Foods with Potential Prooxidant and Antioxidant Effects Involved in Parkinson's Disease.
Oxidative stress plays a fundamental role in the pathogenesis of Parkinson's disease (PD). Oxidative stress appears to be responsible for the gradual dysfunction that manifests via numerous cellular pathways throughout PD progression. This review will describe the prooxidant effect of excessive consumption of processed food. Processed meat can affect health due to its high sodium content, advanced lipid oxidation end-products, cholesterol, and free fatty acids. During cooking, lipids can react with proteins to form advanced end-products of lipid oxidation. Excessive consumption of different types of carbohydrates is a risk factor for PD. The antioxidant effects of some foods in the regular diet provide an inconclusive interpretation of the environment's mechanisms with the modulation of oxidation stress-induced PD. Some antioxidant molecules are known whose primary mechanism is the neuroprotective effect. The melatonin mechanism consists of neutralizing reactive oxygen species (ROS) and inducing antioxidant enzyme's expression and activity. N-acetylcysteine protects against the development of PD by restoring levels of brain glutathione. The balanced administration of vitamin B3, ascorbic acid, vitamin D and the intake of caffeine every day seem beneficial for brain health in PD. Excessive chocolate intake could have adverse effects in PD patients. The findings reported to date do not provide clear benefits for a possible efficient therapeutic intervention by consuming the nutrients that are consumed regularly.


Prevalence and risk of inappropriate dosing of direct oral anticoagulants in two Swiss atrial fibrillation registries.
Direct oral anticoagulants (DOACs) have a favourable risk-benefit profile compared to vitamin K-antagonists (VKAs) in atrial fibrillation (AF). Dosing is based on age, weight and renal function, without need of routine monitoring. In two prospective, multicentre AF cohorts (Swiss-AF, BEAT-AF) patients were stratified as receiving VKAs or adequately-, under- or overdosed DOACs, according to label. Primary outcome was a composite of major adverse clinical events (MACE), defined as cardiovascular death, myocardial infarction (MI), ischaemic stroke and systemic embolism. Secondary outcomes included major bleeding. Adjustment for confounding was performed. Median follow-up was 4 years. Of 3236 patients, 1875 (58%) were on VKAs and 1361 (42%) were on DOACs, of which 1137 (83%) were adequately-, 134 (10%) over- and 90 (7%) under-dosed. Compared to adequately dosed individuals, overdosed patients were more likely to be older and female. Underdosing correlated with concomitant aspirin therapy and coronary artery disease. Both groups had higher CHA2DS2-VASc scores. Patients on overdosed DOACs had higher incidence of MACE (HR 1.75; CI 1.10-2.79; adjusted-HR: 1.22) and major bleeding (HR 1.99; CI 1.14-3.48; adjusted-HR: 1.51). Underdosing was not associated with a higher incidence of MACE (HR 0.94; CI 0.46-1.92; adjusted-HR 0.61) or major bleeding (HR 1.07; CI 0.46-2.46; adjusted-HR 0.82). After adjustment, all CIs crossed 1.0. Inappropriate DOAC-dosing was more prevalent in multimorbid patients, but did not correlate with higher risks of adverse events after adjusting for confounders. DOAC prescription should follow label.


Paradoxical activation of endothelial nitric oxide synthase by NADPH oxidase.
Increased formation of reactive oxygen species (ROS) has been identified as a causative factor in endothelial dysfunction by reducing NO bioavailability and uncoupling endothelial nitric oxide synthase (eNOS). However, the specific contribution of ROS to endothelial function is not well understood. A major source of intracellular ROS is the NADPH oxidase (Nox) family of enzymes. The goal of the current study was to directly assess the contribution of NADPH oxidase derived superoxide to eNOS function by expressing Nox5, a single gene product that constitutively produces superoxide within cells. Paradoxically, we found that instead of inhibiting eNOS, coexpression of Nox5 increased NO release from both bovine and human endothelial cells. To establish the functional significance of this observation in intact blood vessels, the endothelium of mouse aorta was transduced with Nox5 or control adenoviruses. Nox5 potently inhibited Ach-induced relaxation and potentiated contractile responses to phenylephrine. In precontracted aortae, acute exposure to superoxide dismutase induced significant vascular relaxation in vessels exposed to Nox5 versus control and unmasked the ability of Nox5 to activate eNOS in blood vessel endothelium. These findings suggest that ROS inhibit eNOS function via consumption of NO rather than direct inhibition of enzymatic activity.


A Novel Approach to Pod Count Estimation Using a Depth Camera in Support of Soybean Breeding Applications.
Improving soybean (Glycine max L. (Merr.)) yield is crucial for strengthening national food security. Predicting soybean yield is essential to maximize the potential of crop varieties. Non-destructive methods are needed to estimate yield before crop maturity. Various approaches, including the pod-count method, have been used to predict soybean yield, but they often face issues with the crop background color. To address this challenge, we explored the application of a depth camera to real-time filtering of RGB images, aiming to enhance the performance of the pod-counting classification model. Additionally, this study aimed to compare object detection models (YOLOV7 and YOLOv7-E6E) and select the most suitable deep learning (DL) model for counting soybean pods. After identifying the best architecture, we conducted a comparative analysis of the model's performance by training the DL model with and without background removal from images. Results demonstrated that removing the background using a depth camera improved YOLOv7's pod detection performance by 10.2% precision, 16.4% recall, 13.8% mAP@50, and 17.7% firstname.lastname@example.com:0.95 score compared to when the background was present. Using a depth camera and the YOLOv7 algorithm for pod detection and counting yielded a firstname.lastname@example.com of 93.4% and firstname.lastname@example.com:0.95 of 83.9%. These results indicated a significant improvement in the DL model's performance when the background was segmented, and a reasonably larger dataset was used to train YOLOv7.


Attention and information processing efficiency in patients with Chronic Fatigue Syndrome.
In this study a battery of attentional tests and a verbal memory task were administered to outpatients with Chronic Fatigue Syndrome (CFS) in order to evaluate aspects of attention that have not been explored in this group to date. In addition, this study was designed to further examine memory function and to extend the few reports investigating the rate of cognitive processing independent of motor speed and the possibility of a modality-specific impairment of information processing. Twenty-nine patients with CFS and 22 healthy controls matched for age, gender, intelligence, and education were included in this study. The results show that patients with CFS do not seem to be impaired for modification of phasic arousal level, nor for visual selective attention requiring shifting of attention in the visuospatial field. The results further support the presence of reduced information processing speed and efficiency, and strengthen the evidence of a global non-modality-specific attentional dysfunction in patients with CFS. In this study the poor performance of patients with CFS on recall of verbal information was due to poor initial storage rather than to a retrieval failure.


Geometric and topological characterization of the cytoarchitecture of islets of Langerhans.
The islets of Langerhans are critical endocrine micro-organs that secrete hormones regulating energy metabolism in animals. Insulin and glucagon, secreted by beta and alpha cells, respectively, are responsible for metabolic switching between fat and glucose utilization. Dysfunction in their secretion and/or counter-regulatory influence leads to diabetes. Debate in the field centers on the cytoarchitecture of islets, as the signaling that governs hormonal secretion depends on structural and functional factors, including electrical connectivity, innervation, vascularization, and physical proximity. Much effort has therefore been devoted to elucidating which architectural features are significant for function and how derangements in these features are correlated or causative for dysfunction, especially using quantitative network science or graph theory characterizations. Here, we ask if there are non-local features in islet cytoarchitecture, going beyond standard network statistics, that are relevant to islet function. An example is ring structures, or cycles, of α and δ cells surrounding β cell clusters or the opposite, β cells surrounding α and δ cells. These could appear in two-dimensional islet section images if a sphere consisting of one cell type surrounds a cluster of another cell type. To address these issues, we developed two independent computational approaches, geometric and topological, for such characterizations. For the latter, we introduce an application of topological data analysis to determine locations of topological features that are biologically significant. We show that both approaches, applied to a large collection of islet sections, are in complete agreement in the context both of developmental and diabetes-related changes in islet characteristics. The topological approach can be applied to three-dimensional imaging data for islets as well.


Pilot Study of Mindfulness Training on the Self-Awareness of Motor Symptoms in Parkinson's Disease - A Randomized Controlled Trial.
Objective: This study aims to evaluate feasibility and effects of a newly developed mindfulness intervention tailored to specific needs of patients with Parkinson's disease (PD). Background: The phenomenon of impaired self-awareness of motor symptoms (ISAm) in PD might be reduced by increasing patients' mindfulness. A PD-specific mindfulness intervention has been developed and evaluated as a potential treatment option: IPSUM ("Insight into Parkinson's Disease Symptoms by using Mindfulness"). Methods: IPSUM's effectiveness is evaluated by comparing an intervention with a waitlist-control group. Applying a pre-post design, patients were assessed before, directly after and 8weeks after treatment. The primary outcome was the change in a quantitative ISAm score from baseline to post-assessment. Secondary outcome measures were PD-related affective changes and neuropsychological test performance. Feasibility was evaluated via feedback forms. Results: In total, 30 non-depressed and non-demented PD patients were included (intervention: n=14, waitlist-control: n=16). ISAm score did not change significantly, but the training group showed greater performance in sustained attention and language tasks over time. Additional changes included greater mindfulness as well as less sleeping problems and anxiety. Cognitive disturbances, apathy, and sleeping problems worsened only in the waitlist-control group. Patients' feedback regarding the training concept and material was excellent. Conclusion: Insight into Parkinson's Disease Symptoms by using Mindfulness has not been capable of reducing ISAm in PD patients but appears to be a feasible and effective concept to, among others, support mental health in the mid-term. It has to be noted though that the study was stopped beforehand because of the SARS CoV-2 pandemic. The lack of findings might therefore be caused by a lack of statistical power. The need for further research to better understand the mechanisms of ISAm and its connection to mindfulness in PD is highlighted.


Fish oil enhances targeted apoptosis during colon tumor initiation in part by downregulating Bcl-2.
We have shown that fish oil is protective against colon tumorigenesis, primarily by upregulating apoptosis. Production of prostaglandin E2 (PGE2) in colon cancer cells by cyclooxygenase (COX)-I and -II is known to inhibit apoptosis by induction of bcl-2. Because we have shown that fish oil downregulates PGE2 and COX-II, we hypothesized that this upregulation of apoptosis would be coincident with a downregulation of bcl-2. Bcl-2 was localized within the colonic crypt by quantitative immunohistochemistry (IHC), and scraped colonic mucosa was used for immunoblot analysis of bcl-2. The tissue used for bcl-2 analysis was from the rats used to determine apoptosis. Briefly, tissues were collected from rats consuming diets containing either corn oil or fish oil at 3, 6, 9, and 12 h after carcinogen injection. The correlation between bcl-2 and apoptosis was also determined. Bcl-2 expression decreased until 9 h (P < 0.05), whereas apoptosis increased until 9 h (P < 0.01). Bcl-2 expression and apoptosis were negatively correlated in both the proximal (P < 0.05) and distal colon (P < 0.005). Fish oil decreased bcl-2 expression (P < 0.05) and increased apoptosis (P < 0.05) in the top third of the crypt in the distal colon. In conclusion, one pathway by which fish oil may mediate apoptosis and thus protect against colon tumorigenesis is by downregulation of anti-apoptotic bcl-2.


Parametric number covariance in quantum chaotic spectra.
We study spectral parametric correlations in quantum chaotic systems and introduce the number covariance as a measure of such correlations. We derive analytic results for the classical random matrix ensembles using the binary correlation method and obtain compact expressions for the covariance. We illustrate the universality of this measure by presenting the spectral analysis of the quantum kicked rotors for the time-reversal invariant and time-reversal noninvariant cases. A local version of the parametric number variance introduced earlier is also investigated.


[Personality-specific disposition to stomach cancer].
24 patients (10 female and 14 male) with a histologically evident stomach cancer underwent a series of psychoanalytical interviews and psychological tests (TAT). The method consisted of an analysis of early childhood conditions, the structure of personality, the object relationships, as well as the psychic causes for the stomach cancer. Among the results was that the loss of one parent or an equivalent early loss was significantly more frequent in stomach cancer patients than in the average population. Their predominant sibling position was the so-called sandwich-position. In regard to the structure of personality a constantly persisting false assimilation of inner conflicts presents itself as the essential item of the premorbid structure. The initiating factor for the stomach cancer was a statistically significantly often experienced severe trauma based on a significantly often experienced object loss, especially during childhood, as well as on a family disposition in the relation of 1:50. In addition to that the following conspicuous features were responsible for the formation of the stomach cancer: A persisting problem of separation (Oedipus conflicts), a resignation in an apathetic reaction (excessive demands), an inability to release aggression in a "normal" way and a direction of the aggression against the person himself.


Adaptive behavior in autism: Minimal clinically important differences on the Vineland-II.
Autism Spectrum Disorder (ASD) is associated with persistent impairments in adaptive abilities across multiple domains. These social, personal, and communicative impairments become increasingly pronounced with development, and are present regardless of IQ. The Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) is the most commonly used instrument for quantifying these impairments, but minimal clinically important differences (MCIDs) on Vineland-II scores have not been rigorously established in ASD. We pooled data from several consortia/registries (EU-AIMS LEAP study, ABIDE-I, ABIDE-II, INFOR, Simons Simplex Collection and Autism Treatment Network [ATN]) and clinical investigations and trials (Stanford, Yale, Roche) resulting in a data set of over 9,000 individuals with ASD. Two approaches were used to estimate MCIDs: distribution-based methods and anchor-based methods. Distribution-based MCID [d-MCID] estimates included the standard error of the measurement, as well as one-fifth and one-half of the covariate-adjusted standard deviation (both cross-sectionally and longitudinally). Anchor-based MCID [a-MCID] estimates include the slope of linear regression of clinician ratings of severity on the Vineland-II score, the slope of linear regression of clinician ratings of longitudinal improvement category on Vineland-II change, the Vineland-II change score maximally differentiating clinical impressions of minimal versus no improvement, and equipercentile equating. Across strata, the Vineland-II Adaptive Behavior Composite standardized score MCID estimates range from 2.01 to 3.2 for distribution-based methods, and from 2.42 to 3.75 for sample-size-weighted anchor-based methods. Lower Vineland-II standardized score MCID estimates were observed for younger and more cognitively impaired populations. These MCID estimates enable users of Vineland-II to assess both the statistical and clinical significance of any observed change. Autism Res 2018, 11: 270-283. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. The Vineland Adaptive Behavior Scales (2nd edition; Vineland-II) is the most widely used scale for assessing day-to-day "adaptive" skills. Yet, it is unknown how much Vineland-II scores must change for those changes to be regarded as clinically significant. We pooled data from over 9,000 individuals with ASD to show that changes of 2-3.75 points on the Vineland-II Composite score represent the "minimal clinically-important difference." These estimates will help evaluate the benefits of potential new treatments for ASD.


Impairment of an electroconvulsive stimulus on reconsolidation of memories established by conditioning.
The deduced memory consolidation and reconsolidation phases are sensitive to similar amnesic and memory-enhancing treatment. Electroconvulsive stimulus has been well known to impair memory consolidation. Therefore, we hypothesized that electroconvulsive stimulus might disrupt reconsolidation for conditioning-established memories. Delivery of a 200-msec electroconvulsive stimulus (500 V, 25 mA) between mouse pinnas immediately after recall of the cocaine-induced conditioned place preference (CPP) impaired the reconsolidation and subsequent expression of this memory. In contrast, the electroconvulsive stimulus (500 V, 25 mA, lasting for 200 ms) did not affect subsequent cocaine-induced CPP performance when the recall procedure was omitted. Systemic pentobarbital injection immediately after the CPP test did not affect subsequent cocaine-induced CPP. Interestingly, several regimens of electroconvulsive stimulus given immediately after the recall of cocaine-induced CPP did not affect subsequent CPP performance when mice were anesthetized by pentobarbital throughout the ECS regimens. Finally, delivery of the ECS (500 V, 25 mA, lasting for 200 ms) immediately after the reactivation of passive avoidance (PA) and food-induced CPP impaired subsequent performance of these memories in the retest. Taken together, we conclude that a short-lasting electroconvulsive stimulus can deteriorate the reconsolidation of various forms of memory established by conditioning.


Enantioselective total synthesis of FR900482.
The development of two approaches for the enantioselective total synthesis of FR900482 is described. A precursor for the formation of the benzazocine ring was assembled effectively by a modification of the Sonogashira coupling of an aryl triflate with a chiral acetylene unit derived from tartaric acid and the subsequent novel ketone formation via conjugate addition of pyrrolidine to the o-nitrophenylacetylene derivative. The first-generation approach to the key pentacyclic intermediate of our racemic total synthesis utilizes an intramolecular Mitsunobu reaction of an omega-hydroxynitrobenzenesulfonamide to form the benzazocine ring and a stepwise sequence to construct the hydroxymethyl group at the C(7) position. The key intermediate could be synthesized in optically pure form via formation of the characteristic hydroxylamine hemiacetal and a stereoselective epoxide formation. In the second-generation approach, the N-hydroxybenzazocine ring could be constructed directly from an omega-formylnitrobenzene derivative by intramolecular reductive hydroxylamination. The crucial stereoselective hydroxymethylation and the formation of the hydroxylamine hemiacetal could be performed efficiently by a one-pot sequence. After leading to the pentacyclic key intermediate, the total synthesis of (+)-FR900482 was accomplished by a modification of our protocol established in the racemic total synthesis. Stereochemical issues involved in the hydroxymethylation at the C(7) position and formation of the hydroxylamine hemiacetal are also discussed in detail.


Growing season net ecosystem CO2 exchange of two desert ecosystems with alkaline soils in Kazakhstan.
Central Asia is covered by vast desert ecosystems, and the majority of these ecosystems have alkaline soils. Their contribution to global net ecosystem CO2 exchange (NEE) is of significance simply because of their immense spatial extent. Some of the latest research reported considerable abiotic CO2 absorption by alkaline soil, but the rate of CO2 absorption has been questioned by peer communities. To investigate the issue of carbon cycle in Central Asian desert ecosystems with alkaline soils, we have measured the NEE using eddy covariance (EC) method at two alkaline sites during growing season in Kazakhstan. The diurnal course of mean monthly NEE followed a clear sinusoidal pattern during growing season at both sites. Both sites showed significant net carbon uptake during daytime on sunny days with high photosynthetically active radiation (PAR) but net carbon loss at nighttime and on cloudy and rainy days. NEE has strong dependency on PAR and the response of NEE to precipitation resulted in an initial and significant carbon release to the atmosphere, similar to other ecosystems. These findings indicate that biotic processes dominated the carbon processes, and the contribution of abiotic carbon process to net ecosystem CO2 exchange may be trivial in alkaline soil desert ecosystems over Central Asia.


The politicisation of suburbanisation in Belgium: towards an urban–suburban divide.
The electoral and political consequences of suburbanisation recently regained interest in the Anglo-Saxon literature, pointing to a growing polarisation between city and suburban fringe. This paper analyses these processes in the Antwerp urban region and shows the development of a similar electoral divide that is supported by the political parties involved. These observations add to the existing evidence that city–suburban polarisation in Belgium cannot be simply equated with the Anglo-Saxon experience, where a complete suburban fencing off from the city is observable. Rather, because of the comparatively limited development of functions in the Belgian suburbs, a suburban discourse emerges that focuses on safe and accessible cities for the suburban user, yet without much reference to its present inhabitants.


Graphene oxide-polysulfone filters for tap water purification, obtained by fast microwave oven treatment.
The availability of clean, pure water is a major challenge for the future of our society. 2-Dimensional nanosheets of GO seem promising as nanoporous adsorbent or filters for water purification; however, their processing in macroscopic filters is challenging, and their cost vs. standard polymer filters is too high. Here, we describe a novel approach to combine graphene oxide (GO) sheets with commercial polysulfone (PSU) membranes for improved removal of organic contaminants from water. The adsorption physics of contaminants on the PSU-GO composite follows Langmuir and Brunauer-Emmett-Teller (BET) models, with partial swelling and intercalation of molecules in between the GO layers. Such a mechanism, well-known in layered clays, has not been reported previously for graphene or GO. Our approach requires minimal amounts of GO, deposited directly on the surface of the polymer, followed by stabilization using microwaves or heat. The purification efficiency of the PSU-GO composites is significantly improved vs. benchmark commercial PSU, as demonstrated by the removal of two model contaminants, rhodamine B and ofloxacin. The excellent stability of the composite is confirmed by extensive (100 hours) filtration tests in commercial water cartridges.


Penicillinase (beta-lactamase) induction in Bacillus licheniformis under Pseudogratuitous conditions by 2-(2'-carboxyphenyl)-benzoyl-6-aminopenicillanic acid.
Induction of penicillinase (beta-lactamase) in Bacillus licheniformis 749 by 2-(2'-carboxyphenyl)-benzoyl-6-aminopenicillanic acid (CBAP) was examined, since this compound was reported to be a gratuitous inducer of penicillinase in Staphylococcus aureus. The specific activity of enzyme optimally induced by CBAP is slightly more than that formed in response to cephalosporin C and threefold the level induced by benzylpenicillin. The optimal inducer concentration of CBAP was not inhibitory toward the growth of penicillinase-deficient mutants, unlike benzylpenicillin or cephalosporin C which showed marked toxicities. CBAP is hydrolyzed by the Bacillus penicillinase, but as indicated by its "physiological efficiency" (V(max)/K(m)), CBAP is a poor substrate at low concentrations. At very high concentrations, CBAP inhibited benzylpenicillin hydrolysis. The overall effectiveness of CBAP as an inducer can be attributed to its low "physiological efficiency" which enables the use of nontoxic levels of CBAP for induction without its rapid hydrolysis. Although CBAP is not a true gratuitous inducer, operationally it approaches gratuity for induction of B. licheniformis penicillinase better than other known inducers.


An online air pollution forecasting system using neural networks.
In this work, an online air pollution forecasting system for Greater Istanbul Area is developed. The system predicts three air pollution indicator (SO(2), PM(10) and CO) levels for the next three days (+1, +2, and +3 days) using neural networks. AirPolTool, a user-friendly website (http://airpol.fatih.edu.tr), publishes +1, +2, and +3 days predictions of air pollutants updated twice a day. Experiments presented in this paper show that quite accurate predictions of air pollutant indicator levels are possible with a simple neural network. It is shown that further optimizations of the model can be achieved using different input parameters and different experimental setups. Firstly, +1, +2, and +3 days' pollution levels are predicted independently using same training data, then +2 and +3 days are predicted cumulatively using previously days predicted values. Better prediction results are obtained in the cumulative method. Secondly, the size of training data base used in the model is optimized. The best modeling performance with minimum error rate is achieved using 3-15 past days in the training data set. Finally, the effect of the day of week as an input parameter is investigated. Better forecasts with higher accuracy are observed using the day of week as an input parameter.


Phase Separation Multi-phase Flow Using an Aqueous Two-phase System of a Polyethylene Glycol/Dextran Mixed Solution.
Polyethylene glycol/dextran mixed solution as an aqueous two-phase system was fed into a fused-silica capillary tube under different conditions, resulting in phase transformation leading to phase separation multi-phase flow through/along a liquid-liquid interface. As one flow-type example, when 6.4 wt% polyethylene glycol and 9.7 wt% dextran aqueous solution containing 1.0 mM Rhodamine B was fed into the capillary tube at 3°C, tube radial distribution flow (annual flow) was observed through bright-field microscopy. Tube radial distribution flow consisted of a dextran-rich inner phase and polyethylene glycol-rich outer phase. We also examined the distribution of proteins, such as bovine serum albumin, hemoglobin, and lysozyme, in the inner and outer phases through use of double capillary tubes with different inner diameters. The protein distribution was greater in the inner (dextran-rich) phase than the outer (polyethylene glycol-rich) phase. The distribution ratios of the three proteins (ratio of the inner/outer protein concentration) were 2.3, 4.2, and 1.8, respectively. The proteins concentrated in the dextran-rich phase through tube radial distribution flow of a polyethylene glycol/dextran mixed solution.


BGP: identifying gene-specific branching dynamics from single-cell data with a branching Gaussian process.
High-throughput single-cell gene expression experiments can be used to uncover branching dynamics in cell populations undergoing differentiation through pseudotime methods. We develop the branching Gaussian process (BGP), a non-parametric model that is able to identify branching dynamics for individual genes and provide an estimate of branching times for each gene with an associated credible region. We demonstrate the effectiveness of our method on simulated data, a single-cell RNA-seq haematopoiesis study and mouse embryonic stem cells generated using droplet barcoding. The method is robust to high levels of technical variation and dropout, which are common in single-cell data.


Simultaneous bilateral ganglion cysts of the anterior cruciate ligaments.
Intra-articular ganglion cysts of the anterior cruciate ligament (ACL) are rare, and bilateral ganglion cysts are even rarer. These cysts may cause intermittent or chronic nonspecific knee discomfort. Although three cases of bilateral ganglion cysts have been reported in the literature, the knees were not simultaneously affected in those cases. Herein, we report the case of a 56-year-old woman who presented with simultaneous bilateral ganglion cysts of the ACL that were symptomatic. She was successfully treated with arthroscopic resection and debridement. We also present a brief review of the literature, highlighting the aetiology, diagnosis and management of ganglion cysts of the ACL. To the best of our knowledge, this is the first report of simultaneous bilateral intra-articular ganglion cysts of the ACL.


Dynamic modelling of heart rate response under different exercise intensity.
Heart rate is one of the major indications of human cardiovascular response to exercises. This study investigates human heart rate response dynamics to moderate exercise. A healthy male subject has been asked to walk on a motorised treadmill under a predefined exercise protocol. ECG, body movements, and oxygen saturation (SpO2) have been reliably monitored and recorded by using non-invasive portable sensors. To reduce heart rate variation caused by the influence of various internal or external factors, the designed step response protocol has been repeated three times. Experimental results show that both steady state gain and time constant of heart rate response are not invariant when walking speed is faster than 3 miles/hour, and time constant of offset exercise is noticeably longer than that of onset exercise.


Introductory lecture: origins and applications of efficient visible photoluminescence from silicon-based nanostructures.
A variety of silicon-based nanostructures with dimensions in the 1-5 nm range now emit tunable photoluminescence (PL) spanning the visible range. Achievement of high photoluminescence quantum efficiency (PLQY) relies critically on their surface chemistry passivation and an impressive "tool box" of options have been developed. Two distinct PL bands are dominant. The "S-Band" (red-green emission with Slow microsecond decay) has PLQY that has steadily improved from ∼3% in 1990 to 65 ± 5% by 2017. The "F-Band" (blue-yellow with Fast nanosecond decay) has reported PLQY values that have improved from ∼0.1% in 1994 to as high as ∼90% by 2016. The vast literature on both bands is surveyed and for the S-band, size-structure-PL correlations and selective photo-excitation studies are highlighted. Resonant photoexcitation and single quantum dot studies have revealed the key role of quantum confinement and the excitonic phonon-assisted nature of the radiative transitions. For the F-band, in contrast, specific phenomenological studies are highlighted that demonstrate similar emission without the presence of silicon nanostructures. Low PLQY F-band emission from pure silicon-silica core shell systems is probably associated with oxide-related defects, but ultrahigh PLQY from many lower temperature synthesis routes is likely to be from carbon-based nanostructures or chromophores, not silicon nanostructures. Potential applications for both PL bands include sensing, medical imaging, theranostics, photovoltaics, LED colour converters and nano-thermometry. Emerging "green" synthesis routes are mentioned. If scalability and cost are significantly improved then a number of other proposed uses of ultra-efficient PL from "nano-Si" could become viable in cosmetics, catalysis, security and forensics.


Postoperative radiotherapy in stage I/II endometrial cancer: retrospective analysis of 883 patients treated at the University of Florence.
The efficacy of postoperative radiotherapy (RT) in the treatment of early-stage endometrial carcinoma (EC) is still under debate. This study was aimed to review the outcome and adverse effects in patients treated for EC with postoperative RT at a single center. A total of 883 patients with pathological stages I to II EC were retrospectively analyzed. Surgery consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy, or vaginal hysteroannessiectomy in 532 patients (60.2%) with pelvic lymphadenectomy in 351 patients (39.8%). Seven hundred forty-seven patients (84.6%) underwent whole pelvic RT (WPRT) and 136 (15.4%) combined WPRT and vaginal brachytherapy (BT) boost. At a median follow-up of 9 years (range, 1.2-27.6 years), we observed 10.6% disease relapse. Forty-seven patients experienced local recurrence (LR), and 38 patients experienced distant metastases (DMs). At univariate analysis, age at diagnosis (P < 0.0001), stage (P < 0.04), and histological subtype (P < 0.0001) resulted in significant prognostic factors. At multivariate analysis, histotype emerged as an independent relapse predictor (P = 0.0001). Acute WPRT-related toxicity was mild; diarrhea was the most common adverse effect (19.8%). We recorded long-term adverse effects in 7.8% of the patients. Our study showed that patients with early-stage EC have a good outcome in overall survival and disease-free survival. In our experience, standard surgery (including hysterectomy and bilateral salpingo-oophorectomy followed by WPRT with or without BT) showed an acceptable toxicity profile.


Dobutamine stress echocardiography and thallium-201 SPECT for detecting ischaemic dilated cardiomyopathy in patients with heart failure.
A diagnosis of ischaemic aetiology of a dilated cardiomyopathy has important therapeutic and prognostic implications. In such patients, abnormal ECG and atypical symptoms limit the usefulness of standard ECG-ergometry in detecting myocardial ischaemia. To assess the values of high-dose dobutamine stress echocardiography and of Thallium-201 SPECT (exercise-reinjection-rest protocol) in differentiating between ischaemic and non-ischaemic dilated cardiomyopathy, 37 patients with suspected myocardial ischemia, low ventricular ejection fraction (23 +/- 5%) and heart failure were studied. Coronary artery disease was defined as >50% coronary stenosis in at least one coronary artery. By dobutamine stress echocardiography, ischaemic dilated cardiomyopathy was considered present when either an ischaemic response (biphasic response or direct deterioration) or a scar (fixed dyssynergy) was documented in at least two segments. By Thallium-201 SPECT, severe perfusion defects, either reversible (ischaemia) or fixed (scar), in at least two segments were considered markers of ischaemic dilated cardiomyopathy. Twenty-three patients had ischaemic dilated cardiomyopathy, while 14 had normal coronary arteries. The presence of myocardial ischaemia and/or scar by dobutamine stress echocardiography identified patients with ischaemic dilated cardiomyopathy with a sensitivity of 100% and a specificity of 86%. The sensitivity of Thallium-201 SPECT was 92%, its specificity was 69%. Three of the four false positive results occurred in patients with left bundle branch block. Thirty-two patients were concordantly classified by the two techniques (agreement=86%, k=0.73). Both dobutamine stress echocardiography and Thallium-201 SPECT are sensitive techniques for detecting the ischaemic aetiology of dilated cardiomyopathy. The specificity is lower, particularly by SPECT, when left ventricular branch block is present.


Effects of electroacupuncture on experimental periodontitis in rats.
Acupuncture has shown the capability of modulating the immuno-inflammatory response of the host. This study aims to evaluate the effects of electroacupuncture (EA) on ligature-induced periodontitis in rats. Thirty-two animals were divided into four groups: 1) control; 2) experimental periodontitis (EP); 3) sham-treated (EP/EA-sham); and 4) treated with EA (EP/EA). For the EP groups, a ligature was placed around the right mandibular first molars at day 1. Sessions of EA or EA-sham were assigned every other day. For EA treatment, large intestine meridian points LI4 and LI11 and stomach meridian points ST36 and ST44 were used. EA-sham was performed in off-meridian points. Animals were euthanized at day 11. Histomorphometric and microtomographic analyses were performed. Immunolabeling patterns for the receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase (TRAP) were assessed. Expressions of interleukin (IL)-1β, matrix metalloproteinase (MMP)-8, IL-6, and cyclooxygenase (COX)-2 messenger RNAs (mRNAs) were evaluated by quantitative reverse transcription-polymerase chain reaction. Data were analyzed statistically (P <0.05, analysis of variance). Histomorphometric and microtomographic analyses demonstrated that group EP/EA presented reduced alveolar bone loss when compared to group EP (P <0.05). Reduced RANKL immunolabeling and fewer TRAP-positive multinucleated cells were observed in the EA-treated group in relation to group EP. No differences were observed in OPG expression among groups. EA treatment decreased the genic expression of IL-1β and MMP-8 (P <0.05), increased the mRNA expression of IL-6 (P <0.05), and did not modify the genic expression of COX-2 in animals with EP (P >0.05). It can be concluded that EA reduced periodontal tissue breakdown and the expression of some proinflammatory mediators and a proresorptive factor in EP in rats.


Encephalopathy Associated with Influenza B in a Healthy Young Man.
A 19-year-old man presented with a fever, convulsions, and loss of consciousness at our hospital. The patient had a Glasgow Coma Scale score of 12. Influenza B virus infection was diagnosed using the rapid test kit, and an eight-fold increase in the serum levels of anti-influenza B virus antibody was confirmed using the complement fixation test. Brain magnetic resonance imaging showed multifocal high-signal lesions, and an electroencephalogram showed diffuse slowing of the background activity, indicating acute encephalopathy. After treatment with peramivir and methylprednisolone for 3 days, the patient was discharged without any neurological impairment. This was a case of influenza B infection associated with acute encephalopathy in a healthy young man.


COVID-19 in children: Pathogenesis and current status.
Background: Since its initial description in December 2019 in Wuhan, China, coronavirus disease 2019 (COVID-19) has rapidly progressed into a worldwide pandemic, which has affected millions of lives. Unlike the disease in adults, the vast majority of children with COVID-19 have mild symptoms and are largely spared from severe respiratory disease. However, there are children who have significant respiratory disease, and some may develop a hyperinflammatory response similar to that seen in adults with COVID-19 and in children with Kawasaki disease (KD), which has been termed multisystem inflammatory syndrome in children (MIS-C). Objective: The purpose of this report was to examine the current evidence that supports the etiopathogenesis of COVID-19 in children and the relationship of COVID-19 with KD and MIS-C as a basis for a better understanding of the clinical course, diagnosis, and management of these clinically perplexing conditions. Results: The pathogenesis of COVID-19 is carried out in two distinct but overlapping phases of COVID-19: the first triggered by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) itself and the second by the host immune response. Children with KD have fewer of the previously described COVID-19-associated KD features with less prominent acute respiratory distress syndrome and shock than children with MIS-C. Conclusion: COVID-19 in adults usually includes severe respiratory symptoms and pathology, with a high mortality. It has become apparent that children are infected as easily as adults but are more often asymptomatic and have milder disease because of their immature immune systems. Although children are largely spared from severe respiratory disease, they can present with a SARS-CoV-2-associated MIS-C similar to KD.


Coding communication in consultation: Accurate, reliable, and efficient analysis.
Given the importance of consultation in school psychology practice, more research is needed to examine the types of interpersonal communication through which consultation is effective. This study revisited Erchul and Schulte (1990), which investigated the amount of transcription and coding of consultation sessions required for reliable and accurate estimates of particular consultation communication variables. Using Linguistic Inquiry and Word Count, this study examined tone, interrogatives, clout, affect, and use of the 1st-person plural pronoun within the instructional consultation, assessment, and teaming process. Results partially aligned with Erchul and Schulte in that tone, interrogatives, and clout could be reliably and accurately assessed by analyzing 1 complete consultation session or segments of 2 sessions. Affect and pronoun use could not be reliably and accurately measured by sampling segments of consultation sessions. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Entangled fates of holobiont genomes during invasion: nested bacterial and host diversities in Caulerpa taxifolia.
Successful prevention and mitigation of biological invasions requires retracing the initial steps of introduction, as well as understanding key elements enhancing the adaptability of invasive species. We studied the genetic diversity of the green alga Caulerpa taxifolia and its associated bacterial communities in several areas around the world. The striking congruence of α and β diversity of the algal genome and endophytic communities reveals a tight association, supporting the holobiont concept as best describing the unit of spreading and invasion. Both genomic compartments support the hypotheses of a unique accidental introduction in the Mediterranean and of multiple invasion events in southern Australia. In addition to helping with tracing the origin of invasion, bacterial communities exhibit metabolic functions that can potentially enhance adaptability and competitiveness of the consortium they form with their host. We thus hypothesize that low genetic diversities of both host and symbiont communities may contribute to the recent regression in the Mediterranean, in contrast with the persistence of highly diverse assemblages in southern Australia. This study supports the importance of scaling up from the host to the holobiont for a comprehensive understanding of invasions.


Demystified...adhesion molecule deficiencies.
The basic physiology of leucocyte emigration from the intravascular space into the tissues is now known to be dependent on a class of cell surface molecules that have come to be known as adhesion molecules. Many cell-cell interactions are dependent on adhesion and signal transduction via the various adhesion molecules, particularly the integrins. The study of the functions of these molecules has been enhanced by the development of blocking and activating monoclonal antibodies, knockout mice, and by the rare "experiments of nature" in the human population, in whom there is absence or dysfunction of one of the adhesion molecules. This review describes these leucocyte adhesion defects and discusses how they have provided important insights into the function of these molecules.


Treatment of sleep disturbance in alcohol recovery: a national survey of addiction medicine physicians.
Sleep disturbance is common among patients in recovery from alcoholism and can precipitate relapse. Though sleep complaints are commonly managed with medication, little is known about their management among recovering alcoholic patients. We performed a postal survey of a self-weighted, random systematic sample of 503 members of the American Society of Addiction Medicine (ASAM) to examine addiction medicine physicians' medical management of sleep disturbance among patients in early recovery from alcoholism. After 3 mailings, 311 (62%) responded. Of responents, 64% have offered pharmacological treatment to an insomniac, alcoholic patient in the first 3 months after detoxification, but only 22% offered medication to more than half of such patients. Trazodone was the preferred therapy, chosen first by 38% of respondents, followed by other sedating antidepressants (12%), and antihistamines (12%). The mean duration of therapy for trazodone and other sedating antidepressants exceeded one month. Experts in addiction medicine appear reluctant to prescribe medication to sleep-disturbed patients in early recovery from alcoholism. When they do prescribe, trazodone, other sedating antidepressants and antihistamines are favored, despite limited evidence for or against this indication. Although the treatment of disordered sleep among alcoholic patients in early recovery may have merit to prevent relapse, controlled studies of these sleep agents are needed.


Vasopressin for hemorrhagic shock management: revisiting the potential value in civilian and combat casualty care.
The evolution of trauma care is driven by a synergistic relationship between civilian and military medical systems. Although the characteristics of civilian injuries differ from those encountered on the battlefield, the pathophysiologic process of dying is the same and dominated by exsanguination and central nervous trauma. As such, therapies that interfere with the physiologic ability to compensate hemorrhage may play a key role to buy time until hemostatic surgery can be initiated. From a variety of remedies with the potential to prolong the compensation phase or to reverse the decompensation phase of shock, arginine vasopressin (AVP) is one of the most promising and best-evaluated drugs. Animal studies and various case report series provide some evidence that AVP may improve blood pressure even when conventional therapies fail, thus preventing hypovolemic cardiac arrest and enabling resuscitation from fatal hemorrhage. On the basis of this civilian experience, it seems reasonable to consider AVP for hypotensive resuscitation in the austere, resource-constrained battlefield environment. However, the significance of AVP as a rescue medication for life-threatening hemorrhage has yet to be proven.


A disability prevention programme for community-dwelling frail older persons.
To describe and justify a primary care interdisciplinary programme for community-dwelling frail older people aimed to prevent disability. Disability is a negative outcome of frailty among older persons. Policy reports and research studies emphasize the need for programmes to reduce disability progression. Between 2008 and 2010 we developed such a programme. Following the Intervention Mapping protocol, a research team and a multidisciplinary professional developed the programme. Literature reviews and an expert meeting led to identification of basic elements, theory-based methods and practical tools. THE PROGRAMME: The general practitioner and the practice nurse comprise the core team that can be extended by other professionals such as occupational and physical therapist. The programme includes six steps: (1) screening, (2) assessment, (3) analysis and preliminary action plan, (4) agreement on an action plan, (5) execution of the action plan (toolbox parts) and (6) evaluation and follow-up. The main features are: identifying risks for developing disability and targeting risk factors using professional standards and the 5A Behavioural Change Model to support self management, and identifying problems in performing activities and enhancing meaningful activities based on the Model of Human Occupation. Screening, individual assessment, tailor-made and client-centred care, self-management support, case management and interdisciplinary cooperation are important principles in delivering the programme. The disability-prevention programme seems promising for addressing the needs of frail older people for independent living and for targeting risk factors. Its feasibility and effects are currently being tested in a randomized controlled trial.


The effect of thiopurine drugs on DNA methylation in relation to TPMT expression.
The thiopurine drugs 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) are well-established agents for the treatment of leukaemia but their main modes of action are controversial. Thiopurine methyltransferase (TPMT) metabolises thiopurine drugs and influences their cytotoxic activity. TPMT, like DNA methyltransferases (DNMTs), transfers methyl groups from S-adenosylmethionine (SAM) and generates S-adenosylhomocysteine (SAH). Since SAM levels are dependent on de novo purine synthesis (DNPS) and the metabolic products of 6-TG and 6-MP differ in their ability to inhibit DNPS, we postulated that 6-TG compared to 6-MP would have differential effects on changes in SAM and SAH levels and global DNA methylation, depending on TPMT status. To test this hypothesis, we used a human embryonic kidney cell line with inducible TPMT. Although changes in SAM and SAH levels occurred with each drug, decrease in global DNA methylation more closely reflected a decrease in DNMT activity. Inhibition was influenced by TPMT for 6-TG, but not 6-MP. The decrease in global methylation and DNMT activity with 6-MP, or with 6-TG when TPMT expression was low, were comparable to 5-aza-2'-deoxycytidine. However, this was not reflected in changes in methylation at the level of an individual marker gene (MAGE1A). The results suggest that a non-TPMT metabolised metabolite of 6-MP and 6-TG and the TPMT-metabolised 6-MP metabolite 6-methylthioguanosine 5'-monophosphate, contribute to a decrease in DNMT levels and global DNA methylation. As demethylating agents have shown promise in leukaemia treatment, inhibition of DNA methylation by the thiopurine drugs may contribute to their cytotoxic affects.


Resveratrol induces FasL-related apoptosis through Cdc42 activation of ASK1/JNK-dependent signaling pathway in human leukemia HL-60 cells.
Trans-resveratrol, a phytoalexin found at high levels in grapes and in grape products such as red wine, has been shown to prevent carcinogenesis or antitumor growth in murine models. Here we dissect the detailed signaling pathway involved in resveratrol-induced apoptosis. Our data showed that treatment with resveratrol-induced activation of apoptosis signal-regulating kinase 1, a mitogen-activated protein kinase kinase kinase, in turn, activated the downstream kinases c-Jun N-terminal kinase and p38 mitogen-activated protein kinase, but not extracellular signal-regulated kinase. Transfection with a dominant-negative c-Jun N-terminal kinase expression vector reduced FasL expression and DNA fragmentation induced by resveratrol. However, inhibition of p38 mitogen-activated protein kinase activity by treatment with SB203580 (p38 mitogen-activated protein kinase specific inhibitor) or expression of mutant p38 mitogen-activated protein kinase expression vector did not alter the apoptosis and FasL expression in response to resveratrol. Furthermore, genetic inhibition of apoptosis signal-regulating kinase 1 signaling inhibited not only the activation of c-Jun N-terminal kinase, but also the expression of FasL and apoptosis. Similarly, over-expression of wild-type apoptosis signal-regulating kinase 1 strengthened the resveratrol-induced c-Jun N-terminal kinase activation, FasL expression and subsequent apoptosis. These results suggest the possible involvement of apoptosis signal-regulating kinase 1/c-Jun N-terminal kinase signaling in the regulation of FasL expression and subsequent apoptosis induced by resveratrol in HL-60 cells. Resveratrol also activated the small GTP-binding protein Cdc42, rather than other members such as RhoA or Rac1. Expression of a mutant Cdc42 (N17 Cdc42) dramatically reduced resveratrol-induced c-Jun N-terminal kinase activity, FasL expression and apoptotic cell death. These results showed that resveratrol induced apoptosis through the Cdc42/apoptosis signal-regulating kinase 1/c-Jun N-terminal kinase/FasL signaling cascade in HL-60 cells.


Roles of Pancreatic Islet Catecholamine Neurotransmitters in Glycemic Control and in Antipsychotic Drug-Induced Dysglycemia.
Catecholamine neurotransmitters dopamine (DA) and norepinephrine (NE) are essential for a myriad of functions throughout the central nervous system, including metabolic regulation. These molecules are also present in the pancreas, and their study may shed light on the effects of peripheral neurotransmission on glycemic control. Though sympathetic innervation to islets provides NE that signals at local α-cell and β-cell adrenergic receptors to modify hormone secretion, α-cells and β-cells also synthesize catecholamines locally. We propose a model where α-cells and β-cells take up catecholamine precursors in response to postprandial availability, preferentially synthesizing DA. The newly synthesized DA signals in an autocrine/paracrine manner to regulate insulin and glucagon secretion and maintain glycemic control. This enables islets to couple local catecholamine signaling to changes in nutritional state. We also contend that the DA receptors expressed by α-cells and β-cells are targeted by antipsychotic drugs (APDs)-some of the most widely prescribed medications today. Blockade of local DA signaling contributes significantly to APD-induced dysglycemia, a major contributor to treatment discontinuation and development of diabetes. Thus, elucidating the peripheral actions of catecholamines will provide new insights into the regulation of metabolic pathways and may lead to novel, more effective strategies to tune metabolism and treat diabetes.


Silicon substrate as a novel cell culture device for myoblast cells.
Tissue and organ regeneration via transplantation of cell bodies in-situ has become an interesting strategy in regenerative medicine. Developments of cell carriers to systematically deliver cell bodies in the damage site have fall shorten on effectively meet this purpose due to inappropriate release control. Thus, there is still need of novel substrate to achieve targeted cell delivery with appropriate vehicles. In the present study, silicon based photovoltaic (PV) devices are used as a cell culturing substrate for the expansion of myoblast mouse cell (C2C12 cells) that offers an atmosphere for regular cell growth in vitro. The adherence, viability and proliferation of the cells on the silicon surface were examined by direct cell counting and fluorescence microscopy. It was found that on the silicon surface, cells proliferated over 7 days showing normal morphology, and expressed their biological activities. Cell culture on silicon substrate reveals their attachment and proliferation over the surface of the PV device. After first day of culture, cell viability was 88% and cell survival remained above 86% as compared to the seeding day after the seventh day. Furthermore, the DAPI staining revealed that the initially scattered cells were able to eventually build a cellular monolayer on top of the silicon substrate. This study explored the biological applications of silicon based PV devices, demonstrating its biocompatibility properties and found useful for culture of cells on porous 2-D surface. The incorporation of silicon substrate has been efficaciously revealed as a potential cell carrier or vehicle in cell growth technology, allowing for their use in cell based gene therapy, tissue engineering, and therapeutic angiogenesis.


Sexual selection hinders adaptation in experimental populations of yeast.
Sexual selection, the suite of processes that lead to differential mating success among individuals, probably influences the evolutionary trajectory of populations. Because sexual selection often shifts traits away from their survival optima, strong sexual selection pressures are thought to increase potential for population extinction, especially during environmental change. Sexual selection pressures may also increase the opportunity for speciation by accelerating the generation of pre-zygotic isolation among populations. These relationships remain largely untested experimentally. Here, we allow populations of baker's yeast, Saccharomyces cerevisiae, to evolve for approximately 250 generations with altered sex ratios in order to test the effect of the strength of sexual selection on the fate of populations. We find that populations experiencing stronger sexual selection are less able to adapt to a novel environment compared with populations experiencing weaker sexual selection or no sex, and that strong sexual selection erases the benefits of sexual reproduction. This pattern persists when fitness is assayed in a closely related environment. We also identify a trend that may suggest the beginning of pre-zygotic isolation between populations experiencing stronger sexual selection, though this is not statistically significant. These results highlight the importance of sexual selection in shaping macroevolutionary patterns and biodiversity.


Life Cycle Assessment of Biogas Production in Small-scale Household Digesters in Vietnam.
Small-scale household digesters have been promoted across Asia as a sustainable way of handling manure. The major advantages are that they produce biogas and reduce odor. However their disadvantages include the low recycling of nutrients, because digestate is dilute and therefore difficult to transport, and the loss of biogas as a result of cracks and the intentional release of excess biogas. In this study, life cycle assessment (LCA) methodology was used to assess the environmental impacts associated with biogas digesters in Vietnam. Handling 1,000 kg of liquid manure and 100 kg of solid manure in a system with a biogas digester reduced the impact potential from 4.4 kg carbon dioxide (CO2) equivalents to 3.2 kg CO2 equivalents compared with traditional manure management. However, this advantage could easily be compromised if digester construction is considered in the LCA or in situations where there is an excess of biogas which is intentionally released. A sensitivity analysis showed that biogas digesters could be a means of reducing global warming if methane emissions can be kept low. In terms of eutrophication, farms with biogas digesters had 3 to 4 times greater impacts. In order to make biogas digesters sustainable, methods for recycling digestates are urgently required.


Pralatrexate, a dihydrofolate reductase inhibitor for the potential treatment of several malignancies.
Pralatrexate, a 10-deazaaminopterin derivative, is being developed by Allos Therapeutics Inc for the potential treatment of malignancies. The folate analog inhibits dihydrofolate reductase and was developed to overcome the limitations of the folate analog methotrexate. Compared with methotrexate in preclinical studies, pralatrexate demonstrated superior intracellular transport via the reduced folate carrier, and increased accumulation within cells by enhanced polyglutamylation. Preclinical studies in vitro and in models of B-cell lymphomas, T-cell lymphomas and NSCLC indicated that pralatrexate exhibited antitumor activity that was superior to the activity of other antifolates. In phase I clinical trials, the DLT for pralatrexate was mucositis, which could be abrogated with folic acid and vitamin B12 supplementation. The administration of pralatrexate to patients with T-cell lymphomas and NSCLC resulted in significant tumor remissions. At the time of publication, pralatrexate was in phase II clinical trials for the treatment of peripheral T-cell lymphoma, a phase I/II trial in combination with gemcitabine for the treatment of non-Hodgkin's lymphoma, and a phase IIb trial in comparison with erlotinib in patients with NSCLC. Because of the limited therapies available for peripheral T-cell lymphoma, pralatrexate could have a secure niche for the treatment of this indication, if ongoing clinical trials and future phase III trials confirm the efficacy of the drug. In contrast, for pralatrexate to be incorporated into the accepted treatment options for NSCLC, the drug will need to prove clear superiority to established agents.


Surveying polypeptide and protein domain conformation and association with FlAsH and ReAsH.
Recombinant polypeptides and protein domains containing two cysteine pairs located distal in primary sequence but proximal in the native folded or assembled state are labeled selectively in vitro and in mammalian cells using the profluorescent biarsenical reagents FlAsH-EDT2 and ReAsH-EDT2. This strategy, termed bipartite tetracysteine display, enables the detection of protein-protein interactions and alternative protein conformations in live cells. As proof of principle, we show that the equilibrium stability and fluorescence intensity of polypeptide-biarsenical complexes correlates with the thermodynamic stability of the protein fold or assembly. Destabilized protein variants form less stable and less bright biarsenical complexes, which allows discrimination of live cells expressing folded polypeptide and protein domains from those containing disruptive point mutations. Bipartite tetracysteine display may provide a means to detect early protein misfolding events associated with Alzheimer's disease, Parkinson's disease and cystic fibrosis; it may also enable high-throughput screening of compounds that stabilize discrete protein folds.


The Role of Transporters in Future Chemotherapy.
The expression of membrane transporter is often altered in cancer cells compared to their corresponding healthy cells. Since these proteins, classified into solute carriers (SLCs) and ATP-binding cassettes (ABCs), can carry not only endogenous compounds, nutrients, and metabolites, but also drugs across the cell membranes, they have a crucial role in drug exposure and clinical outcomes of chemotherapeutics. Curiously, up-regulation of SLCs can be exploited to deliver chemotherapeutics, their prodrugs, and diagnostic radio-tracers to gain cancer cell-selective targeting, as exemplified with L-type amino acid transporter 1 (LAT1). SLCs can also be inhibited to limit the nutrient uptake of cancer cells and thus, cell growth and proliferation. Furthermore, LAT1 can be utilized to deliver ABC-inhibitors selectively into the cancer cells to block the efflux of other chemotherapeutics suffering from acquired or intrinsic efflux transport-related multidrug resistance (MDR). Taking into account the current literature, compounds that can affect transporter up- or down-regulation of transporters in a cancer cell-selective manner could be a valuable tool and promising chemotherapy form in the future.


Developing and validating five-construct model of customer satisfaction in beauty and cosmetic E-commerce.
Grounded on the American Customer Satisfaction Framework (ACSF) of Bryant (1995), the European Customer Satisfaction Framework Model (ECSF) of Anderson and Fornell (2000), and Eleven-factor Customer Satisfaction Model of Hokanson (1995), this study develops reliable and valid five constructs of customer satisfaction theoretical model and build up a questionnaire in the unique context of Beauty and Cosmetic Online Shopping in the Vietnamese market. More specifically, we identified five main constructs including 5 implementation constructs (i.e., online shopping experience, customer service, external incentives, security/privacy, and personal characteristics), and one outcome construct (i.e., customer satisfaction). A detailed questionnaire was then developed with items for these constructs along with the questions on the personal characteristics of the respondents. The questionnaire was sent to randomly consumers via online channels including Facebook. The target participants are Vietnamese people who have experience in shopping online products like beauty and cosmetics. Based on 334 full responses have been received, we use Exploratory Factor Analysis (EFA) to test for 167 observations to ensure that all items in each scale reflected sufficiently the scope of each construct. This technique helps to identify the underlying dimensions of consumer satisfaction. Furthermore, we also employ Confirmatory Factor Analysis (CFA) to validate the constructs and items in questionnaire. To do this, we have used the sample of 167 responses. Finally, together with results from SEM models, our study contributes to providing a reliable and valid questionnaire which fully reflect for our self-constructed theoretical model of five constructs including Online shopping experience (OSE), External incentives (EI), Seller service (SS), and Security/privacy (SP), as well as personal characteristics (PC).


Antineophobic effect of the neuroactive steroid 3alpha-hydroxy-5beta-pregnan-20-one in male rats.
The neuroactive steroid 3alpha-hydroxy-5beta-pregnan-20-one (pregnanolone) and benzodiazepine receptor (BZR) agonists share sedative, anxiolytic, and anticonvulsant properties. Recent evidence suggests that like BZR agonists, pregnanolone may also modulate feeding responses. The present experiments examined the behavioral mechanisms responsible for any hyperphagic effect of pregnanolone. The effect of pregnanolone (1-10 mg/kg i.p.) on the intake and microstructure of licking for two sucrose solutions (1 and 3%) in well familiarized nondeprived male rats under either light or dark conditions was examined. Pregnanolone had no effect on either intake or the duration or number of bouts of licking in these experiments, although in all cases the intrabout lick rate was significantly reduced at the highest dose. Pregnanolone (1-10 mg/kg) also failed to increase intake of a sweet wet mash in familiarized nondeprived male rats. However, in a food choice test where both novel and familiar food items were available, pregnanolone (1-3 mg/kg) significantly increased the time spent eating the novel food. These results suggest that unlike BZR agonists, which enhance feeding responses directly, pregnanolone may facilitate feeding secondarily via an attenuation of anxiety.


[Comparative biology and feeding behavior of Rhodnius neglectus and Rhodnius robustus (Triatominae) under laboratory conditions].
The vector competence of triatomine insects is determined by studying their biology and feeding behavior under field and/or laboratory conditions. Factors including the number of bites, the amount of blood ingested and defecation time have implications for trypanosome transmission. The biological and behavioral parameters of Rhodnius neglectus and R. robustus were compared under experimental conditions to estimate differences in the potential transmission of trypanosomes. The insects were observed daily to determine the period of nymphal development, mortality, detection of food source, number of bites, time of blood meal intake, amount of blood ingested, time elapsed between the end of the meal and the first defecation and the frequency of defecation. Although the nymphal development of R. neglectus (156.4 ± 25.05d) was lower than that of R. robustus (204.7 ± 13.22d), the mortality between species was similar (63.8 and 65% respectively).R. robustus and R. neglectus quickly located the food source, especially in the first instar (2.5 and 1.6 min, respectively). Although the time of blood meal intake was similar between the species, R. robustus ingested a larger amount of blood on average at all stages and exhibited higher values for the fifth instar. Nymphs of R. neglectus bit more frequently, and they defecated faster and more often than those of R. robustus. Under laboratory conditions, R. neglectus has a greater potential for transmission of Trypanosoma cruzi and T. rangeli than does R. robustus, an attribute that should be further evaluated in experimental infections.


Evaluating the Communication of Online Social Support: A Mixed-Methods Analysis of Structure and Content.
Social support in online self-help groups has been found to benefit participants with emotional instability or mental illness. Many studies have employed content analysis to reveal categories of social support, claiming the prevalence of emotional and informational support can aid support seekers. In the studies, optimal matching theory is used to explain the helpfulness of these types of support. This article argues that content analysis is unpersuasive in its claim that support seekers benefit from social support; participants' communicative behaviors should also be considered to evaluate the potential advantages and drawbacks of such groups. Drawing on a mixed-method approach of conversation analysis and content analysis, this study investigates the sequential structure and content of social support in communication in six online self-help groups for anxiety and depression (OSGADs). The main findings show that optimal matching theory may not be suitable for elucidating how support seekers receive help due to the immediate provision of social support and little interaction otherwise. In addition, results identify expressed understanding/empathy and advice as prominent support categories in OSGADs, with most thread openers requesting support indirectly.


[Cardiosynchronized perfusion of the coronary sinus as a method of myocardial revascularization].
The possibility of revascularization of the myocardium in acute ischemia by means of cardiosynchronized retrograde perfusion of the coronary sinus with arterial blood was studied. Signs of a decrease of the ischemic zone and improvement in the metabolism of the intact myocardium were noted.


Cryoglobulins, circulating immune complexes, and complement activation in cerebral malaria.
A total of 32 patients with Plasmodium falciparum malaria were studied. Of these, 23 had benign infections, and 9 had typical cerebral malaria. Cryoglobulins, circulating immune complexes detected by a C1q-binding assay, and hypocomplementemia were found in eight of nine patients with cerebral malaria. Raised levels of complement component 3 breakdown products (C3d) were found in the seven patients tested. Peak levels of circulating immune complexes and C3d were associated with thrombocytopenia. In contrast, in patients with benign Plasmodium falciparum malaria, cryoglobulins and circulating immune complexes were found only in 3 of 23 patients. Similarly, hypocomplementemia was detected only in 5 of 23 patients. These observations suggest that the intensity of the immune response and of the associated complement activation may be important factors in the pathogenesis of cerebral malaria.


Analyzing the locomotory gaitprint of Caenorhabditis elegans on the basis of empirical mode decomposition.
The locomotory gait analysis of the microswimmer, Caenorhabditis elegans, is a commonly adopted approach for strain recognition and examination of phenotypic defects. Gait is also a visible behavioral expression of worms under external stimuli. This study developed an adaptive data analysis method based on empirical mode decomposition (EMD) to reveal the biological cues behind intricate motion. The method was used to classify the strains of worms according to their gaitprints (i.e., phenotypic traits of locomotion). First, a norm of the locomotory pattern was created from the worm of interest. The body curvature of the worm was decomposed into four intrinsic mode functions (IMFs). A radar chart showing correlations between the predefined database and measured worm was then obtained by dividing each IMF into three parts, namely, head, mid-body, and tail. A comprehensive resemblance score was estimated after k-means clustering. Simulated data that use sinusoidal waves were generated to assess the feasibility of the algorithm. Results suggested that temporal frequency is the major factor in the process. In practice, five worm strains, including wild-type N2, TJ356 (zIs356), CL2070 (dvIs70), CB0061 (dpy-5), and CL2120 (dvIs14), were investigated. The overall classification accuracy of the gaitprint analyses of all the strains reached nearly 89%. The method can also be extended to classify some motor neuron-related locomotory defects of C. elegans in the same fashion.


Hypoxia as a target for drug combination therapy of liver cancer.
Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer deaths worldwide. The standard of care for intermediate HCC is transarterial chemoembolization, which combines tumour embolization with locoregional delivery of the chemotherapeutic doxorubicin. Embolization therapies induce hypoxia, leading to the escape and proliferation of hypoxia-adapted cancer cells. The transcription factor that orchestrates responses to hypoxia is hypoxia-inducible factor 1 (HIF-1). The aim of this work is to show that targeting HIF-1 with combined drug therapy presents an opportunity for improving outcomes for HCC treatment. HepG2 cells were cultured under normoxic and hypoxic conditions exposed to doxorubicin, rapamycin and combinations thereof, and analyzed for viability and the expression of hypoxia-induced HIF-1α in response to these treatments. A pilot study was carried out to evaluate the antitumour effects of these drug combinations delivered from drug-eluting beads in vivo using an ectopic xenograft murine model of HCC. A therapeutic doxorubicin concentration that inhibits the viability of normoxic and hypoxic HepG2 cells and above which hypoxic cells are chemoresistant was identified, together with the lowest effective dose of rapamycin against normoxic and hypoxic HepG2 cells. It was shown that combinations of rapamycin and doxorubicin are more effective than doxorubicin alone. Western Blotting indicated that both doxorubicin and rapamycin inhibit hypoxia-induced accumulation of HIF-1α. Combination treatments were more effective in vivo than either treatment alone. mTOR inhibition can improve outcomes of doxorubicin treatment in HCC.


Mortality in Pedigrees with Acute Intermittent Porphyria.
High mortality rates have been reported in historical cohorts of acute intermittent porphyria (AIP) patients. The mortality associated with (hydroxymethylbilane synthase) HMBS variant heterozygosity is unknown. This study estimates all-cause mortality in pedigrees with HMBS gene variants that cause AIP. We collected data on the lifespan of individuals in Dutch AIP pedigrees and performed analyses using the family tree mortality ratio method. This gave us standardized mortality ratios for these pedigrees compared to the Dutch general population as a primary outcome. Between 1810 and 2017, the overall mortality in these pedigrees was identical to that of the general Dutch population: (SMR 1.01, p = 0.441). However, compared with the general population the SMR was significantly higher in women aged 45−64 years (SMR 1.99, p = 0.00003), which was based on excess mortality between 1915 and 1964 (SMR 1.94, p < 0.00002). In men aged 70−74 years, the SMR was 1.55 (p = 0.0021), based on excess mortality that occurred between 1925 and 1964 (SMR 1.92, p = 0000000003). Overall, mortality from HMBS variant heterozygosity was not increased compared with the general population. Severe excess mortality occurred in young women and old men between 1915 and 1964. Heterozygotes reached a normal lifespan during the past half-century, in parallel with disease awareness and the prevention of new attacks through family counselling.


Supplementation of L-carnitine improves mitochondrial enzymes in heart and skeletal muscle of aged rats.
Aging is characterized by a general decline in physiological functions that affects many tissues and increases the risk of death. Deterioration of mitochondria, the major source and target of reactive oxygen species (ROS), is implicated in aging and a variety of age-related diseases. In the present study, the activities of citric acid cycle enzymes, such as isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase, were found to be decreased in aged rats as well as that of electron-transferring enzymes such as NADH dehydrogenase and cytochrome c oxidase. After supplementation of carnitine to aged rats, the activities of these enzymes reverted nearer to that of young control rats. These findings suggest that L-carnitine improves the activities of mitochondrial enzymes, increases the electron flow through the electron transport chain, and improves reducing equivalence, thereby improves energy status in aged rats.


Analysis and prediction of antibacterial peptides.
Antibacterial peptides are important components of the innate immune system, used by the host to protect itself from different types of pathogenic bacteria. Over the last few decades, the search for new drugs and drug targets has prompted an interest in these antibacterial peptides. We analyzed 486 antibacterial peptides, obtained from antimicrobial peptide database APD, in order to understand the preference of amino acid residues at specific positions in these peptides. It was observed that certain types of residues are preferred over others in antibacterial peptides, particularly at the N and C terminus. These observations encouraged us to develop a method for predicting antibacterial peptides in proteins from their amino acid sequence. First, the N-terminal residues were used for predicting antibacterial peptides using Artificial Neural Network (ANN), Quantitative Matrices (QM) and Support Vector Machine (SVM), which resulted in an accuracy of 83.63%, 84.78% and 87.85%, respectively. Then, the C-terminal residues were used for developing prediction methods, which resulted in an accuracy of 77.34%, 82.03% and 85.16% using ANN, QM and SVM, respectively. Finally, ANN, QM and SVM models were developed using N and C terminal residues, which achieved an accuracy of 88.17%, 90.37% and 92.11%, respectively. All the models developed in this study were evaluated using five-fold cross validation technique. These models were also tested on an independent or blind dataset. Among antibacterial peptides, there is preference for certain residues at N and C termini, which helps to demarcate them from non-antibacterial peptides. Both the termini play a crucial role in imparting the antibacterial property to these peptides. Among the methods developed, SVM shows the best performance in predicting antibacterial peptides followed by QM and ANN, in that order. AntiBP (Antibacterial peptides) will help in discovering efficacious antibacterial peptides, which we hope will prove to be a boon to combat the dreadful antibiotic resistant bacteria. A user friendly web server has also been developed to help the biological community, which is accessible at http://www.imtech.res.in/raghava/antibp/.


A case of Vibrio vulnificus infection complicated with fulminant purpura: gene and biotype analysis of the pathogen.
Introduction.Vibrio vulnificus (V. vulnificus) causes a severe infection that develops in the compromised host. Its pathophysiology is classified into three types: (1) primary septicaemia, (2) gastrointestinal illness pattern and (3) wound infection pattern. Of these, primary septicaemia is critical. V. vulnificus can be classified into three biotypes and two genotypes and its pathogenicity is type-dependent. Case presentation. A 47-year-old man presented to a local hospital with chief complaints of fever, bilateral lower limb pain and diarrhoea. He had no history of foreign travel or known medical problems. He was in septic shock and developed fulminant purpura within 24 h of the onset. High-dose vasopressor and antibiotic administration failed to alter his status and he died 3 days after the onset of symptoms. V. vulnificus was isolated from blood, skin and nasal discharge cultures. Biotype and gene analysis of the microbe isolated identified it as Biotype 3, mainly reported in Israel in wound infections, and Genotype E, implicating an environmental isolate. These typing analyses indicated that the microbe isolated could be classified as a type with low pathogenicity. Conclusion. This case highlighted that Biotype 3 and Genotype E can also cause primary septicaemia. Although the majority of reports on Biotype 3 have been from the Middle East, this experience with the present case provided evidence that the habitat of Biotype 3 V. vulnificus has been extending to East Asia as well.


Beyond catalysis: N-heterocyclic carbene complexes as components for medicinal, luminescent, and functional materials applications.
This tutorial review compiles the advances that have been achieved in using transition metal complexes containing N-heterocyclic carbene ligands as components for materials. Applications of metal carbene complexes in fields different from catalysis are remarkably scarce. During the last few years, promising results have been accomplished in particular by utilizing such complexes as antimicrobial and cytotoxic agents, as photoactive sites in luminescent materials, for self-assembly into liquid crystalline materials and metallosupramolecular structures, and as synthons for molecular switches and conducting polymeric materials. These initial achievements clearly underline the great potential of N-heterocyclic carbene complexes in various fields of materials science.


The Simultaneity of Coronary Artery Ectasia and Intracranial Arterial Dolichoectasia: A Rare Case Report.
In the present study, we report a case of multiple coronary artery ectasias (CAE) and multiple intracranial arterial dolichoectasias (IADEs). A 60-year-old female presented to the emergency department twice with chest pain and mild elevation of troponin and T-wave changes. Peripheral coronary angiography showed severe ectasia and stenosis of certain segments of the left main coronary artery (LMCA), left anterior descending (LAD), first obtuse marginal (OM1), distal left circumflex (LCX), and bilateral subclavian arteries. The patient was treated medically. Two weeks later, she presented with dizziness. Head computerized tomography (CT) angiography showed severe IADE involving the vertebrobasilar system, intracranial internal carotid arteries, and bilateral middle cerebral arteries. No neurovascular intervention was performed due to the complexity of the findings. CAE is an abnormal dilatation of a coronary artery segment of at least 1.5 times the size of a normal coronary artery. The slow flow phenomenon may lead to ischemia and thrombosis, which can result in acute coronary syndrome. IADE comprises a dilatation and elongation of the arteries that affects both the anterior and posterior cerebral circulation, often causing neurological complications such as ischemic stroke, intracranial hemorrhage, or compression of surrounding neural structures. We report this case due to the rarity of coexisting IADE and CAE. A rarefaction of elastic tissue of the media with degeneration of the internal elastic lamina, in addition to matrix metalloproteinase dysfunction, is a common pathological mechanism for this condition. The management of CAE and IADE is mostly conservative, essentially treating the risk factors and administering antiplatelet and anticoagulant agents. In some patients, angioplasty vs. surgical treatment may be applied.


Conjunctival Goblet Cell Function: Effect of Contact Lens Wear and Cytokines.
This review focuses on conjunctival goblet cells and their essential function in the maintenance of eye health. The main function of goblet cells is to produce and secrete mucins that lubricate the ocular surface. An excess or a defect in those mucins leads to several alterations that makes goblet cells central players in maintaining the proper mucin balance and ensuring the correct function of ocular surface tissues. A typical pathology that occurs with mucous deficiency is dry eye disease, whereas the classical example of mucous hyperproduction is allergic conjunctivitis. In this review, we analyze how goblet cell number and function can be altered in these diseases and in contact lens (CL) wearers. We found that most published studies focused exclusively on the goblet cell number. However, recent advances have demonstrated that, along with mucin secretion, goblet cells are also able to secrete cytokines and respond to them. We describe the effect of different cytokines on goblet cell proliferation and secretion. We conclude that it is important to further explore the effect of CL wear and cytokines on conjunctival goblet cell function.


[Fetal death in placental abruption: comparison of two different time periods].
To compare the incidence of placental abruption (PA), fetal death and the profile of maternal factors associated with fetal death in pregnancies affected by placental abruption during two different time periods in the same hospital. retrospective study between January 1, 1994 and December 31, 1997 and April 1, 2001 and March 31, 2005, including singleton pregnancies with a birth weight higher than 500 g and gestational age of more than 20 weeks. Factors analyzed were maternal age, race, obstetric history, presence of arterial hypertension or premature rupture of membranes, presence of genital bleeding, presence of amniotic fluid contaminated with blood, characteristics of uterine tonus, occurrence of renal insufficiency, postpartum coagulopathy, puerperal anemia, gestational age and weight at birth. there were 7692 births in the 1994-1997 period, placental abruption incidence of 0.78% (60 cases); 8644 births occurred in the 2001-2005 period, placental abruption incidence of 0.59% (51 cases), with no statistical difference. During the 1994-1997 period, proportion of cases without genital bleeding was significantly higher in the group whose fetuses died compared to cases of live born fetuses (57.9% vs 22.0%; p=0.01). During the 2001-2005 period, proportion of cases with uterine hypertonia was significantly higher in the group whose fetuses died compared to cases of live born fetuses (66.7% vs 29.3%; p=0.04). Postpartum maternal complications were more frequent in cases of fetal death during both periods (31.6% vs 4.9%; p=0.009; and 50% vs 5.1%; p=0.001, respectively). Placental abruption continues to be a serious obstetric problem, with fatal consequences, especially when the placental abruption area is large. Maternal clinical symptoms are more severe in cases of fetal death.


The cognitive effect of anticholinergics for patients with overactive bladder.
Overactive bladder (OAB) is often treated with medications that block the cholinergic receptors in the bladder (known as anticholinergics). The effect of this medication class on cognition and risk of dementia has been increasingly studied over the past 40 years after initial studies suggested that the anticholinergic medication class could affect memory. Short-term randomized clinical trials demonstrated that the administration of the anticholinergic oxybutynin leads to impaired memory and attention, and large, population-based studies showed associations between several different anticholinergic medications and dementia. However, trials involving anticholinergics other than oxybutynin have not shown such substantial effects on short-term cognitive function. This discordance in results between short-term cognitive safety of OAB anticholinergics and the long-term increased dementia risk could be explained by the high proportion of patients using oxybutynin in the OAB subgroups of the dementia studies, or a study duration that was too short in the prospective clinical trials on cognition with other OAB anticholinergics. Notably, all studies must be interpreted in the context of potential confounding factors, such as when prodromal urinary symptoms associated with the early stages of dementia lead to an increase in OAB medication use, rather than the use of OAB medication causing dementia. In patients with potential risk factors for cognitive impairment, the cautious use of selected OAB anticholinergic agents with favourable physicochemical and pharmacokinetic properties and clinical trial evidence of cognitive safety might be appropriate.


The hyperparathyroidism-jaw tumour syndrome in a Portuguese kindred.
The hyperparathyroidism-jaw tumour (HPT-JT) syndrome is an autosomal dominant disease characterized by the occurrence of parathyroid tumours and fibro-osseous tumours of the jaw bones. Some HPT-JT patients may also develop renal abnormalities, which include Wilms' tumours, hamartomas and polycystic disease. The HPT-JT gene has been mapped to chromosome 1q25-q31, and we report the clinical and genetic findings in a kindred from central Portugal. HPT-JT was observed in six members from three generations; all had primary hyperparathyroidism (five had parathyroid adenomas, one a parathyroid carcinoma). Ossifying jaw fibromas affecting the maxilla and/or mandible were observed in 5/6. Renal cysts (<2.5 cm) were observed in four. Genetic studies using 18 polymorphic loci from chromosome 1q25-q31, together with leukocyte DNA from 11 family members and tumour DNA from three parathyroids (two adenomas and one carcinoma), revealed loss of tumour heterozygosity in the parathyroid carcinoma only, and the retained haplotype was found to cosegregate with the disease in the six affected members. A new Portuguese kindred with the HPT-JT syndrome that maps to chromosome 1q25-q31 has been identified, and these findings will help in the further characterization of this inherited disorder.


Magnitude and leading causes of in-hospital mortality at Aminu Kano Teaching Hospital, Kano, northern Nigeria: a 4-year prospective analysis.
Population based mortality data are scarce especially in developing countries including Nigeria. Despite its limitations, hospital mortality analysis assesses the quality of health-care delivery and provides a proximate measure of mortality. We reviewed the magnitude and causes of death among in-patients in a tertiary hospital in northern Nigeria. Analysis of mortality rate and causes of death for the period 2005-2008 (inclusive) in Aminu Kano Teaching Hospital. Causes of death were prospectively entered on a database and classified according to the International Classification of Diseases (ICD- 10). Out of 51,975 patients admitted to the hospital, 4,029 of them died. This gives a mortality rate of 7.8% (95% Confidence Interval of 7.5% to 8.0%). Specifically, of the 15,484 males admitted, 2,361 died giving a mortality rate of 15.2% while of the 36,491 females admitted, 1,668 died giving a mortality rate of 4.6%. The median age for all patients that died was 32.4 years (range: less than 1 day to 101 years), but 36.1 years (range: less than 1 day to 101 years) for the male and 29.3 (range: less than 1 day to 87 years) for the female subsets. The ten most common causes of mortality were HIV/AIDS (8.3%), Septicaemia (6.8%), cerebrovascular disease (6.3%), chronic renal failure (3.9%) chronic liver disease (3.3%), diabetes mellitus (3.2), neonatal jaundice (2.9%), severe birth asphyxia (2.6%), prematurity (2.5%) and bronchopneumonia (2.4%). The mortality rate and causes of death are comparable to similar centres. Regular mortality audits could identify management errors and prevent recurrence of avoidable deaths.


Surveillance issues in inflammatory bowel disease: ulcerative colitis.
This review article on the surveillance of patients with ulcerative colitis provides an overview of the criteria for evaluating screening and surveillance programs and applies the criteria to the available evidence to determine the effectiveness of the surveillance of patients with ulcerative colitis. We examine the clinical outcomes associated with surveillance, the additional clinical time required to confirm the diagnosis of dysplasia and cancer, compliance with surveillance and follow-up, and the effectiveness of the individual components of a surveillance program, including colonoscopy and pathologist's interpretation. The disability associated with colectomy is considered, as are the cost and acceptability of surveillance programs. Patients with long-standing ulcerative colitis are at risk for developing colorectal cancer. Recommended surveillance colonoscopy should be supported. New endoscopic and histopathologic techniques to improve the identification of high-risk patients may enhance the effectiveness and cost-effectiveness of surveillance practices.


An Examination of How People Appraise and Manage Health-Related Financial Uncertainty.
While health care is one of the largest stressors across all incomes and political affiliations, it is unclear how people with health-related financial uncertainty appraise and manage this ambiguity. Using the lens of Uncertainty Management Theory (UMT) and a thematic analysis of semi-structured, in-depth interviews with 17 individuals facing financial and health struggles, we uncovered how intersecting financial and medical uncertainty exacerbated participants' medical worries, worsening and compromising their mental and physical health. Additionally, we revealed how participants managed health-related financial uncertainty through seeking social support, seeking information to reduce financial burden, enacting financial concessions, making health sacrifices, avoiding information and thoughts about health costs, and adapting to chronic financial uncertainty. This study extends UMT by foregrounding the ways individuals' environmental resources (i.e., limited financial means) can jeopardize tending to their health, illustrating how uncertainty management is connected not only to communication strategies but also to health behaviors, such as tapering or skipping medications or procedures.


The incidence of whiplash trauma and the effects of different factors on recovery.
We performed a prospective study of patients with a whiplash trauma to the cervical spine to describe the incidence of these injuries and to evaluate prognostic factors for disability and recovery. A total of 356 patients were enrolled in the study. All the patients received a comprehensive questionnaire after the injury, and 296 cases responded to the follow-up protocol more than 1 year after the accident. Disability related to the whiplash trauma was used as the outcome variable for the assessment of prognostic factors. The annual incidence of acute whiplash trauma in the catchment area was 4.2 per 1,000 inhabitants and 3.2 per 1,000 for whiplash-associated disorder grades 1-3. Thirty-two percent reported persisting disability at follow-up. The following factors were significantly associated with a poor prognosis: pretraumatic neck pain, low educational level, female gender, and whiplash-associated disorder grades 2-3.


Radiation dose distributions and their optimization.
The current situation in the radiotherapy treatment of carcinoma of the larynx is discussed from a physicist's point of view and in the light of the results of one series of patients. The results suggest that the spatial distribution of dose obtainable with supervoltage irradiation for treatment of T1, to T4 No Mo cases is not far from the ideal, and that it is not difficult to prescribe an optimal distribution. A significant difference in the rate of local cure was found between those treated to a CRE value greater than 1,750 and those treated to less than 1,750. Gothenburg results supporting this finding are quoted. Methods are suggested of optimizing the dose distribution in time by increasing the effect on tumor cells without exceeding an acceptable tolerance to normal tissues.


Change in intersegmental foot and ankle motion after a high tibial osteotomy in genu varum patients.
High tibial osteotomy (HTO) is a well-established treatment for medial compartment knee osteoarthritis (OA), which shifts the weight-bearing axis from the medial to the lateral side of the knee. As the adjacent ankle joint may be directly affected by the change in biomechanics, this study aimed to evaluate the change in the intersegmental foot and ankle motion after HTO in patients with genu varum. The study included 24 patients who underwent HTO, and 48 older healthy participants as a control group. Segmental foot kinematics were evaluated using a 3D multisegment foot model, and gait data of temporal and spatial parameters were obtained. After HTO, normalized stride length significantly increased with a tendency for increases in gait speed. In hallux kinematics relative to the forefoot, the sagittal motions of both the patients and the control group were similar throughout the majority of the gait cycle. In forefoot kinematics relative to the hindfoot, the pre-HTO state revealed significant pronation throughout the gait cycle, while the post-HTO state showed a similar position and motion to the control group. In hindfoot kinematics relative to the tibia, coronal motions of the pre-HTO state showed supination throughout the gait cycle, while supination during the stance phase decreased after HTO. Genu varum patients with medial compartment knee OA showed different gait parameters and intersegmental motion during gait when compared with age- and gender-matched controls. The effect of HTO was demonstrated by the normalization of midfoot compensation in patients with genu varum.