Neuroprotective effects of naturally occurring polyphenols on quinolinic acid-induced excitotoxicity in human neurons.
Quinolinic acid (QUIN) excitotoxicity is mediated by elevated intracellular Ca(2+) levels, and nitric oxide-mediated oxidative stress, resulting in DNA damage, poly(ADP-ribose) polymerase (PARP) activation, NAD(+) depletion and cell death. We evaluated the effect of a series of polyphenolic compounds [i.e. epigallocatechin gallate (EPCG), catechin hydrate, curcumin, apigenin, naringenin and gallotannin] with antioxidant properties on QUIN-induced excitotoxicity on primary cultures of human neurons. We showed that the polyphenols, EPCG, catechin hydrate and curcumin can attenuate QUIN-induced excitotoxicity to a greater extent than apigenin, naringenin and gallotannin. Both EPCG and curcumin were able to attenuate QUIN-induced Ca(2+) influx and neuronal nitric oxide synthase (nNOS) activity to a greater extent compared with apigenin, naringenin and gallotannin. Although Ca(2+) influx was not attenuated by catechin hydrate, nNOS activity was reduced, probably through direct inhibition of the enzyme. All polyphenols reduced the oxidative effects of increased nitric oxide production, thereby reducing the formation of 3-nitrotyrosine and poly (ADP-ribose) polymerase activity and, hence, preventing NAD(+) depletion and cell death. In addition to the well-known antioxidant properties of these natural phytochemicals, the inhibitory effect of some of these compounds on specific excitotoxic processes, such as Ca(2+) influx, provides additional evidence for the beneficial health effects of polyphenols in excitable tissue, particularly within the central nervous system.


Dobutamine stress echocardiography predicts surgical outcome in patients with an aortic aneurysm and peripheral vascular disease.
This study was conducted to assess the utility of dobutamine stress echocardiography for determining the presence of significant coronary artery disease and for predicting surgical outcome and long-term prognosis in patients scheduled to undergo peripheral vascular or aortic aneurysm surgery. Assessment of coronary artery disease in patients scheduled to undergo peripheral vascular surgery can avoid perioperative complications. Dobutamine stress echocardiography was performed in 98 consecutive patients scheduled to undergo aortic or peripheral vascular surgery. Intravenous dobutamine was infused in a graded fashion, with two-dimensional digital echocardiographic monitoring of ventricular function and segmental wall motion. Group 1 (n = 70) consisted of patients who exhibited a normal response to dobutamine infusion (negative dobutamine study); group 2 (n = 23) comprised those patients with an abnormal response to dobutamine, characterized by the development of new or worsening wall motion abnormalities at rest, indicating the presence of myocardial ischemia (positive dobutamine study). Five patients with an inconclusive dobutamine study (because of inadequate heart rate) were excluded from analysis. No major adverse effects occurred with testing in any patient. Sixty-eight of 70 patients with a negative study had peripheral vascular or aortic surgery performed without perioperative cardiac events (2 patients refused surgery). Nineteen of 23 patients with a positive study underwent coronary angiography and all had > 50% lumen narrowing in one or more major coronary artery distributions; 13 underwent coronary artery bypass grafting or angioplasty before peripheral vascular or aortic surgery and all had an uneventful perioperative period. Four of the 10 patients from group 2 who did not undergo coronary revascularization had a perioperative cardiac event (myocardial infarction in 2, an ischemic episode requiring urgent coronary bypass grafting in 1 and congestive heart failure in 1). Positive and negative dobutamine study results are significant predictors of the presence or absence of perioperative events (20% vs. 0%, p = 0.003). A positive test warrants coronary angiography and further medical or surgical intervention, or both, but a negative test indicates a low likelihood of perioperative cardiac complications of aortic or peripheral vascular surgery. During the long-term follow-up period in this study (group 1 mean, 24 months; group 2 mean, 15 months), two patients (3%) from group 1 and three (15%) from group 2 developed cardiac complications (p = 0.038). Thus, dobutamine stress echocardiography is safe and can predict surgical outcome in patients undergoing aortic aneurysm repair or surgery for occlusive disease of the peripheral arteries. In addition, a negative test result is a strong predictor of decreased perioperative and long-term cardiac morbidity and mortality.


Whispering Gallery Mode Carousel--a photonic mechanism for enhanced nanoparticle detection in biosensing.
Individual nanoparticles in aqueous solution are observed to be attracted to and orbit within the evanescent sensing ring of a Whispering Gallery Mode micro-sensor with only microwatts of driving power. This Carousel trap, caused by attractive optical gradient forces, interfacial interactions, and the circulating momentum flux, considerably enhances the rate of transport to the sensing region, thereby overcoming limitations posed by diffusion on such small area detectors. Resonance frequency fluctuations, caused by the radial Brownian motion of the nanoparticle, reveal the radial trapping potential and the nanoparticle size. Since the attractive forces draw particles to the highest evanescent intensity at the surface, binding steps are found to be uniform.


Exploiting open source 3D printer architecture for laboratory robotics to automate high-throughput time-lapse imaging for analytical microbiology.
Growth in open-source hardware designs combined with the low-cost of high performance optoelectronic and robotics components has supported a resurgence of in-house custom lab equipment development. We describe a low cost (below $700), open-source, fully customizable high-throughput imaging system for analytical microbiology applications. The system comprises a Raspberry Pi camera mounted on an aluminium extrusion frame with 3D-printed joints controlled by an Arduino microcontroller running open-source Repetier Host Firmware. The camera position is controlled by simple G-code scripts supplied from a Raspberry Pi singleboard computer and allow customized time-lapse imaging of microdevices over a large imaging area. Open-source OctoPrint software allows remote access and control. This simple yet effective design allows high-throughput microbiology testing in multiple formats including formats for bacterial motility, colony growth, microtitre plates and microfluidic devices termed 'lab-on-a-comb' to screen the effects of different culture media components and antibiotics on bacterial growth. The open-source robot design allows customization of the size of the imaging area; the current design has an imaging area of ~420 × 300mm, which allows 29 'lab-on-a-comb' devices to be imaged which is equivalent 3480 individual 1μl samples. The system can also be modified for fluorescence detection using LED and emission filters embedded on the PiCam for more sensitive detection of bacterial growth using fluorescent dyes.


The D-ring, not the A-ring, rotates in Synechococcus OS-B' phytochrome.
Phytochrome photoreceptors in plants and microorganisms switch photochromically between two states, controlling numerous important biological processes. Although this phototransformation is generally considered to involve rotation of ring D of the tetrapyrrole chromophore, Ulijasz et al. (Ulijasz, A. T., Cornilescu, G., Cornilescu, C. C., Zhang, J., Rivera, M., Markley, J. L., and Vierstra, R. D. (2010) Nature 463, 250-254) proposed that the A-ring rotates instead. Here, we apply magic angle spinning NMR to the two parent states following studies of the 23-kDa GAF (cGMP phosphodiesterase/adenylyl cyclase/FhlA) domain fragment of phytochrome from Synechococcus OS-B'. Major changes occur at the A-ring covalent linkage to the protein as well as at the protein residue contact of ring D. Conserved contacts associated with the A-ring nitrogen rule out an A-ring photoflip, whereas loss of contact of the D-ring nitrogen to the protein implies movement of ring D. Although none of the methine bridges showed a chemical shift change comparable with those characteristic of the D-ring photoflip in canonical phytochromes, denaturation experiments showed conclusively that the same occurs in Synechococcus OS-B' phytochrome upon photoconversion. The results are consistent with the D-ring being strongly tilted in both states and the C15=C16 double bond undergoing a Z/E isomerization upon light absorption. More subtle changes are associated with the A-ring linkage to the protein. Our findings thus disprove A-ring rotation and are discussed in relation to the position of the D-ring, photoisomerization, and photochromicity in the phytochrome family.


Endogenous alpha-synuclein influences the number of dopaminergic neurons in mouse substantia nigra.
The presynaptic protein α-synuclein is central to the pathogenesis of α-synucleinopathies. We show that the presence of endogenous mouse α-synuclein leads to higher number of dopaminergic neurons in the substantia nigra of wild-type C57Bl/6J mice compared with C57Bl/6S mice with a spontaneous deletion of the α-synuclein gene or C57Bl/6J mice with a targeted deletion of the α-synuclein gene. This effect of α-synuclein on dopaminergic neuron occurs during development between E10.5 and E13.5 and persists in adult life supporting the involvement of α-synuclein in the development of a subset of dopaminergic neurons.


Immunotargeting of catalase to ACE or ICAM-1 protects perfused rat lungs against oxidative stress.
The pulmonary endothelium is susceptible to oxidative insults. Catalase conjugated with monoclonal antibodies (MAbs) against endothelial surface antigens, angiotensin-converting enzyme (MAb 9B9) or intercellular adhesion molecule-1 (MAb 1A29), accumulates in the lungs after systemic injection in rats (V. Muzykantov, E. Atochina, H. Ischiropoulos, S. Danilov, and A. Fisher. Proc. Natl. Acad. Sci. USA 93: 5213-5218, 1996). The present study characterizes the augmentation of antioxidant defense by these antibody-catalase conjugates in isolated rat lungs perfused for 1 h with catalase conjugated with either MAb 9B9, MAb 1A29, or control mouse IgG. Approximately 20% of the injected dose of Ab-125I-catalase accumulated in the perfused rat lungs (vs. <5% for IgG-125I-catalase). After elimination of nonbound material, the lungs were perfused further for 1 h with 5 mM hydrogen peroxide (H2O2). H2O2 induced an elevation in tracheal and pulmonary arterial pressures (126 +/- 7 and 132 +/- 5%, respectively, of the control level), lung wet-to-dry weight ratio (7.1 +/- 0.4 vs. 6.0 +/- 0.01 in the control lungs), and ACE release into the perfusate (436 +/- 20 vs. 75 +/- 7 mU in the control perfusates). Both MAb 9B9-catalase and MAb 1A29-catalase significantly attenuated the H2O2-induced elevation in 1) angiotensin-converting enzyme release to the perfusate (215 +/- 14 and 217 +/- 38 mU, respectively), 2) lung wet-to-dry ratio (6.25 +/- 0.1 and 6.3 +/- 0.3, respectively), 3) tracheal pressure (94 +/- 4 and 101 +/- 4%, respectively, of the control level), and 4) pulmonary arterial pressure (103 +/- 3 and 104 +/- 7%, respectively, of the control level). Nonconjugated catalase, nonconjugated antibodies, nonspecific IgG, and IgG-catalase conjugate had no protective effect, thus confirming the specificity of the effect of MAb-catalase. These results support a strategy of catalase immunotargeting for protection against pulmonary oxidative injury.


Expression of nm23/nucleoside diphosphate kinase-A protein in endometrial carcinoma.
A metastatic tumor suppressor role for the nm23 gene product in breast carcinoma has been proposed. The biologic significance of nm23/NDP kinase-A (NDPK-A) expression in endometrial carcinoma remains undetermined. We sought to (1) characterize the pattern and intensity of nm23 protein expression in endometrial carcinoma and (2) assess the relationship between intensity/pattern of nm23 protein immunostaining and treatment response assessed by progression-free survival and survival to death. Formalin-fixed paraffin-embedded sections from 234 patients with endometrial cancer were immunostained with a mouse monoclonal IgG to nm23/NDPK-A protein. In most specimens of endometrial carcinoma (67.5%), nm23 expression was strongly upregulated. No association was found between either intensity (0 vs 1, 2, 3) or pattern (nuclear membrane vs cytoplasmic) of immunostaining and FIGO stage, ploidy status, histologic subtype, myometrial invasion, progression-free survival, or survival to death. Absence of nm23 staining (0 vs 1, 2, 3) was significantly associated with lower tumor grades (P = 0.02). For stage I patients, moderate to strong nm23 immunostaining intensity (2, 3) was associated with a trend toward diminished progression-free survival (P = 0.08). Our data imply a heterogeneity of nm23 protein expression and possible distinct biologic roles for nm23 in endometrial compared with breast or ovarian carcinoma.


ACASI and face-to-face interviews yield inconsistent estimates of domestic violence among women in India: The Samata Health Study 2005-2009.
Audio computer-assisted self-interviews (ACASI) are increasingly used in health research to improve the accuracy of data on sensitive behaviors. However, evidence is limited on its use among low-income populations in countries like India and for measurement of sensitive issues such as domestic violence. We compared reports of domestic violence and three less sensitive behaviors related to household decision making and spousal communication in ACASI and face-to-face interviews (FTFI) among 464 young married women enrolled in a longitudinal study of gender-based power and adverse health outcomes in low-income communities in Bangalore, India. We used a test-retest design. At the 12-month study visit, we elicited responses from each participant through FTFI first, followed by ACASI. At the 24-month visit, we reversed the order, implementing ACASI first, followed by FTFI. Univariable log-linear regression models and kappa statistics were used to examine ACASI's effects on self-reports. Regression results showed significantly lower reporting in ACASI relative to FTFI at both visits, including for domestic violence (12-month risk ratio [RR] = 0.61, 95% CI = 0.52, 0.73; 24-month RR = 0.74, 95% CI = 0.62, 0.89). Response agreement between interview modes, calculated by kappa scores, was universally low, though highest for domestic violence (12-month κ = 0.45; 24-month κ = 0.48). Older age and greater educational attainment appeared associated with higher response agreement. Greater reporting in FTFI may be due to social desirability bias for the less sensitive questions and perceptions of therapeutic benefit for domestic violence. These results cast doubt on the appropriateness of using ACASI for measurement of sensitive behaviors in India.


Autonomously Navigating a Surgical Tool Inside the Eye by Learning from Demonstration.
A fundamental challenge in retinal surgery is safely navigating a surgical tool to a desired goal position on the retinal surface while avoiding damage to surrounding tissues, a procedure that typically requires tens-of-microns accuracy. In practice, the surgeon relies on depth-estimation skills to localize the tool-tip with respect to the retina in order to perform the tool-navigation task, which can be prone to human error. To alleviate such uncertainty, prior work has introduced ways to assist the surgeon by estimating the tool-tip distance to the retina and providing haptic or auditory feedback. However, automating the tool-navigation task itself remains unsolved and largely unexplored. Such a capability, if reliably automated, could serve as a building block to streamline complex procedures and reduce the chance for tissue damage. Towards this end, we propose to automate the tool-navigation task by learning to mimic expert demonstrations of the task. Specifically, a deep network is trained to imitate expert trajectories toward various locations on the retina based on recorded visual servoing to a given goal specified by the user. The proposed autonomous navigation system is evaluated in simulation and in physical experiments using a silicone eye phantom. We show that the network can reliably navigate a needle surgical tool to various desired locations within 137 μm accuracy in physical experiments and 94 μm in simulation on average, and generalizes well to unseen situations such as in the presence of auxiliary surgical tools, variable eye backgrounds, and brightness conditions.


Isolation and excision of murine aorta; a versatile technique in the study of cardiovascular disease.
Cardiovascular disease is a broad term describing disease of the heart and/or blood vessels. The main blood vessel supplying the body with oxygenated blood is the aorta. The aorta may become affected in diseases such as atherosclerosis and aneurysm. Researchers investigating these diseases would benefit from direct observation of the aorta to characterize disease progression as well as to evaluate efficacy of potential therapeutics. The goal of this protocol is to describe proper isolation and excision of the aorta to aid investigators researching cardiovascular disease. Isolation and excision of the aorta allows investigators to look at gross morphometric changes as wells as allowing them to preserve and stain the tissue to look at histologic changes if desired. The aorta may be used for molecular studies to evaluate protein and gene expression to discover targets of interest and mechanisms of action. This technique is superior to imaging modalities as they have inherent limitations in technology and cost. Additionally, primary isolated cells from a freshly isolated and excised aorta can allowing researchers to perform further in situ and in vitro assays. The isolation and excision of the aorta has the limitation of having to sacrifice the animal however, in this case the benefits outweigh the harm as it is the most versatile technique in the study of aortic disease.


A Monte Carlo Analysis of Error Associated With Two-Wavelength Algorithms for Retinal Oximetry.
Two-wavelength algorithms aimed at the extrapolation of retinal vasculature optical properties are being used in the clinical setting. Although robust, this approach has some clear mathematical limitations. We have conducted an in-depth study of this methodology and report on the limits and benefit of this approach. We used a well-tested, voxel-based Monte Carlo model of light transfer into biological tissue combined with a seven-layer model of the human fundus to create reflectance maps of retina vessels at different oxygenation levels. This study shows that the two-wavelength approach works remarkably well in the optimal scenario of known calibration arteries and veins. Errors as a result of choroidal pigmentation and discrepancies in vessel size can be minimized with numerical approaches. When the calibration process deviates largely from physiological values, the technique fails with large errors. The two-wavelength approach is convenient, easy to implement, and suitable in studies where relative rather than absolute knowledge of retinal oximetry is necessary. A robust calibration step is paramount when using this approach.


Interrater Reliability in Interpretation of Neuropathic Pediatric Urodynamic Tracings: An Expanded Multicenter Study.
Urodynamic findings often guide treatment for neuropathic bladder and are reported as objective data points in multi-institutional trials. However, urodynamic interpretation can be variable. In a pilot study pediatric urologists interpreting videourodynamics exhibited only moderate agreement despite similar training and practice patterns. We hypothesized the pilot study variability would be replicated in a multi-institutional study. We developed an anonymous electronic survey that contained 20 scenarios, each with a brief patient history, 1 urodynamic tracing and fluoroscopic imagery. All videourodynamics were completed during routine care of patients with neuropathic bladder at a single institution. Pediatric urologists from Centers for Disease Control and Prevention Urologic Protocol sites were invited to complete an interpretation instrument for each scenario. Fleiss kappa and 95% confidence limits were reported, with Fleiss kappa 1.00 corresponding to perfect agreement. The survey was completed by 14 pediatric urologists at 7 institutions. Substantial agreement was seen for assessment of fluoroscopic bladder shape (Fleiss kappa 0.73), while moderate agreement was observed for assessment of bladder safety, end filling detrusor pressure and bladder capacity (Fleiss kappa 0.50, 0.56 and 0.54, respectively). Fair agreement was seen for electromyographic synergy and presence of detrusor overactivity (Fleiss kappa 0.21 and 0.35, respectively). Experienced pediatric urologists demonstrate variability during interpretation of videourodynamic tracings. Subjectivity of assessment of electromyographic activity and detrusor overactivity was confirmed in this expanded study. Future work to improve the reliability of videourodynamic interpretation would improve the quality of clinical care and the quality of multi-institutional studies that use urodynamic data points as outcomes.


Effect of intraarticular inoculation of mesenchymal stem cells in dogs with hip osteoarthritis by means of objective force platform gait analysis: concordance with numeric subjective scoring scales.
Subjective pain assessment scales have been widely used for assessing lameness in response to pain, but the accuracy of these scales has been questioned. To assess scale accuracy, 10 lame, presa Canario dogs with osteoarthritis (OA) associated with bilateral hip dysplasia were first treated with mesenchymal stem cells. Then, potential lameness improvement was analyzed using two pain scales (Bioarth and visual analog scale). These data were compared with similar data collected using a force platform with the same animals during a period of 6 months after treatment. The F test for intraclass correlation showed that concordance in pain/lameness scores between the 2 measuring methodologies was not significant (P value ≥ 0.9213; 95 % confidence interval, -0.56, 0.11). Although subjective pain assessment showed improvement after 6 months, force platform data demonstrated those same animals had returned to the initial lameness state. Use of pain assessment scales to measure lameness associated with OA did not have great accuracy and concordance when compared with quantitative force platform gait analysis.


A novel Smart Routing Protocol for remote health monitoring in Medical Wireless Networks.
In a Medical Wireless Network (MWN), sensors constantly monitor patient's physiological condition and movement. Inter-MWN communications are set up between the Patient Server and one or more Centralized Coordinators. However, MWNs require protocols with little energy consumption and the self-organizing attribute perceived in ad-hoc networks. The proposed Smart Routing Protocol (SRP) selects only the nodes with a higher residual energy and lower traffic density for routing. This approach enhances cooperation among the nodes of a Mobile Ad Hoc Network. Consequently, SRP produces better results than the existing protocols, namely Conditional Min-Max Battery Cost Routing, Min-Max Battery Cost Routing and AdHoc On-demand Distance Vector in terms of network parameters. The performance of the erstwhile schemes for routing protocols is evaluated using the network simulator Qualnet v 4.5.


In vitro antagonistic inhibitory effects of palm seed crude oils and their main constituent, lauric acid, with oxacillin in Staphylococcus aureus.
Infections caused by Staphylococcus aureus are a serious global threat, and with the emergence of antibiotic resistance, even more difficult to treat. One of the possible complications in antistaphylococcal therapy represents negative interactions of antibiotics with food. In this study, the in vitro interaction between oxacillin and crude palm seed oil from Astrocaryum vulgare, Cocos nucifera, and Elaeis guineensis against nine strains of S. aureus was determined using the checkerboard method. Lauric acid was identified as a major constituent of all tested oils by gas chromatography. The results showed strong concentration dependent antagonistic interactions between palm oils and oxacillin with values of fractional inhibitory concentrations indices ranging from 4.02 to 8.56 at concentrations equal or higher than 1024 µg/mL of the tested oils. Similarly, lauric acid in combination with oxacillin produced antagonistic action with fractional inhibitory concentration indices ranging from 4.01 to 4.28 at 1024 µg/mL. These findings suggest that interference between oxacillin and palm oils and their constituents can negatively affect the treatment of staphylococcal infections in humans and other animals.


The cell biology of receptor-mediated virus entry.
The cell imposes multiple barriers to virus entry. However, viruses exploit fundamental cellular processes to gain entry to cells and deliver their genetic cargo. Virus entry pathways are largely defined by the interactions between virus particles and their receptors at the cell surface. These interactions determine the mechanisms of virus attachment, uptake, intracellular trafficking, and, ultimately, penetration to the cytosol. Elucidating the complex interplay between viruses and their receptors is necessary for a full understanding of how these remarkable agents invade their cellular hosts.


Influence of proton pump inhibitor use in gastrointestinal polyps.
Proton pump inhibitors (PPIs) are the most potent anti-acid agents and are extensively used worldwide. PPI-induced hypergastrinemia is one of the very few side effects associated with these drugs. However, because hypergastrinemia is related to the occurrence of colonic adenomatous polyps, the purpose of this study was to analyze the relationship between the occurrence of gastrointestinal polyps and hypergastrinemia induced by PPIs. This study included 259 patients who underwent colonoscopy and esophagogastroduodenoscopy between January and August 2007. Chart records, including medication history and fasting plasma gastrin level, were reviewed and analyzed. Any subtle polypoid lesions in the stomach and colon were sampled by biopsy for histological examination. Helicobacter pylori infection status was examined by a rapid urea test during esophagogastroduodenoscopy. All patients underwent endoscopy examinations. A total of 122 patients were receiving PPI treatment for either peptic ulcer disease or reflux esophagitis and were included as the study group. The remaining 137 patients were not treated with PPIs and served as the non-PPI group. The mean fasting gastrin level in PPI users versus non-PPI users was 121.8 ng/L versus 56.8 ng/L, respectively (p < 0.001). Although the prevalence of gastric gland polyps was higher in the PPI group (65.6% vs. 37.2%, p < 0.001), there was no difference in the prevalence of colonic adenomatous polyps observed (22.13% vs. 22.62%, p = 0.928). In conclusion, the prevalence of gastric polyps, particularly fundic gland polyps, was higher among PPI users. However, the prevalence of colonic polyps was not affected by PPI use, regardless of past history of colonic adenomatous polyps.


Multiplex PCR point of care testing versus routine, laboratory-based testing in the treatment of adults with respiratory tract infections: a quasi-randomised study assessing impact on length of stay and antimicrobial use.
Laboratory-based respiratory pathogen (RP) results are often available too late to influence clinical decisions such as hospitalisation or antibiotic treatment due to time delay in transport of specimens and testing schedules. Ward-based i.e. point of care (POC) testing providing rapid results may alter the clinical management pathway. FilmArray® RP polymerase chain reaction (PCR) systems were placed in three in-patient and out-patient medical areas. Patients presenting with influenza-like illness /upper respiratory tract infection +/- lower RTI were recruited between January-July 2015. FilmArray® POC testing occurred on even days of the month (intervention) or routine, laboratory-based RP PCR testing +/- atypical serology on odd days (control). The primary outcome was length of hospital stay. The secondary outcomes were impact on the use of antimicrobials, readmissions, all-cause mortality, length of ward stay and turn-around time (TAT) (time to result from admission). Of 606 eligible patients, 545 (89.9%) were included; 211 in the control arm and 334 in the intervention arm. 20% of control arm patients and 24% of intervention arm patients had an RP detected. POC testing was not associated with the primary outcome measure, length of stay, but reduced the TAT from 39.5 h to 19.0 h, p < 0.001. Only the prescribing decision differed between study arms, p < 0.001. When antivirals were given, the intervention was associated with a reduction in the median time to the first dose of 36 h and allowed appropriate treatment of mycoplasma infection. We found no association between respiratory PCR POC testing and length of stay or most of the secondary outcomes except the antimicrobial prescribing decision. This was probably due to a delay in initiating FilmArray® testing. Despite this, POC testing allowed time-critical antivirals to be given significantly faster, appropriate mycoplasma treatment and results were available considerably faster than routine, laboratory-based testing. Ward-staff of all grades performed POC testing without difficulty suggesting potential use across many divergent healthcare settings. Further studies evaluating the implementation of rapid respiratory PCR POC testing and the effect on length of stay and antimicrobial use are required. ISRCTN10470967 , Retrospectively Registered, 30/6/2015.


Expression analysis of the polypyrimidine tract binding protein (PTBP1) and its paralogs PTBP2 and PTBP3 during Xenopus tropicalis embryogenesis.
The PTB (polypyrimidine tract binding protein) family of RNA-binding proteins plays a critical role in development through the regulation of post-transcriptional events. We have determined expression patterns of the three members of this gene family ptbp1, ptbp2 and ptbp3 during Xenopus tropicalis embryogenesis using whole-mount in situ hybridization. Our results show that each paralog presents a unique pattern of expression. ptbp1 is the prevalent maternal mRNA and is differentially expressed in the three germ layers. Later in development, it is widely expressed in the embryo including the epidermis, the dermatome, the intermediate mesoderm, the lateral plate mesoderm and the neural crest. ptbp2 expression is restricted to the nervous system including the brain, the neural retina and the spinal cord and the intermediate mesoderm. In addition to being expressed in erythroid precursors, ptbp3 is present in specific subdomains of the brain and the spinal cord, as well as in the posterior part of the notochord, suggesting it may play a role in the patterning of the nervous system. In the eye, each of the three genes is expressed in a specific structure which emphasizes their non-redundant function during development. Strickingly, our experiments also revealed that none of the three paralogs was expressed in the myotome, suggesting that the absence of PTB activity is a key determinant to display myotomal splicing patterns.


Association of Escherichia coli O157:H7 with houseflies on a cattle farm.
The ecology of Escherichia coli O157:H7 is not well understood. The aims of this study were to determine the prevalence of and characterize E. coli O157:H7 associated with houseflies (HF). Musca domestica L. HF (n = 3,440) were collected from two sites on a cattle farm over a 4-month period and processed individually for E. coli O157:H7 isolation and quantification. The prevalence of E. coli O157:H7 was 2.9 and 1.4% in HF collected from feed bunks and a cattle feed storage shed, respectively. E. coli O157:H7 counts ranged from 3.0 x 10(1) to 1.5 x 10(5) CFU among the positive HF. PCR analysis of the E. coli O157:H7 isolates revealed that 90.4, 99.2, 99.2, and 100% of them (n = 125) possessed the stx1, stx2, eaeA, and fliC genes, respectively. Large populations of HF on cattle farms may play a role in the dissemination of E. coli O157:H7 among animals and to the surrounding environment.


Nonlocal effect on optic spectrum of a periodic dielectric-metal stack.
On the basis of the formalism of the Boltzmann kinetic equation for the distribution function of the conduction electrons, the photonic band structure of binary dielectric-metal superlattice is theoretically studied. Using the constitutive nonlocal relation between the electrical current density and the electric field inside the metallic layer, the dispersion equation for photonic eigenmodes in the periodic stack is analytically expressed in terms of the surface impedances at the interfaces of the metal and dielectric layers. In the case of very thin metallic layers, the optic spectrum for the superlattice exhibits narrow pass bands as a result of the strong contrast between the impedances of the dielectric and the metal. The narrow pass bands are attributed to Fabry-Perot resonances in the relatively-thick dielectric layer. The metal nonlocality is well pronounced in the infrared and, therefore, the nonlocal effect upon the photonic band structure of the superlattice can be strong when the Fabry-Perot resonance bands are in that frequency range. Our results for the photonic spectrum have been compared with those obtained within the local Drude-Lorentz model. Noticeably differences not only in the the magnitude, but also in the sign of the real part of the Bloch wave number in the Fabry-Perot resonance bands, have been found.


Evaluation of a Digital Diabetes Prevention Program Adapted for Low-Income Patients, 2016-2018.
We examined the effects of a digitally delivered, type 2 diabetes mellitus prevention program (DPP) for a low-income population. We conducted a nonrandomized clinical trial with matched controls. The intervention group was offered a digital DPP, a web-based and mobile-based program including 52 weeks of participation in an educational curriculum, health coaching, and peer support. A total of 227 participants enrolled. At baseline, 34.6 was the mean body mass index, and 5.8 was the mean HbA1c. For the intervention group, mean weight loss was 4.4% at the 12-month follow-up. The modified DPP successfully engaged participants and resulted in weight loss. Low-income patients with prediabetes benefitted from a digitally delivered diabetes intervention. This prevention method should be accessible to a low-income population.


The expression and localization of synaptic vesicle antigens at neuromuscular junctions in vitro.
To examine the biochemical differentiation of presynaptic nerve terminals in vitro, we studied the expression and localization at synapses of two synaptic vesicle-specific antigens, synapsin I and protein p65. We purified these proteins from brain and raised a rabbit antiserum against each of them. Chick synapsin I had a slightly smaller molecular weight than its mammalian homologue, although the two share several properties. With the anti-p65 serum, the protein p65 could be detected consistently in presynaptic terminals at the neuromuscular junction in vivo, as had been previously shown for synapsin I. These antisera proved sufficiently sensitive to allow a study of the developmental expression of the antigens in embryonic chick brain, using protein blots. The two antigens are not coordinately regulated; protein p65 was detected substantially sooner in development that was synapsin I. Both synapsin I and protein p65 are expressed by ciliary ganglion neurons in vitro, as assessed by immunofluorescence using the affinity-purified antisera. The two antigens co-localized at all times in culture. Neurons grown alone were reliably stained only after 4 to 5 days in culture, but comparable levels of staining were found after 1 day when neurons were co-cultured with embryonic myotubes. In the co-cultures, staining was initially high in growth cones and neurites, but the brightest staining became confined to sites of nerve-muscle contact over 4 to 5 days in culture. In mature cultures, patches of bright staining for the vesicle antigens coincided with patches of acetylcholine receptors, suggesting that the antigens had become localized at synapses. The time course of this localization process suggests that it corresponds to the morphological maturation of synapses. It should be possible to exploit this system to obtain information about the molecules and processes involved in the induction of presynaptic differentiation.


A critical appraisal of the scientific basis of commercial genomic profiles used to assess health risks and personalize health interventions.
Predictive genomic profiling used to produce personalized nutrition and other lifestyle health recommendations is currently offered directly to consumers. By examining previous meta-analyses and HuGE reviews, we assessed the scientific evidence supporting the purported gene-disease associations for genes included in genomic profiles offered online. We identified seven companies that offer predictive genomic profiling. We searched PubMed for meta-analyses and HuGE reviews of studies of gene-disease associations published from 2000 through June 2007 in which the genotypes of people with a disease were compared with those of a healthy or general-population control group. The seven companies tested at least 69 different polymorphisms in 56 genes. Of the 56 genes tested, 24 (43%) were not reviewed in meta-analyses. For the remaining 32 genes, we found 260 meta-analyses that examined 160 unique polymorphism-disease associations, of which only 60 (38%) were found to be statistically significant. Even the 60 significant associations, which involved 29 different polymorphisms and 28 different diseases, were generally modest, with synthetic odds ratios ranging from 0.54 to 0.88 for protective variants and from 1.04 to 3.2 for risk variants. Furthermore, genes in cardiogenomic profiles were more frequently associated with noncardiovascular diseases than with cardiovascular diseases, and though two of the five genes of the osteogenomic profiles did show significant associations with disease, the associations were not with bone diseases. There is insufficient scientific evidence to conclude that genomic profiles are useful in measuring genetic risk for common diseases or in developing personalized diet and lifestyle recommendations for disease prevention.


Assessing behavioural and cognitive domains of autism spectrum disorders in rodents: current status and future perspectives.
The establishment of robust and replicable behavioural testing paradigms with translational value for psychiatric diseases is a major step forward in developing and testing etiology-directed treatment for these complex disorders. Based on the existing literature, we have generated an inventory of applied rodent behavioural testing paradigms relevant to autism spectrum disorders (ASD). This inventory focused on previously used paradigms that assess behavioural domains that are affected in ASD, such as social interaction, social communication, repetitive behaviours and behavioural inflexibility, cognition as well as anxiety behaviour. A wide range of behavioural testing paradigms for rodents were identified. However, the level of face and construct validity is highly variable. The predictive validity of these paradigms is unknown, as etiology-directed treatments for ASD are currently not on the market. To optimise these studies, future efforts should address aspects of reproducibility and take into account data about the neurodevelopmental underpinnings and trajectory of ASD. In addition, with the increasing knowledge of processes underlying ASD, such as sensory information processes and synaptic plasticity, phenotyping efforts should include multi-level automated analysis of, for example, representative task-related behavioural and electrophysiological read-outs.


Role of the nanocrystallinity on the chemical ordering of Co(x)Pt(100-x) nanocrystals synthesized by wet chemistry.
Co(x)Pt(100-x) nanoalloys have been synthesized by two different chemical processes either at high or at low temperature. Their physical properties and the order/disorder phase transition induced by annealing have been investigated depending on the route of synthesis. It is demonstrated that the chemical synthesis at high temperature allows stabilization of the fcc structure of the native nanoalloys while the soft chemical approach yields mainly poly or non crystalline structure. As a result the approach of the order/disorder phase transition is strongly modified as observed by high-resolution transmission electron microscopy (HR-TEM) studies performed during in situ annealing of the different nanoalloys. The control of the nanocrystallinity leads to significant decrease in the chemical ordering temperature as the ordered structure is observed at temperatures as low as 420 °C. This in turn preserves the individual nanocrystals and prevents their coalescence usually observed during the annealing necessary for the transition to an ordered phase.


Exploring adverse drug events at the class level.
While the association between a drug and an adverse event (ADE) is generally detected at the level of individual drugs, ADEs are often discussed at the class level, i.e., at the level of pharmacologic classes (e.g., in drug labels). We propose two approaches, one visual and one computational, to exploring the contribution of individual drugs to the class signal. Having established a dataset of ADEs from MEDLINE, we aggregate drugs into ATC classes and ADEs into high-level MeSH terms. We compute statistical associations between drugs and ADEs at the drug level and at the class level. Finally, we visualize the signals at increasing levels of resolution using heat maps. We also automate the exploration of drug-ADE associations at the class level using clustering techniques. Using our visual approach, we were able to uncover known associations, e.g., between fluoroquinolones and tendon injuries, and between statins and rhabdomyolysis. Using our computational approach, we systematically analyzed 488 associations between a drug class and an ADE. The findings gained from our exploratory techniques should be of interest to the curators of ADE repositories and drug safety professionals. Our approach can be applied to different drug-ADE datasets, using different drug classification systems and different signal detection algorithms.


Web-drive based source measure unit for automated evaluations of ionic liquid-gated MoS2 transistors.
For reliable characterization of two-dimensional semiconducting devices and continuous monitoring in toxic environments, construction of an electrical characterization-based massive database using a portable source measure unit (SMU) with a WiFi connection is desirable. The web-drive based SMU using a microcontroller developed here exhibits superior voltage source performance (∼1 mV) and voltage/current measurement (∼0.15 mV/∼1 nA) capabilities, with automatic construction of a measurement database for online storage using web-drive based software, which can be applied for reliable electrical characterization. Electrical characterization of ionic liquid-gated MoS2 transistors was achieved with the designed SMU and showed results comparable with those obtained using a commercial semiconductor characterization system. Ionic liquid-gated transistors only require a small gate bias (∼1.5 V) for on-state operation because of the high gate capacitance originating from the thin dielectric layer constructed of an electrical double layer, which makes the device a promising candidate for low power consumption applications. Finally, several electrical parameters of the ionic liquid-gated transistor were extracted from the datasets and uploaded to the web-drive.


Pyoderma gangrenosum preceding the onset of extranodal natural killer/T-cell lymphoma: A case report.
Pyoderma gangrenosum (PG) is a neutrophilic dermatosis that may be associated with systemic diseases. The association of PG with lymphoid malignancies has rarely been reported. Extranodal natural killer/T-cell lymphoma (ENKTL) is a rare but aggressive entity with a poor prognosis. Here, we report the case of a patient who had idiopathic PG refractory to systemic steroids and subsequently developed ENKTL. A 70-year-old man presented with a 2-month history of intermittent fever and multifocal painful papules, plaques, and ulcerations on his extremities. The histological and culture results of the lesions were consistent with those of PG. A thorough work-up was performed and did not demonstrate any underlying systemic diseases including malignancy. The PG lesions were refractory to systemic steroid therapy. An enlarging nodule was observed over his right infraorbital area 4 months after the onset of the skin eruptions. The nodule was later biopsied and diagnosed as ENKTL by using histopathological and immunohistochemical studies. Fludeoxyglucose positron emission tomography/computed tomography revealed multiple intense fludeoxyglucose-avid masses in the bones and lungs, suggesting multiorgan metastases. The patient rejected chemotherapy and died 4 weeks after the diagnosis. The present case indicates that in any patient with idiopathic PG refractory to conventional therapy, the presence of any underlying disease or malignancy must be thoroughly evaluated. The present case serves as a reminder that when assessing patients with PG, clinicians should increase their awareness regarding the delayed association with malignancy, even in the absence of a concomitant systemic disease at presentation. Furthermore, the prompt evaluation of any suspicious lesions in the context of PG for the possibility of a malignant nature can improve the prognosis, particularly in cases of aggressive malignancy. Understanding the cutaneous spectrum of ENKTL is crucial because of its variable clinical appearance and aggressive nature. Our case demonstrates that PG can be a presenting sign of ENKTL.


Epifaunistic arthropod parasites of the four-striped mouse, Rhabdomys pumilio, in the Western Cape Province, South Africa.
Flea, lice, mite, and tick species associated with 510 Rhabdomys pumilio were collected at 9 localities in the Western Cape Province, South Africa. The aims of the study were first to quantify the species richness, prevalence, and relative mean intensity of infestation of epifaunistic arthropod species associated with R. pumilio, and second to determine temporal variations in the mean abundance of the parasitic arthropods. Each mouse was examined under a stereoscopic microscope and its parasites were removed, identified, and quantified. The epifaunal population was made up of more than 25,000 individuals and included 8 flea, 1 sucking louse, 11 mite, and 13 ixodid tick species. Female-biased sex ratios were noted for 9 (30%) of the ectoparasite species. Three undescribed mite and 1 undescribed tick species were recovered, and new locality records for 2 flea, the louse, and 2 mite species were documented. A phoretic host association between a nonparasitic mite species, Psylloglyphus uilenbergi kivuensis, and 3 flea species, Chiastopsylla rossi, Hypsophthalmus temporis, and Listropsylla agrippinae, was recorded. The mean abundance of the parasitic mite and insect species were higher during the cold wet season, whereas ticks were more numerous during the warm dry months. The large number of ectoparasite species on R. pumilio, a locally abundant and regionally widespread species, is of medical and veterinary importance particularly in relation to the transmission of pathogens such as Anaplasma marginale, Babesia caballi, and Babesia canis to domestic animals; Rickettsia conori; Yersinia pestis; and the viral disease Crimean-Congo hemorrhagic fever to humans.


LLCMDA: A Novel Method for Predicting miRNA Gene and Disease Relationship Based on Locality-Constrained Linear Coding.
MiRNAs are small non-coding regulatory RNAs which are associated with multiple diseases. Increasing evidence has shown that miRNAs play important roles in various biological and physiological processes. Therefore, the identification of potential miRNA-disease associations could provide new clues to understanding the mechanism of pathogenesis. Although many traditional methods have been successfully applied to discover part of the associations, they are in general time-consuming and expensive. Consequently, computational-based methods are urgently needed to predict the potential miRNA-disease associations in a more efficient and resources-saving way. In this paper, we propose a novel method to predict miRNA-disease associations based on Locality-constrained Linear Coding (LLC). Specifically, we first reconstruct similarity networks for both miRNAs and diseases using LLC and then apply label propagation on the similarity networks to get relevant scores. To comprehensively verify the performance of the proposed method, we compare our method with several state-of-the-art methods under different evaluation metrics. Moreover, two types of case studies conducted on two common diseases further demonstrate the validity and utility of our method. Extensive experimental results indicate that our method can effectively predict potential associations between miRNAs and diseases.


Straylight from glistenings in intraocular lenses: In vitro study.
To assess light scattering from intraocular lenses (IOLs) with different numbers of laboratory-induced glistenings and create a model for predicting glistening effects on straylight. Rotterdam Ophthalmic Institute, Rotterdam, the Netherlands. Experimental study. Glistenings were induced in 7 Acrysof IOLs using an accelerated aging method. To create different numbers of glistenings, the IOLs were immersed in a balanced salt solution at temperatures ranging from 37°C to 60°C and cooled to room temperature. The glistenings were analyzed with a microscope. Light scattering from the IOLs was assessed using a commercial straylight meter (C-Quant) adapted for in vitro evaluation of IOLs at a 2.5-degree and 7.0-degree scatter angle. A model was proposed relating straylight increase to the total number and surface portion (total number × area) of glistenings. Results were compared to the Mie theory. The number of induced glistenings ranged from 114 to 12 386 per mm2, and the surface portion ranged from 1.4% to 26.9%. At 2.5 degrees, the range in the straylight parameter was 1.49 to 72.49 deg2/steradian (sr); at 7.0 degrees, it was 1.72 to 62.87 deg2/sr. Straylight was proportionally related to the total number of glistenings (0.0046 × total number) (R2 = 0.96) and the surface portion (217 × surface portion) (R2 = 0.97). The measurements agreed well with Mie theory. Straylight from glistenings in IOLs had an accurate proportional association with their total number and surface portion. The proposed model proved effective in predicting straylight from glistenings. Numerous glistenings are needed to cause significant straylight elevation.


Predictors of outcomes following reablement in community-dwelling older adults.
Reablement is a rehabilitation intervention for community-dwelling older adults, which has recently been implemented in several countries. Its purpose is to improve functional ability in daily occupations (everyday activities) perceived as important by the older person. Performance and satisfaction with performance in everyday life are the major outcomes of reablement. However, the evidence base concerning which factors predict better outcomes and who receives the greatest benefit in reablement is lacking. The objective of this study was to determine the potential factors that predict occupational performance and satisfaction with that performance at 10 weeks follow-up. The sample in this study was derived from a nationwide clinical controlled trial evaluating the effects of reablement in Norway and consisted of 712 participants living in 34 municipalities. Multiple linear regression was used to investigate possible predictors of occupational performance (COPM-P) and satisfaction with that performance (COPM-S) at 10 weeks follow-up based on the Canadian Occupational Performance Measure (COPM). The results indicate that the factors that significantly predicted better COPM-P and COPM-S outcomes at 10 weeks follow-up were higher baseline scores of COPM-P and COPM-S respectively, female sex, having a fracture as the major health condition and high motivation for rehabilitation. Conversely, the factors that significantly predicted poorer COPM-P and COPM-S outcomes were having a neurological disease other than stroke, having dizziness/balance problems as the major health condition and having pain/discomfort. In addition, having anxiety/depression was a predictor of poorer COPM-P outcomes. The two regression models explained 38.3% and 38.8% of the total variance of the dependent variables of occupational performance and satisfaction with that performance, respectively. The results indicate that diagnosis, functional level, sex and motivation are significant predictors of outcomes following reablement.


Functional organization of crayfish abdominal ganglia: I. The flexor systems.
For insect ganglia, Altman (Advances in Physiological Science, Vol. 23. Neurobiology of Invertebrates. New York: Pergamon Press, pp. 537-555, '81) proposed that individual neuropils control different motor activities. A corollary of this hypothesis is that motor neurons involved in many behavioral functions should branch in more neuropils than those active in fewer behaviors. In crayfish, the abdominal fast-flexor muscles are active only during the generation of the powerstroke for tailflips, whereas the slow-flexor muscles are involved in the maintenance of body posture. The slow flexors are thus active in many of the crayfish's behavioral activities. To test the generality of Altman's idea, we filled groups of crayfish fast-flexor and slow-flexor motor neurons with cobalt chloride and described their shapes with respect to the ganglionic structures through which they pass. Individual fast flexors were also filled intracellularly with HRP. Ganglia containing well-filled neurons were osmicated, embedded in plastic, and sectioned. Unstained sections were examined by light microscopy and pertinent sections were photographed. We found that the paths of the larger neurites were invariant, that the dendritic domains of fast and slow motor neurons occupied distinctive sets of neuropils, and that dendrites of slow motor neurons branched in more ganglionic structures than did those of fast motor neurons. These results are consistent with Altman's hypothesis.


Regulation of phyllotaxis.
Plant architecture is characterized by a high degree of regularity. Leaves, flowers and floral organs are arranged in regular patterns, a phenomenon referred to as phyllotaxis. Regular phyllotaxis is found in virtually all higher plants, from mosses, over ferns, to gymnosperms and angiosperms. Due to its remarkable precision, its beauty and its accessibility, phyllotaxis has for centuries been the object of admiration and scientific examination. There have been numerous hypotheses to explain the nature of the mechanistic principle behind phyllotaxis, however, not all of them have been amenable to experimental examination. This is due mainly to the delicacy and small size of the shoot apical meristem, where plant organs are formed and the phyllotactic patterns are laid down. Recently, the combination of genetics, molecular tools and micromanipulation has resulted in the identification of auxin as a central player in organ formation and positioning. This paper discusses some aspects of phyllotactic patterns found in nature and summarizes our current understanding of the regulatory mechanism behind phyllotaxis.


CD8⁺ MAIT cells infiltrate into the CNS and alterations in their blood frequencies correlate with IL-18 serum levels in multiple sclerosis.
Recent findings indicate a pathogenic involvement of IL-17-producing CD8(+) T cells in multiple sclerosis (MS). IL-17 production has been attributed to a subset of CD8(+) T cells that belong to the mucosal-associated invariant T (MAIT) cell population. Here, we report a reduction of CD8(+) MAIT cells in the blood of MS patients compared with healthy individuals, which significantly correlated with IL-18 serum levels in MS patients. In vitro stimulation of peripheral blood mononuclear cells from healthy individuals and MS patients with IL-18 specifically activated CD8(+) MAIT cells. Moreover, IL-18 together with T-cell receptor stimulation induced, specifically on CD8(+) MAIT cells, an upregulation of the integrin very late antigen-4 that is essential for the infiltration of CD8(+) T cells into the CNS. Notably, we were able to identify CD8(+) MAIT cells in MS brain lesions by immunohistochemistry while they were almost absent in the cerebrospinal fluid (CSF). In summary, our findings indicate that an IL-18-driven activation of CD8(+) MAIT cells contributes to their CNS infiltration in MS, in turn leading to reduced CD8(+) MAIT-cell frequencies in the blood. Therefore, CD8(+) MAIT cells seem to play a role in the innate arm of immunopathology in MS.


Cross-sectional relations of multiple biomarkers representing distinct biological pathways to plasma markers of collagen metabolism in the community.
Hyperhomocysteinemia, neurohormonal activation, inflammation and altered fibrinolysis have been linked to atherothrombosis as well as to myocardial fibrosis and heart failure. Hence, we related a panel of biomarkers representing these pathways to plasma markers of collagen metabolism in a large community-based sample. We related nine biomarkers representing select biologic pathways (independent variables: C-reactive protein, B-type natriuretic peptide, N-terminal proatrial natriuretic peptide, aldosterone, renin, fibrinogen, D-dimer, plasminogen activator inhibitor-1 and homocysteine) to three plasma markers of collagen turnover [dependent variables, separate models for each: aminoterminal propeptide of type III collagen, tissue inhibitor of metalloproteinases-1 and matrix metalloproteinase-9 (present versus absent)] in 921 Framingham Heart study participants (mean age 57 years; 58% women). Participants were separated a priori into those with left ventricular end-diastolic dimensions and wall thickness below sex-specific median values (referent group) and either measure at least 90th sex-specific percentile ('remodeled' group). We used stepwise multivariable regression analysis adjusting for cardiovascular risk factors to relate the panel of systemic biomarkers to the three biomarkers of collagen metabolism. Plasma homocysteine was positively related to all three markers of collagen metabolism in the remodeled group and to aminoterminal propeptide of type III collagen and tissue inhibitor of metalloproteinases-1 in the referent group. Plasminogen activator inhibitor-1 was positively related to aminoterminal propeptide of type III collagen and tissue inhibitor of metalloproteinases-1 in both groups, whereas the natriuretic peptides were associated positively with these collagen markers in the referent group. In our large community-based sample, plasma homocysteine and plasminogen activator inhibitor-1 were positively related to circulating collagen biomarkers, consistent with experimental studies implicating these pathways in cardiovascular collagen turnover.


Evaluation of commercial kits for the identification of Neisseria gonorrhoeae.
Eight identification methods were evaluated against 100 isolates of Neisseria gonorrhoeae and 21 non-gonococcal Neisseria strains. The methods examined included four commercial biochemical kits, API NH, RapID NH, Gonochek II and Neisseria Preformed Enzyme Test (PET), three immunological kits, Phadebact Monoclonal GC test, GonoGen II and MicroTrak, and one in-house carbohydrate-utilization method, cystine trypticase agar (CTA) sugars. The percentage of isolates unambiguously identified as N. gonorrhoeae by each of the methods was as follows: API NH, 66 %; RapID NH, 64 %; GonoChek II, 66 %; Neisseria PET, 66 %; Phadebact Monoclonal GC OMNI test, 99 %; GonoGen II, 100 %; MicroTrak, 100 %; and CTA sugars, 96 %. The low sensitivity of the biochemical kits for the identification of N. gonorrhoeae was due to a lack of the enzyme proline iminopeptidase (Pip) in 34 % of the isolates examined. All the biochemical kits utilized the presence of this enzyme as a marker for N. gonorrhoeae. The Phadebact Monoclonal GC kit, GonoGen II, MicroTrak, CTA sugars and the API NH kit all exhibited high specificity, but non-gonococcal Neisseria were misidentified as N. gonorrhoeae using RapID NH (two strains), Gonochek II (11 strains) and Neisseria PET (11 strains). Whilst the isolates examined in this study may not be truly representative, they do indicate that N. gonorrhoeae isolates lacking the enzyme Pip can give anomalous results when using commercially available biochemical tests and that some non-pathogenic Neisseria species are still being misidentified using some biochemical kits. This further reinforces the recommendation that any dubious biochemical result should be confirmed with an immunological test.


Clustering visual field test points based on rates of progression to improve the prediction of future damage.
To develop new visual field (VF) sectors based on pointwise rates of glaucomatous VF progression ("progression regions") and to evaluate their usefulness for predicting future progression. A training dataset consisting of 10 VFs from each of 412 eyes in 412 open-angle glaucoma patients and a validation dataset consisting of 15 VFs from each of 71 eyes in 45 patients were investigated. First, using the training dataset, the VF was divided into small regions, according to the rates of progression of all 52 test points in the VF. Then, using the initial four VFs of the validation dataset, total deviation (TD) values in the 10th VF were predicted by applying linear regression analysis in derived regions and the absolute prediction error was calculated. The analysis was iterated, predicting TD values of the 10th VF, but each time including an additional VF in the regression (from five to nine VFs). Absolute prediction errors were then compared with conventional pointwise linear regression (PLR) and regression based on Nouri-Mahdavi (NM) sectors. Twenty-three progression regions were derived. In general, absolute prediction errors were significantly smaller for regression based on these regions compared with PLR and NM sectors. Predictions of VF progression can be improved by dividing the VF into small regions based on clusters of test points with similar progression rates.


AllergoOncology: ultra-low IgE, a potential novel biomarker in cancer-a Position Paper of the European Academy of Allergy and Clinical Immunology (EAACI).
Elevated serum IgE levels are associated with allergic disorders, parasitosis and specific immunologic abnormalities. In addition, epidemiological and mechanistic evidence indicates an association between IgE-mediated immune surveillance and protection from tumour growth. Intriguingly, recent studies reveal a correlation between IgE deficiency and increased malignancy risk. This is the first review discussing IgE levels and links to pathological conditions, with special focus on the potential clinical significance of ultra-low serum IgE levels and risk of malignancy. In this Position Paper we discuss: (a) the utility of measuring total IgE levels in the management of allergies, parasitosis, and immunodeficiencies, (b) factors that may influence serum IgE levels, (c) IgE as a marker of different disorders, and d) the relationship between ultra-low IgE levels and malignancy susceptibility. While elevated serum IgE is generally associated with allergic/atopic conditions, very low or absent IgE may hamper anti-tumour surveillance, indicating the importance of a balanced IgE-mediated immune function. Ultra-low IgE may prove to be an unexpected biomarker for cancer risk. Nevertheless, given the early stage of investigations conducted mostly in patients with diseases that influence IgE levels, in-depth mechanistic studies and stratification of malignancy risk based on associated demographic, immunological and clinical co-factors are warranted.


Beyond price: individuals' accounts of deciding to pay for private healthcare treatment in the UK.
Delivering appropriate and affordable healthcare is a concern across the globe. As countries grapple with the issue of delivering healthcare with finite resources and populations continue to age, more health-related care services or treatments may become an optional 'extra' to be purchased privately. It is timely to consider how, and to what extent, the individual can act as both a 'patient' and a 'consumer'. In the UK the majority of healthcare treatments are free at the point of delivery. However, increasingly some healthcare treatments are being made available via the private healthcare market. Drawing from insights from healthcare policy and social sciences, this paper uses the exemplar of private dental implant treatment provision in the UK to examine what factors people considered when deciding whether or not to pay for a costly healthcare treatment for a non-fatal condition. Qualitative interviews with people (n = 27) who considered paying for dental implants treatments in the UK. Data collection and analysis processes followed the principles of the constant comparative methods, and thematic analysis was facilitated through the use of NVivo qualitative data software. Decisions to pay for private healthcare treatments are not simply determined by price. Decisions are mediated by: the perceived 'status' of the healthcare treatment as either functional or aesthetic; how the individual determines and values their 'need' for the treatment; and, the impact the expenditure may have on themselves and others. Choosing a private healthcare provider is sometimes determined simply by personal rapport or extant clinical relationship, or based on the recommendation of others. As private healthcare markets expand to provide more 'non-essential' services, patients need to develop new skills and to be supported in their new role as consumers.


Effect of cosyntropin during adrenal venous sampling on subtype of primary aldosteronism: analysis of surgical outcome.
We investigated the clinical significance of ACTH stimulation during adrenal venous sampling (AVS) by surgical outcome of primary aldosteronism (PA). Multicenter retrospective study by Japan PA study. We allocated 314 patients with both basal and ACTH-stimulated AVS data who underwent adrenalectomy to three groups: basal lateralization index (LI) ≥2 with ACTH-stimulated LI ≥4 on the ipsilateral side (Unilateral (U) to U group, n = 245); basal LI <2 with ACTH-stimulated LI ≥4 (Bilateral (B) to U group, n = 15); and basal LI ≥2 with ACTH-stimulated LI <4 (U to B group, n = 54). We compared surgical outcomes among the groups using the Primary Aldosteronism Surgical Outcome (PASO) criteria. Compared with U to U group, U to B group had poor clinical and biochemical outcomes and low rates of adrenal adenoma as pathological findings (P = 0.044, 0.006, and 0.048, respectively), although there were no significant differences between U to U and B to U groups. All patients in U to B group with clinical and biochemical benefits, however, had adrenal adenoma as pathological findings and could be well differentiated from those with poor surgical outcomes via basal LI (>8.3), but not ACTH-stimulated LI. These results were similar even when we defined each group based on a cut-off value of 4 for basal LI. Although PA patients in U to B group had worse surgical outcomes than did those in U to U group, basal LI could discriminate among patients with better surgical outcomes in U to B group.


Telepsychiatry in an Era of Digital Mental Health Startups.
Telepsychiatry practiced by psychiatrists is evidence-based, regulated, private, and effective in diverse settings. The use of telemedicine has grown since the COVID-19 pandemic as people routinely obtain more healthcare services online. At the same time, there has been a rapid increase in the number of digital mental health startups that offer various services including online therapy and access to prescription medications. These digital mental health firms advertise directly to the consumer primarily through digital advertising. The purpose of this narrative review is to contrast traditional telepsychiatry and the digital mental health market related to online therapy. In contrast to standard telepsychiatry, most of the digital mental health startups are unregulated, have unproven efficacy, and raise concerns related to self-diagnosis, self-medicating, and inappropriate prescribing. The role of digital mental health firms for people with serious mental illness has not been determined. There are inadequate privacy controls for the digital mental health firms, including for online therapy. We live in an age where there is widespread admiration for technology entrepreneurs and increasing emphasis on the role of the patient as a consumer. Yet, the business practices of digital mental health startups may compromise patient safety for profits. There is a need to address issues with the digital mental health startups and to educate patients about the differences between standard medical care and digital mental health products.


Investigation and identification of protein carbonylation sites based on position-specific amino acid composition and physicochemical features.
Protein carbonylation, an irreversible and non-enzymatic post-translational modification (PTM), is often used as a marker of oxidative stress. When reactive oxygen species (ROS) oxidized the amino acid side chains, carbonyl (CO) groups are produced especially on Lysine (K), Arginine (R), Threonine (T), and Proline (P). Nevertheless, due to the lack of information about the carbonylated substrate specificity, we were encouraged to develop a systematic method for a comprehensive investigation of protein carbonylation sites. After the removal of redundant data from multipe carbonylation-related articles, totally 226 carbonylated proteins in human are regarded as training dataset, which consisted of 307, 126, 128, and 129 carbonylation sites for K, R, T and P residues, respectively. To identify the useful features in predicting carbonylation sites, the linear amino acid sequence was adopted not only to build up the predictive model from training dataset, but also to compare the effectiveness of prediction with other types of features including amino acid composition (AAC), amino acid pair composition (AAPC), position-specific scoring matrix (PSSM), positional weighted matrix (PWM), solvent-accessible surface area (ASA), and physicochemical properties. The investigation of position-specific amino acid composition revealed that the positively charged amino acids (K and R) are remarkably enriched surrounding the carbonylated sites, which may play a functional role in discriminating between carbonylation and non-carbonylation sites. A variety of predictive models were built using various features and three different machine learning methods. Based on the evaluation by five-fold cross-validation, the models trained with PWM feature could provide better sensitivity in the positive training dataset, while the models trained with AAindex feature achieved higher specificity in the negative training dataset. Additionally, the model trained using hybrid features, including PWM, AAC and AAindex, obtained best MCC values of 0.432, 0.472, 0.443 and 0.467 on K, R, T and P residues, respectively. When comparing to an existing prediction tool, the selected models trained with hybrid features provided a promising accuracy on an independent testing dataset. In short, this work not only characterized the carbonylated substrate preference, but also demonstrated that the proposed method could provide a feasible means for accelerating preliminary discovery of protein carbonylation.


Effectiveness of Cognitive Orientation to daily Occupational Performance over and above functional hand splints for children with cerebral palsy or brain injury: a randomized controlled trial.
Functional hand splinting is a common therapeutic intervention for children with neurological conditions. The aim of this study was to investigate the effectiveness of the Cognitive Orientation to daily Occupational Performance (CO-OP) approach over and above conventional functional hand splinting, and in combination with splinting, for children with cerebral palsy or brain injury. A multisite, assessor-blinded, parallel, randomized controlled trial was conducted in Australia. Participants (n = 45) were randomly allocated to one of three groups; (1) splint only (n = 15); (2) CO-OP only (n = 15); (3) CO-OP + splint (n = 15). Inclusion: age 4-15 years; diagnosis of cerebral palsy or brain injury; Manual Ability Classification System I-IV; hand function goals; sufficient language, cognitive and behavioral ability. Primary outcome measures were the Canadian Occupational Performance Measure (COPM) and Goal Attainment Scale (GAS). Treatment duration for all groups was 2 weeks. CO-OP was provided in a group format, 1 h per day for 10 consecutive weekdays, with parents actively involved in the group. Hand splints were wrist cock-up splints that were worn during task practice. Three individual goals were set and all participants were encouraged to complete a daily home program of practicing goals for 1 h. Analyses were conducted on an intention to treat basis. The COPM showed that all three groups improved from baseline to immediately post-treatment. GAS showed a statistically significant difference immediately post-intervention between the splint only and CO-OP only groups p = 0.034), and the splint only and CO-OP + splint group (p = 0.047) favoring CO-OP after controlling for baseline. The CO-OP Approach™ appeared to enhance goal achievement over and above a functional hand splint alone. There was no added benefit of using hand splints in conjunction with CO-OP, compared to CO-OP alone. Hand splints were not well tolerated in this population. Practice of functional goals, through CO-OP or practice at home, leads to goal achievement for children with cerebral palsy or brain injury. Registered with the Australian New Zealand Clinical Trials Registry ( ACTRN12613000690752 ) on 24/06/2013.


Reconfigurable frequency coding of triggered single photons in the telecom C-band.
In this work, we demonstrate reconfigurable frequency manipulation of quantum states of light in the telecom C-band. Triggered single photons are encoded in a superposition state of three channels using sidebands up to 53 GHz created by an off-the-shelf phase modulator. The single photons are emitted by an InAs/GaAs quantum dot grown by metal-organic vapor-phase epitaxy within the transparency window of the backbone fiber optical network. A cross-correlation measurement of the sidebands demonstrates the preservation of the single photon nature; an important prerequisite for future quantum technology applications using the existing telecommunication fiber network.


Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000-17: analysis for the Global Burden of Disease Study 2017.
Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood diarrhoea. We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor estimates. The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54·0% (95% uncertainty interval [UI] 38·1-65·8), 17·4% (7·7-28·4), and 59·5% (34·2-86·9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy coverage. By co-analysing geospatial trends in diarrhoeal burden and its key risk factors, we could assess candidate drivers of subnational death reduction. Further, by doing a counterfactual analysis of the remaining disease burden using key risk factors, we identified potential intervention strategies for vulnerable populations. In view of the demands for limited resources in LMICs, accurately quantifying the burden of diarrhoea and its drivers is important for precision public health. Bill & Melinda Gates Foundation.


Evaluation of a new surgical light source for difficult visibility procedures.
A new lighting device for open surgery of difficult access wounds was designed: the Extender add-on. The performance of the Extender is evaluated and compared with the conventional solutions used in the operating room (OR) on illumination quality. A cylindrical setup was built to measure the distribution of light in a simulated pelvic wound. The light was provided by a head-mounted light, an OR light, and a pair of Extender prototypes. The results showed that the Extender prototypes provided 12.2 lumens inside the wound, whereas the head-mounted light gave 5.7 lumens. The Extenders provided smoothly angular distributed light from 0° to 180°, whereas the head-mounted light and OR light only provided light from 115° to 180°. The Extender prototypes had a promising performance in terms of light distribution. It is expected that a more accurately produced Extender will increase performance in terms of illumination quantity and illumination distribution smoothness even further.


Cooperation, behavioural synchrony and status in social networks.
In this paper we present a new approach to modelling group coordination, based on dyadic synchronisation in a non-panmictic, structured network (a problem that applies widely to all species that live in medium to large groups). Using this approach, we present three models with three new theoretical results. (1) Multi-layered networks are optimal for groups that face costs associated with maintaining relationships among the members, combined with costs associated with information flows. (2) The presence of a social hierarchy can be an adaptive feature of the community: the steeper the optimal social hierarchy is, the fewer relationships group members need to have. (3) Falling communication costs lead to a less steep optimal social hierarchy in communities in which socially useful information is evenly distributed, but to an even steeper social hierarchy in groups in which socially useful information is uneven. Thus we show how, when communication is costly, cooperation can give rise to communities that are socially highly structured.


Evidence from deuterium nuclear magnetic resonance for the temperature-dependent reversible self-association of erythrocyte band 3 in dimyristoylphosphatidylcholine bilayers.
Band 3, isolated from human erythrocytes, has been reconstituted into bilayers of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) deuterated in the terminal methyl groups of the choline head group. By use of Triton X-100 for selective extraction and purification of band 3 and then cholate for subsequent solubilization with the lipid, a number of reconstituted complexes were produced by exhaustive detergent dialysis with protein:lipid weight ratios of between 0.32:1 and 1.25:1. Electron micrographs of negatively stained complexes showed that this method produced large vesicles of greater than 300-nm diameter. Deuterium nuclear magnetic resonance (NMR) spectra from the choline methyl deuterons in bilayer lipid above the liquid-crystal-gel phase transition temperature were shown to change systematically with increasing concentrations of band 3 in the bilayers. The measured quadrupole splittings, taken as the separation of the turning points in the recorded spectra, decreased from a value of 1.28 kHz for pure lipid to 0.98 kHz for bilayers with a protein:lipid ratio of 1.25:1 at 26 degrees C. At 35 degrees C, a more pronounced decrease in the quadrupole splittings was measured. The data from the complexes with protein:lipid ratios up to 0.7:1 (w/w) obey the mathematical treatment for a rapid two-site exchange between lipids at the protein-lipid interface and the bulk lipid phase. The temperature dependence of the measured quadrupole splitting with respect to the protein:lipid ratio indicates that the amount of lipid at the protein-lipid interface increases with increasing temperature.(ABSTRACT TRUNCATED AT 250 WORDS)


Polarization smoothing in a convergent beam.
A birefringent wedge in a collimated 351-nm beam provides polarization smoothing at the Omega laser facility and provided it for the Nova laser. At the National Ignition Facility, the best place to put such an optic is after the final focus lens. In a converging beam, a flat birefringent plate can closely mimic the polarization-smoothing action of a wedge. In this new design the flat plate is nearly a Z-cut crystal; for the wedges, the optical axis of the crystal lies far from the plate normal.


'We can work together, talk together': an Aboriginal Health Care Home.
Objective The aim of this study was to identify an Aboriginal community's aspirations for health service improvement during implementation of the Commonwealth's Health Care Homes (HCH) reform. Methods This study was a qualitative study consisting of Aboriginal-controlled phenomenological enquiry in a large Aboriginal community in north-central Arnhem Land. Results A representative sample of 60 Aboriginal health service users identified shortcomings in their current experience of primary health care, including low cultural security. These shortcomings reduced access to care. Participants described several ways that care could be reorientated to match their needs during HCH implementation. Principally, patients voiced the need for: (1) restructuring care teams to foster culturally secure relationship-based care; and (2) reorientating the Aboriginal Health Practitioner role from acute care to strength-based competencies as the focal point of care continuity: self-management support, care coordination and navigation, health coaching and cultural mentorship for non-Aboriginal staff. Conclusions For HCH to be successful, service providers need to engage with service users to identify and implement patient-centred strategies to improve access, acceptability and patient activation. What is known about the topic? Success of the Commonwealth's HCH reform is contingent on improving care access and patient activation to better manage chronic conditions What does this paper add? This is the first opportunity that this Aboriginal community has had to articulate their aspirations for high quality healthcare. Beyond the strong alignment with the HCH building blocks, their care preferences posit practical and achievable workforce and delivery system reforms that may improve primary health care in other remote Aboriginal communities. What are the implications for practitioners? The long-term success of the HCH reform will require iterative engagement with service users to identify and implement patient-centred strategies to improve access and acceptability of care. Service model alignment with patient care preferences will improve patient activation and is particularly important when working with vulnerable populations.


Higher Dihydrotestosterone Is Associated with the Incidence of Lung Cancer in Older Men.
Advancing age is associated with increased cancer incidence, but the role of sex hormones as risk predictors for common cancers in older men remains uncertain. This study was performed to assess associations of testosterone (T), dihydrotestosterone (DHT) and estradiol (E2), with incident prostate, lung and colorectal cancer in community-dwelling older men. Plasma T, DHT and E2 were assayed using liquid chromatography-mass spectrometry between 2001 and 2004 in 3690 men. Cancer outcomes until 20 June 2013 were ascertained using data linkage. Analyses were performed using proportional hazards competing-risks models, and adjustments were made for potential confounding factors including smoking status. Results are expressed as subhazard ratios (SHR). There were 348, 107 and 137 cases of prostate, lung and colorectal cancers respectively during a median of 9.1-year follow-up. Mean T was comparable in current and non-smokers, whilst mean DHT was lower in ex- and current smokers compared to non-smokers. After adjusting for confounders including smoking, higher T or DHT was associated with an increased incidence of lung cancer (SHR = 1.30, 95% CI 1.06-1.60; p = 0.012 per 1 SD increase in T and SHR = 1.29, 95% CI 1.08-1.54; p = 0.004 for DHT). Sex hormones were not associated with prostate or colorectal cancer. In older men, higher T or DHT predict increased incidence of lung cancer over the next decade. Sex hormones are not associated with incident prostate or colorectal cancer. Further studies are warranted to determine if similar associations of sex hormones with lung cancer are present in other populations and to investigate potential underlying mechanisms.


The cost of hemodialysis in Iran.
The use of dialysis in patients with end-stage renal disease (ESRD) remains one of the most resource-intensive and hence, expensive therapeutic interventions. The purpose of this study was to assess the cost of hemodialysis (HD) in Iran. This study was conducted in the Department of Nephrology at the Imam Khomeini Hospital of Tehran University of Medical Sciences, Iran, between April 2006 and June 2007. Patients with ESRD on chronic HD were involved in the study. Relevant data were collected using interview and questionnaire. Analyzed costs included: transportation plus absence from work, treatment instruments, drugs and other medical procedures, diet, staff salary, equipment and building support services, non-medical supplies, depreciation of installations and equipments, depreciation of reverse osmosis (RO) and building rent. Sixty-three patients of whom 47.7% were males and 52.3% were females, with mean age of 47 +/- 12 years were studied. The estimated cost of each HD session was about 74 US dollars by which an annual cost of $11549 could be estimated for each patient. Transportation and work leaves (28.9%), staff costs and salaries (21.5%), and treatment instruments (21.1%) were among the greatest expenses. We conclude that the annual cost of dialysis in Iran is similar to other developing countries, but significantly less than the cost in developed countries.


Genetic diversity in new members of the reticulocyte binding protein family in Thai Plasmodium vivax isolates.
Plasmodium vivax merozoites specifically invade reticulocytes. Until recently, two reticulocyte-binding proteins (Pvrbp1 and Pvrbp2) expressed at the apical pole of the P. vivax merozoite were considered to be involved in reticulocyte recognition. The genome sequence recently obtained for the Salvador I (Sal-I) strain of P. vivax revealed additional genes in this family, and in particular Pvrbp2a, Pvrbp2b (Pvrbp2 has been renamed as Pvrbp2c) and two pseudogenes Pvrbp2d and Pvrbp3. It had been previously found that Pvrbp2c is substantially more polymorphic than Pvrbp1. The primary goal of this study was to ascertain the level of polymorphism of these new genes. The sequence of the Pvrbp2a, Pvrbp2b, Pvrbp2d and Pvrbp3 genes were obtained by amplification/cloning using DNA purified from four isolates collected from patients that acquired the infection in the four cardinal regions of Thailand (west, north, south and east). An additional seven isolates from western Thailand were analyzed for gene copy number variation. There were significant polymorphisms exhibited by these genes (compared to the reference Sal-I strain) with the ratio of mutations leading to a non-synonymous or synonymous amino acid change close to 3∶1 for Pvrbp2a and Pvrbp2b. Although the degree of polymorphism exhibited by these two genes was higher than that of Pvrbp1, it did not reach the exceptional diversity noted for Pvrbp2c. It was interesting to note that variations in the copy number of Pvrbp2a and Pvrbp2b occurred in some isolates. The evolution of different members of the Pvrbp2 family and their relatively high degree of polymorphism suggests that the proteins encoded by these genes are important for parasite survival and are under immune selection. Our data also shows that there are highly conserved regions in rbp2a and rbp2b, which might provide suitable targets for future vaccine development against the blood stage of P. vivax.


Effect of heat stress on cell activity and cell morphology of the tropical rhizobium, Sinorhizobium arboris.
The effect of heat stress on the growth, physiological state, cell activity and cell morphology of the tropical Sinorhizobium arboris strain HAMBI 2190 was studied. The cells were chromosomally tagged with the firefly luciferase gene, luc. Since the bioluminescence phenotype is dependent on cellular energy reserves it was used as an indicator of the metabolic status of the cell population under various heat conditions. Variations in the numbers and lengths of growth phases between individual cultures indicated that the growth pattern at 40 degrees C was disturbed compared to growth at 37 or 28 degrees C. In addition, the cell morphology was changed radically. The number of culturable cells and the luciferase activity declined when the cultures were incubated at 40 degrees C. By contrast, under all conditions studied, the cells could be stained with 5-(and 6-)sulfofluorescein diacetate, indicating esterase activity. This demonstrated that although the culturability and cellular energy reserves decreased considerably during heat stress, a majority of the of S. arboris cell population maintained basal enzyme activity.


DSM-5 and paraphilic disorders.
Given that paraphilic disorders are diagnosed largely in forensic settings, virtually every significant change in the criteria has forensic implications. Several controversial changes were considered during the DSM-5 revision process, but most were ultimately not included in the published text. However, any changes that make it easier to assign a paraphilic disorder diagnosis to an individual must be considered with caution. Criterion A for paraphilic disorders has been changed to reduce one potential risk that could result in false-positive diagnoses (i.e., allowing evaluators to diagnose a paraphilic disorder based entirely on the presence of sexual acts). In contrast, many of the other changes including some of those in the text, make it easier to diagnose a specific paraphilia and thus increase the risk of false-positive diagnoses. Since the assignment of a paraphilic disorder diagnosis can result in adverse legal consequences, the actual forensic impact of the changes will depend on how the legal system incorporates these new definitions into statutes and case law.


An autopsy study describing causes of death and comparing clinico-pathological findings among hospitalized patients in Kampala, Uganda.
Information on causes of death in HIV-infected patients in Sub-Saharan Africa is mainly derived from observational cohort and verbal autopsy studies. Autopsy is the gold standard to ascertain cause of death. We conducted an autopsy study to describe and compare the clinical and autopsy causes of death and contributory findings in hospitalized HIV-infected and HIV-uninfected patients in Uganda. Between May and September 2009 a complete autopsy was performed on patients that died on a combined infectious diseases gastroenterology ward in Mulago Hospital in Kampala, Uganda. Autopsy cause of death and contributing findings were based on the macro- and microscopic post-mortem findings combined with clinical information. Clinical diagnoses were reported by the ward doctor and classified as confirmed, highly suspected, considered or not considered, based on information derived from the medical chart. Results are reported according to HIV serostatus. Fifty-three complete autopsies were performed in 66% HIV-positive, 21% HIV-negative and 13% patients with an unknown HIV serological status. Infectious diseases caused death in 83% of HIV-positive patients, with disseminated TB as the main diagnosis causing 37% of deaths. The spectrum of illness and causes of death were substantially different between HIV-positive and HIV-negative patients. In HIV-positive patients 12% of postmortem diagnoses were clinically confirmed, 27% highly suspected, 16% considered and 45% not considered. In HIV-negative patients 17% of postmortem diagnoses were clinically highly suspected, 42% considered and 42% not considered. Autopsy examination remains an important tool to ascertain causes of death particularly in settings with limited access to diagnostic testing during life. HIV-positive patients continue to die from treatable and clinically undiagnosed infectious diseases. Until rapid-point of care testing is available to confirm common infections, empiric treatment should be further investigated.


Every death counts: measurement of maternal mortality via a census.
Methods for measuring maternal mortality at national and subnational levels in the developing world lag far behind the demand for estimates. We evaluated use of the national population census as a means of measuring maternal mortality by assessing data from five countries (Benin, Islamic Republic of Iran, Lao People's Democratic Republic, Madagascar, and Zimbabwe) which identified maternal deaths in their censuses. Standard demographic methods were used to evaluate the completeness of reporting of adult female deaths and births in the year prior to the census. The results from these exercises were used to adjust the data. In four countries, the numbers of adult female deaths needed to be increased and three countries required upward adjustment of the numbers of recent births. The number of maternal deaths was increased by the same factor as that used for adult female deaths on the assumption that the proportion of adult female deaths due to maternal causes was correct. Age patterns of the various maternal mortality indicators were plausible and consistent with external sources of data for other populations. Our data suggest that under favourable conditions a national census is a feasible and promising approach for the measurement of maternal mortality. Moreover, use of the census circumvents several of the weaknesses of methods currently in use. However, it should also be noted that careful evaluation of the data and adjustment, if necessary, are essential. The public health community is urged to encourage governments to learn from the experience of these five countries and to place maternal mortality estimation in the hands of statistical agencies.


Control, prevention and eradication of Salmonella enteritidis infection in broiler and broiler breeder flocks.
Salmonella enteritidis was identified by serological and bacteriological techniques in two clinically normal breeder flocks in an integrated broiler organisation in Northern Ireland. The organism was transmitted vertically to clinically affected progeny flocks. The infected breeder flocks were slaughtered and the infection throughout the organisation controlled and subsequently eradicated. A working group, consisting of the senior management of the broiler organisation and veterinary staff from the Veterinary Research Laboratories at Stormont, was formed to establish procedures to minimise the risk of the reintroduction of salmonella infection, by preventing vertical transmission from grandparent flocks, or lateral transmission from personnel, other animal species and fomites, or transmission through the feed. All feed was heated to a minimum of 70 degrees C for 12 minutes immediately before it was pelleted and subsequently transported to the flocks through a dedicated system of conveyor belts, bins and lorries. A comprehensive system for monitoring the efficacy of the preventive procedures was established and is now used throughout the poultry industry of Northern Ireland.


Rates of brain development in mammals including man.
The paper considers the absolute rates at which the brain grows in different mammals and the relative rates of growth for the various subareas. It concludes that the various mammals are much more similar in the rates of growth of the brain than of the body. The rate of growth of the human brain is within the range of variation expected. Indirect evidence is presented that the different mammalian orders may differ in the relative rates of growth of the neocortex and other brain areas.