18.8% and stabilized efficiency of 17.9% are fabricated.


Geometric rectification of camera-captured document images.
Compared to typical scanners, handheld cameras offer convenient, flexible, portable, and non-contact image capture, which enables many new applications and breathes new life into existing ones. However, camera-captured documents may suffer from distortions caused by non-planar document shape and perspective projection, which lead to failure of current OCR technologies. We present a geometric rectification framework for restoring the frontal-flat view of a document from a single camera-captured image. Our approach estimates 3D document shape from texture flow information obtained directly from the image without requiring additional 3D/metric data or prior camera calibration. Our framework provides a unified solution for both planar and curved documents and can be applied in many, especially mobile, camera-based document analysis applications. Experiments show that our method produces results that are significantly more OCR compatible than the original images.


Metabolic control analysis of de novo sunflower fatty acid biosynthesis.
We have obtained a simulation of the final steps of de novo fatty acid biosynthesis in sunflower control line RHA-274. For this simulation, we have used data from the evolution of fatty acids during seed formation and from the biochemical characterization of beta-keto-acyl-ACP synthetase II (FASII), stearoyl-ACP desaturase (SAD) and acyl-ACP thioesterase activities and the program GEPASI (based on the metabolic control-analysis theory). When physiological data from high- and medium-stearic acid mutants seed development were used with this model the predicted changes in SAD and TE were very similar to those actually found in the biochemical characterization of these mutants. However, the model had to be modified when results from high-palmitic mutants, accumulating unusual fatty acids like palmitoleic, asclepic and palmitolinoleic acids, were used. The emerging model, that fits all of our results, predicts the existence of a dynamic channelling between the FASII complex and SAD, that channelling being responsible for the alternative pathway starting with the desaturation of palmitic acid by the stearoyl-ACP desaturase. This channelling is consistent with our previous results. For instance, the determination of SAD activity on sunflower seed crude extracts only rendered oleic acid when the stearic acid used as a substrate was obtained from a KASII assay, but not when the stearic acid came from in vitro synthesis using acyl-ACP synthetase from Escherichia coli. This theoretical approximation will be very useful in predicting the evolution of the system when introducing new or modified activities; similar approximations in other oil-seed crops could be of great interest.


Chronometric comparison of actual and imaged complex movement patterns.
The authors' aim in this study was to consider the functional equivalence of internal imagery, external imagery, and action execution. Sixteen elite gymnasts imaged and performed a complex gymnastic vault. Ten performers imaged from an internal perspective, and 6 used an external perspective. Although the results revealed that the time to image the entire motor task did not significantly differ from the time required to physically perform it, irrespective of the imagery perspective used, the temporal organization of the action was different within the imagery conditions than it was in the physical condition. The results do not provide support for the principle of temporal functional equivalence. The authors discuss the results in light of recent findings from the cognitive neuroscience and psychology literatures.


Alternative therapies in patients with non-muscle invasive bladder cancer.
Bladder cancer (BC) is one of the leading causes of cancer-related deaths worldwide. Despite, the majority of the cases were diagnosed as non-muscle invasive bladder cancer (NMIBC) with favorable prognosis, it has tendency to recur or progress to a higher grade or stage. The first line treatment of patients with NMIBC is transurethral resection with adjuvant therapies primarily intravesical Bacillus Calmette-Guérin (BCG) immunotherapy. However, in a portion of patients whose BCG treatment failed, alternative treatments may be required. Furthermore, intravesical BCG may be contraindicated in or untolerated by a group of patients. For these patients, some treatment options are readily available and a variety of them are currently under clinical investigation. In this review, these alternative therapies have been summarized.


The magnitude of an iatrogenic disorder: a systematic review of the incidence of venous thromboembolism for general medical inpatients.
Venous thromboembolism (VTE) is recognized as a potential serious complication of hospitalization, and anticoagulant prophylaxis is widely recommended for medical inpatients. The purpose of this review was to systematically inspect the literature to determine the incidence of VTE without anticoagulant prophylaxis for hospitalized general medical patients. A systematic review was performed using MEDLINE and Cochrane Collaboration searches of the English-language literature. References of the retrieved articles were reviewed for additional studies, and pharmaceutical companies were contacted directly to identify unpublished studies. Studies were eligible if they reported the incidence of symptomatic or asymptomatic VTE in hospitalized general medical patients and included a group which did not receive prophylaxis. Eight trials were identified. Study design, quality, and results were heterogeneous. The incidence of symptomatic VTE without prophylaxis was examined in three trials; the incidence was 2.3% in the only randomized trial, and was 0.8% and 6.2% in two observational studies. The incidence of asymptomatic VTE ranged from 3.7% to 26.0% (median 12.8%). Risk factors identified were older age, prior VTE, and obesity. Though there is little high quality evidence, the best estimate of the incidence of hospital-acquired VTE for general medical patients is approximately 2% for patients at moderate to high risk and <1% for patients at low risk. Further studies are needed to more precisely define a low risk group for whom anticoagulant prophylaxis is unnecessary.


Observation of Young's double-slit interference with the three-photon N00N state.
Spatial interference of quantum mechanical particles exhibits a fundamental feature of quantum mechanics. A two-mode entangled state of N particles known as N00N state can give rise to non-classical interference. We report the first experimental observation of a three-photon N00N state exhibiting Young's double-slit type spatial quantum interference. Compared to a single-photon state, the three-photon entangled state generates interference fringes that are three times denser. Moreover, its interference visibility of 0.49 ± 0.09 is well above the limit of 0.1 for spatial super-resolution of classical origin.


Heterogeneity in the respiratory symptoms of patients with mild-to-moderate COPD.
The burden of symptoms varies markedly between patients with COPD and is only weakly correlated with lung function impairment. While heterogeneity in lung function decline and exacerbations have been previously studied, the extent of heterogeneity in symptoms and the factors associated with this heterogeneity are not well understood. A sample of the general Canadian population ≥40 years with persistent airflow limitation was followed for up to 3 years. Participants reported whether they experienced chronic coughing, phlegm, wheezing, or dyspnea during visits at 18-month intervals. We used mixed-effect logistic regression models (separately for each symptom) to assess overall heterogeneity in the occurrence of symptoms between individuals, and the proportion of variation in symptom burden explained by lung function vs all other clinical characteristics of participants. Four hundred forty-nine participants (53% male, mean age 67 years) contributed 968 visits in total, and 89% of patients reported at least one symptom during follow-up. There was substantial heterogeneity in the individual-specific probabilities for the occurrence of symptoms. This heterogeneity was highest for wheeze and dyspnea (IQR of probabilities: 0.13-0.78 and 0.19-0.81, respectively). FEV1 explained 28% of the variation between individuals in the occurrence of dyspnea, 8% for phlegm, 3% for cough, and 2% for wheeze. All clinical characteristics of participants (including FEV1) explained between 26% of heterogeneity in the occurrence of cough to 49% for dyspnea. There is marked heterogeneity in the burden of respiratory symptoms between COPD patients. The ability of lung function and other commonly measured clinical characteristics to explain this heterogeneity differs between symptoms.


OMIGA: Optimized Maker-Based Insect Genome Annotation.
Insects are one of the largest classes of animals on Earth and constitute more than half of all living species. The i5k initiative has begun sequencing of more than 5,000 insect genomes, which should greatly help in exploring insect resource and pest control. Insect genome annotation remains challenging because many insects have high levels of heterozygosity. To improve the quality of insect genome annotation, we developed a pipeline, named Optimized Maker-Based Insect Genome Annotation (OMIGA), to predict protein-coding genes from insect genomes. We first mapped RNA-Seq reads to genomic scaffolds to determine transcribed regions using Bowtie, and the putative transcripts were assembled using Cufflink. We then selected highly reliable transcripts with intact coding sequences to train de novo gene prediction software, including Augustus. The re-trained software was used to predict genes from insect genomes. Exonerate was used to refine gene structure and to determine near exact exon/intron boundary in the genome. Finally, we used the software Maker to integrate data from RNA-Seq, de novo gene prediction, and protein alignment to produce an official gene set. The OMIGA pipeline was used to annotate the draft genome of an important insect pest, Chilo suppressalis, yielding 12,548 genes. Different strategies were compared, which demonstrated that OMIGA had the best performance. In summary, we present a comprehensive pipeline for identifying genes in insect genomes that can be widely used to improve the annotation quality in insects. OMIGA is provided at http://ento.njau.edu.cn/omiga.html .


Non-aqueous silicone elastomer gels as a vaginal microbicide delivery system for the HIV-1 entry inhibitor maraviroc.
Aqueous semi-solid polymeric gels, such as those based on hydroxyethylcellulose (HEC) and polyacrylic acid (e.g. Carbopol®), have a long history of use in vaginal drug delivery. However, despite their ubiquity, they often provide sub-optimal clinical performance, due to poor mucosal retention and limited solubility for poorly water-soluble actives. These issues are particularly pertinent for vaginal HIV microbicides, since many lead candidates are poorly water-soluble and where a major goal is the development of a coitally independent, once daily gel product. In this study, we report the use of a non-aqueous silicone elastomer gel for vaginal delivery of the HIV-1 entry inhibitor maraviroc. In vitro rheological, syringeability and retention studies demonstrated enhanced performance for silicone gels compared with a conventional aqueous HEC gel, while testing of the gels in the slug model confirmed a lack of mucosal irritancy. Pharmacokinetic studies following single dose vaginal administration of a maraviroc silicone gel in rhesus macaques showed higher and sustained MVC levels in vaginal fluid, vaginal tissue and plasma compared with a HEC gel containing the same maraviroc loading. The results demonstrate that non-aqueous silicone gels have potential as a formulation platform for coitally independent vaginal HIV microbicides.


Autonomic and behavioural thermoregulation in tennis.
This report describes physiological and behavioural mechanisms behind the control of body temperature and thermal comfort during competitive singles tennis. Thermoregulatory responses and workload were observed during "best of three sets" tennis matches among 25 players. In total, 94 matches were played in ambient temperatures ranging from 14.5 to 38.4 degrees C. The thermal environment was assessed by dry bulb, wet bulb and natural wet bulb temperatures, globe temperature and wind speed. Core body and skin temperatures were recorded each minute throughout the match, and body mass and fluid intake were measured before the match, after 30 minutes of play and at the completion of the match to determine sweat rate. Subjective ratings of thermal strain included thermal comfort, sweatiness and perceived exertion. Workload observations included match, game and point durations, and the proportion of match time spent in play (effective playing time). Change in rectal temperature was positively correlated with point duration (p<0.001) and effective playing time (p<0.05). Sweat rate showed positive associations with air (p<0.0001), rectal (p<0.03) and skin (p<0.0001) temperature. Thermal comfort was reduced with increasing rectal (p<0.03) and skin (p<0.0001) temperature. Point duration and effective playing time were reduced when conditions were rated increasingly difficult (p<0.002 and p<0.0002, respectively). Autonomic (increase in sweat rate) and behavioural (reduction in workload) thermoregulation are responsible for the control of body temperature and thermal comfort during tennis.


How the brain blinks: towards a neurocognitive model of the attentional blink.
When people monitor a visual stream of rapidly presented stimuli for two targets (T1 and T2), they often miss T2 if it falls into a time window of about half a second after T1 onset-the attentional blink (AB). We provide an overview of recent neuroscientific studies devoted to analyze the neural processes underlying the AB and their temporal dynamics. The available evidence points to an attentional network involving temporal, right-parietal and frontal cortex, and suggests that the components of this neural network interact by means of synchronization and stimulus-induced desynchronization in the beta frequency range. We set up a neurocognitive scenario describing how the AB might emerge and why it depends on the presence of masks and the other event(s) the targets are embedded in. The scenario supports the idea that the AB arises from "biased competition", with the top-down bias being generated by parietal-frontal interactions and the competition taking place between stimulus codes in temporal cortex.


Homeless people's access to primary care physiotherapy services: an exploratory, mixed-method investigation using a follow-up qualitative extension to core quantitative research.
The purpose of this study was to appraise referrals of homeless patients to physiotherapy services and explore perceptions of barriers to access. This exploratory mixed-method study used a follow-up qualitative extension to core quantitative research design. Over 9 months, quantitative data were gathered from the healthcare records of homeless patients referred to physiotherapy by a general practitioner (GP) practice, including the number of referrals and demographic data of all homeless patients referred. Corresponding physiotherapy records of those people referred to physiotherapy were searched for the outcome of their care. Qualitative semi-structured telephone interviews, based on the quantitative findings, were carried out with staff involved with patient care from the referring GP practice and were used to expand insight into the quantitative findings. Two primary care sites provided data for this study: a GP practice dedicated exclusively to homeless people and the physiotherapy department receiving their referrals. Quantitative data from the healthcare records of 34 homeless patient referrals to physiotherapy were collected and analysed. In addition, five staff involved in patient care were interviewed. 34 referrals of homeless people were made to physiotherapy in a 9-month period. It was possible to match 25 of these to records from the physiotherapy department. Nine (36%) patients did not attend their first appointment; seven (28%) attended an initial appointment, but did not attend a subsequent appointment and were discharged from the service; five (20%) completed treatment and four patients (16%) had ongoing treatment. Semi-structured interviews revealed potential barriers preventing homeless people from accessing physiotherapy services, the complex factors being faced by those making referrals and possible ways to improve physiotherapy access. Homeless people with musculoskeletal problems may fail to access physiotherapy treatment, but opportunities exist to make access to physiotherapy easier.


Modeling species distributions from heterogeneous data for the biogeographic regionalization of the European bryophyte flora.
The definition of biogeographic regions provides a fundamental framework for a range of basic and applied questions in biogeography, evolutionary biology, systematics and conservation. Previous research suggested that environmental forcing results in highly congruent regionalization patterns across taxa, but that the size and number of regions depends on the dispersal ability of the taxa considered. We produced a biogeographic regionalization of European bryophytes and hypothesized that (1) regions defined for bryophytes would differ from those defined for other taxa due to the highly specific eco-physiology of the group and (2) their high dispersal ability would result in the resolution of few, large regions. Species distributions were recorded using 10,000 km2 MGRS pixels. Because of the lack of data across large portions of the area, species distribution models employing macroclimatic variables as predictors were used to determine the potential composition of empty pixels. K-means clustering analyses of the pixels based on their potential species composition were employed to define biogeographic regions. The optimal number of regions was determined by v-fold cross-validation and Moran's I statistic. The spatial congruence of the regions identified from their potential bryophyte assemblages with large-scale vegetation patterns is at odds with our primary hypothesis. This reinforces the notion that post-glacial migration patterns might have been much more similar in bryophytes and vascular plants than previously thought. The substantially lower optimal number of clusters and the absence of nested patterns within the main biogeographic regions, as compared to identical analyses in vascular plants, support our second hypothesis. The modelling approach implemented here is, however, based on many assumptions that are discussed but can only be tested when additional data on species distributions become available, highlighting the substantial importance of developing integrated mapping projects for all taxa in key biogeographically areas of Europe, and the Mediterranean peninsulas in particular.


Sesamin alleviates blood-brain barrier disruption in mice with experimental traumatic brain injury.
Sesamin, a major lignan of sesame oil, was reported to have neuroprotective effects in several brain injury models. However, its protective action in maintaining blood-brain barrier (BBB) integrity has not been studied. In this study we investigated the effects of sesamin on the BBB in a mouse model of traumatic brain injury (TBI) and explored the underlying mechanisms. Adult male C57BL/6 mice were subjected to a controlled cortical impact (CCI) injury and then received sesamin (30 mg·kg-1·d-1, ip). The mice were euthanized on the 1st and 3rd days after CCI injury and samples were collected for analysis. Sesamin treatment significantly attenuated CCI-induced brain edema on the 1st and 3rd days after the injury, evidenced by the decreases in water content, tissue hemoglobin levels, Evans blue extravasation and AQP4 expression levels in the ipsilateral cortical tissue compared with the vehicle-treated group. Furthermore, sesamin treatment significantly alleviated CCI-induced loss of the tight junction proteins ZO-1 and occludin in the brain tissues. The neuroprotective mechanisms of sesamin were further explored in cultured mouse brain microvascular bEnd.3 cells subjected to biaxial stretch injury (SI). Pretreatment with sesamin (50 μmol/L) significantly alleviated SI-induced loss of ZO-1 in bEnd.3 cells. Furthermore, we revealed that pretreatment with sesamin significantly attenuated SI-induced oxidative stress and early-stage apoptosis in bEnd.3 cells by decreasing the activation of ERK, p-38 and caspase-3. In conclusion, sesamin alleviates BBB disruption at least partly through its anti-oxidative and anti-apoptotic effects on endothelial cells in CCI injury. These findings suggest that sesamin may be a promising potential therapeutic intervention for preventing disruption of the BBB after TBI.


SMR forum: improving face-to-face relationships.
In this paper, the author suggests that the key element to successful implementation of solutions to managerial problems lies in the improvement of face-to-face relationships. He goes on to articulate the factors involved in building and maintaining effective interpersonal communication. Particular attention is given to the repair strategies and skills needed to mend damaged relationships. Ed.


Self-assembly in vitro of purified CA-NC proteins from Rous sarcoma virus and human immunodeficiency virus type 1.
The internal structural proteins of retroviruses are proteolytically processed from the Gag polyprotein, which alone is able to assemble into virus-like particles when expressed in cells. All Gag proteins contain domains corresponding to the three structural proteins MA, CA, and NC. We have expressed the CA and NC domains together as a unit in Escherichia coli, both for Rous sarcoma virus (RSV) and for human immunodeficiency virus type 1 (HIV-1). We also expressed a similar HIV-1 protein carrying the C-terminal p6 domain. RSV CA-NC, HIV-1 CA-NC, and HIV-1 CA-NC-p6 were purified in native form by classic methods. After adjustment of the pH and salt concentration, each of these proteins was found to assemble at a low level of efficiency into structures that resembled circular sheets and roughly spherical particles. The presence of RNA dramatically increased the efficiency of assembly, and in this case all three proteins formed hollow, cylindrical particles whose lengths were determined by the size of the RNA. The optimal pH at which assembly occurred was 5.5 for the RSV protein and 8.0 for the HIV-1 proteins. The treatment of the RSV CA-NC cylindrical particles with nonionic detergent, with ribonuclease, or with viral protease caused disassembly. These results suggest that RNA plays an important structural role in the virion and that it may initiate and organize the assembly process. The in vitro system described should facilitate the dissection of assembly pathways in retroviruses.


Baerveldt drainage implants in eyes with a preexisting scleral buckle.
To describe the surgical insertion of a Baerveldt drainage implant and postoperative visual acuity and intraocular pressure (IOP) outcomes in patients with a preexisting scleral buckle. Medical records of all patients with a preexisting scleral buckle who underwent insertion of a Baerveldt drainage implant at Bascom Palmer Eye Institute, Miami, Fla, from January 1, 1994, through December 31, 1998, were reviewed. Outcome measures included visual acuity and IOP at 1 year. At 1 year postoperatively, 14 (88%) of 16 patients had stable or improved visual acuity. Preoperatively, mean IOP was 30.9 mm Hg and the mean number of antiglaucoma medications was 3.4; at 1 year postoperatively, mean IOP was 12.0 mm Hg and the mean number of antiglaucoma medications was 0.8 (P<.001). Nine patients (56%) achieved an IOP of greater than 5 and no greater than 21 mm Hg without medication, and an additional 7 (44%) achieved this level of IOP control with medication. No patient required further surgery for uncontrolled IOP during the follow-up interval, which ranged from 19. 1 to 45.5 months. Baerveldt drainage device insertion behind or over a preexisting encircling band is often successful in managing refractory glaucoma in patients who have undergone previous scleral buckling procedures. Arch Ophthalmol. 2000;118:1509-1513


Computed tomographic findings in canine pyothorax and correlation with findings at exploratory thoracotomy.
To describe computed tomographic (CT) findings in canine spontaneous pyothorax and compare them to surgical findings and to assess the utility of CT in guiding case management. Records from 2003 to 2010 were reviewed to identify dogs, with spontaneous pyothorax, which had undergone CT. Cases were managed medically or surgically. CT images and surgery reports were reviewed and compared for surgical cases. Twelve dogs were included. Eight were managed surgically, three were managed medically and one died before management. Pleural fluid was present in all dogs on CT (n=12) and at surgery (n=8). Pleural gas was identified in five dogs on CT. Pleural thickening was detected in eight dogs on CT (seven visceral, one parietal and six mediastinal) and eight dogs at surgery (seven visceral, eight parietal and six mediastinal), six of which were identified by CT. Abnormal pulmonary parenchyma was detected in 10 dogs on CT and 5 dogs at surgery, all of which were identified by CT. Mediastinal involvement was detected in 10 dogs on CT and 6 dogs at surgery, 5 of which were identified by CT. CT and surgical findings are similar in most cases of canine spontaneous pyothorax. CT may be a useful diagnostic tool for guiding case management.


User acceptance of a picture archiving and communication system (PACS) in a Saudi Arabian hospital radiology department.
Compared with the increasingly widespread use of picture archiving and communication systems (PACSs), knowledge concerning users' acceptance of such systems is limited. Knowledge of acceptance is needed given the large (and growing) financial investment associated with the implementation of PACSs, and because the level of user acceptance influences the degree to which the benefits of the systems for healthcare can be realized. A Technology Acceptance Model (TAM) was used to assess the level of acceptance of the host PACS by staff in the radiology department at King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia. A questionnaire survey of 89 PACS users was employed to obtain data regarding user characteristics, perceived usefulness (PU) (6 items), perceived ease of use (PEU) (4 items), a change construct (4 items), and a behavior (acceptance) construct (9 items). Respondents graded each item in each construct using five-point likert scales. Surveyed users reported high levels of PU (4.33/5), PEU (4.15/5), change (4.26/5), and acceptance (3.86/5). The three constructs of PU, PEU, and change explained 41 % of the variation in PACS user acceptance. PU was the most important predictor, explaining 38 % of the variation on its own. The most important single item in the explanatory constructs was that users found PACS to have improved the quality of their work in providing better patient care. Technologists had lower acceptance ratings than did clinicians/radiologists, but no influence on acceptance level was found due to gender, age, or length of experience using the PACS. Although not directly measured, there appeared to be no cultural influence on either the level of acceptance or its determinants. User acceptance must be considered when an organization implements a PACS, in order to enhance its successful adoption. Health organizations should adopt a PACS that offers all required functions and which is likely to generate high PU on the part of its users, rather than a system that is easy to use. Training/familiarization programs should aim at establishing high levels of PU in all users, particularly technologists. Health organizations are advised to measure all the factors that influence the acceptance of a PACS by their staff, in order to optimize the productivity of the system and realize the potential benefits to the greatest extent possible.


YY1 regulates vitamin D receptor/retinoid X receptor mediated transactivation of the vitamin D responsive osteocalcin gene.
The responsiveness of genes to steroid hormones is principally mediated by functional interactions between DNA-bound hormone receptors and components of the transcriptional initiation machinery, including TATA-binding protein, TFIIB, or other RNA polymerase II associated factors. This interaction can be physiologically modulated by promoter context-specific transcription factors to facilitate optimal responsiveness of gene expression to hormone stimulation. One postulated regulatory mechanism involves the functional antagonism between hormone receptors and nonreceptor transcription factors interacting at the same hormone response element. Here we demonstrate that the multifunctional regulator YY1 represses 1,25-dihydroxyvitamin D3 (vitamin D)-induced transactivation of the bone tissue-specific osteocalcin gene. We identify YY1 recognition sequences within the vitamin D response element (VDRE) of the osteocalcin gene that are critical for YY1-dependent repression of vitamin D-enhanced promoter activity. We show that YY1 and vitamin D receptor (VDR)/retinoid X receptor heterodimers compete for binding at the osteocalcin VDRE. In addition, we find that YY1 interacts directly with TFIIB, and that one of the two tandemly repeated polypeptide regions of TFIIB spanning the basic domain is responsible for this interaction. TFIIB and VDR can also interact directly, and these factors synergize to mediate transactivation. Our results suggest that YY1 regulates vitamin D enhancement of osteocalcin gene transcription in vivo by interfering with the interactions of the VDR with both the VDRE and TFIIB.


Bone tissue engineering: state of the art and future trends.
Although several major progresses have been introduced in the field of bone regenerative medicine during the years, current therapies, such as bone grafts, still have many limitations. Moreover, and in spite of the fact that material science technology has resulted in clear improvements in the field of bone substitution medicine, no adequate bone substitute has been developed and hence large bone defects/injuries still represent a major challenge for orthopaedic and reconstructive surgeons. It is in this context that TE has been emerging as a valid approach to the current therapies for bone regeneration/substitution. In contrast to classic biomaterial approach, TE is based on the understanding of tissue formation and regeneration, and aims to induce new functional tissues, rather than just to implant new spare parts. The present review pretends to give an exhaustive overview on all components needed for making bone tissue engineering a successful therapy. It begins by giving the reader a brief background on bone biology, followed by an exhaustive description of all the relevant components on bone TE, going from materials to scaffolds and from cells to tissue engineering strategies, that will lead to "engineered" bone. Scaffolds processed by using a methodology based on extrusion with blowing agents.


A class of sterol 14-demethylase inhibitors as anti-Trypanosoma cruzi agents.
Chronic infection with the protozoan parasite Trypanosoma cruzi is a major cause of morbidity and mortality in Latin America. Drug treatments for the associated illness, Chagas disease, are toxic and frequently unsuccessful. In a screening effort against the drug target protein farnesyltransferase, we identified a series of disubstituted imidazoles with highly potent anti-T. cruzi activity that apparently acted through a mechanism independent of protein farnesylation. Metabolic labeling studies of T. cruzi suggested that sterol biosynthesis was inhibited. Combined GC/MS analysis confirmed depletion of cellular sterols and suggested that the site of action was sterol 14-demethylase, a cytochrome P450 enzyme. Spectral studies with recombinant T. cruzi sterol 14-demethylase demonstrated that the compounds bind directly to this enzyme. Two of the compounds were well absorbed when given orally to mice, gave sustained plasma levels, and were well tolerated. The compounds were administered orally to mice with acute T. cruzi infection and caused dramatic decrease in parasitemia and led to 100% survival. These disubstituted imidazole compounds can be prepared by a relatively short synthetic route and represent a structural class with potent anti-T. cruzi activity.


Effect of submaximal repetitive exercise on knee coactivation in young and middle-aged women.
Coactivation of the knee extensors and flexors increases knee joint contact forces, which may lead to degradation of the articular surfaces. This study investigated the effect of neuromuscular fatigue induced by submaximal, repetitive, dynamic contractions on coactivation of knee musculature in young and middle-aged women. Data from 10 young women (24.6±1.8 years) and 8 middle-aged women (55.4±4.2 years) were analyzed. Measures included peak knee extension and flexion torques and the average amplitude of surface electromyography of rectus femoris and biceps femoris. Coactivation ratios were calculated from these activations. To induce fatigue, participants completed up to ten sets of 50 concentric knee extension and flexion contractions at 60°/s. A two-factor analysis of variance was used to determine the effect of age and fatigue. The young group showed higher peak torque compared with the middle-aged group (P<.001). During flexion, biceps femoris activity increased after fatigue when both groups were considered together (P=.018). During extension, biceps femoris activity was higher in the middle-aged than young group (P=.043). Middle-aged women exhibited a trend for greater coactivation during knee extension compared with young women (P=.066). This coactivation likely contributed to extension torque decrements in middle-aged women.


Exploring strategies for the design of artificial transcription factors: targeting sites proximal to known regulatory regions for the induction of gamma-globin expression and the treatment of sickle cell disease.
Artificial transcription factors can be engineered to interact with specific DNA sequences to modulate endogenous gene expression within cells. A significant hurdle to implementation of this approach is the selection of the appropriate DNA sequence for targeting. We reasoned that a good target site should be located in chromatin, where it is accessible to DNA-binding proteins, and it should be in the close vicinity of known transcriptional regulators of the gene. Here we have explored the efficacy of these criteria to guide our selection of potential regulators of gamma-globin expression. Several zinc finger-based transcriptional activators were designed to target the sites proximal to the -117-position of the gamma-globin promoter. This region is proximal to the binding sites of known and potential natural transcription factors. Design and study of three transcription factors identified the potent transcriptional activator, gg1-VP64-HA. This transcription factor was able to interact directly with the gamma-globin promoter and up-regulate expression of reporter gene constructs as well as the endogenous gene in a selective manner. Transfection of a gg1-VP64-HA expression vector or retroviral delivery of this transcription factor into the erythroleukemia cell line K562 resulted in an increase of fetal hemoglobin. The gamma-globin content of cells expressing gg1-vp64-HA showed up to 16-fold higher levels of fetal hemoglobin than the native K562 cell line. These transcriptional activators constitute a novel class of regulators of the globin locus that may be suitable for treatment of diseases arising from mutations in this locus such as sickle cell disease and thalassemic diseases.


Effect of Apium graveolens Extract Administration on the Pharmacokinetics of Captopril in the Plasma of Rats.
Apium graveolens (celery) is an edible and traditionally medicinal plant that is used worldwide, among others for the treatment of hypertension. Combining celery with antihypertensive drugs can affect the pharmacodynamics and pharmacokinetics of the latter drugs. The aim of the study is to assess the effects of administrating the celery extract on captopril pharmacokinetics. Sprague-Dawley strain rats were divided into two groups (n = 6). Group I was given captopril (10 mg/kg Body Weight (BW)) orally, while Group II was pretreated with celery extract orally (40 mg/kg BW) an hour before administration of captopril. The blood samples were withdrawn at various intervals after drug administration. The captopril concentration was determined using liquid chromatography-mass spectrometry (LC-MS/MS) and from the blood data, the values of Ke, Cmax, Tmax, T1/2, and area under the curve (AUC) were calculated. The results showed that oral administration of the celery extract increased Cmax (38.67%), T1/2 (37.84%), and AUC (58.10%) and decreased Ke (27.45%) of captopril in Group II (celery + captopril) compared with Group I (captopril). In conclusion, celery extract can alter the pharmacokinetic of captopril when given in combination. The combination might be beneficial for the treatment of hypertension, as celery causes an increase in the plasma level of captopril, which can enhance its efficacy.


Measurement of magnetic field in dentistry.
The principal objective was to measure the magnetic fields occurring in dental surgeries at simultaneous subtraction of direct ground component of the magnetic field. A specifically designed instrument with the Hall probe was used for the measurement. It consisted of two amplifiers and a low frequency filter. Its task was to measure mean square values of the field (RMS) dependent on the position in space. Qualitative and quantitative analyses of the investigated variables enabled making conclusions about the magnetic fields in dental surgeries. A number of studies have shown that many dental instruments produce radiation with magnetic field higher than 40 G, at a significant decrease in power of the magnetic field with increasing distance from the source. It has also been reported that instruments of older generations produce stronger magnetic fields than do the new ones.


Practices and Perceptions of Family Centered Care among Healthcare Providers: A Cross-sectional Study in a Pediatric Hospital.
This study aimed to: (1) investigate the extent to which Family Centered Care (FCC) principles are currently applied in clinical practice by healthcare providers working in inpatient units; (2) evaluate the extent to which FCC principles are perceived as necessary; and (3) examine the associations between FCC principles and socio-demographic and job characteristics of participants. Design and Methods A cross-sectional study was conducted at a large pediatric hospital using the Italian version of the FCC Questionnaire Revised (FCCQ-R). Univariate and multivariate analyses were performed. Data from 469 healthcare providers were used for analysis. Scores for the FCC daily practices (Current activities) were significantly lower than those for their perceived necessity (Necessary activities) (p < .001). Participants who were male, younger, with work experience >20 years and working in rehabilitation reported a significantly higher perception of Current activities of FCC than others. The older and the more educated the participants, the greater was the perceived necessity of FCC activities. Female, older, and less experienced participants employed by the hospital but not working in the rehabilitation setting perceived a greater gap between Necessary and Current activities of FCC. Scores for the Current and Necessary activities of FCC were lower than those reported in other studies. The lower scores in the Current activities and the significant gap can be due to organizational barriers or lack of skills, but the lower scores in the Necessary activities should be interpreted as a deficit of knowledge about FCC. There is a need for further education about FCC in order to increase its perceived relevance in clinical practice.


Headache yesterday in Europe.
Surveys enquiring about burden of headache over a prior period of time (e.g., 3 months) are subject to recall bias. To eliminate this as far as possible, we focused on presence and impact of headache on the preceding day ("headache yesterday"). Adults (18-65 years) were surveyed from the general populations of Germany, Italy, Lithuania, Luxembourg and the Netherlands, from a work-force population in Spain and from mostly non-headache patient populations of Austria, France and U.K. A study of non-responders in some countries allowed detection of potential participation bias where initial participation rates were low. Participation rates varied between 11% and 59% (mean 27%). Non-responder studies suggested that, because of participation bias, headache prevalence might be overestimated in initial responders by up to 2% (absolute). Across all countries, 1,422 of 8,271 participants (15-17%, depending on correction for participation bias) had headache yesterday lasting on average for 6 hours. It was bad or very bad in 56% of cases and caused absence from work or school in 6%. Among those who worked despite headache, 20% reported productivity reduced by >50%. Social activities were lost by 24%. Women (21%) were more likely than men (12%) to have headache yesterday, but impact was similar in the two genders. With recall biases avoided, our findings indicate that headache costs at least 0.7% of working capacity in Europe. This calculation takes into account that most of those who missed work could make up for this later, which, however, means that leisure and social activities are even more influenced by headache.


Cutinase A of Botrytis cinerea is expressed, but not essential, during penetration of gerbera and tomato.
The plant pathogen Botrytis cinerea can infect undamaged plant tissue directly by penetration of the cuticle. This penetration has been suggested to be enzyme-mediated, and an important role for cutinase in the infection process has been proposed. In this study the expression of the cutinase encoding gene cutA of B. cinerea was analyzed using a cutA promoter-GUS reporter gene fusion. Transformants containing the fusion construct were examined for GUS expression on gerbera flowers and tomato fruits. High GUS activity was detected from the onset of conidial germination and during penetration into epidermal cells, indicating that cutA is expressed during the early stages of infection. To determine the biological relevance of cutinase A for successful penetration, cutinase A-deficient mutants were constructed by gene disruption. Pathogenicity of two transformants lacking a functional cutA gene was studied on gerbera flowers and tomato fruits. Their ability to penetrate and cause symptoms was unaltered compared to the wild-type strain. These results exclude an important role for cutinase A during direct penetration of host tissue by B. cinerea.


In situ structural and microangiographic assessment of human skin lesions with high-speed OCT.
We demonstrate noninvasive structural and microvascular contrast imaging of different human skin diseases in vivo using an intensity difference analysis of OCT tomograms. The high-speed swept source OCT system operates at 1310 nm with 220 kHz A-scan rate. It provides an extended focus by employing a Bessel beam. The studied lesions were two cases of dermatitis and two cases of basal cell carcinoma. The lesions show characteristic vascular patterns that are significantly different from healthy skin. In case of inflammation, vessels are dilated and perfusion is increased. In case of basal cell carcinoma, the angiogram shows a denser network of unorganized vessels with large vessels close to the skin surface. Those results indicate that assessing vascular changes yields complementary information with important insight into the metabolic demand.


An innate immune system cell is a major determinant of species-related susceptibility differences to fungal pneumonia.
Rats and mice are considered resistant and susceptible hosts, respectively, for experimental cryptococcosis. For both species, alveolar macrophages (AM) are central components of the host response to pulmonary Cryptococcus neoformans infection. We explored the role of AM in three strains of mice and three strains of rats during cryptococcal infection by comparing the outcome of infection after macrophage depletion using liposomal clodronate. AM depletion was associated with enhancement and amelioration of disease in rats and mice, respectively, as measured by lung fungal burden. The apparent protective role for AM in rats correlated with enhanced anti-cryptococcal activity as measured by phagocytic activity, oxidative burst, lysozyme secretion, and ability to limit intracellular growth of C. neoformans. Furthermore, rat AM were more resistant to lysis in association with intracellular infection. In summary, differences in AM function in rats and mice suggest an explanation for the species differences in susceptibility to C. neoformans based on the inherent efficacy of a central effector cell of the innate immune system.


Mapping of visual receptive fields by tomographic reconstruction.
The moving bar experiment is a classic paradigm for characterizing the receptive field (RF) properties of neurons in primary visual cortex (V1). Current approaches for analyzing neural spiking activity recorded from these experiments do not take into account the point-process nature of these data and the circular geometry of the stimulus presentation. We present a novel analysis approach to mapping V1 receptive fields that combines point-process generalized linear models (PPGLM) with tomographic reconstruction computed by filtered-back projection. We use the method to map the RF sizes and orientations of 251 V1 neurons recorded from two macaque monkeys during a moving bar experiment. Our cross-validated goodness-of-fit analyses show that the PPGLM provides a more accurate characterization of spike train data than analyses based on rate functions computed by the methods of spike-triggered averages or first-order Wiener-Volterra kernel. Our analysis leads to a new definition of RF size as the spatial area over which the spiking activity is significantly greater than baseline activity. Our approach yields larger RF sizes and sharper orientation tuning estimates. The tomographic reconstruction paradigm further suggests an efficient approach to choosing the number of directions and the number of trials per direction in designing moving bar experiments. Our results demonstrate that standard tomographic principles for image reconstruction can be adapted to characterize V1 RFs and that two fundamental properties, size and orientation, may be substantially different from what is currently reported.


Polymerase chain reaction amplification of three different Trypanosoma cruzi DNA sequences from human chagasic cardiac tissue.
Chagas' disease is caused by the hemoflagellate protozoan Trypanosoma cruzi. The most common, serious manifestation of Chagas' disease is a progressive inflammatory cardiomyopathy, which occurs decades after primary infection. The inability to consistently demonstrate T. cruzi by histologic techniques in inflammatory cardiac lesions has suggested that the parasites' persistence may not be required for the pathology of the chronic phase. In this report we further analyze the persistence and localization of T. cruzi DNA in the hearts of seven patients with chronic chagasic cardiomyopathy, along with four indeterminate patients and seven control patients seronegative for T. cruzi infection. In the seven patients with chronic chagasic cardiomyopathy, we extracted DNA from selected inflammatory foci-positive (IFP) and inflammatory foci-negative (IFN) areas of' hematoxylin and eosin-stained cardiac tissue. We then used polymerase chain reaction methodology to amplify three different T. cruzi sequences (a minicircle sequence [MCS], a satellite repetitive sequence [RS], and, a low copy number sequence within the gene coding for a flagellar protein [FPS]). The MCS was detected in approximately 100% of both the IFP and IFN areas analyzed. The RS was detected in 37.5% and 23% of the IFP and IFN areas, respectively (difference not statistically significant; P > 0.10, degrees of freedom = 1, G test of independence = 1.9522). The FPS was rarely detected (2%), and was only present in DNA extracted from IFP areas. The MCS was also detected in most indeterminate cases (none of whom had inflammatory lesions) although with a markedly diminished amplification signal relative to cardiomyopathy cases. The MCS was not amplified from the cardiac tissues from seronegative controls. These results suggest that the quantity of T. cruzi DNA persisting in hearts of patients with Chagas' disease correlates with cardiomyopathy, but may not be preferentially associated with inflammatory foci.


Antibody deficiency due to a missense mutation in CD19 demonstrates the importance of the conserved tryptophan 41 in immunoglobulin superfamily domain formation.
Immunoglobulin superfamily (IgSF) domains are conserved structures present in many proteins in eukaryotes and prokaryotes. These domains are well-capable of facilitating sequence variation, which is most clearly illustrated by the variable regions in immunoglobulins (Igs) and T cell receptors (TRs). We studied an antibody-deficient patient suffering from recurrent respiratory infections and with impaired antibody responses to vaccinations. Patient's B cells showed impaired Ca(2+) influx upon stimulation with anti-IgM and lacked detectable CD19 membrane expression. CD19 sequence analysis revealed a homozygous missense mutation resulting in a tryptophan to cystein (W52C) amino acid change. The affected tryptophan is CONSERVED-TRP 41 located on the C-strand of the first extracellular IgSF domain of CD19 and was found to be highly conserved, not only in mammalian CD19 proteins, but in nearly all characterized IgSF domains. Furthermore, the tryptophan is present in all variable domains in Ig and TR and was not mutated in 117 Ig class-switched transcripts of B cells from controls, despite an overall 10% amino acid change frequency. In vitro complementation studies and CD19 western blotting of patient's B cells demonstrated that the mutated protein remained immaturely glycosylated. This first missense mutation resulting in a CD19 deficiency demonstrates the crucial role of a highly conserved tryptophan in proper folding or stability of IgSF domains.


Transactional sex and HIV: understanding the gendered structural drivers of HIV in fishing communities in Southern Malawi.
In Southern Malawi, the fishing industry is highly gendered, with men carrying out the fishing and women processing, drying and selling the fish. Research has shown that individuals living in fishing communities in low-income countries are particularly vulnerable to HIV infection. One of the key drivers of HIV in fishing communities is transactional sex. In the fishing industry this takes the form of "fish-for-sex" networks where female fish traders exchange sex with fishermen for access to or more favourable prices of fish. By controlling the means of production, the power dynamics in these exchanges favour men and can make it more difficult for women to negotiate safe sex. Qualitative methods were used to collect data on gendered drivers of transactional sex in the fishing community and how different groups perceive HIV risk in these transactions. Observation, focus group discussions and semi-structured interviews were undertaken with members of the fishing communities, including men and women directly and indirectly involved in fishing. In fishing communities transactional sex was prevalent across a spectrum ranging from gift giving within relationships, to sex for fish exchanges, to sex worker encounters. Power differences between couples in transactional sexual encounters shape individual's abilities to negotiate condom use (with women being at a particularly disadvantaged negotiating position). The context and motivations for transactional sex varied and was mediated by economic need and social position both of men and women. Female fish traders new to the industry and boat crew members who travelled for work and experienced difficult living conditions often engaged in transactional sex. Transactional sex is common in Malawian fishing communities, with women particularly vulnerable in negotiations because of existing gendered power structures. Although knowledge and understanding of the HIV risk associated with transactional sex was common, this did not appear to result in the adoption of risk reduction strategies. This suggests that specially targeted strategies to increase women's economic empowerment and tackle the structural drivers of women's HIV risk could be important in fishing communities.


Alpha 1-adrenergic inositol trisphosphate production in brown adipocytes is Na+ dependent.
In order to investigate the ionic requirements for inositol trisphosphate production, brown adipocytes were prelabelled with myo-[3H]inositol and the formation of inositol trisphosphates and inositol bisphosphates as a consequence of alpha 1-adrenergic stimulation was monitored. Omission of Ca2+ from the incubation medium diminished the norepinephrine-induced increase in inositol trisphosphate levels, but it would seem that this reduction can be fully accounted for by a decreased level of the 'inactive' isomer inositol 1,3,4-trisphosphate. Omission of Na+ fully abolished the norepinephrine-induced inositol trisphosphate response. However, it was observed that the presence of Li+ in the incubation medium could fully reconstitute the ability of the cells to yield the early response of inositol trisphosphate production; Li+ could, however, not substitute for Na+ in the entire alpha 1-adrenergic cellular pathway. It was concluded that the Na+-dependent step is found in the coupling mechanism between the alpha 1-receptor and the activation of the phosphodiesterase responsible for inositol trisphosphate production. Thus, all events in the alpha 1-adrenergic pathway which are consequences of IP3 production should appear to be Na+-dependent in these cells.


Production of full-length soluble Plasmodium falciparum RH5 protein vaccine using a Drosophila melanogaster Schneider 2 stable cell line system.
The Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) has recently emerged as a leading candidate antigen against the blood-stage human malaria parasite. However it has proved challenging to identify a heterologous expression platform that can produce a soluble protein-based vaccine in a manner compliant with current Good Manufacturing Practice (cGMP). Here we report the production of full-length PfRH5 protein using a cGMP-compliant platform called ExpreS(2), based on a Drosophila melanogaster Schneider 2 (S2) stable cell line system. Five sequence variants of PfRH5 were expressed that differed in terms of mutagenesis strategies to remove potential N-linked glycans. All variants bound the PfRH5 receptor basigin and were recognized by a panel of monoclonal antibodies. Analysis following immunization of rabbits identified quantitative and qualitative differences in terms of the functional IgG antibody response against the P. falciparum parasite. The antibodies induced by one protein variant were shown to be qualitatively similar to responses induced by other vaccine platforms. This work identifies Drosophila S2 cells as a clinically-relevant platform suited for the production of 'difficult-to-make' proteins from Plasmodium parasites, and identifies a PfRH5 sequence variant that can be used for clinical production of a non-glycosylated, soluble full-length protein vaccine immunogen.


The environmental sustainability of data-driven health research: A scoping review.
Data-Driven and Artificial Intelligence technologies are rapidly changing the way that health research is conducted, including offering new opportunities. This will inevitably have adverse environmental impacts. These include carbon dioxide emissions linked to the energy required to generate and process large amounts of data; the impact on the material environment (in the form of data centres); the unsustainable extraction of minerals for technological components; and e-waste (discarded electronic appliances) disposal. The growth of Data-Driven and Artificial Intelligence technologies means there is now a compelling need to consider these environmental impacts and develop means to mitigate them. Here, we offer a scoping review of how the environmental impacts of data storage and processing during Data-Driven and Artificial Intelligence health-related research are being discussed in the academic literature. Using the UK as a case study, we also offer a review of policies and initiatives that consider the environmental impacts of data storage and processing during Data-Driven and Artificial Intelligence health-related research in the UK. Our findings suggest little engagement with these issues to date. We discuss the implications of this and suggest ways that the Data-Driven and Artificial Intelligence health research sector needs to move to become more environmentally sustainable.


Exome Sequencing Provides Evidence of Polygenic Adaptation to a Fat-Rich Animal Diet in Indigenous Siberian Populations.
Siberia is one of the coldest environments on Earth and has great seasonal temperature variation. Long-term settlement in northern Siberia undoubtedly required biological adaptation to severe cold stress, dramatic variation in photoperiod, and limited food resources. In addition, recent archeological studies show that humans first occupied Siberia at least 45,000 years ago; yet our understanding of the demographic history of modern indigenous Siberians remains incomplete. In this study, we use whole-exome sequencing data from the Nganasans and Yakuts to infer the evolutionary history of these two indigenous Siberian populations. Recognizing the complexity of the adaptive process, we designed a model-based test to systematically search for signatures of polygenic selection. Our approach accounts for stochasticity in the demographic process and the hitchhiking effect of classic selective sweeps, as well as potential biases resulting from recombination rate and mutation rate heterogeneity. Our demographic inference shows that the Nganasans and Yakuts diverged ∼12,000-13,000 years ago from East-Asian ancestors in a process involving continuous gene flow. Our polygenic selection scan identifies seven candidate gene sets with Siberian-specific signals. Three of these gene sets are related to diet, especially to fat metabolism, consistent with the hypothesis of adaptation to a fat-rich animal diet. Additional testing rejects the effect of hitchhiking and favors a model in which selection yields small allele frequency changes at multiple unlinked genes.


The use of radiopaque templates for predictable implant placement.
The functional and esthetic needs of the patient who is to receive an implant-retained prosthesis can be established with the help of a provisional restoration that is duplicated in a radiopaque radiographic template. The computer tomogram prepared with the aid of the template allows the evaluation of the implant sites in relation to the outline of the planned restoration. The radiographic template is converted into the surgical template, which contains information regarding the optimal position and angulation of implants. Because the surgical template is a modification of the radiographic template, which rests rigidly on the teeth during all procedures, implant placement is more predictable.


Antinuclear Antibody-Negative Lupus Nephritis with Full House Nephropathy: A Case Report and Review of the Literature.
Lupus nephritis (LN) is a serious and common complication of systemic lupus erythematosus (SLE) that predisposes to significant morbidity and mortality. Studies show that prompt diagnosis and treatment improves patient survival. We present a case of a 49-year-old female with an atypical presentation of LN who initially presented with new-onset hypertension, edema, arthritis, serositis and recently diagnosed leukocytoclastic vasculitis who later developed acute kidney injury, hematuria and nephrotic syndrome. Laboratory testing showed mixed cryoglobulinemia and elevated perinuclear anti-neutrophil cytoplasmic (p-ANCA) and myeloperoxidase (MPO) antibodies. SLE-related serologies were negative. Kidney biopsy showed diffuse proliferative global glomerulonephritis with a full-house nephropathy pattern on immunofluorescence suggestive of LN. Due to high clinical suspicion and renal biopsy findings, she was treated for LN with prompt renal response to immunosuppression. Cryoglobulins, p-ANCA and MPO titers normalized and the negative SLE serologies remained negative. Literature review on antinuclear antibody (ANA)-negative and seronegative LN revealed the following patient presentations: (1) renal-limited or renal and extra-renal manifestations of SLE with negative serologies and (2) renal and extra-renal manifestations of SLE with negative serologies at presentation who develop positive serologies later in follow-up. Both groups represent a unique and challenging cohort of patients who may require longer follow-up and further testing to rule out other glomerular diseases that may mimic LN on renal biopsy. The absence of SLE-related serologies should be weighed against a high pre-test probability of ANA-negative or seronegative LN. If highly suspected, the patient should be treated promptly with close monitoring.


Comparative Effectiveness of Acupuncture and Antiarrhythmic Drugs for the Prevention of Cardiac Arrhythmias: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Introduction and Objectives: This study was designed to systematically evaluate the effectiveness of acupuncture treatment for arrhythmia compared to existing drug therapy. Methods: Randomized controlled trials (RCTs) were identified through searches of the MEDLINE, CNKI, Embase, and Cochrane databases (1970 through 2016) and hand searches of cross-references from original articles and reviews. Clinical trials that randomized arrhythmia patients to acupuncture therapy vs. conventional drugs, sham acupuncture, or bed rest were included for analysis. Results: A total of 13 trials with 797 patients met the criteria for analysis. The results of the meta-analysis showed no statistically significant difference between acupuncture and conventional treatment for paroxysmal supraventricular tachycardia (PSVT) (n = 203; RR, 1.18; 95% CI 0.78-1.79; I2 = 80%; P = 0.44). However, in the ventricular premature beat (VPB) group, it showed a significant benefit of acupuncture plus oral administration of anti-arrhythmic drug (AAD) on response rates compared with the oral administration of AAD (n = 286; RR, 1.15; 95% CI 1.05-1.27; I2 = 0%; P = 0.002). Finally, when compared with the sinus tachycardia (ST) cases without any treatment, acupuncture has benefited these patients (n = 120; MD, 18.80, 95% CI 12.68-24.92; I2 = 81%; P < 0.00001). Conclusions: In summary, our meta-analysis demonstrates that clinical efficacy of acupuncture is not less than AAD for PSVT. Furthermore, in sub-group analysis, acupuncture with or without AAD, shows a clear benefit in treating VPB and ST. However, more definitive RCTs are warranted to guide clinical practice.


An allele of an ancestral transcription factor dependent on a horizontally acquired gene product.
Changes in gene regulatory circuits often give rise to phenotypic differences among closely related organisms. In bacteria, these changes can result from alterations in the ancestral genome and/or be brought about by genes acquired by horizontal transfer. Here, we identify an allele of the ancestral transcription factor PmrA that requires the horizontally acquired pmrD gene product to promote gene expression. We determined that a single amino acid difference between the PmrA proteins from the human adapted Salmonella enterica serovar Paratyphi B and the broad host range S. enterica serovar Typhimurium rendered transcription of PmrA-activated genes dependent on the PmrD protein in the former but not the latter serovar. Bacteria harboring the serovar Typhimurium allele exhibited polymyxin B resistance under PmrA- or under PmrA- and PmrD-inducing conditions. By contrast, isogenic strains with the serovar Paratyphi B allele displayed PmrA-regulated polymyxin B resistance only when experiencing activating conditions for both PmrA and PmrD. We establish that the two PmrA orthologs display quantitative differences in several biochemical properties. Strains harboring the serovar Paratyphi B allele showed enhanced biofilm formation, a property that might promote serovar Paratyphi B's chronic infection of the gallbladder. Our findings illustrate how subtle differences in ancestral genes can impact the ability of horizontally acquired genes to confer new properties.


Streptococcus milleri head and neck abscesses: a case series.
Streptococcus milleri infections and abscesses in the head and neck region have been previously reported, but there is still a dearth of clinical literature on this topic. To add to the available reports and to promote a better understanding and awareness of this clinically important entity, we present this retrospective review of 7 cases of head and neck abscess caused by S milleri infection. We have placed particular emphasis on antibiotic sensitivity patterns. These patients-6 men and 1 woman, aged 28 to 73 years (mean: 42.7)-had been seen at a district general hospital in Gosford, Australia, over a 6-month period. All patients had undergone surgical intervention and had been treated with intravenous antibiotics. All the S milleri cultures were sensitive to penicillin G, cephalexin, and erythromycin. Six of these patients experienced a resolution of their abscess, while 1 patient died from overwhelming sepsis. We believe that the initiation of penicillin G, cephalexin, or erythromycin is a good starting point for empiric therapy. S milleri should be considered as a causative organism in a patient who presents with a head and neck abscess, especially in the presence of a dental infection. Such a patient should be monitored closely for airway obstruction and distal infective sequelae. Also in this article, we compare our findings with those reported in two other published series.


Surgical treatment of posterior cruciate ligament injury.
Successful posterior cruciate ligament (PCL) reconstruction is challenging because of the complex structures and difficult reconstruction techniques that are required. The reported results have been inconsistent. Variables that affect the results of surgery to restore PCL function include combined associated ligaments injury, difficulty to duplicate PCL anatomy, wide variation in broad femoral insertion footprint, difficulty in accurate placement of the transtibial tunnel, tunnel erosion, high internal graft stresses and graft elongation. The outcome of conservative treatment of isolated PCL injuries with mild or moderate laxity is generally acceptable. However, more severe straight posterior laxity or combined injury patterns usually lead to a worse prognosis. Surgical reconstruction for PCL can achieve satisfactory results for most patients if adequate surgical principles and techniques are followed. Recent studies on the anatomy and the biomechanics of PCL have led to a better understanding of its biomechanical properties for the reconstruction. It has been generally agreed that surgical reconstruction is indicated for symptomatic severe posterior knee instability and multiple ligament injuries for better functional recovery after PCL injuries. Accepted surgical techniques for the treatment of PCL tears include primary repair for PCL avulsion fracture, as well as open or arthroscopic reconstruction using the transtibial or tibial inlay technique. Controversy continues over the choice of graft tissue, one or two bundle reconstruction, location of tunnel placement, knee position when securing the graft, and fixation technique. From the accumulated clinical experience and surgical concepts in clinical practice, we have developed various surgical techniques to improve the outcomes of reconstruction.