A Synthetic Biology Approach Using Engineered Bacteria to Detect Perfluoroalkyl Substance (PFAS) Contamination in Water.
Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic compounds used industrially for a wide variety of applications. These PFAS compounds are very stable and persist in the environment. The PFAS contamination is a growing health issue as these compounds have been reported to impact human health and have been detected in both domestic and global water sources. Contaminated water found on military bases poses a potentially serious health concern for active duty military, their families, and the surrounding communities. Previous detection methods for PFAS in contaminated water samples require expensive and time-consuming testing protocols that limit the ability to detect this important global pollutant. The main objective of this work was to develop a novel detection system that utilizes a biological reporter and engineered bacteria as a way to rapidly and efficiently detect PFAS contamination. The United States Air Force Academy International Genetically Engineered Machine team is genetically engineering Rhodococcus jostii strain RHA1 to contain novel DNA sequences composed of a propane 2-monooxygenase alpha (prmA) promoter and monomeric red fluorescent protein (mRFP). The prmA promoter is activated in the presence of PFAS and transcribes the mRFP reporter. The recombinant R. jostii containing the prmA promoter and mRFP reporter respond to exposure of PFAS by activating gene expression of the mRFP. At 100 µM of perfluorooctanoic acid, the mRFP expression was increased 3-fold (qRT-PCR). Rhodococcus jostii without exposure to PFAS compounds had no mRFP expression. This novel detection system represents a synthetic biology approach to more efficiently detect PFAS in contaminated samples. With further refinement and modifications, a similar system could be readily deployed in the field around the world to detect this critical pollutant.


Chasing after Non-cyanobacterial Nitrogen Fixation in Marine Pelagic Environments.
Traditionally, cyanobacterial activity in oceanic photic layers was considered responsible for the marine pelagic dinitrogen (N2) fixation. Other potentially N2-fixing bacteria and archaea have also been detected in the pelagic water column, however, the activity and importance of these non-cyanobacterial diazotrophs (NCDs) remain poorly constrained. In this perspective we summarize the N2 fixation rates from recently published studies on photic and aphotic layers that have been attributed to NCD activity via parallel molecular measurements, and discuss the status, challenges, and data gaps in estimating non-cyanobacterial N2 fixation NCNF in the ocean. Rates attributed to NCNF have generally been near the detection limit thus far (<1 nmol N L-1 d-1). Yet, if considering the large volume of the dark ocean, even low rates of NCNF could make a significant contribution to the new nitrogen input to the ocean. The synthesis here shows that nifH transcription data for NCDs have been reported in only a few studies where N2 fixation rates were detected in the absence of diazotrophic cyanobacteria. In addition, high apparent diversity and regional variability in the NCDs complicate investigations of these communities. Future studies should focus on further investigating impacts of environmental drivers including oxygen, dissolved organic matter, and dissolved inorganic nitrogen on NCNF. Describing the ecology of NCDs and accurately measuring NCNF rates, are critical for a future evaluation of the contribution of NCNF to the marine nitrogen budget.


Inflammatory pseudotumor of the spleen: clinical impact in surgical treatment.
An inflammatory pseudotumor of the spleen is a rare benign tumor and designated as mass-like lesions with histologic features of nonspecific inflammation and mesenchymal repair although its etiopathogenesis still remains unknown. Here we describe the case of an inflammatory pseudotumor of the spleen in a 57-year-old woman, whose lesion was accidentally found and thought to be lymphoma at first. Generally splenic tumors are difficult to diagnose exactly before surgery, then the patient underwent splenectomy, followed by histopathological diagnosis of inflammatory pseudotumor of the spleen. The optimal management of the asymptomastic patient with such disease is still controversial. The clinical and pathological features of previously reported cases are also reviewed in this paper.


Can a Back Pain E-mail Discussion Group improve health status and lower health care costs?: A randomized study.
Given the high health care utilization, limited evidence for the effectiveness of back pain interventions, and the proliferation of e-mail health discussion groups, this study seeks to determine if the Internet can be used to improve health status and health care utilization for people with chronic back pain. Randomized controlled trial. Participants included 580 people from 49 states with chronic back pain having at least 1 outpatient visit in the past year, no "red-flag" symptoms, and access to e-mail. Major exclusion criteria included continuous back pain for more than 90 days causing major activity intolerance and/or receiving disability payments. Closed, moderated, e-mail discussion group. Participants also received a book and videotape about back pain. Controls received a subscription to a non-health-related magazine of their choice. Pain, disability, role function, health distress, and health care utilization. At 1-year treatment, subjects compared with controls demonstrated improvements in pain (P =.045), disability (P =.02), role function (P =.007), and health distress (P =.001). Physician visits for the past 6 months declined by 1.5 visits for the treatment group and by 0.65 visits for the control group (P =.07). Mean hospital days declined nearly 0.20 days for the treated group vs and increased 0.04 days for the control group (P =.24). An e-mail discussion group can positively affect health status and possibly health care utilization. It may have a place in the treatment of chronic recurrent back pain.


LROC analysis of detector-response compensation in SPECT.
Localization ROC (LROC) observer studies examined whether detector response compensation (DRC) in ordered-subset, expectation-maximization (OSEM) reconstructions helps in the detection and localization of hot tumors. Simulated gallium (Ga-67) images of the thoracic region were used in the study. The projection data modeled the acquisition of attenuated 93- and 185-keV photons with a medium-energy parallel-hole collimator, but scatter was not modeled. Images were reconstructed with five strategies: 1) OSEM with no DRC; 2) OSEM preceded by restoration filtering; 3) OSEM with iterative DRC; 4) OSEM with an ideal DRC; and 5) filtered backprojection (FBP) with no DRC. All strategies included attenuation correction. There were four LROC studies conducted. In a study using a single tumor activity, the ideal DRC offered the best performance, followed by iterative DRC, restoration filtering, OSEM with no DRC, and FBP. Statistical significance at the 5% level was found between all pairs of strategies except for restoration filtering and OSEM with no DRC. A similar ranking was found for a more realistic study using multiple tumor activities. Additional studies considered the effects of OSEM iteration number and tumor activity on the detection improvement that iterative DRC offered with respect to OSEM with no DRC.


Evaluation of aggrecan and adipokine levels in temporomandibular joint synovial fluid.
The aim of this study was to investigate the effect various mediators in synovial fluid (SF) on the pathogenesis of temporomandibular disorders (TMD) and to evaluate the relationship between clinical and radiological features of temporomandibular joint (TMJ) diseases. Patients who had received SF sample during arthrocentesis because of TMD were included in this study. Clinical and radiological records were evaluated retrospectively. Enzyme-Linked ImmunoSorbent Assay (ELISA) method was used for analysis of aggrecan, adiponectin, resistin, apelin, Vascular Endothelial Growth Factor (VEGF) and Prostaglandin E2 (PGE2) in SFs. 59 joints of 41 patients were included in the study. Anterior disc displacement with reduction (ADDwR) was detected in 22 joints, anterior disc displacement without reduction (ADDwoR) was detected in 29 joints and osteoarthritis (OA) in 8. In OA group, PGE2 level was significantly higher than the other groups (p = 0.029). Aggrecan and PGE2 levels were statistically higher in joints with localized pain (p = 0.030, p = 0.029). The aggrecan level was statistically significant higher in patients who had degenerative changes in radiological examinations (p = 0.044). Resistin was correlated with PGE2 and aggrecan (p = 0.011), and apelin showed positive correlation with VEGF (p˂0.001). The detection of aggrecan and adipokines in SF may be a precursor of degenerative joint disease and it should be taken into account that the presence of localized pain in the joint area may be an early sign of degenerative changes.


The functions of the amyloid precursor protein gene.
The amyloid precursor protein (APP) gene and its protein products have multiple functions in the central nervous system and fulfil criteria as neuractive peptides: presence, release and identity of action. There is increased understanding of the role of secretases (proteases) in the metabolism of APP and the production of its peptide fragments. The APP gene and its products have physiological roles in synaptic action, development of the brain, and in the response to stress and injury. These functions reveal the strategic importance of APP in the workings of the brain and point to its evolutionary significance.


Equifinality and its violations in a redundant system: multifinger accurate force production.
We explored a hypothesis that transient perturbations applied to a redundant system result in equifinality in the space of task-related performance variables but not in the space of elemental variables. The subjects pressed with four fingers and produced an accurate constant total force level. The "inverse piano" device was used to lift and lower one of the fingers smoothly. The subjects were instructed "not to intervene voluntarily" with possible force changes. Analysis was performed in spaces of finger forces and finger modes (hypothetical neural commands to fingers) as elemental variables. Lifting a finger led to an increase in its force and a decrease in the forces of the other three fingers; the total force increased. Lowering the finger back led to a drop in the force of the perturbed finger. At the final state, the sum of the variances of finger forces/modes computed across repetitive trials was significantly higher than the variance of the total force/mode. Most variance of the individual finger force/mode changes between the preperturbation and postperturbation states was compatible with constant total force. We conclude that a transient perturbation applied to a redundant system leads to relatively small variance in the task-related performance variable (equifinality), whereas in the space of elemental variables much more variance occurs that does not lead to total force changes. We interpret the results within a general theoretical scheme that incorporates the ideas of hierarchically organized control, control with referent configurations, synergic control, and the uncontrolled manifold hypothesis.


Pterostilbene alleviates cerebral ischemia and reperfusion injury in rats by modulating microglial activation.
Ischemic stroke is a severe neurological disease without known effective therapy. Microglia-mediated neuroinflammation plays an important role in ischemic stroke. Therefore, finding a safe and effective microglial activation inhibitor might lead to an effective therapeutic strategy against ischemic stroke. In this project, our goal was to explore both the mechanism and effect of pterostilbene in MCAO/R rats. The potential effect of pterostilbene on ischemic stroke was tested using MCAO/R rats and its effect on microglial activation was tested in LPS-stimulated BV-2 cells. In vivo, pterostilbene decreased the neurological scores, brain water content and infarct volume in MCAO/R rats. Pterostilbene increased the number of mature neurons, decreased the number of activated microglia, and reduced iNOS and IL-1β mRNA expression. Pterostilbene inhibited phosphorylated-IκBα expression, thus promoting IκBα expression and inhibiting ROS overexpression. In vitro, pterostilbene inhibited the expression of inflammatory cytokines and suppressed NAPDH activity as well as activation of both the NF-κB pathway and ROS production. To our knowledge, our study is the first to demonstrate that pterostilbene-mediated alleviation of cerebral ischemia and reperfusion injury in rats may be correlated with the inhibition of the ROS/NF-κB-mediated inflammatory pathway in microglia, indicating the potential for the use of pterostilbene as a candidate therapeutic compound for ischemic stroke.


Lidocaine/Phenylephrine Nasal Spray versus Nebulization Prior to Nasoendoscopy: A Randomized Controlled Trial.
Objective To objectively compare the nasal decongestion potency of lidocaine/phenylephrine when delivered with a nasal nebulizer and a nasal spray before a rigid nasoendoscopic examination. Study Design Open-label randomized controlled trial. Setting Multicenter study. Methods This prospective clinical trial involved 106 participants with untreated chronic rhinitis. Fifty-three participants had 400 μL of lidocaine/phenylephrine administered into the right nostril with a nasal nebulizer, while the remaining 53 participants had 400 μL administered with a nasal spray. The control was the left nostril. Nasal resistance at 150-Pa fixed pressure was evaluated with an active anterior rhinomanometry at 5, 10, 15, and 30 minutes postintervention. Pain score was assessed subjectively by applying pressure to the inferior turbinate 30 minutes after intervention. Results There was an overall reduction in nasal resistance of the right nostril when lidocaine/phenylephrine was administered with the nasal nebulizer in comparison with the nasal spray. However, a statistically significant difference in nasal resistance was seen only at 5 minutes ( P = .047), 15 minutes ( P = .016), and 30 minutes ( P = .036). The examining endoscopist further supported the degree of nasal decongestion via subjective assessment of the nasal cavity ( P = .001). Pain scores obtained after the intervention showed a significant decrease in pain threshold when the nasal nebulizer was used instead of the nasal spray ( P = .040). Conclusions This study suggests that the delivery of lidocaine/phenylephrine to the nasal cavity by the nasal nebulizer provides better decongestive and analgesic potency as compared with the delivery by nasal sprays.


A self-powered ultraviolet detector based on a single ZnO microwire/p-Si film with double heterojunctions.
Recently, self-powered devices based on a p-n heterojunction have been widely reported, but there are few reports about self-powered UV detectors based on a single ZnO microwire/p-Si film with double heterojunctions. Compared with the common p-n heterojunction type devices, the fabricated devices with double heterojunctions based on a single n-type ZnO microwire and a p-type Si film exhibited excellent electrical performance such as an ideal rectification behaviour and a low turn-on voltage. At zero bias, the fabricated device can deliver a photocurrent of 71 nA, a high photosensitivity of about 3.17 × 10(3) under UV light (0.58 mW cm(-2)) illumination and a fast rising and falling time of both less than 0.3 s. Furthermore, the photocurrent increased with the rising of the optical intensity at low power intensities. The physical mechanism has been explained by energy band diagrams.


Urethro-vesical dysfunction in progressive autonomic failure with multiple system atrophy.
Fourteen patients with progressive autonomic failure and multiple system atrophy have been investigated by urodynamic, electromyographic and neurohistochemical means and the results compared with a series of age-matched controls. Three fundamental abnormalities of lower urinary tract function have been identified: (1) Involuntary detrusor contractions in response to bladder filling. It is suggested that these may be the result of a loss of inhibitory influences from the corpus striatum and substantia nigra. (2) Loss of the ability to initiate a voluntary micturition reflex. This may reflect the degeneration of neurons in pontine and medullary nuclei and in the sacral intermediolateral columns. In addition, these studies have demonstrated a significant reduction in the density of acetylcholinesterase-containing nerves in bladder muscle. (3) Profound urethral dysfunction. This appears to be partly due to a loss of proximal urethral sphincter tone, which causes bladder neck incompetence. In addition, the function of the striated component of the urethral sphincter is impaired. Individual motor units recorded from this muscle were clearly abnormal when compared with controls and suggested that reinnervation had occurred. We suggest that this is the result of degeneration of a specific group of sacral anterior horn cells known as Onuf's nucleus. The evidence that these particular motor units are affected, while others are spared, poses fundamental questions about the nature of selective vulnerability in degenerative diseases of the nervous system.


Simulation Training in Orthopaedic Surgery.
Simulation training encompasses all methods of learning technical skills that do not require practicing on a live patient. Surgical training typically uses an apprenticeship model, in which responsibility is gradually shifted from attending surgeon to the trainee over years of experiences with live patients. Skill acquisition from simulation modalities can prevent unnecessary harm to patients if trainees have practice and experience from simulation before participation in live surgeries. Surgeons are morally required to prevent unnecessary harm to patients, regardless of whether they are consequentialist or nonconsequentialist in one's metaethics. It is the authors' opinion that simulation training is a moral imperative, as there is early empirical evidence for preventing harm to patients and it should be incorporated to the extent it is feasible in every surgical training program. Further definitive studies need to be performed.


Bowel preparation affects the amplitude and spatiotemporal organization of colonic propagating sequences.
Colonic manometry is performed using either colonoscopically assisted catheter placement, after bowel preparation, or nasocolonic intubation of the unprepared bowel. There has been little systematic evaluation of the effects of bowel cleansing upon colonic propagating pressure wave sequences. Eight healthy volunteers underwent nasocolonic placement of a water-perfused silicone catheter which recorded pressures at 16 recording sites each spaced 7.5 cm apart in the unprepared colon for 24 h. These measures were compared with those obtained in another eight healthy volunteers in whom the catheter was placed to the caecum at colonoscopy in the prepared colon. The colonic motor responses to meals and morning waking, and the normal nocturnal suppression did not differ between the two groups, nor were the overall frequency, regional dependence nor extent of propagating sequences (PS) influenced by bowel preparation. Bowel preparation did result in a significant increase in the frequency of high amplitude PS (22 +/- 7 vs 8 +/- 4 HAPS/24 h; P = 0.003). Additionally, a number of the measures of spatiotemporal organization among consecutive PS (linkage among sequences and predefecatory stereotypical patterning) were significantly altered by bowel preparation. The overall frequency of PSs, the colonic responses to physiological stimuli such a meal and morning waking and nocturnal suppression, are not influenced by prior bowel preparation. However, investigators wishing to study HAPS frequency, or the more complex spatiotemporal relationships among consecutive PSs, should control for bowel preparation when making comparisons among study groups.


Edge extraction by active defocusing.
A novel edge extraction method that employs an active defocusing technique is presented. The method is based on the principle that a Laplacian-of-Gaussian (LOG) operation can be approximated by a Difference-of-Gaussian (DOG) operation. While such an operation is usually done in digital image processing, it can also be very effective conducted in a combination of optical techniques and digital processing. In this edge extraction method, a focused image of an object in a scene is first acquired. The image of the scene is then slightly defocused by changing the focal length of the camera. A real time subtraction operation is applied to subtract the defocused image from the previously acquired image. It produces a residual image that emphasizes abrupt intensity variations. An objective evaluation, called an edge index, is performed on the resulting image. The amount of defocusing is carefully adjusted according to this measurement so that a desired edge image is generated. Boundaries of objects can then be obtained by further enhancement of the edge image. Since this edge detection method is an optical-based process aided by digital processing, it is fast and relatively inexpensive.


Analysis of ionic conductance mechanisms in motor cells mediating inking behavior in Aplysia californica.
1. The release of ink in response to a noxious stimulus is a relatively stereotyped behavior produced by strong and long-lasting stimuli. The purpose of this series of papers is to determine the quantitative extent to which the known voltage- and time-dependent ionic conductance mechanisms and synaptic influences can account for the ink gland motor neurons' firing pattern and, thus, the features of the behavior. 2. Four voltage- and time-dependent ionic currents have been analyzed. These include a fast transiet Na+-mediated inward current, a slower Ca2+-mediated inward current, a fast transient K+-mediated outward current, and a slower delayed outward current also mediated by K+ ions. 3. The current-voltage (I-V) relationships, equilibrium potentials, and steady-state activation and inactivation characteristics appear qualitatively similar to comparable currents observed in other gastropod neurons. 4. The recovery from inactivation of the delayed outward current has two time constants, one comparable to the inactivation time constant and the other more than an order of magnitude larger. The fast transient K+ current also appears to have a similar slow recovery from inactivation. 5. The synaptic current contributing to the firing pattern of the ink motor cells is a complex function of time. Initially, the synaptic conductance is high and the equilibrium potential near 0 mV. But, with time there is a gradual decrease in synaptic conductance and shift in the equilibrium potential to more depolarized levels.


Operative Repair of Medial Patellofemoral Ligament Injury Versus Knee Brace in Children With an Acute First-Time Traumatic Patellar Dislocation: A Randomized Controlled Trial.
A lateral patellar dislocation (LPD) is the most common traumatic knee injury with hemarthrosis in children. The redislocation rate is high. Varying operative and nonoperative treatments have been advocated with no consensus on the best treatment. (1) To evaluate if arthroscopic-assisted repair of the medial patellofemoral ligament (MPFL) in patients with an acute first-time traumatic LPD would reduce the recurrence rate and offer better objective/subjective knee function compared with a knee brace without repair. (2) To study the presence of anatomic patellar instability risk factors (APIFs) and their association with a redislocation. Randomized controlled trial; Level of evidence, 1. This was a prospective series of 74 skeletally immature patients aged 9 to 14 years (38 girls and 36 boys; mean age, 13.1 years) with a first-time traumatic LPD, with clinical examinations, radiographs, magnetic resonance imaging, and diagnostic arthroscopic surgery performed within 2 weeks of the index injury. The child was randomized to either (1) a knee brace (KB group) for 4 weeks and physical therapy or (2) arthroscopic-assisted repair (R group) of the MPFL with anchors, 4 weeks with a soft cast splint, and physical therapy. The follow-up time was 2 years. The redislocation rate was significantly lower in the R group than in the KB group at final follow-up: 8 patients (22%) versus 16 patients (43%), respectively ( P = .047). The Knee injury and Osteoarthritis Outcome Score for children sport/play and quality of life subscales had lower scores in the R group compared with the KB group; the significant differences were among those with redislocations. The mean Kujala score was excellent in the KB group (95.9) and good in the R group (90.9). An impaired Limb Symmetry Index (median, 83%) for concentric quadriceps torque at 90 deg/s was found only in the R group. Eighty-one percent of the study patients had ≥2 APIFs. Trochlear dysplasia (trochlear depth <3 mm) had the highest odds ratio for redislocations (2.35 [95% CI, 0.69-8.03]), with no significant association between APIFs and a redislocation. Operative repair of an MPFL injury in the acute phase in skeletally immature children with a primary traumatic LPD significantly reduced the redislocation rate but did not improve subjective or objective knee function compared with a knee brace without repair. The majority of the patients in both groups were satisfied with their knee function. There was a high representation of APIFs, which needs to be considered when evaluating the risk of redislocations. Registration: ISRCTN 39959729 (Current Controlled Trials).


Global synthesis and critical evaluation of pharmaceutical data sets collected from river systems.
Pharmaceuticals have emerged as a major group of environmental contaminants over the past decade but relatively little is known about their occurrence in freshwaters compared to other pollutants. We present a global-scale analysis of the presence of 203 pharmaceuticals across 41 countries and show that contamination is extensive due to widespread consumption and subsequent disposal to rivers. There are clear regional biases in current understanding with little work outside North America, Europe, and China, and no work within Africa. Within individual countries, research is biased around a small number of populated provinces/states and the majority of research effort has focused upon just 14 compounds. Most research has adopted sampling techniques that are unlikely to provide reliable and representative data. This analysis highlights locations where concentrations of antibiotics, cardiovascular drugs, painkillers, contrast media, and antiepileptic drugs have been recorded well above thresholds known to cause toxic effects in aquatic biota. Studies of pharmaceutical occurrence and effects need to be seen as a global research priority due to increasing consumption, particularly among societies with aging populations. Researchers in all fields of environmental management need to work together more effectively to identify high risk compounds, improve the reliability and coverage of future monitoring studies, and develop new mitigation measures.


Improving management of type 2 diabetes in South Asian patients: a systematic review of intervention studies.
Optimal control of type 2 diabetes is challenging in many patient populations including in South Asian patients. We systematically reviewed studies on the effect of diabetes management interventions targeted at South Asian patients with type 2 diabetes on glycaemic control. Systematic review of MEDLINE, EMBASE and CINAHL databases for randomised controlled trials (RCTs) and pre-post-test studies (January 1990 to February 2014). Studies were stratified by where interventions were conducted (South Asia vs Western countries). Patients originating from Pakistan, Bangladesh or India with type 2 diabetes. Change in glycated haemoglobin (HbA1c). Secondary end points included change in blood pressure, lipid levels, anthropomorphics and knowledge. 23 studies (15 RCTs) met criteria for analysis with 7 from Western countries (n=2532) and 16 from South Asia (n=1081). Interventions in Western countries included translated diabetes education, additional clinical care, written materials, visual aids, and bilingual community-based peers and/or health professionals. Interventions conducted in South Asia included yoga, meditation or exercise, community-based peers, health professionals and dietary education (cooking exercises). Among RCTs in India (5 trials; n=390), 4 demonstrated significant reductions in HbA1c in the intervention group compared with usual care (yoga and exercise interventions). Among the 4 RCTs conducted in Europe (n=2161), only 1 study, an education intervention of 113 patients, reported a significant reduction in HbA1c with the intervention. Lipids, blood pressure and knowledge improved in both groups with studies from India more often reporting reductions in body mass index and waist circumference. Overall, there was little improvement in HbA1c level in diabetes management interventions targeted at South Asians living in Europe compared with usual care, although other outcomes did improve. The smaller studies in India demonstrated significant improvements in glycaemic and other end points. Novel strategies are needed to improve glycaemic control in South Asians living outside of India.


Signalling cascades in mechanotransduction: cell-matrix interactions and mechanical loading.
Mechanical loading of articular cartilage stimulates the metabolism of resident chondrocytes and induces the synthesis of molecules to maintain the integrity of the cartilage. Mechanical signals modulate biochemical activity and changes in cell behavior through mechanotransduction. Compression of cartilage results in complex changes within the tissue including matrix and cell deformation, hydrostatic and osmotic pressure, fluid flow, altered matrix water content, ion concentration and fixed charge density. These changes are detected by mechanoreceptors on the cell surface, which include mechanosensitive ion channels and integrins that on activation initiate intracellular signalling cascades leading to tissue remodelling. Excessive mechanical loading also influences chondrocyte metabolism but unlike physiological stimulation leads to a quantitative imbalance between anabolic and catabolic activity resulting in depletion of matrix components. In this article we focus on the role of mechanical signalling in the maintenance of articular cartilage, and discuss how alterations in normal signalling can lead to pathology.


Effect of traumatic injury on membrane phosphatase activity in cat spinal cord.
The enzymatic activities of the spinal cord membrane phosphatases, (Na,K)ATPase, KpNPPase, 5'-nucleotidase, MgATPase, and MgpNPPase, were determined following contusion injury. Within 30 min after injury, the activities of (Na,K)ATPase, KpNPPase, and 5'-nucleotidase were suppressed at the injury site and remained suppressed for 24 h. Considerable loss of (Na,K)ATPase and KpNPPase activity was seen along the longitudinal axis of the spinal cord for the first 4 h after injury, whereas at 24 h after injury, there was almost complete restitution in the activity of those enzymes. No similar changes in activity were observed for the MgATPase, whereas the activity of the MgpNPPase progressively worsened with time at the injury site. The deduce the pathobiochemical process that accounts for the loss of spinal membrane phosphatase activity, spinal cord membranes were incubated in vitro in the presence of a superoxide anion-generating system, as well as in the presence of trypsin and lysolecithin. It was found that superoxide anions inhibited only the activity of transport phosphatase, KpNPPase, whereas trypsin inhibited the activity of both KpNPPase and MgpNPPase. No inhibition of 5'-nucleotidase was observed by superoxide anions; however, the activity of 5'-nucleotidase was enhanced by trypsin, lysolecithin, or both in concert. These results suggest that the pathobiochemical process that accounts for the loss of spinal membrane phosphatase activity that follows injury can be attributed to the concerted effects of free radical attack as well as the activation of proteolytic and lipolytic enzymes. Inactivation of spinal membrane phosphatase can occur by direct attack of these processes on the membrane or by loss of membrane material, e.g., solubilization.


Usefulness of heparin in initial management of patients with recent transient ischemic attacks.
We evaluated the efficacy of short-term intravenous heparin therapy in 74 patients with recent transient ischemic attacks (TIAs). The patients were treated after hospitalization until operation or long-term medical treatment was instituted. Heparin was given in a continuous infusion to maintain an activated partial thromboplastin time of 1 1/2 to 2 1/2 times control values. During the treatment period, 12 patients (16.2%) had recurrent TIAs and five (6.8%) had cerebral infarction. Bleeding complications occurred in nine patients (12.2%). In this limited series, heparin did not prevent recurrent TIAs or cerebral infarction among high-risk patients with recent TIAs.


Differential expression and characterization of proto-oncogene product Ha-Ras GTPase in camel tissues.
Pas proto-oncogene product is known to be involved in transducing signals for growth, differentiation and oncogenesis in mammalian cells. Using a monoclonal antibody to human Ha-Ras, a camel homolog of Ha-Ras protein having an apparent molecular mass of 21 kDa was identified. The expression level of Ha-Ras protein in various tissues of camel was compared with that of mouse tissues. In camel it was found that expression of Ha-Ras protein was highest in the kidney and moderate in the liver. Expression of Ha-Ras in camel lung, testis, spleen, heart, brain, intestine and muscle was found to be very low. While Ha-Ras expression in mouse was found to be highest in the intestine. A moderate expression of Ha-Ras was found in mouse testis, kidney and heart. The kidney tissue extract of camel was immunoprecipitated using the same human Ha-Ras antibody. Biochemical characterization of the immunoprecipitate revealed that like most other G proteins, the camel homolog of Ras is a GTPase. The GTPase activity was found to be stimulated specifically by recombinant human Ras GAP p120 and neurofibromin. It suggests that both camel and human share the same Ras mediated growth signaling process and that human Ras GAP might be able to complement camel Ras GAP function. Camel homolog of Raf-1 and MAP kinase (member of Ras signaling pathway) were also identified by immunoblot. This is the first demonstration showing the existence of a Ras mediated growth signal transduction pathway in camel.


Tracheostomy in Mechanically Ventilated Patients With SARS-CoV-2-ARDS: Focus on Tracheomalacia.
The SARS-CoV-2 pandemic increased the number of patients needing invasive mechanical ventilation, either through an endotracheal tube or through a tracheostomy. Tracheomalacia is a rare but potentially severe complication of mechanical ventilation, which can significantly complicate the weaning process. The aim of this study was to describe the strategies of airway management in mechanically ventilated patients with respiratory failure due to SARS-CoV-2, the incidence of severe tracheomalacia, and investigate the factors associated with its occurrence. This retrospective, single-center study was performed in an Italian teaching hospital. All adult subjects admitted to the ICU between February 24, 2020, and June 30, 2020, treated with invasive mechanical ventilation for respiratory failure caused by SARS-CoV-2 were included. Clinical data were collected on the day of ICU admission, whereas information regarding airway management was collected daily. A total of 151 subjects were included in the study. On admission, ARDS severity was mild in 21%, moderate in 62%, and severe in 17% of the cases, with an overall mortality of 40%. A tracheostomy was performed in 73 (48%), open surgical technique in 54 (74%), and percutaneous Ciaglia technique in 19 (26%). Subjects who had a tracheostomy performed had, compared to the other subjects, a longer duration of mechanical ventilation and longer ICU and hospital stay. Tracheomalacia was diagnosed in 8 (5%). The factors associated with tracheomalacia were female sex, obesity, and tracheostomy. In our population, approximately 50% of subjects with ARDS due to SARS-CoV-2 were tracheostomized. Tracheostomized subjects had a longer ICU and hospital stay. In our population, 5% were diagnosed with tracheomalacia. This percentage is 10 times higher than what is reported in available literature, and the underlying mechanisms are not fully understood.


Korean Red Ginseng Extract Enhances the Anticancer Effects of Sorafenib through Abrogation of CREB and c-Jun Activation in Renal Cell Carcinoma.
Although application of sorafenib in the treatment of human renal cell carcinoma (RCC) remains one of the best examples of successful targeted therapy, majority of RCC patients suffer from its side effects as well as develop resistance to this targeted therapy. Thus, there is a need to promote novel alternative therapies for the treatment of RCC. In this study, we investigated whether Korean red ginseng extract (KRGE) could inhibit the proliferation and induce chemosensitization in human renal cancer cells. Also, we used a human phospho-antibody array containing 46 antibodies against signaling molecules to examine a subset of phosphorylation events after KRGE and sorafenib combination treatment. Korean red ginseng extract suppressed the proliferation of two RCC cell lines; activated caspase-3; caused poly(ADP-ribose) polymerase cleavage; abrogated the expression of B-cell lymphoma 2, B-cell lymphoma extra large, survivin, inhibitors of apoptosis proteins-1/2, cyclooxygenase-2, cyclin D1, matrix metallopeptidase-9, and vascular endothelial growth factor; and upregulated pro-apoptotic gene products. Interestingly, KRGE enhanced the cytotoxic and apoptotic effects of sorafenib in RCC cells. The combination treatment of KRGE and sorafenib more clearly suppressed cyclic adenosine monophosphate response element-binding protein and c-Jun phosphorylation and induced phosphorylation of p53 than did the individual treatment regimen. Our results clearly demonstrate that KRGE can enhance the anticancer activity of sorafenib and may have a substantial potential in the treatment of RCC. Copyright © 2017 John Wiley & Sons, Ltd.


Permeability of lactating-rat mammary gland Golgi membranes to monosaccharides.
The Golgi-membrane vesicles present in particulate preparations of lactating rat mammary gland were biosynthetically loaded with [14C]lactose. This lactose was effectively retained by particles sedimented after exposure to 0.25 M-disaccharide, but was partly lost after exposure to 0.25 M-glucose or other solutes of similar size. Loss of lactose was time-, concentration- and temperature-dependent and varied with the solute structure. This behaviour is ascribed to the presence of protein in the Golgi membrane, forming a specific carrier or channel that serves to supply glucose for lactose synthesis.


Quality of care and risk of incident atrial fibrillation in patients with newly diagnosed heart failure: a nationwide cohort study.
Incident atrial fibrillation (AF) is an adverse prognostic indicator in heart failure (HF); identifying modifiable targets may be relevant to reduce the incidence and morbidity of AF. Therefore, we examined the association between quality of HF care and risk of AF. Using the Danish Heart Failure Registry, we conducted a nationwide registry-based cohort study of all incident HF patients diagnosed between 2008 and 2018 and without history of AF. Quality of HF care was assessed by seven process performance measures, including echocardiographic examination, New York Heart Association classification, treatment with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta-blockers, and mineralocorticoid antagonists, physical training, and patient education. In the main analysis, we examined adherence with all measures in a cohort of 25 100 patients (mean age 68.5 ± 13.2 years; 33.6% women). The median follow-up was 3.1 years. Cox proportional hazard regressions estimated the hazard ratios (HRs) with 95% confidence intervals (95% CIs) between the number of fulfilled measures and incident AF. In a multivariable-adjusted analysis with 0 fulfilled performance measures as reference, the HRs (95% CIs) were 1: 0.78 (0.61-1.00), 2: 0.63 (0.49-0.80), 3: 0.53 (0.36-0.80), 4: 0.64 (0.44-0.94), 5: 0.56 (0.39-0.82), 6: 0.51 (0.35-0.74), and 7: 0.49 (0.33-0.73), with a significant decreasing linear trend (P < 0.001). In patients with incident HF, fulfilment of guideline-based process performance measures was associated with decreased long-term risk of AF. This study supports initiatives to improve the quality of care for patients with HF to prevent incident AF.


Zosteriform spread of herpes simplex virus type 2 genital infection in the guinea-pig.
A model of herpes simplex virus type 2 (HSV-2) infection was developed in the guinea-pig that permits investigation of the role of neural spread of virus in the pathogenesis of genital skin disease. After HSV-2 inoculation of an abraded area lateral to the external genital skin, virus was first detected in the ipsilateral (to the inoculation site) peripheral nerves or genital skin on day 2 or 3 post-inoculation followed by detection in the ipsilateral dorsal root ganglia and spinal cord on day 3 or 4. Virus also spread to the contralateral dorsal root ganglia, contralateral peripheral nerves and contralateral genital skin on day 4 or 5 although lesions were only rarely detected on the contralateral side. Genital skin lesions first developed on day 5 and were followed by the development of lesions along the medial aspect of the ipsilateral hindlimb. Virus was first detected in the vaginal vault on day 4 or 5. The development of lesions appeared to be unrelated to vaginal virus replication but was associated with the recovery of virus from peripheral nerves. Recurrent genital skin lesions were seen more commonly on the inoculated side than the contralateral side. Since the development of skin lesions appeared to result from virus emerging from nerve endings, an event similar to the terminal event that is believed to be involved in the development of recurrent lesions, we now have a model which may be useful in further exploring the pathogenesis of herpetic disease.


Anemia among Schoolchildren with Malaria and Soil-Transmitted Helminth Coinfections after Repeated Rounds of Mass Drug Administration in Muheza District, Tanzania.
Coinfections with malaria and soil-transmitted helminths (STHs) has been common among school-aged children in Tanzania. However, after a countrywide scaling up of interventions for malaria and STHs, there are limited data on the prevalence of malaria-STH coinfections and its effect on anemia in schoolchildren in Tanzania. We assessed the distribution and risk factors for malaria, STHs, and malaria-STH coinfections, and its relation to anemia among 445 primary schoolchildren in Muheza district. A semi-structured questionnaire was used to collect demographic characteristics of the children. Malaria rapid diagnostic test (mRDT) was used to diagnose malaria infection. Soil-transmitted helminths were diagnosed using the Kato-Katz technique. Primary outcome was anemia, defined as hemoglobin concentration < 11 g/dL. Chi-square (χ2) or Fisher's exact tests, Kruskal-Wallis or t-test, and logistic models were used as appropriate. Overall, the prevalence of malaria, STHs, malaria-STH coinfection, and anemia were 18.4%, 6.1%, 1.6%, and 19.8%, respectively. Anemic children were more likely to have malaria (adjusted odds ratio [aOR] = 4.538, 95% CI: 2.189-9.409), whereas frequent use of bed nets was associated with reduced risk of malaria (aOR = 0.234, 95% CI: 0.130-0.42). On the other hand, not always using latrines and eating raw uncooked food increased the risk of STH infection. The prevalence of anemia was high and was associated with both malaria and malaria-STH infections, therefore calling for more integrated malaria-STH control approaches to target school-aged children.


Evaluation of the LightCycler methicillin-resistant Staphylococcus aureus (MRSA) advanced test for detection of MRSA nasal colonization.
Rapid detection of methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization is crucial for the prevention and control of MRSA infections in health care settings. The LightCycler MRSA Advanced Test (Roche Diagnostics) is a commercially available real-time PCR assay for direct detection of MRSA nasal colonization by targeting of the staphylococcal cassette chromosome mec (SCCmec)-orfX junction. The diagnostic performance of the assay was compared with that of ChromID MRSA agar (bioMérieux) culture and an in-house duplex real-time PCR assay. Among 1,246 nasal swab specimens collected from 2 general hospitals in Hong Kong, 174 (14%) were considered true positive for MRSA. Chromogenic culture and the in-house real-time PCR assay identified 147 (84.5%) and 133 (76.4%) true-positive cases with specificities of 100% and 98.6%, respectively. Based on the target melting temperature (Tm) values (57.0 to 62.0 °C) defined by the manufacturer, the LightCycler MRSA Advanced Test identified only 85 (48.9%) true-positive specimens. Interestingly, an additional 60 (34.5%) true-positive specimens were detected despite atypical Tm values of 55 °C, providing overall sensitivity and specificity values of 83.3% and 99%, respectively. Among isolates with Tm values of 55 °C, most were typed as clonal complex 45 (CC45). By sequence analysis of the SCCmec-orfX junction, characteristic single-nucleotide polymorphisms (SNPs) were identified only in isolates with Tm values of 55°C and not in those with typical Tm values. It is conceivable that those SNPs were located inside the target region of the proprietary hybridization probes, which resulted in a Tm shift in the melting curve analysis. Our study highlights the importance of a global evaluation of commercial kits so that the interpretation algorithm covers different lineages of MRSA clones prevalent in various geographical regions.


RNase H-Driven crRNA Switch Circuits for Rapid and Sensitive Detection of Various Analytical Targets.
The clustered regularly interspaced short palindromic repeats (CRISPR/Cas12a) system has exhibited great promise in the rapid and sensitive molecular diagnostics for its trans-cleavage property. However, most CRISPR/Cas system-based detection methods are designed for nucleic acids and require target preamplification to improve sensitivity and detection limits. Here, we propose a generic crRNA switch circuit-regulated CRISPR/Cas sensor for the sensitive detection of various targets. The crRNA switch is engineered and designed in a blocked state but can be activated in the presence of triggers, which are target-induced association DNA to initiate the trans-cleavage activity of Cas12a for signal reporting. Additionally, RNase H is introduced to specifically hydrolyze RNA duplexed with the DNA trigger, resulting in the regeneration of the trigger to activate more crRNA switches. Such a combination provides a generic and sensitive strategy for the effective sensing of the p53 sequence, thrombin, and adenosine triphosphate. The design is incorporated with nucleic acid nanotechnology and extensively broadens the application scope of the CRISPR technology in biosensing.


Prevalence of Co-occurring Medical and Behavioral Conditions/Symptoms Among 4- and 8-Year-Old Children with Autism Spectrum Disorder in Selected Areas of the United States in 2010.
We compared the prevalence of various medical and behavioral co-occurring conditions/symptoms between 4- and 8-year-olds with autism spectrum disorder (ASD) from five sites in the Autism and Developmental Disabilities Monitoring Network during the 2010 survey year, accounting for sociodemographic differences. Over 95% of children had at least one co-occurring condition/symptom. Overall, the prevalence was higher in 8- than 4-year-olds for 67% of co-occurring conditions/symptoms examined. Further, our data suggested that co-occurring conditions/symptoms increased or decreased the age at which children were first evaluated for ASD. Similarly, among the 8-year-olds, the prevalence of most co-occurring conditions/symptoms was higher in children with a previous ASD diagnosis documented in their records. These findings are informative for understanding and screening co-occurring conditions/symptoms in ASD.


Targeting Pancreatic Cancer Cells and Stellate Cells Using Designer Nanotherapeutics in vitro.
Pancreatic cancer (PC) is characterized by a robust desmoplastic environment, which limits the uptake of the standard first-line chemotherapeutic drug gemcitabine. Enhancing gemcitabine delivery to the complex tumor microenvironment (TME) is a major clinical challenge. Molecular crosstalk between pancreatic cancer cells (PCCs) and pancreatic stellate cells (PSCs) plays a critical role in desmoplastic reaction in PCs. Herein, we report the development of a targeted drug delivery system to inhibit the proliferation of PCCs and PSCs in vitro. Using gold nanoparticles as the delivery vehicle, the anti-EGFR antibody cetuximab (C225/C) as a targeting agent, gemcitabine as drug and polyethylene glycol (PEG) as a stealth molecule, we created a series of targeted drug delivery systems. Fabricated nanoconjugates were characterized by various physicochemical techniques such as UV-Visible spectroscopy, transmission electron microscopy, HPLC and instrumental neutron activation analysis (INAA). Targeted gemcitabine delivery systems containing mPEG-SH having molecular weights of 550 Da or 1000 Da demonstrated superior efficacy in reducing the viability of both PCCs and PSCs as compared to their non-targeted counterparts. EGFR-targeted pathway was further validated by pre-treating cells with C225 followed by determining cellular viability. Taken together, in our current study we have developed a PEGylated targeted nanoconjugate ACG44P1000 that showed enhanced selectivity towards pancreatic cancer cells and pancreatic stellate cells, among others, for gemcitabine delivery. We will investigate the ability of these optimized conjugates to inhibit desmoplasia and tumor growth in vivo in our future studies.


Appetitive behavior of the honey bee Apis mellifera in response to phenolic compounds naturally found in nectars.
The honey bee is the most frequently used species in pollination services for diverse crops. In onion crops (Allium cepa), however, bees avoid visiting certain varieties, being attracted differently to male sterile (MS) and fertile (OP) lines. These differences might be based on the phenolic profiles of the cultivars' nectars. To understand the relationship between nectar composition and pollinator attraction to different onion lines, we tested sensory and cognitive abilities and palatability in honey bees exposed to MS and OP onion nectars and sugar solutions mimicking them. We evaluated the proboscis extension response (PER) after antennal contact (unconditioned response) to MS or OP onion nectars, finding no statistical differences, which indicates similar gustatory perception for the two nectars. We also performed food uptake assays to test palatability of different artificial nectars, considering their flavonoids and potassium content. The presence of potassium decreased the palatability of the artificial nectars. Finally, we evaluated the bees' cognitive abilities when the reward (unconditioned stimulus) offered during conditioning PER assays presents differences in composition. We found that potassium by itself impaired learning; however, such impairment was even higher when naringenin and quercetin were added in the unconditioned stimulus (MS nectar mimic). Interestingly, potassium together with luteolin (OP nectar mimic) improved learning. Our study demonstrates that the differences in the nectars' flavonoid profiles combined with their high potassium content could explain the previously reported differences in attractiveness between onion lines, suggesting an important role of nectar compounds other than sugars for the attractiveness of flowers to pollinators.


Nucleoside analog stavudine depletes mitochondrial DNA with no organelle loss in mouse oocytes.
Nucleoside reverse transcriptase inhibitors (NRTIs) are the basis of antiretroviral treatment of HIV-positive patients. Several studies have shown decreased fertility and fecundity among HIV-positive women under antiretroviral treatment. Oocyte impaired competence has been hypothesized to be one of the main mechanisms underlying of this decreased fertility. NRTI side effects are thought to be due to the induced mitochondrial dysfunction. Stavudine, a widely used NRTI, causes persistent mitochondrial damage in various tissues. In order to gain insights into possible mechanisms of HIV-related diminished fertility, we studied the effects of stavudine on mouse oocyte mitochondria. Mitochondrial volume, protein assay and ATP contents were unaltered by stavudine treatment, but we found mitochondrial Cox I depletion in liver and oocytes. Our findings suggest that stavudine induces mtDNA depletion without organelle loss in mouse oocytes. The decrease in Cox I DNA in treated oocytes likely points to mitochondrial dysfunction, which can impair chances of pregnancy and embryo viability. We propose that the competence of oocytes depends primarily on functional capacity of mitochondria and less on their number.


Spinal infections. Diagnosis and treatment.
Spinal infections encompass a broad spectrum of pathology. Any element of the spine, the vertebrae, disks, surrounding soft tissues, potential spaces, or the cord itself may be involved solely, or more commonly, in combination. Staphylococcus aureus is the organism most frequently found, with Gram negative bacteria often cited in association with infections of the urinary tract and in intravenous drug abusers. Early diagnosis and treatment are essential for optimal outcomes. In some cases, the only necessary treatment consists of parenteral antibiotics and immobilization. However, certain instances require operative intervention. The goals of treatment for any infection of the spine are: early diagnosis with identification of the offending organism, preservation of neurological function or cessation of progressive neurologic deficit, and complete eradication of the infection with a pain-free, stable spine.


Inference for Seemingly Unrelated Varying-Coefficient Nonparametric Regression Models.
This paper is concerned with the inference of seemingly unrelated (SU) varying-coefficient nonparametric regression models. We propose an estimation for the unknown coefficient functions, which is an extension of the two-stage procedure proposed by Linton, et al. (2004) in the longitudinal data framework where they focused on purely nonparametric regression. We show the resulted estimators are asymptotically normal and more efficient than those based on only the individual regression equation even when the error covariance matrix is homogeneous. Another focus of this paper is to extend the generalized likelihood ratio technique developed by Fan, Zhang and Zhang (2001) for testing the goodness of fit of models to the setting of SU regression. A wild block bootstrap based method is used to compute p-value of the test. Some simulation studies are given in support of the asymptotics. A real data set from an ongoing environmental epidemiologic study is used to illustrate the proposed procedures.


Wireless power transfer system rigid to tissue characteristics using metamaterial inspired geometry for biomedical implant applications.
Conventional resonant inductive coupling wireless power transfer (WPT) systems encounter performance degradation while energizing biomedical implants. This degradation results from the dielectric and conductive characteristics of the tissue, which cause increased radiation and conduction losses, respectively. Moreover, the proximity of a resonator to the high permittivity tissue causes a change in its operating frequency if misalignment occurs. In this report, we propose a metamaterial inspired geometry with near-zero permeability property to overcome these mentioned problems. This metamaterial inspired geometry is stacked split ring resonator metamaterial fed by a driving inductive loop and acts as a WPT transmitter for an in-tissue implanted WPT receiver. The presented demonstrations have confirmed that the proposed metamaterial inspired WPT system outperforms the conventional one. Also, the resonance frequency of the proposed metamaterial inspired TX is negligibly affected by the tissue characteristics, which is of great interest from the design and operation prospects. Furthermore, the proposed WPT system can be used with more than twice the input power of the conventional one while complying with the safety regulations of electromagnetic waves exposure.


Can patients taking opioids drive safely? A structured evidence-based review.
A structured evidence-based literature review was completed to determine if there was epidemiological evidence of an association of opioid use and intoxicated driving, motor vehicle accidents (MVA) and MVA fatalities; to rate the quality of this research evidence according to Agency for Health Care Policy and Research (AHCPR) type of evidence and strength and consistency of the evidence rating scales; and according to this evidence determine whether patients taking opioids can drive safely. Relevant references were located from Medline, Psychological Abstracts, Science Citation Index and the National Library of Medicine Data Query databases by appropriate subject headings. A manual search was also performed utilizing the reference lists of the retrieved articles. All references relating to intoxicated driving, MVA and MVA fatalities were retrieved and reviewed in detail. Of these, references addressing opioid use were isolated and research information from these references was placed into tabular form under three major headings: Intoxicated driving and opioids; MVA and opioids; and MVA fatalities and opioids. Data were extracted from these references according to the following format: research question addressed, sample size, statistical analysis and results. The type of evidence each study represented was rated according to the AHCPR type of evidence rating scale. Each research area (intoxicated driving, MVA, MVA fatalities) represented by all the studies in each table was then rated utilizing the strength and consistency of the evidence AHCPR rating scale. Of the 6 reports addressing intoxicated driving, 5 were well designed non-experimental studies and one was a well designed experimental study. All studies in this group reported a prevalence for opioid use which was approximately 1/10 that of the point prevalence use for opioids in the general population. This evidence indicated that opioids probably are not associated with intoxicated driving. Overall, the evidence indicates that opioids are not associated with MVA. Of the 9 studies addressing MVA, 5 were well designed quasi-experimental studies and 4 were well designed experimental studies. All reports in this group except one indicated that opioids are not associated with MVA. Of the 10 studies addressing MVA fatalities, 10 represented Type IV studies. For the vast majority of the studies, the prevalence percentages for an opioid association with MVA fatalities was 1/5 that of the point prevalence percentage for opioid use reported in the general population. Only 1 study reported a possible association between opioid use and MVA fatalities. The evidence in this review indicates that opioids do not appear to be associated with intoxicated driving, MVA and MVA fatalities, and consistently indicated that opioids are not associated with MVA. Although the comparison of point prevalence rates to the point prevalence may be problematic, the results of this systematic review support the contention that patients taking opioids may be allowed to drive. As in all clinical decisions, this determination should be individualized according to clinical factors.


GLABROUS INFLORESCENCE STEMS3 binds to and activates RHD2 and RHD4 genes to promote root hair elongation in Arabidopsis.
Root hairs are crucial in the uptake of essential nutrients and water in plants. This study showed that a zinc finger protein, GIS3 is involved in root hair growth in Arabidopsis. The loss-of-function gis3 and GIS3 RNAi transgenic line exhibited a significant reduction in root hairs compared to the wild type. The application of 1-aminocyclopropane-1-carboxylic acid (ACC), an exogenous ethylene precursor, and 6-benzyl amino purine (BA), a synthetic cytokinin, significantly restored the percentage of hair cells in the epidermis in gis3 and induced GIS3 expression in the wild type. More importantly, molecular and genetic studies revealed that GIS3 acts upstream of ROOT HAIR DEFECTIVE 2 (RHD2) and RHD4 by binding to their promoters. Furthermore, exogenous ACC and BA application significantly induced the expression of RHD2 and RHD4, while root hair phenotype of rhd2-1, rhd4-1, and rhd4-3 was insensitive to ACC and BA treatment. We can therefore conclude that GIS3 modulates root hair development by directly regulating RHD2 and RHD4 expression through ethylene and cytokinin signals in Arabidopsis.


Comparison of statistical and clinical predictions of functional outcome after ischemic stroke.
To determine whether the predictions of functional outcome after ischemic stroke made at the bedside using a doctor's clinical experience were more or less accurate than the predictions made by clinical prediction models (CPMs). A prospective cohort study of nine hundred and thirty one ischemic stroke patients recruited consecutively at the outpatient, inpatient and emergency departments of the Western General Hospital, Edinburgh between 2002 and 2005. Doctors made informal predictions of six month functional outcome on the Oxford Handicap Scale (OHS). Patients were followed up at six months with a validated postal questionnaire. For each patient we calculated the absolute predicted risk of death or dependence (OHS≥3) using five previously described CPMs. The specificity of a doctor's informal predictions of OHS≥3 at six months was good 0.96 (95% CI: 0.94 to 0.97) and similar to CPMs (range 0.94 to 0.96); however the sensitivity of both informal clinical predictions 0.44 (95% CI: 0.39 to 0.49) and clinical prediction models (range 0.38 to 0.45) was poor. The prediction of the level of disability after stroke was similar for informal clinical predictions (ordinal c-statistic 0.74 with 95% CI 0.72 to 0.76) and CPMs (range 0.69 to 0.75). No patient or clinician characteristic affected the accuracy of informal predictions, though predictions were more accurate in outpatients. CPMs are at least as good as informal clinical predictions in discriminating between good and bad functional outcome after ischemic stroke. The place of these models in clinical practice has yet to be determined.


Acute surgical management in idiopathic intracranial hypertension.
Idiopathic intracranial hypertension is a headache syndrome with progressive symptoms of raised intracranial pressure. Most commonly, it is a slow process where surveillance and medical management are the main treatment modalities. We describe herein an acute presentation with bilateral sixth nerve palsies, papilloedema and visual deterioration, where acute surgical intervention was a vision-saving operation.


Cell fate respecification and cell division orientation drive intercalary regeneration in Drosophila wing discs.
To understand the cellular parameters that govern Drosophila wing disc regeneration, we genetically eliminated specific stripes of the wing disc along the proximodistal axis and used vein and intervein markers to trace tissue regeneration. We found that veins could regenerate interveins and vice versa, indicating respecification of cell fates. Moreover, respecification occurred in cells close to the wound. The newly generated domains were intercalated to fill in the missing parts. This intercalation was driven by increased proliferation, accompanied by changes in the orientation of the cell divisions. This reorientation depended on Fat (Ft) and Crumbs (Crb), which acted, at least partly, to control the activity of the effector of the Hippo pathway, Yorkie (Yki). Increased Yki, which promotes proliferation, affected the final shape and size. Heterozygous ft or crb, which normally elicit size and shape defects in regenerated wings, could be rescued by yki heterozygosity. Thus, Ft and Crb act as sensors to drive cell orientation during intercalary regeneration and control Yki levels to ensure a proper balance between proliferation and cell reorientation. We propose a model based on intercalation of missing cell identities, in which a coordinated balance between orientation and proliferation is required for normal organ shape and size.


The effects of L-carnitine supplementation on glycemic control: a systematic review and meta-analysis of randomized controlled trials.
The findings of trials investigating the effect of L-carnitine administration on glycemic control are controversial. This meta-analysis of randomized controlled trials (RCTs) was performed to explore the effects of L-carnitine intake on glycemic control. Two authors independently searched electronic databases including MEDLINE, EMBASE, Cochrane Library, Web of Science, PubMed and Google scholar from 1990 until February 2019, in order to find relevant RCTs. 37 studies with 44 effect sizes met the inclusion criteria and were eligible for the meta-analysis. L-carnitine supplementation resulted in a significant reduction in fasting plasma glucose (FPG) (WMD: -4.57; 95 % CI: -6.88, -2.25), insulin (WMD: -1.21; 95 % CI: -1.85, -0.57), homeostatic model assessment for insulin resistance (HOMA-IR) (WMD: -0.67; 95 % CI: -0.90, -0.44) and HbA1C concentrations (WMD: -0.30; 95 % CI: -0.47, -0.13). L-Carnitine supplementation significantly reduced FPG, insulin, HOMA-IR, and HbA1c levels.


Role of the oropharynx in regulation of glycemia.
Previous studies have demonstrated that reflexes originating from the oral cavity at the start of food intake are necessary to ensure a normal glucose tolerance. In our experiment, the underlying mechanisms of these reflexes were studied in conscious, freely moving rats bearing chronic catheters. A double-isotope technique was used to measure, under non-steady-state conditions, rates of total glucose appearance (total Ra), total glucose disappearance (Rd), gut glucose absorption (gut Ra), hepatic glucose production (HGP), and the metabolic clearance rate of glucose (MCRg). In random order, 1 wk apart, rats either spontaneously drank 1 ml of a 60% glucose solution or were given the same dose into the stomach via a chronic gastric catheter. Glycemia and insulinemia were lower when glucose was taken orally than when the same amount of the substrate was administered intragastrically. Total Ra after glucose administration was the same in both groups throughout the experiment. Despite lower insulin and glucose values, the increase in Rd was initially higher in the oral group than in the intragastric group. This was accompanied by initial higher MCRg values in the oral group than in animals that received the glucose load directly into their stomachs. We conclude that a series of reflexes elicited by oral glucose ingestion improve glucose tolerance by increasing the efficiency of glucose disposal in the early stages after a glucose load, with a smaller amount of insulin released.


Translocon closure to Ca2+ leak in proliferating vascular smooth muscle cells.
Vascular smooth muscle cells have a proliferative phenotype that is important in vascular development, adaptation, and disease. Intracellular calcium handling is thought to play pivotal roles in determining the properties of these cells, and thus previously unrecognized mechanisms for transmembrane calcium movement are of potential interest. An unsolved question is the mechanism of constitutive (passive) calcium leak from the intracellular stores. Studies of other cell types have suggested that the translocon is a calcium leak pathway. Here we investigated the contribution of the translocon in proliferating vascular smooth muscle cells. Calcium leak into the cytoplasm was measured using fura-2, and protein synthesis was measured using radioactive methionine. Puromycin, emetine, and anisomycin are chemicals that inhibit protein synthesis, acting via the translocon; all three agents strongly inhibited protein synthesis in the smooth muscle cells within 1 h. Puromycin, which opens the translocon, evoked a transient increase in cytoplasmic calcium that was similar in amplitude to the calcium rise evoked by thapsigargin. The puromycin effect was abolished by thapsigargin. The treatment of cells for 1 h with emetine or anisomycin, which close the translocon, inhibited the calcium release evoked by puromycin but not the calcium release evoked by extracellular ATP, endothelin-1, or the calcium ionophore ionomycin. Thapsigargin-evoked calcium rises were slightly suppressed by emetine but unaffected by puromycin or anisomycin. The data suggest that the translocon has the capacity to act as a calcium leak pathway in the ribosomal endoplasmic reticulum but that it is normally closed and lacks relevance to physiological calcium leak mechanisms.


Childhood maltreatment history, posttraumatic relational sequelae, and prenatal care utilization.
To test the hypothesis that childhood maltreatment history would be associated with inadequate prenatal care utilization. A post-hoc analysis of a prospective cohort study of the effects of post traumatic stress disorder (PTSD) on pregnancy outcomes. Recruitment took place via prenatal clinics from three academic health systems in southeast Michigan. This analysis included 467 diverse, nulliparous, English-speaking adult women expecting their first infants. Data were gathered from structured telephone interviews at two time points in pregnancy and from prenatal medical records. Contrary to our hypothesis, history of childhood maltreatment was associated with better likelihood of using adequate prenatal care. Risk for inadequate prenatal care occurred in association with the posttraumatic stress and interpersonal sensitivity that can result from maltreatment, with low alliance with the maternity care provider, and with public insurance coverage. Prior mental health treatment was associated with using adequate prenatal care. When childhood maltreatment survivors were resilient or had used mental health treatment, they were more likely to utilize adequate prenatal care. The maternity care relationship or service delivery model (e.g., no continuity of care) as well as structural factors may adversely affect utilization among PTSD-affected survivors. Since inadequate care was associated with adverse outcomes, further studies of these modifiable factors are warranted.


[Characteristics of program-type movements in lesions of various cerebellar systems in man].
Mechanisms of participation of two main cerebellar systems, i.e. lateral and intermedial ones, in control of preprogrammed voluntary movements have been studied in man. Related movements were analyzed in healthy subjects and in groups of patients suffering from different forms of cerebellar and pyramidal disorders. The task consisted of series of dorsal or plantar flexions of foot of increasing amplitudes with minimal amplitude of neighbouring movements. It was shown that both the lateral and intermedial cerebellar lesions were followed by deep alterations in program motor control mechanisms, however the intensity and specific features of alterations in two groups under study differed significantly. In patients suffering from pyramidal lesions the ability to perform programmed movements was lost completely.


Microvesicles transfer mitochondria and increase mitochondrial function in brain endothelial cells.
We have demonstrated, for the first time that microvesicles, a sub-type of extracellular vesicles (EVs) derived from hCMEC/D3: a human brain endothelial cell (BEC) line transfer polarized mitochondria to recipient BECs in culture and to neurons in mice acute brain cortical and hippocampal slices. This mitochondrial transfer increased ATP levels by 100 to 200-fold (relative to untreated cells) in the recipient BECs exposed to oxygen-glucose deprivation, an in vitro model of cerebral ischemia. We have also demonstrated that transfer of microvesicles, the larger EV fraction, but not exosomes resulted in increased mitochondrial function in hypoxic endothelial cultures. Gene ontology and pathway enrichment analysis of EVs revealed a very high association to glycolysis-related processes. In comparison to heterotypic macrophage-derived EVs, BEC-derived EVs demonstrated a greater selectivity to transfer mitochondria and increase endothelial cell survival under ischemic conditions.


Use of cone beam computed tomography in periodontology.
Diagnosis of periodontal disease mainly depends on clinical signs and symptoms. However, in the case of bone destruction, radiographs are valuable diagnostic tools as an adjunct to the clinical examination. Two dimensional periapical and panoramic radiographs are routinely used for diagnosing periodontal bone levels. In two dimensional imaging, evaluation of bone craters, lamina dura and periodontal bone level is limited by projection geometry and superpositions of adjacent anatomical structures. Those limitations of 2D radiographs can be eliminated by three-dimensional imaging techniques such as computed tomography. Cone beam computed tomography (CBCT) generates 3D volumetric images and is also commonly used in dentistry. All CBCT units provide axial, coronal and sagittal multi-planar reconstructed images without magnification. Also, panoramic images without distortion and magnification can be generated with curved planar reformation. CBCT displays 3D images that are necessary for the diagnosis of intra bony defects, furcation involvements and buccal/lingual bone destructions. CBCT applications provide obvious benefits in periodontics, however; it should be used only in correct indications considering the necessity and the potential hazards of the examination.


A position statement from the American Society of Diagnostic and Interventional Nephrology.
A procedure-related complication is an unanticipated adverse event that requires therapy. In order to analyze frequency and severity of complications in the process of quality assurance, it is useful to have a classification of complications, indicating the type and severity. The Clinical Practice Committee of American Society of Diagnostic and Interventional Nephrology has developed a Classification of Complications relating to Hemodialysis Vascular Access Procedures, based on the system first proposed by Beathard in 2006. In this system, the "type" refers to the procedure being performed or vessel entered, and the "grade" is based on the intensity of medical care needed to address the complication. This publication describes 10 Types and 4 Grades of complications.


In vitro fracture resistance of root-filled teeth using new-generation dentine bonding adhesives.
To compare the fracture resistance of root-filled premolar teeth restored with new-generation dentine bonding adhesives. Sixty extracted single-rooted human maxillary premolar teeth were used. Access cavities were prepared, and the roots were instrumented with K-files to an apical size 50 using a step-back technique. Root fillings were accomplished using gutta percha (Sure-Endo, Seoul, Korea) and AH Plus root canal sealer (Dentsply DeTrey, Konstanz, Germany) using the lateral condensation technique. The teeth were then randomly divided into six groups of 10 teeth each. A mesiodistocclusal (MOD) cavity was prepared in the teeth to the level of the canal orifices so that the thickness of the buccal wall of the teeth measured 2 mm at the occlusal surface and 3 mm at the cemento-enamel junction. Preparations were restored using the following adhesive systems: Etch & Prime 3.0 (Degussa AG, Hanau, Germany), Clearfil SE Bond (Kuraray, Osaka, Japan), Prompt L-Pop (ESPE, Seefeld, Germany), Panavia F (Kuraray, Osaka, Japan), Optibond Plus (Kerr, Orange, CA, USA) and Admira Bond (Voco, Cuxhaven, Germany); all preparations except those of the Panavia F and Admira Bond groups were further restored with resin composites. The Panavia F group was restored with amalgam and the Admira Bond group with Ormocer (Voco, Cuxhaven, Germany). The teeth were mounted in a Universal Testing Machine (Hounsfield, Surrey, UK), and the buccal walls were subjected to a slowly increasing compressive force until fracture occurred. The force of fracture of the walls of each tooth was recorded and the results in the various groups were compared. Statistical analysis of the data was accomplished using one-way anova. There was no significant difference in the fracture resistance of any of the test groups. In this laboratory study, the type of dentine bonding agents had no influence in the fracture resistance of teeth.


Polyquant CT: direct electron and mass density reconstruction from a single polyenergetic source.
Quantifying material mass and electron density from computed tomography (CT) reconstructions can be highly valuable in certain medical practices, such as radiation therapy planning. However, uniquely parameterising the x-ray attenuation in terms of mass or electron density is an ill-posed problem when a single polyenergetic source is used with a spectrally indiscriminate detector. Existing approaches to single source polyenergetic modelling often impose consistency with a physical model, such as water-bone or photoelectric-Compton decompositions, which will either require detailed prior segmentation or restrictive energy dependencies, and may require further calibration to the quantity of interest. In this work, we introduce a data centric approach to fitting the attenuation with piecewise-linear functions directly to mass or electron density, and present a segmentation-free statistical reconstruction algorithm for exploiting it, with the same order of complexity as other iterative methods. We show how this allows both higher accuracy in attenuation modelling, and demonstrate its superior quantitative imaging, with numerical chest and metal implant data, and validate it with real cone-beam CT measurements.


[Results of intensive combination treatment of patients with cancer of the rectum].
A comparative analysis of the results of treatment of two groups of patients with carcinoma of the rectum was made for a 6-year period of observation. One group (91 patients) was subjected to the intensive combined radiotherapy. In the preoperative period they received 3000 rad with supervoltage source, 600 rad daily during 9 days. Operations were performed 5-10 days following the irradiation. Surgery alone was performed in the second control group (132 patients). The intensive combined therapy allows a survival to be improved by 15.4% during six years of observation (indices were standardized by sex, age and prognosis). In a group of patients with poor prognosis the combined treatment ameliorated the results by 29% (indices are standardized by sex and age). It is believed that the intensive combined treatment for rectal cancer should be recommended for the health protection practice.


Benzo[a]pyrene-induced DNA damage associated with mutagenesis in primary human activated T lymphocytes.
Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (B[a]P), are widely distributed environmental contaminants exerting toxic effects such as genotoxicity and carcinogenicity, mainly associated with aryl hydrocarbon receptor (AhR) activation and the subsequent induction of cytochromes P-450 (CYP) 1-metabolizing enzymes. We previously reported an up-regulation of AhR expression and activity in primary cultures of human T lymphocyte by a physiological activation. Despite the suggested link between exposure to PAHs and the risk of lymphoma, the potential of activated human T lymphocytes to metabolize AhR exogenous ligands such as B[a]P and produce DNA damage has not been investigated. In the present study, we characterized the genotoxic response of primary activated T lymphocytes to B[a]P. We demonstrated that, following T lymphocyte activation, B[a]P treatment triggers a marked increase in CYP1 expression and activity generating, upon metabolic activation, DNA adducts and double-strand breaks (DSBs) after a 48-h treatment. At this time point, B[a]P also induces a DNA damage response with ataxia telangiectasia mutated kinase activation, thus producing a p53-dependent response and T lymphocyte survival. B[a]P activates DSB repair by mobilizing homologous recombination machinery but also induces gene mutations in activated human T lymphocytes which could consequently drive a cancer process. In conclusion, primary cultures of activated human T lymphocytes represent a good model for studying genotoxic effects of environmental contaminants such as PAHs, and predicting human health issues.


Measurements and simulations of microtubule growth imply strong longitudinal interactions and reveal a role for GDP on the elongating end.
Microtubule polymerization dynamics result from the biochemical interactions of αβ-tubulin with the polymer end, but a quantitative understanding has been challenging to establish. We used interference reflection microscopy to make improved measurements of microtubule growth rates and growth fluctuations in the presence and absence of GTP hydrolysis. In the absence of GTP hydrolysis, microtubules grew steadily with very low fluctuations. These data were best described by a computational model implementing slow assembly kinetics, such that the rate of microtubule elongation is primarily limited by the rate of αβ-tubulin associations. With GTPase present, microtubules displayed substantially larger growth fluctuations than expected based on the no GTPase measurements. Our modeling showed that these larger fluctuations occurred because exposure of GDP-tubulin on the microtubule end transiently 'poisoned' growth, yielding a wider range of growth rates compared to GTP only conditions. Our experiments and modeling point to slow association kinetics (strong longitudinal interactions), such that drugs and regulatory proteins that alter microtubule dynamics could do so by modulating either the association or dissociation rate of tubulin from the microtubule tip. By causing slower growth, exposure of GDP-tubulin at the growing microtubule end may be an important early event determining catastrophe.


Tandemly activated tRNAs as participants in protein synthesis.
While all studies of protein synthesis to date have employed monoaminoacylated transfer RNAs, there have been reports that bisphenylalanyl-tRNA is formed by Thermus thermophilus phenylalanyl-tRNA synthetase. Such tandemly activated tRNAs have now been prepared by chemicoenzymatic techniques and are shown to function in both prokaryotic and mammalian protein synthesizing systems. They exhibit characteristics consistent with their possible utility under extreme conditions in natural systems and have important potential advantages for protein elaboration in cell free systems. Mechanistically, the bisaminoacylated tRNAs bind to the ribosomal A-site and utilize the aminoacyl moiety attached to the 3'-position of the terminal adenosine for addition to the growing polypeptide chain. Following translocation to the P-site and transfer of the formed peptidyl moiety, the donor tRNA dissociates from the ribosome as a monoaminoacylated tRNA capable of functioning in a subsequent polypeptide elongation step.


Contribution of specific residues of the β-solenoid fold to HET-s prion function, amyloid structure and stability.
The [Het-s] prion of the fungus Podospora anserina represents a good model system for studying the structure-function relationship in amyloid proteins because a high resolution solid-state NMR structure of the amyloid prion form of the HET-s prion forming domain (PFD) is available. The HET-s PFD adopts a specific β-solenoid fold with two rungs of β-strands delimiting a triangular hydrophobic core. A C-terminal loop folds back onto the rigid core region and forms a more dynamic semi-hydrophobic pocket extending the hydrophobic core. Herein, an alanine scanning mutagenesis of the HET-s PFD was conducted. Different structural elements identified in the prion fold such as the triangular hydrophobic core, the salt bridges, the asparagines ladders and the C-terminal loop were altered and the effect of these mutations on prion function, fibril structure and stability was assayed. Prion activity and structure were found to be very robust; only a few key mutations were able to corrupt structure and function. While some mutations strongly destabilize the fold, many substitutions in fact increase stability of the fold. This increase in structural stability did not influence prion formation propensity in vivo. However, if an Ala replacement did alter the structure of the core or did influence the shape of the denaturation curve, the corresponding variant showed a decreased prion efficacy. It is also the finding that in addition to the structural elements of the rigid core region, the aromatic residues in the C-terminal semi-hydrophobic pocket are critical for prion propagation. Mutations in the latter region either positively or negatively affected prion formation. We thus identify a region that modulates prion formation although it is not part of the rigid cross-β core, an observation that might be relevant to other amyloid models.


Risk of breast cancer and residential proximity to industrial installations: New findings from a multicase-control study (MCC-Spain).
Breast cancer is the most frequent tumor in women worldwide, although well-established risk factors account for 53%-55% of cases. Therefore, other risk factors, including environmental exposures, may explain the remaining variation. Our objective was to assess the relationship between risk of breast cancer and residential proximity to industries, according to categories of industrial groups and specific pollutants released, in the context of a population-based multicase-control study of incident cancer carried out in Spain (MCC-Spain). Using the current residence of cases and controls, this study was restricted to small administrative divisions, including both breast cancer cases (452) and controls (1511) in the 10 geographical areas recruiting breast cancer cases. Distances were calculated from the respective woman's residences to the 116 industries located in the study area. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance (between 1 km and 3 km) to industrial plants, adjusting for matching variables and other confounders. Excess risk (OR; 95%CI) of breast cancer was found near industries overall (1.30; 1.00-1.69 at 3 km), particularly organic chemical industry (2.12; 1.20-3.76 at 2.5 km), food/beverage sector (1.87; 1.26-2.78 at 3 km), ceramic (4.71; 1.62-13.66 at 1.5 km), surface treatment with organic solvents (2.00; 1.23-3.24 at 3 km), and surface treatment of plastic and metals (1.51; 1.06-2.14 at 3 km). By pollutants, the excess risk (OR; 95%CI) was detected near industries releasing pesticides (2.09; 1.14-3.82 at 2 km), and dichloromethane (2.09; 1.28-3.40 at 3 km). Our results suggest a possible increased risk of breast cancer in women living near specific industrial plants and support the need for more detailed exposure assessment of certain agents released by these plants.


Genotoxicity of organic extracts of urban airborne particulate matter: an assessment within a personal exposure study.
Airborne particulate matter, PM(10) and PM(2.5), are associated with a range of health effects including lung cancer. Their complex organic fraction contains genotoxic and carcinogenic compounds such as polycyclic aromatic hydrocarbons (PAHs) and their derivatives. This study evaluates the genotoxicity of the PM(10) and PM(2.5) organic extracts that were sampled in the framework of a personal exposure study in three French metropolitan areas (Paris, Rouen and Strasbourg), using the comet assay, performed on HeLa S3 cells. In each city, 60-90 non-smoking volunteers composed of two groups of equal size (adults and children) carried the personal Harvard Chempass multi-pollutant sampler during 48h along two different seasons ('hot' and 'cold'). Volunteers were selected so as to live (home and work/school) in 3 different urban sectors contrasted in terms of air pollution within each city (one highly exposed to traffic emissions, one influenced by local industrial sources, and a background urban environment). Genotoxic effects are stronger for PM(2.5) extracts than for PM(10), and greater in winter than in summer. Fine particles collected by subjects living within the traffic proximity sector present the strongest genotoxic responses, especially in the Paris metropolitan area. This work confirms the genotoxic potency of particulate matter (PM(10) and PM(2.5)) organic extracts to which urban populations are exposed.


Straightforward access to mono- and bis-cycloplatinated helicenes that display circularly polarized phosphorescence using crystallization resolution methods.
Enantiopure mono-cycloplatinated-[8]helicene and bis-cycloplatinated-[6]helicene derivatives were prepared through column chromatography combined with crystallization of diastereomeric complexes using a chiral ancillary sulfoxide ligand. The UV-visible spectra, circular dichroism, molar rotations, and (circularly polarized) luminescence activity of these new helical complexes have been examined in detail and analysed with the help of first-principles quantum-chemical calculations.


Women's health custom made: building on the 40 days postpartum for Arab women.
The 40-day postpartum period is characterised in the Middle East and elsewhere by an observance of seclusion, congratulatory visiting, the reciprocal exchange of gifts and money, and a special diet. Based on primary data from in-depth interviews among the Negev Bedouin in Israel, health enhancing practices are reviewed. The data are a subset from a larger study carried out in this setting. Often postnatal checkups, family planning counselling, and immunization services may not be routinely available or used. It is argued that these health services could be provided at the end of the 40-day period for mother and child, as in a pilot study in Tunisia some years ago. Health service provision would thus build on the health enhancing practices of the 40-day period.


Early detection and late cognitive control of emotional distraction by the prefrontal cortex.
Unpleasant emotional distraction can impair the retention of non-emotional information in working memory (WM). Research links the prefrontal cortex with the successful control of such biologically relevant distractors, although the temporal changes in this brain mechanism remain unexplored. We use magnetoencephalography to investigate the temporal dynamics of the cognitive control of both unpleasant and pleasant distraction, in the millisecond (ms) scale. Behavioral results demonstrate that pleasant events do not affect WM maintenance more than neutral ones. Neuroimaging results show that prefrontal cortices are recruited for the rapid detection of emotional distraction, at early latencies of the processing (70-130 ms). Later in the processing (360-450 ms), the dorsolateral, the medial and the orbital sections of the prefrontal cortex mediate the effective control of emotional distraction. In accordance with the behavioral performance, pleasant distractors do not require higher prefrontal activity than neutral ones. These findings extend our knowledge about the brain mechanisms of coping with emotional distraction in WM. In particular, they show for the first time that overriding the attentional capture triggered by emotional distractors, while maintaining task-relevant elements in mind, is based on the early detection of such linked-to-survival information and on its later cognitive control by the prefrontal cortex.


Functional characterization of RYR1 variants identified in malignant hyperthermia susceptible individuals.
Malignant hyperthermia is a pharmacogenetic disorder triggered by halogenated anesthetic agents in genetically predisposed individuals. Approximately 70 % of these individuals carry mutations in RYR1, the gene encoding the ryanodine receptor calcium channel of skeletal muscle. In this study, we performed functional analysis of 5 RYR1 variants identified in members from 8 families who had been diagnosed by the IVCT. Of the 68 individuals enrolled in the study, 43 were diagnosed as MHS, 23 as MHN, and 2 individuals were not tested. Here we demonstrate that the 5 RyR1 variants cause hypersensitivity to RyR1 agonist-mediated calcium release. According to the EMHG scoring matrix these five genetic variants can be classified as follows: c.8638G>A (p.E2880K) and c.11314C>T (p.R3772W) likely pathogenic, c.11416G>A (p.G3806R), c.14627A>G (p.K4876R) and c.14813T>C (p.I4938T), pathogenic (RefSeq NM_000540.3). We propose that the newly functionally characterized RYR1 variants, be included in the panel of variants to be used for the molecular diagnosis of MHS.


Can increased leaf photosynthesis be converted into higher crop mass production? A simulation study for rice using the crop model GECROS.
Various genetic engineering routes to enhance C3 leaf photosynthesis have been proposed to improve crop productivity. However, their potential contribution to crop productivity needs to be assessed under realistic field conditions. Using 31 year weather data, we ran the crop model GECROS for rice in tropical, subtropical, and temperate environments, to evaluate the following routes: (1) improving mesophyll conductance (gm); (2) improving Rubisco specificity (Sc/o); (3) improving both gm and Sc/o; (4) introducing C4 biochemistry; (5) introducing C4 Kranz anatomy that effectively minimizes CO2 leakage; (6) engineering the complete C4 mechanism; (7) engineering cyanobacterial bicarbonate transporters; (8) engineering a more elaborate cyanobacterial CO2-concentrating mechanism (CCM) with the carboxysome in the chloroplast; and (9) a mechanism that combines the low ATP cost of the cyanobacterial CCM and the high photosynthetic capacity per unit leaf nitrogen. All routes improved crop mass production, but benefits from Routes 1, 2, and 7 were ≤10%. Benefits were higher in the presence than in the absence of drought, and under the present climate than for the climate predicted for 2050. Simulated crop mass differences resulted not only from the increased canopy photosynthesis competence but also from changes in traits such as light interception and crop senescence. The route combinations gave larger effects than the sum of the effects of the single routes, but only Route 9 could bring an advantage of ≥50% under any environmental conditions. To supercharge crop productivity, exploring a combination of routes in improving the CCM, photosynthetic capacity, and quantum efficiency is required.


Electrophysiological and behavioral analysis of lip touch as a component of the food stimulus in the snail Lymnaea.
Electrophysiological and video recording methods were used to investigate the function of lip touch in feeding ingestion behavior of the pond snail Lymnaea stagnalis. Although this stimulus was used successfully as a conditioning stimulus (CS) in appetitive learning experiments, the detailed role of lip touch as a component of the sensory stimulus provided by food in unconditioned feeding behavior was never ascertained. Synaptic responses to lip touch in identified feeding motoneurons, central pattern generator interneurons, and modulatory interneurons were recorded by intracellular electrodes in a semi-intact preparation. We showed that touch evoked a complex but characteristic sequence of synaptic inputs on each neuron type. Touch never simply activated feeding cycles but provided different types of synaptic input, determined by the feeding phase in which the neuron was normally active in the rhythmic feeding cycle. The tactile stimulus evoked mainly inhibitory synaptic inputs in protraction-phase neurons and excitation in rasp-phase neurons. Swallow-phase neurons were also excited after some delay, suggesting that touch first reinforces the rasp then swallow phase. Video analysis of freely feeding animals demonstrated that during normal ingestion of a solid food flake the food is drawn across the lips throughout the rasp phase and swallow phase and therefore provides a tactile stimulus during both these retraction phases of the feeding cycle. The tactile component of the food stimulus is strongest during the rasp phase when the lips are actively pressed onto the substrate that is being moved across them by the radula. By using a semi-intact preparation we demonstrated that application of touch to the lips during the rasp phase of a sucrose-driven fictive feeding rhythm increases both the regularity and frequency of rasp-phase motoneuron firing compared with sucrose applied alone.