Selection of wild macrophytes for use in constructed wetlands for phytoremediation of contaminant mixtures.
Constructed wetlands (CWs) offer an alternative to traditional industrial wastewater treatment systems that has been proved to be efficient, cost-effective and environmentally friendly. Most of the time, CWs are planted with proliferative species such as Phragmites australis or with plants originating from nurseries, both representing a risk for the natural biodiversity conservation of aquatic ecosystems located downstream of the CWs. For the removal of metals and organic pollutant mixtures present in industrial effluents, it is necessary to select tolerant plant species that are able to produce a high aboveground biomass and to develop a healthy belowground system. Wild plant species growing in aquatic bodies at industrial outfalls could constitute suitable tolerant species to use in CWs for industrial effluent treatment. To test this hypothesis, we assessed, under laboratory conditions (using an experimental design), the tolerance to mixtures of metals (Al, As, Cd, Cu, Cr, Fe, Mn, Ni, Pb, Sn, Zn) or/and organic pollutants (THC, PHE, PYR, LAS) of five European sub-cosmopolitan native macrophytes (Alisma lanceolatum, Carex cuprina, Epilobium hirsutum, Iris pseudacorus and Juncus inflexus) that had been collected in a polluted Mediterranean wetland, after a field study (crossing ecological relevés and analyses of contaminant concentrations in water and sediments). Our results demonstrated that research on phytoremediation of industrial effluents should focus much more on the use of native macrophytes growing at short distances from industrial discharges (such as C. cuprina in this study), and that root/shoot ratio, aerial height and proportion of green leaves are good and cost-effective indicators of plant tolerance to metals and organic pollutant mixtures in laboratory studies.


Juxtarenal aortic aneurysm after successful repair of ruptured infrarenal aneurysm.
Eight months after successful repair of a ruptured infrarenal aneurysm, a 50-year-old hypertensive male patient was found to have a 2nd aneurysm restricted to the juxtarenal segment of the aorta, and not in continuity with the infrarenal lesion. While there have been reports both of true aneurysms arising independently in the abdominal (infrarenal) and thoracic (suprarenal) aortic segments, and of false aneurysms arising secondary to abdominal aortic repair (at the suture line or as dilatations of residual aneurysmal tissue), we believe our case unusual in that the new aneurysm was a discrete and "true" thoracoabdominal dilatation arising just above the renal arteries and terminating just below the superior mesenteric artery. This strictly juxtarenal dilatation conforms better to a descriptive pattern for atherosclerotic occlusive disease than it does to the standard scheme for classifying thoracoabdominal aortic aneurysms.


Modelling of exposure to respirable and inhalable welding fumes at German workplaces.
The International Agency for Research on Cancer classified welding fumes as carcinogenic to humans, and occupational exposure limits should be established to protect welders. The aim of this study is to estimate exposure levels to inhalable and respirable welding fumes by welding process to use them for exposure assessment in epidemiological studies and to derive occupational exposure limits. In total, 15,473 mass concentrations of inhalable and 9,161 concentrations of respirable welding fumes could be analyzed along with welding-related and sampling information, which were compiled in the German database MEGA between 1983 and 2016. In both particle-size fractions, model-based geometric means of the concentrations were estimated by welding process and material for frequently used welding processes adjusted for sampling time and median-centered for calendar years. The inhalable concentrations were approximately twice the respirable concentrations, with medians of 3 mg/m3 (inter-quartile range: 1.2-7.0 mg/m3) and 1.5 mg/m3 (inter-quartile range: < limit of detection -3.8 mg/m3), respectively. The adjusted geometric means of flux-cored arc welding, metal inert and active gas welding, shielded metal arc welding and torch cutting ranged from 0.9 to 2.2 mg/m3 for respirable welding fumes and from 2.3 to 4.7 mg/m3 for inhalable fumes. In both particle-size fractions, geometric means were between 0.1 and 0.9 mg/m3 when performing tungsten inert gas, autogeneous, resistance, laser, and plasma welding or spraying. Results derived from this large dataset are useful for a quantitative exposure assessment to estimate health risks of welders.


Effect of exposure to p,p´-DDE during the first half of pregnancy in the maternal thyroid profile of female residents in a Mexican floriculture area.
Dichlorodiphenyldichloroethene (p,p´-DDE), the main metabolite of dichlorodiphenyltrichloroethane (DDT), has been associated with changes in human thyroid hormone levels. Maternal thyroid hormones are essential for adequate fetal neurodevelopment during the first half of pregnancy. To evaluate the association between maternal p,p´-DDE concentration and the maternal thyroid profile during the first half of pregnancy. We analyzed the information of 430 pregnant women from a Mexican floriculture area, with a gestational age ≤16 weeks. By questionnaire, we obtained sociodemographic, reproductive, and life-style, information. Serum concentrations of thyroid stimulating hormone (TSH), and total and free T3 and T4 were determined by means of Enzyme-Linked ImmunoSorbent Assay (ELISA). p,p´-DDE was analyzed by Gas Chromatography. The association between p,p´-DDE and thyroid profile was assessed through linear and logistic regression models. Thirty eight percent of women had p,p´-DDE levels below the Limit of Detection and 12.3% below the Limit of Quantification. Within the quantifiable range, median was 53.03ng/g. TSH >2.5 mIU/L was present in 9.3% of women; 47.7% had isolated hypothyroxinemia; 3.5% had subclinical hypothyroidism, and 5.8% had overt hypothyroidism. We observed a significant positive association between quantifiable p,p´-DDE and total T3 serum levels in comparison with those with concentrations below the Limit of Detection (β=0.19; 95% CI=0.06, 0.34). There were no significant associations with other hormones of the thyroid profile or with clinical diagnosis. Our findings suggest that p,p´-DDE exposure, even at low concentrations, could disrupt thyroid homeostasis during pregnancy.


Emerging roles for ectodomain shedding in the regulation of inflammatory responses.
The multistep model of leukocyte recruitment to sites of inflammation has helped elucidate specific molecular cues for each of the individual steps. However, it is less clear how cells transition between the different steps and how the complex interactions are coordinately regulated. Once a leukocyte sticks to the endothelium, it only takes a few minutes to reach the subendothelial basement membrane, so the transitions and regulatory mechanisms must be rapid. We put forward the hypothesis that proteolytic shedding of cell surface proteins provides a mechanism to aid in the rapid transition of cells and coordinate the complex, multistep process of leukocyte recruitment in response to inflammatory stimuli. Support for this hypothesis is provided from analyses of disease states and from studies with protease inhibitors and genetically engineered mutations that prevent "ectodomain shedding" of cell surface proteins and consequently perturb the inflammatory response.


[Effect of physical loading on serum enzyme activity in post-myocardial infarct patients].
The study of patterns of serum AST, ALT, CPK, LDH, and glycogen phosphorylase (GP) activity following bicycle ergometry in 26 male patients 1 to 1.5 months after myocardial infarction demonstrated no increase in AST, ALT and CPK activity, whereas total LDH activity was increased, with a tendency to elevated LDH-1 and LDH-2 fractions, as compared to the baseline, in those cases where exercise was discontinued because of ST depression. Patients with favorable response to bicycle ergometry that continued until the submaximum heart rate for a given age was achieved showed a tendency to elevated LDH-5 that may be a physiological response to exercise. The demonstrated increase in total GP activity, both in patients with exercise-induced ST depression and in those with elevated ST from the leads corresponding to the site of myocardial infarction, may reflect stress-induced reversible ischemia.


Electrogenic K+ transport by the Na(+)-K+ pump in rat cardiac ventricular myocytes.
1. The involvement of electrogenic reaction steps in K+ transport by the Na+, K(+)-ATPase was determined in rat cardiac ventricular myocytes using whole-cell patch clamp techniques. 2. Under K(+)-K+ exchange conditions and in the presence of extracellular K+ or Tl+ at concentrations that stimulated submaximal levels of steady-state Na+,K(+)-ATPase activity, ouabain-sensitive transient currents were observed during ('on') and after ('off') step changes in membrane potential (Vm). 3. The quantity of charge moved during the transient currents depended, in a saturable manner, on the magnitude of the voltage step. Maximal ouabain-sensitive 'on' and 'off' charges were calculated to be 9.6 +/- 0.9 and 9.1 +/- 0.4 fC pF-1 (n = 4), respectively, with an effective valeney of 0.48 +/- 0.07 (n = 7). 4. Kinetics of the transient currents were independent of Vm and Tl+o at positive potentials, but became more rapid at increasingly negative Vm values in an ion concentration-dependent fashion. 5. Those data demonstrate that electrogenic steps participate in K+ transport by the Na+,K(+)-ATPase and that the electrogenic step is extracellular ion binding. 6. The temperature- and Vm-dependent properties of transient charge movements were compared under K(+) -K+ and Na(+) -Na+ exchange conditions. The data suggest that extracellular K+ and Na+ binding occur at different sites in the enzyme or to different enzyme conformations. The sum of the effective valencies, 1.14 +/- 0.12, demonstrates that the electrogenicity of extra-cellular ion binding can explain the Vm dependence of ion transport by the Na+,K(+)-ATPase.


Small-Molecule Acetylation by GCN5-Related N-Acetyltransferases in Bacteria.
Acetylation is a conserved modification used to regulate a variety of cellular pathways, such as gene expression, protein synthesis, detoxification, and virulence. Acetyltransferase enzymes transfer an acetyl moiety, usually from acetyl coenzyme A (AcCoA), onto a target substrate, thereby modulating activity or stability. Members of the GCN5- N -acetyltransferase (GNAT) protein superfamily are found in all domains of life and are characterized by a core structural domain architecture. These enzymes can modify primary amines of small molecules or of lysyl residues of proteins. From the initial discovery of antibiotic acetylation, GNATs have been shown to modify a myriad of small-molecule substrates, including tRNAs, polyamines, cell wall components, and other toxins. This review focuses on the literature on small-molecule substrates of GNATs in bacteria, including structural examples, to understand ligand binding and catalysis. Understanding the plethora and versatility of substrates helps frame the role of acetylation within the larger context of bacterial cellular physiology.


[Congenital mesoblastic nephroma in childhood. Our experience apropos of 3 cases].
Congenital mesoblastic nephroma (CMN) is a rare, generally benign renal tumor. A better knowledge of its natural history has changed the therapeutic approach. Currently, aggressive therapy must be exclusively reserved for the sarcomatous forms or Wilms' tumor with sarcomatoid features. The cell variant reported in our series was treated with efficacy by surgery alone. Early recognition of the lesion, preferably prenatally, is warranted in order to perform surgery early or detect hydrops fetalis, a possible complication of pregnancy.


Electrochemical Tantalum Oxide for Resistive Switching Memories.
Redox-based resistive switching memories (ReRAMs) are strongest candidates for the next-generation nonvolatile memories fulfilling the criteria for fast, energy efficient, and scalable green IT. These types of devices can also be used for selector elements, alternative logic circuits and computing, and memristive and neuromorphic operations. ReRAMs are composed of metal/solid electrolyte/metal junctions in which the solid electrolyte is typically a metal oxide or multilayer oxides structures. Here, this study offers an effective and cheap electrochemical approach to fabricate Ta/Ta2 O5 -based devices by anodizing. This method allows to grow high-quality and dense oxide thin films onto a metallic substrates with precise control over morphology and thickness. Electrochemical-oxide-based devices demonstrate superior properties, i.e., endurance of at least 106 pulse cycles and/or 103 I-V sweeps maintaining a good memory window with a low dispersion in ROFF and RON values, nanosecond fast switching, and data retention of at least 104 s. Multilevel programing capability is presented with both I-V sweeps and pulse measurements. Thus, it is shown that anodizing has a great prospective as a method for preparation of dense oxide films for resistive switching memories.


Cascaded Parsing of Human-Object Interaction Recognition.
This paper addresses the task of detecting and recognizing human-object interactions (HOI) in images. Considering the intrinsic complexity and structural nature of the task, we introduce a cascaded parsing network (CP-HOI) for a multi-stage, structured HOI understanding. At each cascade stage, an instance detection module progressively refines HOI proposals and feeds them into a structured interaction reasoning module. Each of the two modules is also connected to its predecessor in the previous stage, enabling efficient cross-stage information propagation. The structured interaction reasoning module is built upon a graph parsing neural network (GPNN), which efficiently models potential HOI structures as graphs and mines rich context for comprehensive relation understanding. In particular, GPNN infers a parse graph that i) interprets meaningful HOI structures by a learnable adjacency matrix, and ii) predicts action (edge) labels. Within an end-to-end, message-passing framework, GPNN blends learning and inference, iteratively parsing HOI structures and reasoning HOI representations (i.e., instance and relation features). Further beyond relation detection at a bounding-box level, we make our framework flexible to perform fine-grained pixel-wise relation segmentation; this provides a new glimpse into better relation modeling. A preliminary version of our CP-HOI model reached 1st place in the ICCV2019 Person in Context Challenge, on both relation detection and segmentation. In addition, our CP-HOI shows promising results on two popular HOI recognition benchmarks, i.e., V-COCO and HICO-DET.


An approach to the evaluation of peripheral neuropathies.
The clinical evaluation of peripheral neuropathies can be challenging. This article presents an approach based on a structured assessment that asks a series of yes or no questions during the history and examination that leads to localization and characterization of the neuropathy. The final assessment includes further characterization by electrodiagnostic evaluation. At this point, a reasonable differential diagnosis can be generated and appropriate laboratory tests ordered.


Epicardial adipose tissue in obesity-related cardiac dysfunction.
Obesity is associated with the development of heart failure and is a major risk factor for heart failure with preserved ejection fraction (HFpEF). Epicardial adipose tissue (EAT) is a unique visceral fat in close proximity to the heart and is of particular interest to the study of cardiac disease. Small poorly differentiated adipocytes with altered lipid:water content are associated with a proinflammatory secretome and may contribute to the pathophysiology observed in HFpEF. Multimodality imaging approaches can be used to quantify EAT volume and characterise EAT composition. Current research studies remain unclear as to the magnitude of effect that EAT plays on myocardial dysfunction and further work using multimodality imaging techniques is ongoing. Pharmacological interventions, including glucagon-like peptide 1 receptor agonists and sodium-dependent glucose linked transporter 2 inhibitors have shown promise in attenuating the deleterious metabolic and inflammatory changes seen in EAT. Clinical studies are ongoing to explore whether these therapies exert their beneficial effects by modifying this unique adipose deposit.


[Transgenic plants in vaccinology].
The problem of transgenic plants application to production of antigens, antibodies, enzymes, and hormones is discussed. Transgenic plants are a highly effective system for production of bioactive molecules. Prospects for using transgenic plants expressing viral and bacterial antigens for mucosal immunization are discussed.


History of Wrist Arthroscopy.
Wrist arthroscopy has a rich history, drawing on contributions from around the world. Its foundation was laid in Japan with Kenji Takagi and Masaki Watanabe, who developed the arthroscope and the techniques for arthroscopy. Across several decades they advanced the optic and lighting technology, allowing the miniaturization which made wrist arthroscopy technologically feasible. A safe and standardized technique for wrist arthroscopy was evolved by Terry Whipple, Gary Poehling, and James Roth in the 1980s, and they shared this with their fellow surgeons through courses and publications. The techniques then spread across the world, leading to widespread uptake and exploration of new therapeutic possibilities. The worldwide spread of wrist arthroscopy was accelerated by the European Wrist Arthroscopy Society (EWAS), founded in 2005 by Christophe Mathoulin. The Asia Pacific Wrist Association (APWA), founded by PC Ho in 2015, also extended the progression of wrist arthroscopy. This article brings together this history and tells the global story of its development through the recollections of those involved. The manuscript includes some amazing videos of the early historical arthroscopy. There are also videos of Gary and Terry describing some of their special memories of the early politics, developments, and evolution of wrist arthroscopy.


Respiration of Pseudomonas fluorescens as a function of intracellular substrate concentration.
A kinetic method to measure the intracellular concentration of respiratory substrates in short-term starvation-enrichment experiments is proposed. Samples of bacterial suspension from steady-state chemostat cultures were subjected to 25 min starvation, followed by pulse addition of [14C]glucose. Residual substrate utilization rates and respiration rates (uptake of dissolved O2) before and after amendment were recorded. Increases in pool sizes (δL) during transients were calculated on the basis of C balance. The dependence of respiration rate qresp on δL was found to obey modified Michaelis-Menten kinetics: q resp = Q resp (LC+δL)/(K L+LC+δL) [Q resp is maximal respiration rate (29.1 mmol O2 h-1per g biomass C), K L = 12.14 mg C per g biomass C], where LC is the absolute value of the pool size before amendment. Direct chemical determination of LC in cold TCA extracts revealed two fractions. The first fraction was mobile and showed a close correlation with both respiration and L. The second, 'stable', fraction did not correlate with respiration dynamics and was interpreted as material formed artifactually by acid degradation of polymeric cell components.


Developmental Plasticity and Language: A Comparative Perspective.
The growing field of evo-devo is increasingly demonstrating the complexity of steps involved in genetic, intracellular regulatory, and extracellular environmental control of the development of phenotypes. A key result of such work is an account for the remarkable plasticity of organismal form in many species based on relatively minor changes in regulation of highly conserved genes and genetic processes. Accounting for behavioral plasticity is of similar potential interest but has received far less attention. Of particular interest is plasticity in communication systems, where human language represents an ultimate target for research. The present paper considers plasticity of language capabilities in a comparative framework, focusing attention on examples of a remarkable fact: Whereas there exist design features of mature human language that have never been observed to occur in non-humans in the wild, many of these features can be developed to notable extents when non-humans are enculturated through human training (especially with intensive social interaction). These examples of enculturated developmental plasticity across extremely diverse taxa suggest, consistent with the evo-devo theme of highly conserved processes in evolution, that human language is founded in part on cognitive capabilities that are indeed ancient and that even modern humans show self-organized emergence of many language capabilities in the context of rich enculturation, built on the special social/ecological history of the hominin line. Human culture can thus be seen as a regulatory system encouraging language development in the context of a cognitive background with many highly conserved features.


MicroRNA-223 negatively regulates LPS-induced inflammatory responses by targeting NLRP3 in human dental pulp fibroblasts.
To investigate the effect of miR-223 on NLRP3, subsequently regulating the production of the NLRP3/CASP1 inflammasome pathway-mediated proinflammatory cytokines IL-1β and IL-18 in human dental pulp fibroblasts (HDPFs). Human dental pulp tissue (HDPT) and HDPFs were obtained from impacted third molars. The miR-223 mimics and inhibitor or NLRP3 plasmid were used to upregulate or downregulate miR-223 or NLRP3 in HDPFs, respectively. Computational prediction via TargetScan 5.1 and a luciferase reporter assay was conducted to confirm target association. The mRNA and protein expression of NLRP3, caspase-1, IL-1β and IL-18 was determined by qRT-PCR and Western blotting, respectively. The release of IL-1β and IL-18 was analysed by ELISA. The significance of the differences between the experimental and the control groups was determined using one-way analysis of variance; P < 0.05 indicated statistical significance. A decrease in miR-223 and an increase in NLRP3 in HDPT occurred during the transformation of reversible pulpitis into irreversible pulpitis compared to that in healthy pulp tissue (P < 0.05). The computational prediction and luciferase reporter assay confirmed that NLRP3 was a direct target of miR-223 in HDPFs. The miR-223 inhibitor further promoted ATP plus LPS-induced NLRP3/CASP1 inflammasome pathway activation compared to the ATP plus LPS-induced group (P < 0.05). In contrast, the miR-223 mimic significantly inhibited the NLRP3/CASP1 inflammasome pathway activation induced by ATP plus LPS compared to the ATP plus LPS-induced group (P < 0.05). MiR-223 served as a negative regulator involved in the control of the production and secretion of proinflammatory cytokines mediated by the NLRP3/CASP1 inflammasome pathway by targeting NLRP3. These data provide insight into the potential regulatory effects of miRNAs on the NLRP3 inflammasome, thus opening up novel potential therapeutic avenues for future endodontic treatment.


Optimization of single-step gelatin extraction from pink perch (Nemipterus japonicus) skin and bone obtained from surimi industry using a green solvent.
Surimi industry produces a large quantity of byproducts that are currently being utilized to produce low-value commodities. This study aims to extract gelatin from pink perch skin and bone obtained from the surimi industry using a green single-step extraction method. In addition to using a green solvent, that is, acetic acid, the new method combines the multiple steps of pre-treatment and hydrolysis into one single-step extraction process. Response surface methodology was used to optimize extraction parameters (pH, temperature, and time) to maximize yield and l-hydroxyproline (l-hyp) content. The optimum condition for gelatin extraction was obtained at pH 3, 75°C, and 30 min. At optimum conditions, gelatin yield and l-hyp content were observed to be 16.07% and 41.26 mg g-1 , respectively. The gelatin obtained at optimized condition was further compared with commercial bovine gelatin (BG) in terms of chemical composition and textural, functional, and rheological properties. The results suggested that the optimized pink perch gelatin had higher protein content (92.06%), better gel strength (251.08 g), higher imino acid (18.01%), and improved textural and functional properties than the commercially available BG. The optimized single-step gelatin extraction method from pink perch skin and bones is a promising, rapid, and efficient method for the production of good-quality gelatin, which can be further used for the development of high-value products such as food formulations. PRACTICAL APPLICATION: Fish gelatin is widely used in food product development. Most of the existing methods of the development of high-value product such as gelatin, use multi-step process and harsh mineral acid, therefore, are time-consuming and harmful to the environment. This study provides a green single-step gelatin extraction method that provides an efficient, rapid, and convenient method of gelatin extraction and a sustainable solution for fish industry byproduct utilization. The data obtained with this laboratory-scale study provides a strong basis for scale-up studies.


Women's experiences seeking informal sector abortion services in Cape Town, South Africa: a descriptive study.
In settings where abortion is legally restricted, or permitted but not widely accessible, women face significant barriers to abortion access, sometimes leading them to seek services outside legal facilities. The advent of medication abortion has further increased the prevalence of informal sector abortion. This study investigates the reasons for attempting self-induction, methods used, complications, and sources of information about informal sector abortion, and tests a specific recruitment method which could lead to improved estimates of informal sector abortion prevalence among an at-risk population. We recruited women who have sought informal sector abortion services in Cape Town, South Africa using respondent driven sampling (RDS). An initial seed recruiter was responsible for initiating recruitment using a structured coupon system. Participants completed face-to-face questionnaires, which included information about demographics, informal sector abortion seeking, and safe abortion access needs. We enrolled 42 women, nearly one-third of whom reported they were sex workers. Thirty-four women (81%) reported having had one informal sector abortion within the past 5 years, 14% reported having had two, and 5% reported having had three. These women consumed home remedies, herbal mixtures from traditional healers, or tablets from an unregistered provider. Twelve sought additional care for potential warning signs of complications. Privacy and fear of mistreatment at public sector facilities were among the main reported reasons for attempting informal sector abortion. Most women (67%) cited other community members as their source of information about informal sector abortion; posted signs and fliers in public spaces also served as an important source of information. Women are attempting informal sector abortion because they seek privacy and fear mistreatment and stigma in health facilities. Some were unaware how or where to seek formal sector services, or believed the cost was too high. Many informal methods are ineffective and unsafe, leading to potential warning signs of complications and continued pregnancy. Sex workers may be at particular risk of unsafe abortion. Based on these results, it is essential that future studies sample women outside of the formal health sector. The use of innovative sampling methods would greatly improve our knowledge about informal sector abortion in South Africa.


Use of a continuous alfentanil infusion for extracorporeal shock wave lithotripsy in the treatment of renal calculi.
Extracorporeal shock wave lithotripsy (ESWL) is the most widely used treatment for renal calculi. Newer second generation lithotripters are being produced, which are considered to be less painful than their prototypes. Thus, the trend in anesthesia for ESWL is away from general endotracheal and regional anesthesia and toward less involved and more easily monitored techniques such as intravenous analgesia (IVA). This report relates our experience with a continuous alfentanil infusion for ESWL treatment of renal calculi with a nonimmersion second generation Dornier HM-4 lithotripter model. Thirty-five patients treated pre-operatively with droperidol and midazolam, followed by a continuous infusion of alfentanil, reported excellent pain relief via a numerical pain score and manifested little, if any, hypertension or tachycardia. Stone fragmentation, fluoroscopy, and recovery time did not differ between patients receiving IVA or general anesthesia. Potential disadvantages of IVA include elevation of transcutaneous CO 2, bradycardia in 14 patients requiring the use of atropine, slightly longer ESWL time, increased number of shocks needed for fragmentation, and a small failure rate, with 11% of patients requiring general anesthesia. With proper patient selection and respiratory monitoring, IVA is highly recommended for ESWL in the treatment of renal calculi.


The influence of local infiltration analgesia after total hip replacement. A randomized clinical trial.
To determine whether local infiltration analgesia by catheter infusion was superior to conventional analgesia in terms of postoperative pain control after THR. A randomized double-blind clinical trial was performed. There were four groups based on catheter placement and the infusion constituents : 1) Intraarticular catheter + anesthetics ; 2) Intraarticular catheter +placebo ; 3) Subfascial catheter + anesthetics ; 4) Subfascial catheter + placebo. The anesthetic infusion contained bupivacaine (bolus + continuous perfusion up to 36 hours). The placebo solution was physiological serum. The same conventional analgesic schedule was prescribed to all patients. Pain was evaluated by means of PCA shots and the VAS. Side effects, time to start rehabilitation and time to discharge were also analyzed. 100 patients (25 for group). Mean age was 67 years old (SD 12 y/o) and 53% were male. Mean PCA shots was 27 [range 2-87] and mean VAS was 1 [range 0-7]. No differences were found (p>0.05) when these variables were compared between the groups. The use of LIA with bupivacaine using a catheter infusion does not provide better pain control after THR.


Photosensitivity: classification, diagnosis, and treatment.
Photosensitivity disorders are common. Phototoxicity due to excess ultraviolet exposure while on a photosensitizing drug and polymorphic light eruption are two frequent examples. Patients should be encouraged to consider Taylor's ABCDEs: Avoidance, Barrier creams, Clothing, Dihydroxyacetone, and Education.


Geographic atrophy of the retinal pigment epithelium: diagnosis and vision rehabilitation.
Senile macular disease has been found to be a common cause of legal blindness and visual impairment. The spectrum of clinical manifestations can present many variations of exudative and non-exudative disease. Three cases of one manifestation, geographic atrophy of the retinal pigment epithelium, are described with emphasis on differential diagnosis from a clinically similar disease, central areolar choroidal dystrophy. It has been reported that patients with central areolar choroidal dystrophy do not respond well to magnification. We found that patients with geographic atrophy of the retinal pigment respond well to magnification and vision rehabilitation.


Challenges and advances in treating hoarding.
This article introduces an issue of the Journal of Clinical Psychology: In Session devoted to understanding, assessing, and treating hoarding disorder (HD). After a case example is presented, the proposed the Diagnostic and Statistical Manual, 5th Edition criteria for HD are discussed, and the problems associated with hoarding are discussed from a psychotherapeutic and public health perspective. The articles in this issue are then outlined and summarized.


Micropeptides: origins, identification, and potential role in metabolism-related diseases.
With the development of modern sequencing techniques and bioinformatics, genomes that were once thought to be noncoding have been found to encode abundant functional micropeptides (miPs), a kind of small polypeptides. Although miPs are difficult to analyze and identify, a number of studies have begun to focus on them. More and more miPs have been revealed as essential for energy metabolism homeostasis, immune regulation, and tumor growth and development. Many reports have shown that miPs are especially essential for regulating glucose and lipid metabolism and regulating mitochondrial function. MiPs are also involved in the progression of related diseases. This paper reviews the sources and identification of miPs, as well as the functional significance of miPs for metabolism-related diseases, with the aim of revealing their potential clinical applications.


The purification and properties of the lectin from potato tubers, a hydroxyproline-containing glycoprotein.
1. Potato lectin has been purified and shown to be a glycoprotein containing about 50% of carbohydrate. Most of the sugar residues (92%) are arabinose; small amounts of galactose, glucose and glucosamine are also present. 2. The most abundant amino acid is hydroxyproline (16% of the residues), 11.5% of the residues are half-cystine and phenylalanine is absent. The lectin also contains about one residue/molecule of a basic amino acid, not usually found in proteins, which has been tentatively identified as ornithine. There is indirect evidence that the components of the glycoprotein are linked through hydroxyproline and arabinose. 3. By gel filtration in 6m-guanidine-HCl on Sepharose 4B, it was found that both the native glycoprotein and its S-carboxymethylated derivative had subunit molecular weights of 46000 (+/-5000). In a non-denaturing solution, two of these units appear to be associated. 4. The lectin is specifically inhibited in its agglutination reaction by oligosaccharides that contain N-acetylglucosamine. Its specificity is similar to, but not identical with, that of wheat-germ agglutinin.


Accounting for center in the Early External Cephalic Version trials: an empirical comparison of statistical methods to adjust for center in a multicenter trial with binary outcomes.
Clustering of outcomes at centers involved in multicenter trials is a type of center effect. The Consolidated Standards of Reporting Trials Statement recommends that multicenter randomized controlled trials (RCTs) should account for center effects in their analysis, however most do not. The Early External Cephalic Version (EECV) trials published in 2003 and 2011 stratified by center at randomization, but did not account for center in the analyses, and due to the nature of the intervention and number of centers, may have been prone to center effects. Using data from the EECV trials, we undertook an empirical study to compare various statistical approaches to account for center effect while estimating the impact of external cephalic version timing (early or delayed) on the outcomes of cesarean section, preterm birth, and non-cephalic presentation at the time of birth. The data from the EECV pilot trial and the EECV2 trial were merged into one dataset. Fisher's exact method was used to test the overall effect of external cephalic version timing unadjusted for center effects. Seven statistical models that accounted for center effects were applied to the data. The models included: i) the Mantel-Haenszel test, ii) logistic regression with fixed center effect and fixed treatment effect, iii) center-size weighted and iv) un-weighted logistic regression with fixed center effect and fixed treatment-by-center interaction, iv) logistic regression with random center effect and fixed treatment effect, v) logistic regression with random center effect and random treatment-by-center interaction, and vi) generalized estimating equations. For each of the three outcomes of interest approaches to account for center effect did not alter the overall findings of the trial. The results were similar for the majority of the methods used to adjust for center, illustrating the robustness of the findings. Despite literature that suggests center effect can change the estimate of effect in multicenter trials, this empirical study does not show a difference in the outcomes of the EECV trials when accounting for center effect. The EECV2 trial was registered on 30 July 30 2005 with Current Controlled Trials: ISRCTN 56498577.


Effects of temperature on the development of Gregarina cubensis (Apicomplexa: Eugregarinida) parasitizing Blaberus discoidalis (Blattaria: Blaberidae).
Gregarina cubensis is an apicomplexan parasite that infects the intestinal lumen of the death's head cockroach (Blaberus discoidalis). This study evaluated the effects of 3 temperatures on the development and viability of G. cubensis. Three groups of B. discoidalis were inoculated with G. cubensis oocysts and maintained at 15, 27, and 40 C. The alimentary canal was removed from 3 cockroaches in each group every 24 hr until mature gametocysts were found in the rectum or feces, and prepared for histological examination. Gregarina cubensis establishment and development were more rapid at 15 C than at 27 C. Development of G. cubensis at 40 C did not progress beyond the intracellular stage.


Performance Tests of the Second-Order Approximate Internally Contracted Multireference Coupled-Cluster Singles and Doubles Method icMRCC2.
Benchmark results are presented for the second-order approximation of the internally contracted multireference coupled-cluster method with single and double excitations, icMRCC2 [Köhn, Bargholz, J. Chem. Phys. 2019, 151, 041106], which was designed as a multireference analogue of the single-reference second-order approximate coupled-cluster method CC2 [Christiansen, Koch, Jørgensen, Chem. Phys. Lett. 1995, 243, 409-418]. Vertical excitation energies of various small to medium-sized organic molecules are investigated based on established test sets from the literature. Additionally, the spectroscopic constants of ground and excited states of diatomics and the geometric parameters of excited triatomic molecules were determined and compared to the experimental data. The results show that the method clearly extends the applicability of single-reference CC2, including doubly excited states, and also artifacts of CC2 like too low Rydberg excitations and too weak multiple bonds are eliminated. The method is computationally more demanding than standard multireference second-order perturbation theories but improves significantly in accuracy, as shown by the benchmark results. In addition, it is demonstrated that small active spaces are often sufficient to obtain accurate energies with icMRCC2. Example applications like the automerization of cyclobutadiene, the deactivation pathway of ethylene, and the excited states of an iron complex with a noninnocent nitrosyl ligand demonstrate the potential of icMRCC2 in cases with strong multireference character.


Differential expression of the human homologue of drosophila discs large oncosuppressor in histologic samples from human papillomavirus-associated lesions as a marker for progression to malignancy.
High-risk HPVs play a causal role in the development of cervical cancer, and their E6 oncoproteins target h-Dlg for ubiquitin-mediated proteolysis. The h-Dlg oncosuppressor is associated with cell-cell interactions, and deregulation of these structures leads to defective cell adhesion, loss of cell polarity and unregulated proliferation. We evaluated the contribution of this E6 activity in the progression to malignancy in HPV infections by analyzing h-Dlg expression in HPV-associated lesions. We analyzed h-Dlg in cervical, laryngeal, vulvar, colon and kidney histologic samples by Dlg immunohistochemistry. HPV association was ascertained by a PCR-colorimetric method. Although Dlg was certainly expressed in intraepithelial cervical, vulvar and laryngeal HPV-associated lesions, its cellular and tissue distribution patterns were altered compared to normal tissue. However, marked reduction in Dlg levels was observed in HPV-positive invasive cervical carcinomas. To elucidate whether the loss of Dlg was significant for carcinogenesis in general, we investigated Dlg expression in tumors not associated with HPV. In colon and kidney carcinomas, Dlg was expressed, albeit with a different pattern of distribution with respect to the normal tissue. The loss of Dlg may be considered a late-stage marker in cervical carcinogenesis, but alterations in its expression and localization take place during the different dysplastic stages. Dlg downregulation and/or alterations in its localization may contribute to transformation and may explain some of the characteristics of the malignant cells, such as loss of polarity and high migration ability.


Detection of suppressed maturation of the human COQ5 protein in the mitochondria following mitochondrial uncoupling by an antibody recognizing both precursor and mature forms of COQ5.
Yeast Coq5p is required for the biosynthesis of coenzyme Q6 (CoQ6), but its human homolog has not been studied. We purified soluble recombinant human COQ5 protein under native conditions and generated an antibody recognizing both precursor and mature forms of COQ5. Mitochondrial localization of the mature form in 143B cells was demonstrated with this antibody. Moreover, a chemical uncoupler in a dose that suppressed CoQ10 levels downregulated the mature form but augmented the precursor form of COQ5. The results that knockdown of the COQ5 gene reduced CoQ10 levels further indicated the critical role of COQ5 in the biosynthesis of CoQ10.


Protein-protein interactions within paramyxoviruses identified by native disulfide bonding or reversible chemical cross-linking.
Analysis of native disulfide-bonded protein oligomers in paramyxoviruses showed that some viral proteins are consistently present as covalent complexes. In isolated Sendai virus the hemagglutinating protein HN is present in homodimeric and homotetrameric forms, and the minor nucleocapsid protein P exists partly as a monomer and partly as a disulfide-linked homotrimer. Similar disulfide-linked complexes were observed in Newcastle disease virus (strain HP-16), in which HN exists as a homodimer and some of the major nucleocapsid protein NP exists as a homotrimer. Noncovalent intermolecular interactions between proteins were studied with the reversible chemical cross-linkers dimethyl-3,3'-dithiobispropionimidate and methyl 3-[(p-azidophenyl)dithio]propionimidate, which contain disulfide bridges and a 1.1-nm separation between their functional groups. The same results were achieved with both reagents. The conditions of preparation, isolation, and storage of the viruses affected the protein-protein interactions observed upon cross-linking. Homooligomers of the glycoprotein F, the matrix protein M, and the major nucleocapsid protein NP were produced in both Sendai and Newcastle disease viruses after mild cross-linking of all viral preparations examined, but NP-M heterodimer formation in both viruses was most prevalent in early harvest preparations that were cross-linked soon after isolation. The ability of NP and M to form a heterodimer upon cross-linking indicates that the matrix protein layer lies in close proximity (within 1.1 nm) to the nucleocapsid in the newly formed virion. Some noncovalent intermolecular protein interactions in Sendai and Newcastle disease viruses, i.e., those leading to the formation of F, NP, and M homooliogmers upon cross-linking, are more stable to virus storage than others, i.e., those leading to the formation of an NP-M heterodimer upon cross-linking. The storage-induced loss of the ability of NP and M to form a heterodimer is not accompanied by any apparent loss of infectivity. This indicates that some spacial relationships which form during virus assembly can alter after particle formation and are not essential for the ensuing stages of the infectious process.


Oral anticoagulants status after acute ischemic stroke and prognosis in patients with atrial fibrillation.
To investigate the oral anticoagulants (OACs) use after acute ischemic stroke (AIS) and prognosis of patients with atrial fibrillation (AF). This was a real-world follow-up research of AIS patients with AF admitted to 5 hospitals in northwestern China. We visited these individuals every 6 months to check the type, dosage of OACs, and to record IS recurrence, bleeding, and death events and modified Rankin Scale (mRS) scores until December 2022. When one of the following occurring first was endpoint: IS recurrence, death or study end. Patients were divided into continuous anticoagulation group and non-continuous anticoagulation group based on whether they continued to take OACs from the moment they were discharged until the endpoint. We further analyzed the association between anticoagulation persistence and outcomes. Among all 250 patients with OACs indication, 147 patients (58.8 %) received OACs at discharge. Only 37.9 % of patients (39/103) started OACs after discharge. Of the 147 patients treated with OACs, 21.8 % (32/147) discontinued anticoagulation after discharge. 239 of the 250 patients had completed the median 40-month follow-up with 91 patients in continuous anticoagulation group and 148 patients in non-continuous anticoagulation group. In the multivariate COX regression, non-continuous anticoagulation was an independent risk factor for poor prognosis (mRS>2) in AIS patients with AF (1.452[1.011, 2.086], p = 0.043). This study revealed an upward trend in the use rate of OACs, but low OACs rates that meet guideline-based criteria and low anticoagulation persistence in AF patients after AIS in the northwestern China. Discontinuous anticoagulation was associated with an increased risk of poor prognosis in these patients.


[Lyme borreliosis--epidemiology, etiology, diagnosis and therapy].
The tick-borne Lyme Borreliosis may lead to a wide variety of sequels. Besides symptoms involving skin, joints and heart the infection provokes as a neurologic complication a meningopolyneuritis Garin-Bujadoux-Bannwarth in second state and a progressive encephalomyelitis in third state. Unexpected widespread--as modern laboratory investigations proved--the contamination only occasionally inflicts clinical manifestations. Involvement of the nervous system is substantiated by the demonstration of endogenous Borrelia antibodies in the cerebrospinal fluid. This prove is to claim especially for the assumption of a third state neuroborreliosis with progressive encephalomyelitis. Severe damage can be prevented by prompt diagnosis, specific treatment and follow-up.


Biodiversity Areas under Threat: Overlap of Climate Change and Population Pressures on the World's Biodiversity Priorities.
Humans and the ecosystem services they depend on are threatened by climate change. Places with high or growing human population as well as increasing climate variability, have a reduced ability to provide ecosystem services just as the need for these services is most critical. A spiral of vulnerability and ecosystem degradation often ensues in such places. We apply different global conservation schemes as proxies to examine the spatial relation between wet season precipitation, population change over three decades, and natural resource conservation. We pose two research questions: 1) Where are biodiversity and ecosystem services vulnerable to the combined effects of climate change and population growth? 2) Where are human populations vulnerable to degraded ecosystem services? Results suggest that globally only about 20% of the area between 50 degrees latitude North and South has experienced significant change-largely wetting-in wet season precipitation. Approximately 40% of rangelands and 30% of rainfed agriculture lands have experienced significant precipitation changes, with important implications for food security. Over recent decades a number of critical conservation areas experienced high population growth concurrent with significant wetting or drying (e.g. the Horn of Africa, Himalaya, Western Ghats, and Sri Lanka), posing challenges not only for human adaptation but also to the protection and sustenance of biodiversity and ecosystem services. Identifying areas of climate and population risk and their overlap with conservation priorities can help to target activities and resources that promote biodiversity and ecosystem services while improving human well-being.


Costs of revascularization over eight years in the randomized and eligible patients in the Emory Angioplasty versus Surgery Trial (EAST).
The Emory Angioplasty versus Surgery Trial (EAST) was a randomized trial that compared, by intention to treat, the clinical outcome and costs of percutaneous transluminal coronary angioplasty (PTCA) and coronary bypass grafting (CABG) for multivessel coronary artery disease. We present the findings of the economic analysis of EAST through 8 years of follow-up and compare the cost and outcomes of patients randomized in EAST versus patients eligible but not randomized (registry patients). Charges were assessed from hospital UB82 and UB92 bills and professional charges from the Emory Clinic. Hospital charges were reduced to cost through step-down accounting methods. All costs and charges were inflated to 1997 dollars. Costs were assessed for initial hospitalization and for cumulative costs of the initial hospitalization and additional revascularization procedures up to 8 years. Total 8-year costs were $46,548 for CABG and $44,491 for PTCA (p = 0.37). Cost of CABG in the eligible registry group showed a pattern similar to that for randomized patients, but total cost of PTCA was lower for registry patients than for randomized patients. Thus, the primary procedural costs of CABG are more than those for PTCA; this cost advantage, given the limits of measurement, is largely or even completely lost for randomized patients over the course of 8 years because of additional procedures after a first revascularization by PTCA.


PBX3 is essential for leukemia stem cell maintenance in MLL-rearranged leukemia.
Interaction of HOXA9/MEIS1/PBX3 is responsible for hematopoietic system transformation in MLL-rearranged (MLL-r) leukemia. Of these genes, HOXA9 has been shown to be critical for leukemia cell survival, while MEIS1 has been identified as an essential regulator for leukemia stem cell (LSC) maintenance. Although significantly high expression of PBX3 was observed in clinical acute myeloid leukemia (AML) samples, the individual role of PBX3 in leukemia development is still largely unknown. In this study, we explored the specific role of PBX3 and its associated regulatory network in leukemia progression. By analyzing the clinical database, we found that the high expression of PBX3 is significantly correlated with a poor prognosis in AML patients. ChIP-Seq/qPCR analysis in MLL-r mouse models revealed aberrant epigenetic modifications with increased H3K79me2, and decreased H3K9me3 and H3K27me3 levels in LSCs, which may account for the high expression levels of Pbx3. To further examine the role of Pbx3 in AML maintenance and progression, we used the CRISPR/Cas9 system to delete Pbx3 in leukemic cells in the MLL-AF9 induced AML mouse model. We found that Pbx3 deletion significantly prolonged the survival of leukemic mice and decreased the leukemia burden by decreasing the capacity of LSCs and promoting LSC apoptosis. In conclusion, we found that PBX3 is epigenetically aberrant in the LSCs of MLL-r AML and is essential for leukemia development. Significantly, the differential expression of PBX3 in normal and malignant hematopoietic cells suggests PBX3 as a potential prognostic marker and therapeutic target for MLL-r leukemia.


Lipid Droplet Biogenesis and Function in the Endothelium.
Fatty acids (FA) are transported across the capillary endothelium to parenchymal tissues. However, it is not known how endothelial cells (EC) from large vessels process a postprandial surge of FA. This study was designed to characterize lipid droplet (LD) formation in EC by manipulating pathways leading to the formation and degradation of LD. In addition, several functions of LD-derived FA were assessed. LD were present in EC lining the aorta after the peak in plasma triglycerides initiated by a gavage of olive oil in mice, in vivo. Similarly, in isolated aorta, oleic acid treatment generates LD in EC ex vivo. Cultured EC readily form LD largely via the enzyme DGAT (diacylglycerol O-acyltransferase 1) and degrade LD via ATGL (adipocyte triglyceride lipase) after FA loading. Functionally, LD-derived FA are dynamically regulated and function to protect EC from lipotoxic stress and provide FA for metabolic needs. Our results delineate endothelial LD dynamics for the first time in vivo and in vitro. Moreover, LD formation protects EC from lipotoxic stress, regulates EC glycolysis, and provides a source of FA for adjacent cells in the vessel wall or tissues.


Correction of motion artifacts in cone-beam CT using a patient-specific respiratory motion model.
Respiratory motion adversely affects CBCT image quality and limits its localization accuracy for image-guided radiation treatment. Motion correction methods in CBCT have focused on the thorax because of its higher soft tissue contrast, whereas low-contrast tissue in abdomen remains a challenge. The authors report on a method to correct respiration-induced motion artifacts in 1 min CBCT scans that is applicable in both thorax and abdomen, using a motion model adapted to the patient from a respiration-correlated image set. Model adaptation consists of nonrigid image registration that maps each image to a reference image in the respiration-correlated set, followed by a principal component analysis to reduce errors in the nonrigid registration. The model parametrizes the deformation field in terms of observed surrogate (diaphragm or implanted marker) position and motion (inhalation or exhalation) between the images. In the thorax, the model is obtained from the same CBCT images that are to be motion-corrected, whereas in the abdomen, the model uses respiration-correlated CT (RCCT) images acquired prior to the treatment session. The CBCT acquisition is a single 360 degrees rotation lasting 1 min, while simultaneously recording patient breathing. The approximately 600 projection images are sorted into six (in thorax) or ten (in abdomen) subsets and reconstructed to obtain a set of low-quality respiration-correlated RC-CBCT images. Application of the motion model deforms each of the RC-CBCT images to a chosen reference image in the set; combining all images yields a single high-quality CBCT image with reduced blurring and motion artifacts. Repeated application of the model with different reference images produces a series of motion-corrected CBCT images over the respiration cycle, for determining the motion extent of the tumor and nearby organs at risk. The authors also investigate a simpler correction method, which does not use PCA and correlates motion state with respiration phase, thus assuming repeatable breathing patterns. Comparison of contrast-to-noise ratios of pixel intensities within anatomical structures relative to surrounding background tissue provides a quantitative assessment of relative organ visibility. Evaluation in lung phantom, two patient cases in thorax and two in upper abdomen, shows that blurring and streaking artifacts are visibly reduced with motion correction. The boundaries of tumors in the thorax, liver, and kidneys are sharper and more discernible. Repeat application of the method in one thorax case, with reference images chosen at end expiration and end inspiration, indicates its feasibility for observing tumor motion extent. Phase-based motion correction without PCA reduces blurring less effectively; in addition, implanted markers appear broken up, indicating inconsistencies in the phase-based correction. In structures showing 1 cm or more motion excursion, PCA-based motion correction shows the highest contrast-to-noise ratios in the cases examined. Motion correction of CBCT is feasible and yields observable improvement in the thorax and abdomen. The PCA-based model is an important component: First, by reducing deformation errors caused by the nonrigid registration and second, by relating deformation to surrogate position rather than phase, thus accommodating breathing pattern changes between imaging sessions. The accuracy of the method requires confirmation in further patient studies.


The effect of osteotomy dimension on osseointegration to resorbable media-treated implants: a study in the sheep.
The drilling technique and the surface characteristics are known to influence the healing times of oral implants. The influence of osteotomy dimension on osseointegration of microroughned implant surfaces treated with resorbable blasting media was tested in an in vivo model. Ninety-six implants (ø4.5 mm, 8 mm in length) with resorbable blasting media-treated surfaces were placed in the ileum of six sheep. The final osteotomy diameters were 4.6 mm (reamer), 4.1 mm (loose), 3.7 mm (medium), and 3.2 mm (tight). After three and six weeks of healing, the implants were biomechanically tested and histologically evaluated. Statistical analysis was performed using Page L trend test for ordered and paired sample and linear regression, with significance level at p < 0.05. An overall increase in all dependent variables was observed with the reduction of osteotomy diameter. In addition, all osseointegration scores increased over time. At three weeks, the retention was significantly higher for smaller osteotomies. The histological sections depicted intimate contact of bone with all the implant surfaces and osteoblast lines were visible in all sections. The resorbable blasting media microroughed surfaces achieved successful osseointegration for all the instrumentation procedures tested, with higher osseointegration scores for the high insertion torque group.


Optimization of surgery sequencing and scheduling decisions under uncertainty.
Operating rooms (ORs) are simultaneously the largest cost center and greatest source of revenues for most hospitals. Due to significant uncertainty in surgery durations, scheduling of ORs can be very challenging. Longer than average surgery durations result in late starts not only for the next surgery in the schedule, but potentially for the rest of the surgeries in the day as well. Late starts also result in direct costs associated with overtime staffing when the last surgery of the day finishes later than the scheduled shift end time. In this article we describe a stochastic optimization model and some practical heuristics for computing OR schedules that hedge against the uncertainty in surgery durations. We focus on the simultaneous effects of sequencing surgeries and scheduling start times. We show that a simple sequencing rule based on surgery duration variance can be used to generate substantial reductions in total surgeon and OR team waiting, OR idling, and overtime costs. We illustrate this with results of a case study that uses real data to compare actual schedules at a particular hospital to those recommended by our model.


Improved visualization of macular hole lesions with laser biomicroscopy.
We have developed instrumentation to improve the visualization of fine vitreoretinal structures at the macula during slit-lamp biomicroscopy. The instrument, mounted on a slit-lamp microscope, used a green helium-neon laser to deliver a narrow beam, 15 micron(s) in width and 2 mm in length. The intersection of the laser slit with the ocular structures was viewed at an angle, as in conventional slit-lamp biomicroscopy. The instrument was used to examine patients with idiopathic macular holes or cysts. The results indicated that the new illumination was superior due to the narrow width of the beam, the enhanced brightness, and the monochromacy in green, which reduced background scatter. These advantages allowed for visualization of fine retinal structures that are difficult to detect with conventional slit-lamp biomicroscopy. The findings in patients with idiopathic macular hole demonstrated that the operculum was located approximately 500 micron(s) anterior to the surrounding retina and moved minimally. This suggested that the operculum may be supported by partially detached posterior vitreous cortex, and that a macular hole is the result of tangential traction followed by axial traction caused by a contracted and detached cortical vitreous gel.


Stereotactic Radiosurgery for Neurosurgical Patients: A Historical Review and Current Perspectives.
Today, stereotactic radiosurgery is an effective therapy for a variety of intracranial pathology that were treated solely with open neurosurgery in the past. The technique was developed from the combination of therapeutic radiation and stereotactic devices for the precise localization of intracranial targets. Although stereotactic radiosurgery was originally performed as a partnership between neurosurgeons and radiation oncologists, this partnership has weakened in recent years, with some procedures being performed without neurosurgeons. At the same time, neurosurgeons across the United States and Canada have found their stereotactic radiosurgery training during residency inadequate. Although neurosurgeons, residency directors, and department chairs agree that stereotactic radiosurgery education and exposure during neurosurgery training could be improved, a limited number of resources exist for this kind of education. This review describes the history of stereotactic radiosurgery, assesses the state of its use and education today, and provides recommendations for the improvement of neurosurgical education in stereotactic radiosurgery for the future.


Endoscopic trans-sphenoidal pituitary surgery does not impact postoperative nasal quality of life.
The aim of this prospective longitudinal study was to assess both subjective quality of life using questionnaires and objective examination of nasal function with regard to olfaction, nasal air flow and mucociliary clearance in patients after minimally invasive, turbinate-preserving endoscopic transnasal trans-sphenoidal pituitary surgery. Patients undergoing endoscopic transnasal pituitary surgery were recruited prospectively and examined during three study visits, preoperatively and 3 and 6 months postoperatively. We examined nasal function using sniffin' sticks test, rhinomanometry, saccharin transit time test, and endoscopic and radiological scores. In addition, the influence on subjective quality of life and mental health was recorded using the Sinonasal-Outcome-Test-20 (SNOT-20) and the Hospital-Anxiety-and-Depression-Scale (HADS). 20 patients undergoing endoscopic pituitary tumor resections were included. No significant changes in olfaction or mucociliary clearance were noted. Nasal air flow showed a tendency to increase in the postoperative course lacking significance. Both the endoscopy and the radiological scores showed a significant deterioration, especially after 3 months, with a trend towards improvement over time. However, neither the SNOT-20 nor the HADS showed significant changes compared to baseline. Our concept of minimally invasive endoscopic tumor resections on the pituitary gland with preservation of nasal turbinates shows low morbidity for the patient. Despite objectifiable surgery-associated changes in the nose, nasal physiology in terms of smell, airflow and mucociliary clearance can be preserved and the subjective quality of life of our patients remains stable.


RootNav: navigating images of complex root architectures.
We present a novel image analysis tool that allows the semiautomated quantification of complex root system architectures in a range of plant species grown and imaged in a variety of ways. The automatic component of RootNav takes a top-down approach, utilizing the powerful expectation maximization classification algorithm to examine regions of the input image, calculating the likelihood that given pixels correspond to roots. This information is used as the basis for an optimization approach to root detection and quantification, which effectively fits a root model to the image data. The resulting user experience is akin to defining routes on a motorist's satellite navigation system: RootNav makes an initial optimized estimate of paths from the seed point to root apices, and the user is able to easily and intuitively refine the results using a visual approach. The proposed method is evaluated on winter wheat (Triticum aestivum) images (and demonstrated on Arabidopsis [Arabidopsis thaliana], Brassica napus, and rice [Oryza sativa]), and results are compared with manual analysis. Four exemplar traits are calculated and show clear illustrative differences between some of the wheat accessions. RootNav, however, provides the structural information needed to support extraction of a wider variety of biologically relevant measures. A separate viewer tool is provided to recover a rich set of architectural traits from RootNav's core representation.


[Molecular polarity dependence of the transformed steroid effect on Na,K-ATPase].
The transformed steroids containing an additional cycle E (delta-lactone or 16.23-pyranone) or 23-carbethoxy side chain (1.10(-5) M) inhibit Na,K-ATPase from pig kidney medulla. The steroid structure has a noticeable effect on ATPase inhibiton varying from 9 to 35%. The data obtained suggest that the position, stereochemistry and the uneven distribution of polar substituents in the steroid molecule are essential for ATPase inhibition by steroid aglycons.


Depressive Symptoms and Amygdala Volume in Elderly with Cerebral Small Vessel Disease: The RUN DMC Study.
Introduction. Late onset depressive symptoms (LODSs) frequently occur in elderly with cerebral small vessel disease (SVD). SVD cannot fully explain LODS; a contributing factor could be amygdala volume. We investigated the relation between amygdala volume and LODS, independent of SVD in 503 participants with symptomatic cerebral SVD. Methods. Patients underwent FLAIR and T1 scanning. Depressive symptoms were assessed with structured questionnaires; amygdala and WML were manually segmented. The relation between amygdala volume and LODS/EODS was investigated and adjusted for age, sex, intracranial volume, and SVD. Results. Patients with LODS had a significantly lower left amygdala volume than those without (P = 0.02), independent of SVD. Each decrease of total amygdala volume (by mL) was related to an increased risk of LODS (OR = 1.77; 95% CI 1.02-3.08; P = 0.04). Conclusion. Lower left amygdala volume is associated with LODS, independent of SVD. This may suggest differential mechanisms, in which individuals with a small amygdala might be vulnerable to develop LODS.


Design and implementation of an identification system in construction site safety for proactive accident prevention.
Identifying accident precursors using real-time identity information has great potential to improve safety performance in construction industry, which is still suffering from day to day records of accident fatality and injury. Based on the requirements analysis for identifying precursor and the discussion of enabling technology solutions for acquiring and sharing real-time automatic identification information on construction site, this paper proposes an identification system design for proactive accident prevention to improve construction site safety. Firstly, a case study is conducted to analyze the automatic identification requirements for identifying accident precursors in construction site. Results show that it mainly consists of three aspects, namely access control, training and inspection information and operation authority. The system is then designed to fulfill these requirements based on ZigBee enabled wireless sensor network (WSN), radio frequency identification (RFID) technology and an integrated ZigBee RFID sensor network structure. At the same time, an information database is also designed and implemented, which includes 15 tables, 54 queries and several reports and forms. In the end, a demonstration system based on the proposed system design is developed as a proof of concept prototype. The contributions of this study include the requirement analysis and technical design of a real-time identity information tracking solution for proactive accident prevention on construction sites. The technical solution proposed in this paper has a significant importance in improving safety performance on construction sites. Moreover, this study can serve as a reference design for future system integrations where more functions, such as environment monitoring and location tracking, can be added.


[The nature of the humoral hemolytic factors in patients with chronic kidney failure].
The study of erythrodieresis intensity as well as that of its humoral component with identification of hemolytic factors of patients with chronic renal failure (thermal phase) on programmed hemodialysis (HD) showed development of anemia. This is due to intensive red cell destruction induced by enhanced hemolytic activity of the blood serum dependent on both the presence of medium-size peptides the number of which lessens in the course of hemodialysis and growing to the end of the session number of humoral hemolytic factors having molecular mass 80-100 kD. These findings should be considered when estimating efficacy of red cell mass infusions for patients with chronic renal failure basing on parameters of serum hemolytic activity and resistance of donor red cells to hemolyzing effects of the recipient's serum.


Localization of 5S RNA genes on Drosophila chromosomes by RNA-DNA hybridization.
[(3)H]RNA with a high specific activity was prepared from larvae of Drosophila melanogaster grown 4 days in contact with [(3)H]uridine. Purified tritiated 5S RNA was annealed to the DNA of polytene chromosomes, which had been denatured in formamide. The 5S RNA genes are placed within the region 56E-F of the right arm of chromosome 2. This localization was determined from autoradiographs, where the radioactivity from hybrids of [(3)H]RNA and DNA was confined to the 56E-F segment.


Baseline Edmonton Symptom Assessment System and survival in metastatic renal cell carcinoma.
Baseline symptom burden as measured using the Edmonton Symptom Assessment System (esas), a patient-reported, validated, and reliable tool measuring symptom severity in 9 separate domains, might yield prognostic information in patients receiving treatment for metastatic renal cell carcinoma (mrcc) and might add to the existing prognostic models. In this retrospective single-centre cohort study, we included patients receiving first-line sunitinib therapy for mrcc between 2008 and 2012. Baseline variables included information relevant to the pre-existing prognostic models and pre-treatment esas summation scores (added together across all 9 domains), with higher scores representing greater symptom burden. We used Kaplan-Meier curves and Cox regression modelling to determine if symptom burden can provide prognostic information with respect to overall survival. We identified 68 patients receiving first-line therapy for mrcc. Most had intermediate- or poor-risk disease based on both the Memorial Sloan Kettering Cancer Center (mskcc) and the International Metastatic Renal Cell Carcinoma Database Consortium (imdc) models. The median baseline esas summation score was 16 (range: 6-57). In univariable analysis, the hazard ratio for overall survival was 1.270 (p = 0.0047) per 10-unit increase in summation esas. In multivariable analysis, the hazard ratio was 1.208 (p = 0.0362) when controlling for mskcc risk group and 1.240 (p = 0.019) when controlling for imdc risk group. Baseline symptom burden as measured by esas score appears to provide prognostic information for survival in patients with mrcc. Those results should encourage the investigation of patient-reported symptom scales as potential prognostic indicators for patients with advanced cancer.


Cyclopentanoid terpene biosynthesis in a phasmid insect and in catmint.
The stick insect, Anisomorpha buprestoides, and the catmint, Nepeta cataria, produce closely related cyclopentanoid terpenes, anisomorphal and nepetalactone. Tracer experiments with isotopes indicate that anisomorphal is synthesized by the walking stick from normal terpene precursors (acetate or mevalonate). In the catmint plant, isolated leaf disks synthesized nepetalactone, utilizing the same precursors.


Design of metal organic framework-enzyme based bioelectrodes as a novel and highly sensitive biosensing platform.
Nanocomposites combining the mesoporous iron(iii) trimesate MIL-100(Fe) (MIL: Matériaux Institut Lavoisier) and platinum nanoparticles (Pt-NPs) have been used as immobilization matrices of glucose oxidase (GOx). Due to the physico-chemical properties of Pt-NPs (electroactivity) and MIL-100(Fe) (high specific surface area and pore volume, biocompatibility), the resulting GOx-MIL-100(Fe)-PtNP bioelectrode exhibits excellent electrocatalytic performances for glucose detection. This novel glucose biosensor presents a high sensitivity of 71 mA M-1 cm-2 under optimum conditions and a low limit of detection of 5 μM with low response time (<5 s). In contrast, substitution of iron by chromium or aluminum in MIL-100 leads to a much lower sensitivity and higher response time values, suggesting that the iron centres of MIL-100(Fe) may be involved in a synergistic effect which indeed enhances the catalytic oxidation of glucose and biosensor activity. Thus, this work extends the scope of MOF nanoparticles with engineered cores and surface to the field of highly sensitive, durable glucose biosensors.


A compendium of multi-omic sequence information from the Saanich Inlet water column.
Marine oxygen minimum zones (OMZs) are widespread regions of the ocean that are currently expanding due to global warming. While inhospitable to most metazoans, OMZs are hotspots for microbial mediated biogeochemical cycling of carbon, nitrogen and sulphur, contributing disproportionately to marine nitrogen loss and climate active trace gas production. Our current understanding of microbial community responses to OMZ expansion is limited by a lack of time-resolved data sets linking multi-omic sequence information (DNA, RNA, protein) to geochemical parameters and process rates. Here, we present six years of time-resolved multi-omic observations in Saanich Inlet, a seasonally anoxic fjord on the coast of Vancouver Island, British Columbia, Canada that undergoes recurring changes in water column oxygenation status. This compendium provides a unique multi-omic framework for studying microbial community responses to ocean deoxygenation along defined geochemical gradients in OMZ waters.


A novel epigenetic modulating agent sensitizes pancreatic cells to a chemotherapy agent.
Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second leading cause of cancer mortality by 2030. PDAC remains resistant to the majority of systemic chemotherapies. In this paper, we explore if epigenetic sensitization can improve chemotherapy response in PDAC. Multiple PDAC cell lines were tested with serial concentrations of the epigenetic modulators 5-azacitidine (Aza) and guadecitabine (SGI-110). Guadecitabine was effective at inhibiting the expression of DNA Methyltransferase 1 (DNMT1) and in decreasing cell viability at nanomolar concentrations. We also report that guadecitabine has increased efficacy following a delay period or as we reference, a 'rest period'. Sensitization with guadecitabine improved response to the chemotherapeutic agent-Irinotecan- as measured by decreased cell viability and accompanied by an increase in caspase activity. Additional studies are needed to understand the mechanism of action.


Absence of blood-pressure lowering effect of captopril in anephric patients.
Captopril, an orally active inhibitor of angiotensin-I-converting enzyme, was administered in a single dose to five anephric patients who had extremely low plasma renin activities. The drug did not lower blood pressure or significantly alter plasma renin activity in any patient but increased mean arterial pressure slightly in three. These results suggest that the blood-pressure lowering effect of captopril depends on an active renal renin-angiotensin system. Though additional mechanisms, such as accumulation of vasodilator kinins resulting from kininase II inhibition, may also contribute to captopril's action, these mechanisms apparently require the presence of the kidney to have a clinically detectable effect.


Protocols and critical pathways for stroke care.
We have presented a conceptual approach toward developing clinical protocols and critical pathways in a complex multidisciplinary environment with a commitment to clinical excellence, evidence-based practice methodology, and education. The process and the mood surrounding these have been more important in our view than any particular protocol or pathway. They have generated an attitude aiming toward avoidance of complications rather than crisis management. They have contributed to a philosophy of integrative multidisciplinary collaborations among various specialists, house staff, and nursing and paramedical personnel and a greater mutual sensitivity in interactions with medical center management and administration. The overall impact of this global approach has been quantifiable (Fig. 6), although the role(s) of one or more facets of it cannot be independently defined (21, 22). Protocols and clinical pathways should be viewed as components of total quality management. They should not be allowed to restrict the patient's or physician's choice of interventions, they should not inhibit in any way innovation or the introduction of novel methodologies. Yet, protocols and critical pathways should and do generate a pressure on every member of the health-care team, a sense of negative entropy constantly urging a move toward a higher level of excellence and quality.


The surgical management of symptomatic peripheral nerve sheath tumors.
To determine the clinical presentation and morbidity of the surgical management of peripheral nerve sheath tumors (PNSTs). We performed a retrospective chart review of surgically treated PNSTs at the University of Miami between 1991 and 2008. There were a total of 140 cases, including 87 schwannomas, 34 neurofibromas, and 19 malignant peripheral nerve sheath tumors (MPNSTs). The average age of the total study group was 49.0 years; it was significantly lower for patients with neurofibroma. There was a high correlation between neurofibroma tumors and neurofibromatosis-1. Most patients with benign tumors presented with a painful mass, paresthesias, or numbness without significant weakness. Patients who had previously undergone attempted resections and preoperative biopsy had a significantly increased risk (41%) for developing postoperative neurologic deficits when compared with patients who presented with de novo tumors (15%). Intraoperative monitoring appeared to reduce the risk of postoperative motor deficit, particularly in neurofibromas. Most MPNSTs (>80%) were diagnosed at stage IIB or higher and had a combined mortality rate of 31.6% at 78 months. Tumor size was the best predictor of adverse outcome, as all MPNST mortalities occurred in patients with a tumor size of more than 7 cm. PNSTs are a heterogeneous group of lesions. Benign tumors respond well to marginal excision, whereas MPNSTs are aggressive sarcomas that require multimodal management. There was a significantly increased risk of postoperative neurologic deficits in patients who had undergone a previous biopsy, and thus tertiary referral without biopsy is recommended when a PNST is suspected.


P/Halley: the quintessential comet.
Halley's comet is the focus of an international scientific enterprise now under way. Ground-based astronomical observations are already yielding new information about the comet's nucleus and atmosphere. In the coming year, remote and in situ investigations from the ground, Earth orbit, Venus orbit, interplanetary space, and within the comet itself are expected to reveal much more. The climax of the enterprise will be the penetration of an armored European spacecraft into the center of the comet in March 1986.


The impact of different nanoparticle surface chemistry and size on uptake and toxicity in a murine macrophage cell line.
This study investigated the uptake, kinetics and cellular distribution of different surface coated quantum dots (QDs) before relating this to their toxicity. J774.A1 cells were treated with organic, COOH and NH2 (PEG) surface coated QDs (40 nM). Model 20 nm and 200 nm COOH-modified coated polystyrene beads (PBs) were also examined (50 microg ml(-1)). The potential for uptake of QDs was examined by both fixed and live cell confocal microscopy as well as by flow cytometry over 2 h. Both the COOH 20 nm and 200 nm PBs were clearly and rapidly taken up by the J774.A1 cells, with uptake of 20 nm PBs being relatively quicker and more extensive. Similarly, COOH QDs were clearly taken up by the macrophages. Uptake of NH2 (PEG) QDs was not detectable by live cell imaging however, was observed following 3D reconstruction of fixed cells, as well as by flow cytometry. Cells treated with organic QDs, monitored by live cell imaging, showed only a small amount of uptake in a relatively small number of cells. This uptake was insufficient to be detected by flow cytometry. Imaging of fixed cells was not possible due to a loss in cell integrity related to cytotoxicity. A significant reduction (p<0.05) in the fluorescent intensity in a cell-free environment was found with organic QDs, NH2 (PEG) QDs, 20 nm and 200 nm PBs at pH 4.0 (indicative of an endosome) after 2 h, suggesting reduced stability. No evidence of exocytosis was found over 2 h. These findings confirm that surface coating has a significant influence on the mode of NP interaction with cells, as well as the subsequent consequences of that interaction.


Exploring examinee behaviours as validity evidence for multiple-choice question examinations.
Clinical-vignette multiple choice question (MCQ) examinations are used widely in medical education. Standardised MCQ examinations are used by licensure and certification bodies to award credentials that are meant to assure stakeholders as to the quality of physicians. Such uses are based on the interpretation of MCQ examination performance as giving meaningful information about the quality of clinical reasoning. There are several assumptions foundational to these interpretations and uses of standardised MCQ examinations. This study explores the implicit assumption that cognitive processes elicited by clinical-vignette MCQ items are like the processes thought to occur with 'real-world' clinical reasoning as theorised by dual-process theory. Fourteen participants (three medical students, five residents and six staff physicians) completed three sets of five timed MCQ items (total 15) from the Medical Knowledge Self-Assessment Program (MKSAP). Upon answering a set of MCQs, each participant completed a retrospective think aloud (TA) protocol. Using constant comparative analysis (CCA) methods sensitised by dual-process theory, we performed a qualitative thematic analysis. Examinee behaviours fell into three categories: clinical reasoning behaviours, test-taking behaviours and reactions to the MCQ. Consistent with dual-process theory, statements about clinical reasoning behaviours were divided into two sub-categories: analytical reasoning and non-analytical reasoning. Each of these categories included several themes. Our study provides some validity evidence that test-takers' descriptions of their cognitive processes during completion of high-quality clinical-vignette MCQs align with processes expected in real-world clinical reasoning. This supports one of the assumptions important for interpretations of MCQ examination scores as meaningful measures of clinical reasoning. Our observations also suggest that MCQs elicit other cognitive processes, including certain test-taking behaviours, that seem 'inauthentic' to real-world clinical reasoning. Further research is needed to explore if similar themes arise in other contexts (e.g. simulated patient encounters) and how observed behaviours relate to performance on MCQ-based assessments.


Vector averaging occurs downstream from learning in smooth pursuit eye movements of monkeys.
How are sensory-motor transformations organized in a cortical motor system? In general, sensory information is transformed through a variety of signal processing operations in the context of distinct coordinate frameworks. We studied the interaction of two distinct operations in pursuit eye movements, learning and vector-averaging, to gain insight into their underlying coordinate frameworks and their sequence in sensory-motor processing. Learning was induced in the initiation of pursuit eye movements by targets that moved initially at one speed for 100 msec and then increased or decreased to a sustained final speed. Vector averaging was studied by comparing the initial eye acceleration evoked by the simultaneous motion of two targets with that evoked by each target singly. Learning caused specific effects on the direction of the vector-averaged responses to two-target stimuli that included one target moving in the direction used to induce learning. Learned increases or decreases in eye acceleration caused the direction of the responses to two-targets to rotate toward or away from the learning direction. Learning also caused nonspecific changes in the responses to two-target stimuli. After any learning protocol, two-target responses usually became smaller, and their directions rotated away from the axis of the target motion used for learning. Quantitative analysis showed that the specific effects of learning were predicted most closely by a model in which vector averaging occurs downstream from the site(s) of learning. We suggest that the pursuit system creates parallel commands for potential movements to each of the targets in two-target stimuli, and that learning occurs in the coordinates of the potential movements.


Generalized prolate spheroidal wave functions for optical finite fractional Fourier and linear canonical transforms.
Prolate spheroidal wave functions (PSWFs) are known to be useful for analyzing the properties of the finite-extension Fourier transform (fi-FT). We extend the theory of PSWFs for the finite-extension fractional Fourier transform, the finite-extension linear canonical transform, and the finite-extension offset linear canonical transform. These finite transforms are more flexible than the fi-FT and can model much more generalized optical systems. We also illustrate how to use the generalized prolate spheroidal functions we derive to analyze the energy-preservation ratio, the self-imaging phenomenon, and the resonance phenomenon of the finite-sized one-stage or multiple-stage optical systems.


Evolution on a volcanic conveyor belt: using phylogeographic reconstructions and K-Ar-based ages of the Hawaiian Islands to estimate molecular evolutionary rates.
The Hawaiian Islands form as the Pacific Plate moves over a 'hot spot' in the earth's mantle where magma extrudes through the crust to build huge shield volcanos. The islands subside and erode as the plate carries them to the north-west, eventually to become coral atolls and seamounts. Thus islands are ordered linearly by age, with the oldest islands in the north-west (e.g. Kauai at 5.1 Ma) and the youngest in the south-east (e.g. Hawaii at 0.43 Ma). K-Ar estimates of the date of an island's formation provide a maximum age for the taxa inhabiting the island. These ages can be used to calibrate rates of molecular change under the following assumptions: (i) K-Ar dates are accurate; (ii) tree topologies show that derivation of taxa parallels the timing of island formation; (iii) populations do not colonize long after island emergence; (iv) the coalescent point for sister taxa does not greatly predate the formation of the colonized younger island; (v) saturation effects and (vi) among-lineage rate variation are minimal or correctable; and (vii) unbiased standard errors of distances and regressions can be estimated from multiple pairwise comparisons. We use the approach to obtain overall corrected rate calibrations for: (i) part of the mitochondrial cytochrome b gene in Hawaiian drepanidines (0.016 sequence divergence/Myr); (ii) the Yp1 gene in Hawaiian Drosophila (0.019/Myr Kambysellis et al. 1995); and (iii) parts of the mitochondrial 12S and 16S rRNA and tRNAval in Laupala crickets (0.024-0.102/Myr, Shaw 1996). We discuss the reliability of the estimates given the assumptions (i-vii) above and contrast the results with previous calibrations of Adh in Hawaiian Drosophila and chloroplast DNA in lobeliods.


The multi-disciplinary evaluation of a national agri-environment scheme.
With an increasing amount of public funds being spent on agri-environmental schemes effective methods have to be developed to evaluate them. As many schemes have multiple objectives there is a need for a multi-disciplinary approach to any evaluation. A method was developed to assess the degree to which ecological, landscape, historical and access objectives for the Countryside Stewardship Scheme (CSS) in England have been met. The method used a sample of 484 agreements for which data were collected from surveys, a desk study and an interview with the agreement holder. These data were then evaluated by an expert team of an ecologist, landscape architect, landscape historian, and a social scientist specializing in rural affairs. The team were subsequently brought together with a Chair to discuss their findings for each agreement, allocating scores for each of five criteria: agreement negotiation; appropriateness, environmental effectiveness, compliance and side effects. The additionality that each agreement was likely to provide was also assessed. The results of this process suggest that in the majority of cases the CSS agreements should maintain or enhance the environment in terms of ecology, landscape, and landscape history and increase public enjoyment of the countryside. Thirty-six percent of agreements showed high additionality and 38% medium additionality which demonstrates that the CSS is likely to provide a benefit to society. Agreement negotiation, predicted environmental effectiveness and predicted compliance all improved significantly over the period 1996-98. Recommendations made from this project have been implemented by the Government department to improve the CSS. The multi-disciplinary method was successful and, with further development, could be used for assessment of any agri-environment scheme, or potentially any conservation project or broader 'rural development' scheme encompassing environmental, economic and social objectives. A key to success is the need for the criteria to be tailored for the project concerned and clearly established at the beginning.


SDH5 Depletion Enhances Radiosensitivity by Regulating p53: A New Method for Noninvasive Prediction of Radiotherapy Response.
Radiotherapy is an effective treatment for lung cancer but lacks a reliable prediction method. Cell-free nucleic acids in plasma have been reported as a novel tumor marker. Here, we evaluate circulating succinate dehydrogenase 5 (SDH5) mRNA in plasma and SDH5 protein in tumors, assess their predictive value in lung cancer patients undergoing radiotherapy, and explore the underlying mechanisms. Methods: SDH5 expression was measured in peripheral blood samples and fresh tumor specimens from 208 non-small cell lung cancer (NSCLC) patients and correlated with clinical outcomes. SDH5 knockout mice and human xenograft mice were used to evaluate radiosensitivity. Cell growth, apoptosis, and the DNA damage response were assessed. Relevant RNA and protein levels were analyzed by qRT-PCR and Western blotting. Immunoprecipitation and GST pulldown assays were performed to detect protein-protein interactions. Polyubiquitination of p53 was examined by an in vitro ubiquitination assay. Results: Plasma and tumor SDH5 mRNA levels were positively correlated (rho=0.894, P<0.001). Patients with relatively low SDH5 levels in plasma (0.47, 0.12-0.89) and tumors (3.85, 0.96-7.23) had a better prognosis after radiotherapy (median PFS: 30.0 versus 15.0 months, hazard ratio: 0.276, 95% CI: 0.201-0.379, P<0.001). In SDH5 knockout mice, the lung epithelial cells exhibited increased DNA damage after radiation. In human lung xenograft mice, SDH5-deficient tumors had a smaller volume after radiotherapy. Furthermore, SDH5 depletion inhibits p53 degradation via the ubiquitin/proteasome pathway, which promotes apoptosis and enhances radiosensitivity in NSCLC. Conclusion: Our findings provide a novel noninvasive method for prediction of response to radiotherapy and may have significant implications for cancer radiotherapy.


Endemic typhus in Singapore--a re-emerging infectious disease?
Singapore is a modern urban city and endemic typhus is thought to be a disease of the past. This may be due to lack of specific serological testing as indirect immunoperoxidase testing using specific rickettsial antigens (U.S. Army Medical Research Unit, Institute of Medical Research, Kuala Lumpur, Malaysia) has only recently become available. In the last fourteen months, twenty-one cases of endemic typhus were diagnosed in patients hospitalised for acute febrile illnesses at the National University Hospital. We conducted a case control study to define the clinical and laboratory features of endemic typhus in Singapore. Demographic, clinical and laboratory data were reviewed for cases and twenty-one age and sex matched controls who had negative serologic tests as part of a work-up for fever of unknown origin. Apart from a higher initial temperature (39 degrees C vs 37.9 degrees C (p < 0.001)) and ALT(p = 0.002), cases and controls had similar presentations of fever, myalgia, headache, cough, normal WBC and platelet counts. Singapore residents and migrant workers were represented in both groups (p = ns). Endemic typhus remains an important cause of acute febrile illness in Singaporein both the local and migrant worker populations. The presentation is similar to other causes of acute febrile illnesses and the diagnosis will be missed unless it is specifically sought.


Interplay between phosphorylation and palmitoylation mediates plasma membrane targeting and sorting of GAP43.
Phosphorylation and lipidation provide posttranslational mechanisms that contribute to the distribution of cytosolic proteins in growing nerve cells. The growth-associated protein GAP43 is susceptible to both phosphorylation and S-palmitoylation and is enriched in the tips of extending neurites. However, how phosphorylation and lipidation interplay to mediate sorting of GAP43 is unclear. Using a combination of biochemical, genetic, and imaging approaches, we show that palmitoylation is required for membrane association and that phosphorylation at Ser-41 directs palmitoylated GAP43 to the plasma membrane. Plasma membrane association decreased the diffusion constant fourfold in neuritic shafts. Sorting to the neuritic tip required palmitoylation and active transport and was increased by phosphorylation-mediated plasma membrane interaction. Vesicle tracking revealed transient association of a fraction of GAP43 with exocytic vesicles and motion at a fast axonal transport rate. Simulations confirmed that a combination of diffusion, dynamic plasma membrane interaction and active transport of a small fraction of GAP43 suffices for efficient sorting to growth cones. Our data demonstrate a complex interplay between phosphorylation and lipidation in mediating the localization of GAP43 in neuronal cells. Palmitoylation tags GAP43 for global sorting by piggybacking on exocytic vesicles, whereas phosphorylation locally regulates protein mobility and plasma membrane targeting of palmitoylated GAP43.


Pharmacologic enhancement of retromer rescues endosomal pathology induced by defects in the Alzheimer's gene SORL1.
The SORL1 gene (SORLA) is strongly associated with risk of developing Alzheimer's disease (AD). SORLA is a regulator of endosomal trafficking in neurons and interacts with retromer, a complex that is a "master conductor" of endosomal trafficking. Small molecules can increase retromer expression in vitro, enhancing its function. We treated hiPSC-derived cortical neurons that are either fully deficient, haploinsufficient, or that harbor one copy of SORL1 variants linked to AD with TPT-260, a retromer-enhancing molecule. We show significant increases in retromer subunit VPS26B expression. We tested whether endosomal, amyloid, and TAU pathologies were corrected. We observed that the degree of rescue by TPT-260 treatment depended on the number of copies of functional SORL1 and which SORL1 variant was expressed. Using a disease-relevant preclinical model, our work illuminates how the SORL1-retromer pathway can be therapeutically harnessed.